RENAL REPLACEMENT THERAPY

(Primer for Physicians)

Editors
Narinder Pal Singh
Dinesh Khullar
Vineet Behera
Garima Agarwal

Association of Physicians of India

Indian College of Physicians

1
 Contributors
Dr Abhishek Singh Dr Prabhat Chauhan
Consultant Nephrologist Consultant Nephrologist
Max Super Speciality Hospital INHS Asvini
Saket, New Delhi Mumbai

Mr. Anish Kumar Gupta Dr Rakesh Jagprasad Yadav

Consultant (Research & Development) Senior Resident Medicine
FMHS, SGT University INHS Asvini
Gurugram, Haryana Mumbai

Prof Dinesh Khullar Dr Sachin Srivastava

Chairman & HOD, Nephrology Consultant Nephrologist
Max Super Speciality Hospital Command Hospital
Saket, New Delhi Udhampur

Dr Garima Agarwal Dr Sambit Sundaray

Consultant Nephrologist Consultant Nephrologist
Manipal Hospital Command Hospital
Bangalore Bangalore

Prof Narinder Pal Singh Dr Vineet Behera

Professor Medicine & Dean Research Consultant Nephrologist
Eternal University Associate Professor Medicine
Himachal Pradesh INHS Asvini, Mumbai

2
 Preface
Renal Replacement Therapy is the most essential aspect in the management of
chronic kidney diseases. With greater advances in healthcare, there have been
several new developments and modifications in the forms of renal replacement
therapy. Both hemodialysis and peritoneal dialysis have come a long way and the
present forms are far more effective and diverse. Even, the field of renal transplant
has revolutionized with better transplant procedures, newer immunosuppressive
drugs, and newer advances. The new developments bring with them new complexities
and newer set of problems or complications.

APICON is one of the best platforms for updating the ever-dynamic medical field. A
Renal Replacement Therapy workshop and primer will help apprise the medical
students, post graduates, clinicians, subspecialists, practicing physicians and
residents about the concept of Renal Replacement Therapy. This will help them in
better identification of the nuances, advances, functioning, and complications of Renal
Replacement Therapy.

We extend our sincere utmost gratitude to Dr Girish Mathur, President, Association of

Physicians of India, and Dr Alaka Deshpande, Dean, Indian College of Physicians for
their whole hearted support and guidance in this endeavour. We hope that this primer
on Renal Replacement Therapy is helpful to all physicians. We sincerely acknowledge
Mr. Anish Gupta for his editorial assistance.

Happy Reading

Editorial Team

1
 Foreword

The global burden of CKD is rapidly increasing and has become one of the leading
causes of mortality and morbidity around the world. As the world of medical sciences
progress there has been a dynamic change in the management of chronic kidney
disease with renal replacement therapies becoming the most essential part of it.
Hemodialysis, peritoneal dialysis and kidney transplant are the different methods of
renal replacement therapies.

With the increasing number of CKD patients, the majority of nephrology practice is
being devoted to RRT. Most patients report to primary physicians and family
physicians either in the early stages of CKD or with RRT related problems. As
clinicians and physicians of the contemporary era, it has become of utmost importance
to be well versed with the methods, initiation, nuances, and complications of renal
replacement therapies. Dr Narinder Pal Singh and his team has come out with this
excellent book on “Renal Replacement Therapy”. The content and concept are very
well described and will surely contribute the physicians, post graduates and students
with concise and relevant information on the methods, variations and complications of
renal replacement therapy.

I congratulate Dr Narinder Pal Singh, Dr Dinesh Khullar and the entire team of
nephrologists and faculty for their contribution to this book.

Happy reading.

Jai Hind
Dr. YP Munjal
Former – President API
Former – Dean ICP
Former – Director PRF

2
 Foreword
President – API

Chronic kidney disease has emerged as one of the leading causes of mortality
worldwide. Renal replacement therapy which involves hemodialysis, peritoneal
dialysis and kidney transplant, has become the cornerstone in management of
advanced chronic kidney disease or end stage renal disease. Renal replacement
therapy constitutes the bulk of Nephrology practice worldwide today. With increasing
patients of chronic kidney disease, these patients are also presenting to primary care
doctors and physicians.

There has been an unmet need to educate the physician community about the
nuances of renal replacement therapy. Moreover, the role of general physicians and
family physician in the present scenario has become of utmost important.

APICON is one of the leading conferences in the country reaching out to the physicians
and residents to all over the country across all specialties. The precise, authentic and
readable content of APICON is well appreciated among students and clinicians alike.
I congratulate Dr. Narinder Pal Singh and his team to use this platform to conduct a
workshop on Renal Replacement Therapy to educate the young physicians and
residents. The book “Primer on Renal Replacement Therapy” is also a landmark
contribution of nephrology education amongst physicians by providing a concise and
relevant information on the methods, variations and complications of renal
replacement therapy. The concepts are very well described and discussed to get an
understanding of the different types of RRTs, their complications and initial
management.

Jai Hind
Dr. Girish Mathur
President -API

3
 Foreword
Dean – ICP

Chronic kidney disease has been a major cause of morbidity and mortality worldwide.
Nearly one in every ten individuals has chronic kidney disease. The cornerstone of
advanced chronic kidney disease or end stage renal disease has been renal
replacement therapy. Renal replacement therapy involves hemodialysis, peritoneal
dialysis and kidney transplant.

With changing times, there has been an evolution in the field of medicine and there
has been a steady revolution in the renal replacement therapies. This has led to a
huge impact on the health and well-being of chronic kidney disease patients by
extending life, minimizing complications, and improving quality of life.

Moreover, as the number of patients on renal replacement therapy are increasing,

these patients are presenting to general physicians or family physicians with related
problems or complications. Therefore, it is imperative for physicians to be well versed
with the methods of renal replacement therapies, so that they can identify the related
problems and provide initial management before the patient can be referred to a
nephrology centre.

I congratulate Dr Narinder Pal Singh and his entire team for coming out with this book
on “Renal replacement Therapy” which is an excellent book addressing the above
issue. This book is a great primer for all physicians and residents to update their
knowledge about renal replacement therapy. This book is first of its kind for physicians,
which will be a landmark in the annals of Association of Physicians of India and the
Indian College of Physicians. Again, I also appreciate the work of Dr Narinder Pal
Singh, Dr Dinesh Khullar and all nephrologists and faculty who have contributed to this
book. Happy reading and learning.

Jai Hind
Dr. Alaka Deshpande
Dean – ICP

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 Contents

1. Understanding Renal Replacement Therapy…………………………………..06

Narinder Pal Singh, Vineet Behera

2. Hemodialysis Essentials…….…………………………………………………….15
Garima Agarwal

3. Hemodialysis: Vascular Access and Complications…………………………35

Garima Agarwal

4. Peritoneal Dialysis………………………………………………..………………...45
Vineet Behera, Sachin Srivastava

5. Complications of Peritoneal Dialysis……………….……………..……………54

Vineet Behera, Sachin Srivastava, Rakesh Jagprasad Yadav

6. Renal Transplant…………………………………………………….….…………..62
Dinesh Khullar, Abhishek Singh

7. Complications of Renal Transplant………………………………….…………..68

Dinesh Khullar, Abhishek Singh

8. Conservative Kidney Management…………….……………………………...…74

Narinder Pal Singh, Sambit Sundaray, Vineet Behera

9. Renal Replacement Therapy in Acute Kidney Injury…….…………………...80

Vineet Behera, Prabhat Chauhan

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 1
Understanding Renal Replacement Therapy
----------------------------------------------------------------------------------------------------------------

Narinder Pal Singh, Vineet Behera

Understanding Renal Replacement Therapy

Renal replacement therapy (RRT) is the method of replacing non-endocrine renal

function in patients with renal failure namely acute kidney injury or chronic kidney
disease (CKD). The patients with CKD at advanced stage of their disease (i.e., in
CKD stage 5), need some support for replacement of lost kidney function. RRT
encompasses permanent measures to replace lost kidney function through kidney
transplantation, or by clearing the accumulating toxins through hemodialysis or
peritoneal dialysis. As mentioned, the three principal types of RRT are kidney
transplant, hemodialysis and peritoneal dialysis as shown in Figure 1.

Figure -1 Shows the various types of renal replacement therapy.

Kidney transplantation remains the best option of RRT as it the most physiological and
fully takes over all the functions of failed kidneys. But due to constraints of limited
availability of donor organs, this may not be available for all. Accordingly, the chief
mode of RRT for most ESRD patients remains dialysis which is of two types –
Hemodialysis and Peritoneal dialysis.

6
Indications of Renal Replacement Therapy

The absolute indications of RRT are refractory pulmonary edema, refractory

hyperkalemia, anuria, uremic pericarditis and uremic encephalopathy. Apart from
these other indications to initiate RRT in ESRD include severe metabolic acidosis,
serious uremic symptoms like anorexia, vomiting, fatigue, advanced uremia or eGFR
< 10ml/kg/min, and uremic complications like uremic bleeding, uremic pruritus.

HEMODIALYSIS

Principle

Hemodialysis is a process which involves removal of waste products from the blood.
In this technique, blood is taken out from blood vessels (AVF) through cannulas, which
is then passed on through the artificial kidney “the dialyser” which removes the waste
products, and is then returned back to the patient through another set of cannulas.
The dialyser contains a semipermeable membrane separating the blood and
dialysate fluid, both moving in opposite directions. The concentration gradient of
solutes between the blood and the dialysate drives the osmosis, leading to desired
changes in the patient’s serum solutes, such as reduction in BUN and serum
creatinine; and equilibration of key electrolytes like sodium, chloride, and potassium.
This enables removal of extra fluid (solvent) from the blood to achieve in
ultrafiltration.

Adequacy of Dialysis

The standard and optimal dialysis dose for most patients is variable, but in most
cases a hemodialysis for four hours duration, done thrice in a week is considered
optimal.
To measure the exact adequacy of dialysis, we need blood urea nitrogen before and
after each dialysis. A Urea reduction ratio (URR), which is defined as decrease of

7
BUN from predialysis level ([predialysis BUN − postdialysis BUN]/predialysis
BUN × 100%) is the requisite parameter, and a URR of ≥ 65% is considered
adequate. Other better formula may be used, such as Kt/V ≥ 1.2 (where K is
urea clearance in mL/min, t is time of dialysis in minutes, and V is the volume of
distribution of urea.

Settings for Hemodialysis

1. In Center HD – This is the standard form of HD which is performed in a hospital

or dialysis centre. Most centres do a dialysis of 4 hours every 3 days in a week. The
dialysis technician cannulates the AV fistula, calculates the amount of fluid to be
removed, and does the entire dialysis treatment under the supervision of the dialysis
physician and a nurse. The main advantage of in-center hemodialysis is that the
patient is under the direct supervision of dialysis physicians and technicians.

2. Home-based HD – In this, the dialysis equipment and feasibility of RO water, is

made available at patient’s home. This is generally done for patients who are bed
ridden and difficult to ambulate. It is also considered for those who need more
frequent dialysis like about 5 to 7 days per week dialysis of about 2-3 hours each.

Vascular Access for Dialysis

1. Arteriovenous Fistula - Hemodialysis is generally done through a surgically

created arterio-venous fistula (Connection between and artery and vein) or
through a central venous catheter. A new fistula may require 8-12 weeks to
mature and become usable. The common vessels used are radial, brachial,
or femoral artery to an adjacent vein in an end-to side or side-to-side fashion.
A prosthetic graft is used when the vein is not suitable for access creation.

2. Central Vein Catheter – In cases where in an AV fistula cannot be created

or has not been prepared, dialysis may be made by a catheter into a central
vein, known a central venous catheter. The most common used vein for
8
 central venous catheterization is the right internal jugular vein. Catheters may
be placed with a subcutaneous tunnelling and with a fabric cuff that gives a
longer life span and may be used as a temporary alternative to AVF.

Surgically created AVF are better in comparison to central venous catheters because
they are more durable and are less likely to become infected. However,
complications like infections, thrombosis, aneurysm or pseudo aneurysm, may
occur. The key disadvantages with central vein catheters are relatively lower blood
flow, high risk of catheter related infections and thrombosis.

PERITONEAL DIALYSIS

Principle

In Peritoneal Dialysis (PD), the peritoneum acts as the semi-permeable membrane

between the peritoneal cavity containing the peritoneal fluid and the blood capillaries
containing water, solutes and electrolytes. PD is more physiological, a slow
continuous process, does not require vascular access, and can be done at home. In
general, the dialysate is instilled into peritoneal cavity through a PD catheter, kept
inside for few hours for the exchange to occur, and then drained out. PD typically
uses a double-bag technique, in which the patient drains the previous instilled fluid
from the peritoneum into one bag and then reinfuses the dialysate fluid from the other
bag into the peritoneal cavity.

Types of Peritoneal Dialysis

Peritoneal dialysis can be done either manually or by using an automated

device.

1. Continuous Ambulatory Peritoneal Dialysis (CAPD) – This is a manual

method of PD and does not require the use of any machine to do the exchanges. In

9
general, an individual performs 3-4 exchanges of 2-3 L each. The time the fluid
remains in the peritoneum is called the dwell time which varies for about 3-4 hours
during the day and 8 to 12 hours at night.

2. Automated Peritoneal Dialysis (APD) – The manual CAPD fluid exchanges are
replaced by the use of a cycler or an automated PD machine. APD is done through
an automated cycler device with fluid bags of generally 5L size of different
concentrations. This cycler can do multiple number of exchanges of fixed volume of
dialysate, over a fixed period of time. Like over a night APD for 10 hours, 5-6 cycles
of 2L of dialysate can be done with a dwell of 30 minutes.

There are 3 types of APD:

a. Continuous Cyclic Peritoneal Dialysis (CCPD) – It uses a long (12 to 15

hours) daytime dwell of 7.5% CAPD fluid a nigh time exchange of 8-12 hours,
in which the cycler does 6-8 exchanges.
b. Nocturnal Intermittent Peritoneal Dialysis (NIPD) – This involves only
night cycles by the cycler, which during the day time, the peritoneum is left
dry.
c. Tidal Peritoneal Dialysis (TPD) – Tidal PD involves leaving some minimal
dialysate fluid in the peritoneal cavity from one exchange to the next. This is
generally done to avoid problems like pain during drain out, need of frequent
repositioning etc.

Peritoneal Dialysis Access

Peritoneal dialysis requires an intraperitoneal access, usually with a soft silicone

rubber or with a porous polyurethane catheter, known as a PD catheter. The
catheters have multiple pores or openings in the peritoneal end for transport of fluid.
Catheters may be single or double cuffed. A peritoneal catheterization procedure
may be performed in the operating room under direct visualization or at the bedside
by blind insertion of a trocar, or under visualization through a peritoneoscope or by
a percutaneous method. The other end of the catheter, is passed through a
10
subcutaneous tunnel and made to exit the skin through an opening known as the exit
site.

Peritoneal Equilibration Test (PET Test)

The functioning efficacy of peritoneal dialysis and the membrane characteristics of

the peritoneal membrane may be evaluated using the PET test. In this process, in
which the dialysate fluid drained after a 4-hour dwell time is analyzed and compared
with the serum to determine solute clearance rates. This peritoneal equilibrium test
helps determine the patient’s peritoneal transport characteristics, the dose of dialysis
required, and the most appropriate technique.

Comparing Hemodialysis and Peritoneal Dialysis

The key features comparing HD and PD are discussed in table -1
Peritoneal Dialysis Hemodialysis
Dialysis rate Slow process Fast process
Location Domiciliary Hospital/clinic based
Ultrafiltration Osmotic pressure by Hydrostatic pressure by the pump
gradient dextrose in dialysate
Membrane Peritoneal capillaries Dialyser
Access PD Catheter in peritoneal AV fistula or Central venous
cavity catheter
Common a. Peritonitis a. Catheter related infections
Complications b Hyperglycemia b. Vascular access failure
c. Ultrafiltrate failure c. Hypotension
d. Catheter malposition d. Bleeding complications
e. Omental wrap of catheter e. Cardiac arrhythmias
f. Dialysis related disequilibrium
Preferred a. Good residual urine output a. Frequent pulmonary edema
categories b. Underlying heart failure b. Lack of attendants/cannot do PD
c. Scared of injections/blood c. Young working individuals
d. Staying remote areas

Table 1. Comparing HD and PD

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KIDNEY TRANSPLANT

Transplant provides a near complete replacement of kidney functions by transplanting

kidney of another individual. With the recent advancements and successes in kidney
transplants, kidney transplant is now widely considered to be one of the best
treatments for chronic kidney disease. It is by far the best alternative for returning to a
normal life. However, this treatment may not be suitable for everyone depending on
their health requirements. The kidneys are placed in a heterotopic location, in the right
or left iliac fossa with the previous kidneys remaining within the body. Kidney
transplants are of two types - from a live donor or a deceased donor.

a. Live Donor Transplant

In a live donor transplant, the one kidney is removed from a healthy volunteer donor,
who is a family member or a close relative of the individual that includes parents,
siblings, spouse, children and grandparents. Other relatives or friends may also
donate kidney after appropriate permission from authorization committee. The healthy
kidney once removed from the donor’s body is immediately transplanted into the
patient’s body. A series of immunological tests called cross matches are done between
the donor and recipient to look for any sensitization or prior immunological issues. The
donor can return to normal daily activities around four weeks after the transplant
surgery, and they can still live a normal and healthy life after donating a kidney.

b. Deceased Donor Transplant

A Deceased donor or a cadaveric donor involves the transplanting of kidneys from a

brain-dead cadaveric donor. Apart from kidney, heart, liver, lungs, and other organs
may also be harvested. Before the transplant surgery; medical tests are performed on
the donor’s kidneys to ensure its suitability for transplantation. Kidney patients are put
on a city wise and blood group wise, transplant waiting list until a suitable kidney is
found which is compatible to their body.

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Transplant Procedure

The transplant surgery involves placing the new graft kidney and ureter in the right or
left iliac fossa. The renal artery and vein are anastomosed with the recipient’s external
or internal iliac vessels. The ureter is anastomosed with the urinary bladder.

Rejection

Rejection is the immunological process in which the recipient’s immune system

mounts a response against the graft kidney. It can be hyper-acute occurring hours
after a transplant, which can occur due to serious immunological or blood group
mismatch. Acute rejection occurs days to months after transplant, while chronic
rejection may occur late or years after a transplant. The rejection may be of two types
– the T cell mediated or Cellular rejection and B cell rejection of Humoral rejection.
Comparing Renal Transplant with Dialysis
The key advantages and disadvantages comparing renal transplant and dialysis are
highlighted in table 2.
Transplant Dialysis
Effectiveness of RRT 80-90% of normal 40-50% of normal
kidney functions kidney functions
Diet and fluid restrictions Minimal Serious limitations
Problems of anemia and mineral Less More
bone disorder
Long term outcomes and survival Better Less
Cardiovascular and other Less More
morbidities
Need of immunosuppressant drugs Yes, life long Not needed
Risk of infections More Less
Availability Less due to organ Lesser shortage
shortage
Table-2 Compares advantages and disadvantages comparing renal transplant and
dialysis

13
Suggested References
1. Alvarez G, Chrusch C, Hulme T, Posadas-Calleja JG. Renal replacement therapy:
a practical update. Can J Anaesth. 2019 May;66(5):593-604.

2. Fleming GM. Renal replacement therapy review: past, present and future.
Organogenesis. 2011 Jan-Mar;7(1):2-12.

3. Ricci Z, Romagnoli S, Ronco C. Renal Replacement Therapy. F1000Res. 2016 Jan

25;5:F1000 Faculty Rev-103.

4. Villa G, Ricci Z, Ronco C. Renal Replacement Therapy. Crit Care Clin. 2015
Oct;31(4):839-48.

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 2
Hemodialysis Essentials
---------------------------------------------------------------------------------------------------------------------------
Garima Agarwal

Introduction

As chronic kidney disease progresses, patients experience a gradual decline in

function of most organs, this constellation of symptoms associated with advanced
kidney failure is known Uremic Syndrome. This syndrome constitutes a myriad of
functional disturbances such as anemia, mineral bone disease, inflammation, fluid
overload, electrolyte disturbances, vascular calcification, cardiovascular disease and
hypertension. At this stage patient survival and quality of life can only be ensured by
starting the patient on renal replacement therapy (RRT) namely – Dialysis or Kidney
Transplantation.

Dialysis has made survival possible for millions of people throughout the world who
have end-stage kidney disease (ESKD) with limited or no kidney function. The
expansion of dialysis into a form of long-term renal-replacement therapy transformed
the field of nephrology and also created a new area of medical science, which has
been called the physiology of the artificial kidney.

When To Start Dialysis

For patients with chronic kidney disease (CKD), the decision of starting chronic dialysis
is taken together by the treating nephrologist and the patient. Dialysis is effective in
treating uremia and fluid overload; however, patients must undergo dialysis for the rest
of their lives, living with discomfort and certain risks.

Worldwide, there can be variations in when maintenance dialysis for Stage V Chronic
Kidney Disease (CKD) patients is started. In affluent countries, there tends to be an
early initiation of dialysis, based on Glomerular Filtration Rate (GFR) cut offs (which

15
are usually between 10 to15ml/min). However, in lower- and middle-income countries
like India, the practice has typically been to “wait and watch till symptomatic” before
initiating CKD V patients on dialysis. This practice was validated by a randomized,
controlled trial in the IDEAL study (2010), published in the New England Journal of
Medicine, which compared early-start dialysis (i.e., when the estimated GFR was
between 10.0 and 14.0 ml per minute) versus late-start dialysis (i.e. to begin dialysis
when the estimated GFR was between 5.0 and 7.0 ml per minute), which showed no
significant differences in rates of death, cardiovascular events, infectious events,
quality of life, electrolytes or complications of dialysis in both groups. Hence, it proved
that, with careful clinical management of chronic kidney disease, dialysis can be
delayed for patients until more traditional clinical indicators for the initiation of dialysis
are present. Therefore, dialysis should be started only when the benefits from
alleviating uremic symptoms and signs are believed to outweigh the risks and adverse
impact on a patient’s quality of life.

The 2015 KDOQI guidelines suggest that the decision to start dialysis should be based
on uremic signs and symptoms, evidence of protein-energy wasting, and the ability to
medically manage metabolic abnormalities and volume overload and not based upon
the level of kidney function. Indications for initiating chronic dialysis are -

Absolute indications for initiating dialysis –

1. Uremic Pericarditis or Pleuritis – Patients often present with moderate
to large pericardial effusions secondary to uremia.

2. Uremic Encephalopathy – True uremic encephalopathy (that is a

significant alteration in cognitive function in a patient without other causes) is a
rare condition that usually does not occur with eGFR >5 mL/min/1.73 m2.
Emergent dialysis is indicated.

Other indications -
1. Refractory acidosis, hyperkalemia, and hyperphosphatemia despite
adequate dietary restrictions and medications.

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 2. Persistent or difficult to treat volume overload - Volume overload in
CKD patients leads to repeated hospital admission due to refractory
hypertension and pulmonary enema. Among those with low eGFR, the
judicious use of diuretics is often an effective way to treat volume overload.

In such cases, diuretics should not be withheld in order to prevent an increase

in blood urea nitrogen (BUN) and serum creatinine levels. The patient should
be diuresed to euvolemia, or at least to a volume status that is well tolerated;
the BUN and serum creatinine level should be considered then.

3. Declining nutritional status - Anorexia, weight loss, or poor caloric

intake that is not adequately treated by conservative measures is an indication
to initiate dialysis. Patients often complain of early morning nausea or nausea
and vomiting associated with food intake.

4. Fatigue and malaise – Worsening fatigue and malaise develop as

kidney function declines. It is important to rule out other causes such as
anemia, abnormal electrolytes, depression, uncontrolled hypertension or
blood sugars in these patients.

5. Mild cognitive impairment – Cognitive impairment may develop in

older adults as kidney function worsens and is an indication to initiate dialysis.
It is important to exclude progressive dementia in such patients.

The patient should undergo preparation for dialysis. Ideally, the decision to initiate
dialysis should be made after the option of kidney transplantation has been explained,
an evaluation has been conducted for a transplantation, different dialysis modalities
have been discussed, and functioning dialysis access has been worked out.
Hemodialysis (HD) is the most common RRT modality worldwide. The first HD in India
was performed at Christian Medical College (Vellore, Tamil Nadu) in 1961 on an
erstwhile Maharaja under the supervision of Dr. Satoru Nakamoto, who had flown in
from Seattle, Washington (4)

17
HEMODIALYSIS

Hemodialysis is a procedure in which the blood flows outside the body through a
vascular access, via an extracorporeal circuit, passes through a semi permeable
membrane called the dialysis membrane, which removes uremic toxins from it, and is
then returned to the body. In Hemodialysis the dialysis membrane separates the blood
from a solution with specified electrolyte composition called the Dialysate. The goal of
any renal replacement therapy is to replace normal functions of the kidney.
Hemodialysis relies on mechanical methods to remove uremic toxins, balance fluid
and electrolyte levels and correct acid base disturbances.

Hemodialysis is indicated for acute kidney injury as well as chronic kidney disease. In
this chapter we describe in detail the principles, procedure and preparation for chronic
intermittent hemodialysis only. Hemodialysis is used interchangeably here with
chronic intermittent hemodialysis.

Principles of Hemodialysis (HD)

Hemodialysis performs two main functions:

1) Solute removal
2) Fluid Removal

Solute Removal in HD happens via two main mechanisms:

a) Diffusion
b) Convection

Diffusion

Diffusion is defined as movement of solutes from a higher concentration to a lower

concentration via a semi permeable membrane. This is the primary method of solute
removal in Hemodialysis. Diffusion of solutes from blood into the dialysate depends
on the solute concentration and molecular weight. The concentration gradient is
maximized and maintained throughout the length of the membrane by running the

18
dialysate in a flow that is counter current to the blood flow. Small molecules diffuse
quickly whereas larger molecules diffuse much more slowly. There are 3 main groups
of uremic solutes: 1) Small molecules (<500 Da), which are removed during the
diffusion process; 2) Middle and large molecules (50–15,000 Da); and 3) Molecules
bound with proteins weighing 500 Da, which are hard to remove and the dissociation
process is time-consuming (Table 1).

Figure 1 – Diffusion, movement of solute across a semipermeable membrane is driven

by a concentration gradient between the blood and the dialysate. Solutes move from
the side with the higher concentration of particles to the side with the lower
concentration. Diffusion is best for clearing low-molecular-weight solutes such as urea
and creatinine. (5)

Table 1 – Classification of solutes based on molecular weight. (6)

19
Convection

Convection or “solute drag” is the movement of molecules within fluids. This occurs
when a transmembrane pressure is applied on the blood side of the membrane forcing
large amounts of plasma water through the pores of the membrane which drags
solutes with it.

Figure 2 - Convection occurs when solutes are transported across a semipermeable

membrane with plasma water in response to a hydrostatic pressure gradient that is
created on the blood side of the dialysis membrane. Convection enhances the removal
of low- and middle-molecular-weight molecules. (5)

Fluid removal

Fluid removal in HD happens via ultrafiltration. Ultrafiltration is the process by which

plasma water is forced across a semipermeable membrane by hydrostatic pressure.
The primary purpose of ultrafiltration is the removal of excess total body water.

Hemodialysis Equipment
Hemodialysis apparatus includes the following parts –

1. Blood Circuit
The tubing set starts from the Vascular access, the blood flows through this part known
as inflow/” arterial” blood line to the Dialyzer membrane or the Dialyzer. Filtered blood
then moves from dialyzer via an outflow/ “venous” blood line back to the vascular
access. The blood in the dialysis circuit from the vascular access is venous blood, but

20
traditionally inflow and outflow lines are referred to as “arterial’ and “venous’ lines The
components of blood circuit include Inflow and Outflow blood lines.

A) Inflow Blood Line Includes –

i) Sampling port
ii) Saline infusion line
iii) Roller pump - This pump determines the blood flow rate through the
dialyzer. The blood pump is commonly designed in a circular roller fashion
that squeezes segments of blood through a portion of arterial tubing as the
rollers apply pressure to the line. The blood pump typically operates at
speeds ranging from 150-500 mL per min.
iv) Heparin infusion line – connected to an automated Heparin syringe pump.
v) Pressure monitors
(a) Arterial pressure monitor
(b) Dialyzer inflow pressure monitor

B) Outflow Blood Line Includes

i) Venous pressure monitor
ii) Venous ‘drip chamber’ – this allows for the collection and easy removal of
any accumulated air that may have entered the blood line before the blood
is returned to the patient.
iii) Air detector clamp- This is an additional safety device, which is activated by
the presence of air in the blood tubing. When activated the clamp snaps
shut and blood pump is stopped.

Arterial pressures are usually negative ( -80 to -200 mm Hg). Venous pressures
are usually positive, ranging from 50 to 250 mm Hg. Pressures that fall outside of
the acceptable ranges should trigger machine alarms that will stop the blood pump.
Cause of pressure variations should then be identified and rectified.

21
Figure 3 – Blood circuit in Hemodialysis (7)

2. Dialyzer

The dialyzer is where the blood and the dialysis solution circuits interact. It is here that
the movement of fluid and solutes takes place across a semipermeable membrane.
The dialyzers currently in use are called Hollow-fiber dialyzers. The dialyzer is a
cylinder-shaped device filled with hollow polymeric fibers. The dialyser is 2 to 5 cm in
diameter and around 15 to 25 cm in length. Polymeric material (e.g., polycarbonate or
polypropylene) forms the outer cover of the dialyser which encloses a bundle of
thousands of (~8000–16,000) hollow fibers. Typical fibers have an internal diameter
of 180–200 microns and wall thickness of 30–40 microns, yielding 1.0–2.5 m2 of
surface area. Fibers may have features, such as undulations, to distribute dialysate
flow evenly through the fiber bundle. The dialyzer also has inlet and outlet openings
for the two fluids- blood and dialysate.

The blood flows through the hollow fibers and the dialysate flows around on the outside
in counter current flow. Blood and dialysate flows are typically run-in opposite
22
directions (counter current) to improve clearance, but can be run in the same direction
if less solute clearance is desired. The hollow fibers are the site of diffusion and
convection as each of the hollow fibers contain pores which allow the passage of
molecules.

Dialysis membrane are made up of four types of biomaterials: cellulose, substituted

cellulose, mixed cellulose synthetic, and pure synthetic.
i) Cellulose membranes are formed from plant (usually cotton) polysaccharide
and are not expensive. These were used initially but not anymore due to
less biocompatibility and hence more chances of reactions.
ii) Substituted cellulose membranes are formed by removing free hydroxyl
groups from cellulose membranes. These are more biocompatible due to
removal of the hydroxyl group.
iii) Cellulose synthetic membranes are cellulose membranes with a synthetic
material (tertiary amine structure) added to the surface.
iv) Pure synthetic membranes do not contain cellulose materials and are the
most commonly used membranes today. They are highly biocompatible,
have increased middle molecular clearance, hydrophobic and more
expensive. Examples include- Polysulphone, Polyamide, Polyacrylonitrate

Figure 4 – Dialyzer with inlets and outlet for blood and dialysate (5)

23
Figure 5– Hollow-fiber dialyzer

Figure 6 – Hollow-fiber Dialyzer – design components

Choosing a Dialyzer –

Performance of a dialyzer can be judged by two main parameters –

1) Flux refers to the ability to remove or ultrafilter plasma water. High-flux dialyzers
have larger pores capable of removing greater volumes of plasma water. This
is denoted by the ultrafiltration coefficient, or KUF of a dialyzer.

24
 Low-flux dialyzers have a KUF of <10 mL/h/mm Hg and high flux dialyzers >20
mL/h/mm Hg.
High-flux membranes, by nature of their larger pore sizes, also have higher
clearance of middle molecules with sizes similar to molecules such as vitamin
B12 (MW ˜1400 Da) and β2-microglobulin (MW ˜ 12000 Da).

2) Efficiency of a dialyzer refers to its ability to remove small molecular solutes

such as urea; this is usually denoted by the KoA of urea. The KoA is related to
the clearance of a dialyzer (Ko) and the surface area of the dialyzer (A).
It should be recognized that the manufacturer-provided clearance values for
different dialyzers at different blood flows can be useful to help compare
performance, but cannot reliably be used to calculate the dose of dialysis.

Dialyzer solute clearance characteristics are primarily dependent on surface area and
porosity. Dialyzer properties are all provided by the manufacturer in Dialyzer
specification sheets. The information usually provided includes KUF clearance of
solutes such as urea, creatinine, vitamin B12 and phosphate; membrane surface area;
priming volume; fiber length; and fiber wall thickness. It is worthy to note that reported
clearance data for the dialyzer is based on in vitro testing which tends to overestimate
in vivo clearances. It is also important to note that clearance is affected by blood flow,
therefore analysis of clearance at varying blood flows is of relevance. In general, the
clearance values provided by the manufacturer can give the practitioner an idea of the
performance of a particular dialyzer. The priming volume of the dialyzer and the
sterilization method of the dialyzer will also be listed in the dialyzer specifications. The
average priming volume ranges from 50 to 150 mL. Sterilization methods of dialyzers
include ethylene oxide, gamma beam radiation, and heat/steam sterilization.
Sterilization with ethylene oxide has fallen out of favour due to increased rates of
allergic reactions.

Certain dialyzers can be reprocessed and reused. Reused dialyzers are cleaned with
bleach, hydrogen peroxide, or peracetic acid and sterilized with formaldehyde,
glutaraldehyde, or heat. Before reuse, the dialyzers have to be tested for residual
chemical agents and ability to withstand pressure. Fiber bundle volume is also
calculated to ensure the dialyzer has an adequate number of patent hollow fibers to
25
achieve adequate solute clearance. This process can be tedious and labour intensive
and can sometimes outweigh the cost of the dialyzer—as a consequence, many
dialysis units choose single-use dialyzers.

3. Dialysate Solution Circuit

The main components of a typical dialysis circuit include the dialysate concentrate, the
water input, a proportioning system, and a volumetric control system. The dialysate
circuit is usually fitted with monitors including the conductivity monitor, temperature
monitor, and a blood leak detector. Treated water is heated to an appropriate
temperature (˜35.5°-38°C) and any air bubbles in the water are removed by the
deaerator. The water is then mixed with concentrate. In dynamic proportioning
systems bicarbonate is usually added followed by the acid concentrate through the
proportioning system. The job of the proportioning system is to take pre-treated pure
water and mix it with the bicarbonate and acid concentrates to make final dialysate for
delivery to the dialyzer. The level of sodium or bicarbonate in the dialysate can be
adjusted by the proportioning system from input provided to the dialysate machine,
whereas the concentration of the other electrolytes such as potassium and calcium
are relatively fixed and require a change in the concentration in the concentrate. The
mixed product is then tested by the conductivity monitor and tested to ensure that
temperature is appropriate. pH sensors are also sometimes used. The flow of
electricity through solution is proportional to the number of ions dissolved in the
solution. Pure water is a poor conductor of electricity and salty water conducts
electricity more readily. The conductivity monitor ensures that the conductivity of the
dialysate, and therefore the overall electrolyte concentrations, are within the
appropriate range. If the product is not within acceptable conductivity or temperature
range the bypass valve is opened and the dialysate is delivered to the drain preventing
delivery to the patient. Machine alarms due to altered conductivity usually represent
either inaccurate input of the concentrations of electrolytes in the concentrate, an
inappropriately calibrated machine, or problems with the water purification system.
These alarms can indicate malfunction of proportioning or contaminated water which
can be potentially fatal to the patient if the bypass system is not evoked.

26
If the product passes the tests, then it is delivered to the balancing chambers. The
balancing chambers are an intricate set of chambers separated by impermeable
membranes and inflow and outflow valves. The purpose of the balancing chambers is
to balance dialyzer inflow with dialyzer outflow. The ultrafiltration (UF) controller uses
pressure measurements and a separate pump to remove any additional desired
volume from the dialyzer effluent. If no ultrafiltration is desired, these components act
together to ensure that the amount of fluid entering the dialyzer matches the amount
of fluid that leaves the dialyzer. If fluid removal is desired, the amount of fluid in the
dialyzer outflow will exceed the dialysate input.

Other safety systems included in the dialysate circuit include the temperature monitor,
the blood leak detector, and sometimes a pH detector. Standard dialysate temperature
is around 37°C. Lower temperature is associated with shivering and discomfort but
may reduce intradialytic hypotension. Higher temperatures (> 42°C) can lead to
protein denaturation and hemolysis. The blood leak detector serves as a method to
detect the presence of blood in the dialysate. Given that dialysate water is not sterile,
blood should not come in direct contact with the dialysate. If there is a rupture in the
dialysis membrane blood will be found in the dialysate effluent. Additionally, high levels
of myoglobin or hemoglobin in the dialysate effluent can set off the blood leak detector
if a significant amount of pigment is able to pass through the membrane

Figure 7 - Typical components in a dialysate circuit

27
4. Dialysate

The dialysate is a dilute solution of electrolytes and, sometimes, glucose. This is

prepared from purified water and commercially available concentrates. To reduce bulk
and transport costs dialysis fluid is manufactured as concentrates and the dialysis
machines mix it with water in defined proportions to form the final dialysate. Almost all
the dialysis solution used nowadays is bicarbonate based (earlier acetate-based
solutions were also used). It is made from two commercially available concentrates
the “acid” concentrate and the “bicarbonate” concentrate. This solution contains
sodium, magnesium and chloride ions at the same concentration as in normal plasma.
To buffer the pH of the solution, bicarbonate or acetate is also added. Sometimes a
fine-tuning of the dialysate composition is performed to calibrate the treatment on the
patient.

Figure 8 – Composition of a Standard Hemodialysis solution (8)

WATER TREATMENT SYSTEM

Patients are exposed to about 120-200L of water as dialysis solution during each
dialysis 4-hour dialysis session. Any contaminants in the dialysis solution can hence
enter the blood unimpeded and accumulate in the body. City water supply comes from
two main sources – Ground water and surface water, and may can contain many

28
contaminants. Some of these contaminants include particulate matter such as sand,
clay, and plant matter or metals such as copper, zinc, aluminum and lead which can
be leeched from pipes during water transport. Water obtained in proximity of
agriculture may be contaminated with fertilizers and pesticides. Further, heath
authorities of city water systems may add agents such as chlorine and chloramines to
control microbial contamination, fluorides for dental prophylaxis, and occasionally
aluminum sulphate and iron salts are added as flocculating agents to decrease water
turbidity. Water supply may be contaminated with bacteria, endotoxins or microcystins
derived from blue green algae. (Figure 9) These contaminants and additives need to
be removed from the water source prior to being used in the production of dialysate.
All dialysis facilities therefore require a properly designed and maintained water
treatment system to safeguard patients.

Figure 9 – Water contaminants and symptoms related to them

29
Association for the Advancement of Medical Instrumentation (AAMI) and International
Standards Organization (ISO) have developed minimum standards for the purity of
water used to prepare dialysis solution. These are outlined the table below.

Table 2 - Maximum allowable levels for total viable microbial count (TVC) and
endotoxins in dialysis water, in standard and ultrapure dialysis fluid (dialysate) and
online-prepared substitution fluid for treatments like CRRT.

The water treatment system is illustrated in the below figure and there are essentially
three key steps:
1) Pre-Treatment -
2) Primary Purification
3) Distribution

Figure 10 - A typical water purification and distribution system for hemodialysis.

30
Hemodialysis Prescription
The primary goal of hemodialysis is to restore the intracellular and extracellular fluid
environment that is characteristic of normal kidney function (9). The dialysis
prescription for each patient has to individualized based on their specific physiological
status at the time. Dialysis adequacy is measured and its targets are set based on the
clearance of urea during dialysis, which can be readily and accurately measured. Urea
kinetic modelling predicts morbidity and mortality in dialysis patients. The amount of
urea to be removed is usually calculated according to the patient's body size with the
use of the following dimensionless construct, which relates the clearance of urea to its
volume of distribution in the patient: Kt/Vurea, where K is the urea clearance of the
dialyzer, t is the duration of dialysis, and Vurea is the patient's volume of urea
distribution. This construct has been readily adopted by the nephrology community to
calculate the dialysis dose.

Figure 11 – Key Components of Hemodialysis prescription (9)

31
Survival On Hemodialysis

Hemodialysis is now substantially safer than it was in the initial years of the therapy,
and deaths directly related to the dialysis procedure are rare. Improved dialysate
delivery systems, better water quality standards, better training, more reliable
monitoring devices, automated electrolyte controls, and automated safety
mechanisms have reduced the risk of complications. (9)

Indian Perspective
A 2018 estimate put the number of patients on chronic dialysis in India at about
175,000, giving a prevalence of 129 per million population. (10) A systematic review
estimated that about two thirds of all patients with kidney failure died without receiving
dialysis in 2010.

Approximately 9-13% of patients on hemodialysis in India die within 1 year according

to a study in 1998. (11) The adjusted rates of all-cause mortality are 6.3-8.2 times
greater for dialysis patients than the general population. The adequacy of dialysis and
factors such as pre-dialysis care, late referral to specialist and non-compliance affect
patient survival. (12)

Cardiovascular death, specifically sudden cardiac death, remains the leading cause
of death. Other causes of death in dialysis patients include Infections, withdrawal of
dialysis, other known and unknown causes. During the first year of dialysis, however,
rates of sudden cardiac death and other cardiovascular death are both highest during
the first month and decrease thereafter, whereas rates of death due to infection and
withdrawal both peak during the second month of dialysis. (13)

References

1. Cooper BA, Branley P, Bulfone L, Collins JF, Craig JC, Fraenkel MB, et al. A
randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med

32
 [Internet]. 2010;363(7):609–19. Available from:
http://dx.doi.org/10.1056/NEJMoa1000552

2. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 update.

National Kidney Foundation. Am J Kidney Dis. 2015;66(5).

3. UpToDate [Internet]. Uptodate.com. [cited 2023 Jan 18]. Available from:

https://www.uptodate.com/contents/indications-for-initiation-of-dialysis-in-chronic-
kidney-
disease?search=2.%09Uptodate%20Indications%20for%20initiation%20of%20di
alysis%20in%20chronic%20kidney%20disease&source=search_result&selected
Title=1~150&usage_type=default&display_rank=1

4. Chugh KS. Five decades of Indian nephrology: a personal journey. Am J Kidney

Dis [Internet]. 2009;54(4):753–63. Available from:
http://dx.doi.org/10.1053/j.ajkd.2009.06.027

5. Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl

J Med [Internet]. 2012;367(26):2505–14. Available from:
http://dx.doi.org/10.1056/NEJMct1206045

6. Azar AT, Canaud B. Hemodialysis System. In: Modelling and Control of Dialysis
Systems. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013. p. 99–166.

7. Themes UFO. Hemodialysis [Internet]. Abdominal Key. 2016 [cited 2023 Jan 18].
Available from: https://abdominalkey.com/hemodialysis/

8. Daugirdas JT, Ing TS, Blake PG. Handbook of dialysis. 5th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2015.

9. Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med [Internet].

2010;363(19):1833–45. Available from: http://dx.doi.org/10.1056/NEJMra0902710

33
10 Jha V, Ur-Rashid H, Agarwal SK, Akhtar SF, Kafle RK, Sheriff R, et al. The state
. of nephrology in South Asia. Kidney Int [Internet]. 2019;95(1):31–7. Available from:
http://dx.doi.org/10.1016/j.kint.2018.09.001

11 Rao M, Juneja R, Shirly RB, Jacob CK. Haemodialysis for end-stage renal disease
. in Southern India--a perspective from a tertiary referral care centre. Nephrol Dial
Transplant [Internet]. 1998;13(10):2494–500. Available from:
http://dx.doi.org/10.1093/ndt/13.10.2494

12 Chandrashekar A, Ramakrishnan S, Rangarajan D. Survival analysis of patients

. on maintenance hemodialysis. Indian J Nephrol [Internet]. 2014;24(4):206–13.
Available from: http://dx.doi.org/10.4103/0971-4065.132985

13 Weinhandl E, Constantini E, Everson S, Gilbertson D, Li S, Solid C, et al. Peer

. kidney care initiative 2014 report: dialysis care and outcomes in the United States.
Am J Kidney Dis [Internet]. 2015;65(6 Suppl 1):Svi, S1-140. Available from:
http://dx.doi.org/10.1053/j.ajkd.2015.03.021

34
 3
Hemodialysis: Vascular Access & Complications
---------------------------------------------------------------------------------------------------------------------------

Garima Agarwal

VASCULAR ACCESS

Hemodialysis requires a stable vascular access to the bloodstream to permit dialysis

to be performed.
Hemodialysis vascular access can be divided into two main types

1) Vascular access for maintenance HD which includes -

a. Arteriovenous (AV) fistulas
b. Arteriovenous (AV) grafts
c. Tunnelled hemodialysis catheters, also known as ‘permcaths’ or ‘permanent
catheters’
2) Vascular access for urgent start HD which includes temporary central venous
catheters (CVC)

Arteriovenous Fistulas

An AV fistula is a surgically created connection between an artery and vein and is

typically constructed with an end-to-side, vein-to-artery anastomosis. The most
commonly used AV fistulas are in the upper limbs and are created by anastomosing
the radial artery to the cephalic vein (radio cephalic fistula) or by anastomosing the
brachial artery to the cephalic vein (brachiocephalic fistula). Brachio-basillic fistulas
are also commonly created by anastomosing the brachial artery to the basilic vein, but
this fistula is located deeper in the medial aspect of the upper arm and often requires
another procedure of superficialization before use during HD.

35
AV fistulas are the preferred form of vascular access because of their significantly
higher long-term patency rates and lower rate of complications.

Figure 1 – Different types of Vascular access for Hemodialysis (1)

Figure 2 – Arteriovenous (AV) Fistulas (2)

36
Arteriovenous Grafts

AV grafts are constructed by interposing a graft material between an artery and vein,
most commonly polytetrafluoroethylene (PTFE). AV grafts can provide excellent
vascular access in patients who have inadequate vasculature to support an AV fistula.
PTFE has good surgical handling characteristics, and grafts of this material can
usually be used as early as two weeks after placement. However, AV grafts have a
higher long-term complication rate (e.g., infection, thrombosis) compared with AV
fistulas. Common AV grafts include straight forearm (radial artery to cephalic vein),
looped forearm (brachial artery to cephalic or brachial vein), straight upper arm
(brachial artery to axillary vein) and looped upper arm (axillary artery to axillary vein).
Early cannulation AV grafts are also available that can be used within one day of graft
creation

Figure 3 – Arteriovenous (AV) Grafts (2)

Tunnelled Hemodialysis Catheters

Tunnelled hemodialysis catheters are primarily used as intermediate-duration vascular

access during maturation of AV fistulas. These are inserted into the central veins via
a subcutaneous tunnel and are typically cuffed. They can also provide acceptable
long-term access in patients with contraindications to AV access or those who have

37
exhausted all available sites. Nevertheless, tunnelled hemodialysis catheters are
inferior to AV access for long-term access since they provide lower flows and have
higher rates of infection and other complications. Following placement, typically in the
right internal jugular vein, tunnelled hemodialysis catheters can be used immediately.
They can be placed in any central vein, but internal jugular veins are preferred.

Figure 4 - Tunnelled hemodialysis catheters (2)

Central Venous Catheters

Central venous catheters (CVC) are used in the urgent or emergent situations that
require hemodialysis. These kinds of CVCs are typically non-cuffed and non-tunnelled.
The preferred sites for placement of central venous dialysis catheters from most to
least preferred are – Internal jugular veins, Femoral veins, Subclavian veins, Lumbar
veins, and others. Subclavian vein catheters should generally be avoided due to the
high risk of central vein stenosis with them. Femoral catheters should be avoided in
potential kidney transplant candidates due to high risk of infection and thrombosis of
iliac/femoral vessels, which are required for vascular anastomosis during
transplantation. Ideally CVCs for dialysis should be placed under ultrasound guidance
using the Seldinger technique.

38
COMPLICATIONS OF HEMODIALYSIS

Complications on hemodialysis can be divided into

1) Complications during Hemodialysis (4)

a. Intradialytic hypotension
b. Intradialytic Hypertension
c. Muscle cramps
d. Nausea and vomiting
e. Headache
f. Dialysis Disequilibrium syndrome
g. Dialyzer reactions
h. Hemolysis
i. Air Embolism
j. Other complications – chest pain, itching

2) Complications of vascular access

a. Complications of AV Fistula and AV grafts
b. Complications of Tunnelled dialysis catheters
c. Complications of Central venous catheters

Intradialytic Hypotension

Intradialytic hypotension (IDH) or low blood pressure during the hemodialysis

procedure is the most common complication during hemodialysis. The European Best
Practice Guidelines (EBPG) define intradialytic hypotension (IDH) as both a fall in
blood pressure and the occurrence of symptoms needing an intervention (5). Systolic
BP decrease by at least 20 mmHg or a fall in mean arterial pressure by at least
10mmHg is required for the diagnosis of hypotension. Causes of Intradialytic
hypotension are (4)
 Large volume fluid removal during dialysis – This happens due to excessive weight
/ ‘water’ gain by patient, long interval between two dialysis sessions, shortening the

39
 dialysis time, or targeting a post dialysis weight lower than the person’s actual dry
weight. Dry weight is defined as the weight at which patient has no signs of
hypovolemia or hypervolemia.
 Decreased Vasoconstriction – This happens due to higher dialysate temperature
which causes peripheral vasodilation. Ingesting food during hemodialysis may
cause dilation of abdominal or splanchnic vessels which results in hypotension.
Hypovolemia can cause decreased peripheral resistance or cardiac filling.
 Cardiac factors – Diastolic dysfunction or reduced ejection fraction can cause IDH.
 Dialysate composition – decreased levels of calcium, potassium or magnesium in
the dialysate can precipitate hypotension.

Figure 1 – Strategies to reduce intra-dialytic Hypotension (6)

Muscle Cramps
Pathogenesis of muscle cramps during dialysis is not well understood but they are
seen most commonly in association with hypovolemia, large volume ultrafiltration,
hypotension, low serum magnesium or calcium, and low sodium in dialysate.

40
Nausea And Vomiting
Most common cause of nausea and vomiting during dialysis id hypotension. It may
occur due to dialysis disequilibrium syndrome, dialyser reactions or other gastric
disorders.

Headache
Headaches are common in patients during hemodialysis. In case of severe headaches
– neurological causes like intra-cranial bleed, Posterior reversible encephalopathy
syndrome or thrombosis should be ruled out. Most common causes of headaches are
dialysis disequilibrium syndrome, coffee withdrawal or migraines.

Dialysis Disequilibrium Syndrome

Disequilibrium syndrome (DDS) is a rare but serious complication of hemodialysis. In
most cases the presentation is mild and self-limiting, if missed it can rarely turn fatal.
Common presentation of DDS includes fatigue, mild headaches, nausea, vomiting,
altered sensorium, convulsions and coma. This syndrome arises due to sudden
removal of urea from the blood in patients who are highly uremic.
The exact pathophysiology is not well known; however, it is postulated that sudden
removal of urea during the initial dialysis sessions- leads to faster removal of urea
removal from blood than brain. Due to this, an osmotic lag is created between the
blood and the brain, which leads to movement of fluids from blood to brain – causing
cerebral edema and raised intracranial pressure. (6,7)
Management of DDS includes prevention of sudden urea shifts and cerebral edema
in dialysis patients with high urea concentration, such as
 Performing Slow Low Efficiency Dialysis (SLED) or low clearance dialysis by

reducing dialysis time, co current flow, reducing blood flow rate or by using a

less efficient dialyser.

 Using a high sodium in dialysate – this minimizes the osmotic shifts.

 Administration of osmotic agents such as Dextrose, hypertonic saline or

mannitol

41
COMPLICATIONS OF VASCULAR ACCESS

Complications of AV fistulas
Chronic use of AV fistulas leads to a number of complications. The most common
problems associated with AV fistula use are listed in Figure 2.

Figure 2 Complications of chronic AV Fistula use

Complications of AV grafts
 Bleeding – Local bleeding maybe seen post procedure.
 AV graft dysfunction and failure
 Seroma
 Pseudoaneurysm
 Neuropathy — Median nerve dysfunction in long-term dialysis patients is most
often due to local amyloid deposition, leading to carpal tunnel syndrome.
 Graft infection
 Access flow-related problems
 Extremity swelling
 Cardiopulmonary problems
 Vascular steal — Placement of an AV graft can reduce perfusion of the more
distal extremity as a result of shunting ("steal") of arterial blood flow into the
graft. Symptomatic steal occurs in up to 20 percent of patients receiving an
upper extremity access

42
Complications of Tunnelled dialysis catheters and Central Venous Catheters
(CVCs)
Complications of tunnelled dialysis catheters and CVCs can be divided into
Mechanical complications and Infectious complications

Mechanical complications include –

Immediate complications
 Bleeding from insertion site
 Subcutaneous hematoma
 Hemothorax
 Pneumothorax
 Arterial rupture/ puncture

Long term complications

 Access thrombosis
 Central venous stenosis
 Air embolism

Infectious complications include

 Catheter related Blood stream infections (CRBSI)
 Endocarditis
 Osteomyelitisss
 Epidural abscess
 Septic arthritis
 Septic thrombophlebitis
 Sepsis
 Septic shock
 Death

43
References

1. Lawson, J.H., Niklason, L.E. & Roy-Chaudhury, P. Challenges and novel therapies
for vascular access in haemodialysis. Nat Rev Nephrol 16, 586–602 (2020).
2. Atlas of Dialysis Vascular access
https://cdn.ymaws.com/www.asdin.org/resource/resmgr/imported/atlas%20of%20
dialysis%20access.pdf
3. Daugirdas JT, Ing TS, Blake PG. Handbook of dialysis. 5th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2015.
4. Kooman J, Basci A, Pizzarelli F, Canaud B, Haage P, Fouque D, et al. EBPG
guideline on haemodynamic instability. Nephrol Dial Transplant [Internet].
2007;22 Suppl 2(Supplement 2):ii22-44. Available from:
http://dx.doi.org/10.1093/ndt/gfm019
5. Agarwal R. How can we prevent intradialytic hypotension? Curr Opin Nephrol
Hypertens [Internet]. 2012;21(6):593–9. Available from:
http://dx.doi.org/10.1097/MNH.0b013e3283588f3c
6. Saha, M., Allon, M. Diagnosis, Treatment, and Prevention of Hemodialysis
Emergencies. Clin. J. Am. Soc. Nephrol. 12, 357–369 (2017).
www.ncbi.nlm.gov/pubmed/27831511
7. Patel, N., Dalal, P., Panesar, M. Dialysis disequilibrium syndrome: a narrative
review. Semin. Dial. 21, 493–498 (2008). www.ncbi.nlm.gov/pubmed/18764799
8. Stolic R. Most important chronic complications of arteriovenous fistulas for
hemodialysis. Med Princ Pract [Internet]. 2013;22(3):220–8. Available from:
http://dx.doi.org/10.1159/000343669

44
 4
Peritoneal Dialysis
----------------------------------------------------------------------------------------------------------------

Vineet Behera, Sachin Srivastava

Introduction

Peritoneal dialysis (PD) is a modality for renal replacement therapy (RRT) used in
renal failure patients both in acute settings and for maintenance therapy. PD has an
advantage in being the most physiologic, as it is a slow and continuous process with
no requirement of a vascular access as compared to hemodialysis.

Peritoneum- ‘The Dialyzer”

The peritoneal barrier, is made up of tissue cellular-interstitial matrix and blood

vessels, covered with single layer of mesothelial cells which acts as an endogenous
dialyzing membrane. It has a surface area that ranges from 1 to 2m2 in an adult. The
capillary wall’s function has been described by a three-pore model of membrane
transport, in which multiple pores of different sizes are present in peritoneal
membrane, though which the transport occurs. The peritoneal membrane has
specialized water channels (Aquaporin-1), which have small pores of 40 to 50 Å and
large pores of 150 Å. The Aquaporin-1 channels allow transportation of solute-free
water in response to crystalloid-induced osmotic pressure. These small pores and
aquaporin-1 play major roles in the solute and water transport. The small pores
transport small-molecular-size solutes, including electrolytes, by way of both diffusion
and convection.

Principles – Peritoneal Dialysis

The major principles of dialysis through the peritoneal membrane are diffusion (which
is driven by concentration gradients), and convection, (which is driven by osmotic or
hydrostatic pressure gradients). During the diffusion process, the solute concentration

45
gradient between 2 compartments (capillary blood and PD solution in the peritoneal
cavity) permits the solute to move from higher to lower concentration compartment.
The glucose present in dialysis fluid generates ultrafiltration which is in a proportion to
the overall osmotic gradient, the reflection coefficients of the small solutes relative to
the peritoneum.

CAPD Catheter

The main component of peritoneal dialysis is the PD catheter which has one end in
the peritoneum (open end with multiple pores) while another end exits out of skin to
lie outside. The commonly used PD catheter is a silastic or a polyurethane tube which
has side pores present along its intraperitoneal part. It usually has one or two Dacron
cuffs along its length which allows tissue ingrowth and fibrosis in the connective tissue,
and helps to fix the catheter, prevents leakage around the catheter and infection.
Various types of PD catheters are available as given in Figure 1. The most commonly
used are straight catheters, swan neck, and coiled catheters.

Figure 1. Common types of Peritoneal Dialysis Catheters

(Adapted from Comprehensive Clinical Nephrology, John Feehally 6th edition)

46
Figure 2 - shows the various parts of the peritoneal dialysis catheter with its position
inside the peritoneal cavity.

Catheter Insertion Techniques

Catheters are inserted either by percutaneous method, laparoscopically or via open

surgical technique. The catheter is placed into the peritoneum with a subcutaneous
tunnel exiting the skin, as shown in figure-3. Adequate preoperative planning is
required irrespective of any modality of insertion technique.

a. Open Surgical - This technique involves open surgical laparotomy to

expose the peritoneum and inserting the catheter into the peritoneal cavity
under vision. After closure of abdominal wall layers, the peritoneal catheter is
directed through a subcutaneous tunnel up to the skin exit site.

b. Laparoscopic / Peritoneoscopic - Laparoscopy is a less invasive

technique, which is done using laparoscopic ports or peritoneoscope. The
abdomen is insufflated with gas via a Verres needle from a lateral abdominal
wall puncture site, after which camera port is inserted. Thereafter, the CAPD
catheter is inserted under direct visualization with laparoscopic guidance.

47
 c. Percutaneous – This minimally invasive technique is most commonly
practiced by Nephrologists. It involves a percutaneous puncture after which
the insertion is done by a modification of the Seldinger technique – a needle
is introduced into the peritoneum and a guidewire is placed through it.
Thereafter, a peel away sheath is inserted into the peritoneum, the trocar
removed, and the CAPD catheter inserted into the peritoneum through the
peel away sheath.

Figure 3 - Showing PD catheter and its relationship to various anatomical structures

(Adapted from Peritoneal Dialysis Catheter insertion, John H Crabtree, Seminars in
Nephrology, Vol 37, No 1, Jan 2017)

Peritoneal Dialysis Procedure

PD fluids are available commercially in bags and are made of a lactate buffered,
balanced salt solutions with glucose (1.5%, 2.5%, or 4.5%) as the osmotic agent. The
principal osmotic agent in PD is glucose. Other alternative osmotic agents
commercially available are amino acids and icodextrin. Icodextrin is a polydisperse
glucose polymer which is available as a 7.5% solution. Icodextrin is generally used for
long dwell exchanges, for example, overnight, and particularly for fast transporters.

48
In CAPD, nearly 2 to 2.5 liters of dialysis fluid is instilled into the peritoneal cavity for
up to three – four times per day. PD is available in a double bag system with Y-set
tubing system. In the double-bag system, the unused dialysis fluid bag is connected
to an empty sterile drain, and after the patient has connected the system, a frangible
(breakable) pin to the drain bag is opened. Exchange volume can be titrated as per
patient weight and body habitus.

Types of PD

1. CAPD (Continuous ambulatory peritoneal dialysis) - The peritoneal exchanges

are manually 3-4 times a day, done by the patient or his attendant using 2-2.5L
bags.

2. APD (Automated Peritoneal Dialysis) - Patients uses a “cycler” device for carrying
out PD exchanges as shown in. It is advantageous for patients with active day time
routine, as most of the exchanges are done during night time.

The choice between APD and CAPD should be guided by patient and physician
preference, membrane transport status and resource availability.

Figure 4 showing an Automated peritoneal dialysis machine.

49
Peritoneal Dialysis Prescription

Important factors that are considered while deciding on a PD prescription are patient’s
lifestyle or preferences, residual urine output and peritoneum transport characteristics
(e.g. fast or slow transporter as assessed through a PET test).

1. CAPD - Frequency and Volume of exchange, Dialysate Fluid (Tonicity)

and dwell duration (e.g. 04 x cycles of 2L PD fluid Dextrose (2.5%) with dwell
time of 4 hrs). Patients with good urine output and good residual renal function,
can be initiated on CAPD with 3 exchanges. Similarly, patients who are anuric
with weight> 75 kg will require 2.5 L as single exchange volume. So as to
achieve better creatinine clearance, it is advisable to increase dwell volume,
rather than increasing the frequency. Tonicity of the PD fluid used impacts the
ultrafiltration achieved.

2. APD- The manual CAPD fluid exchanges are replaced by the use of a
cycler or an automated PD machine. APD is done through an automated
cycler device with fluid bags of generally 5L size of different concentrations.
This cycler can do multiple number of exchanges of fixed volume of dialysate,
over a fixed period of time. Like over a night APD for 10 hours, 5-6 cycles of
2L of dialysate can be done with a dwell of 30 minutes.

Common Modalities of Peritoneal Dialysis

1. CAPD: Patient does manual exchanges (eg 3 exchanges with 4 hrs dwell time and
1 night time exchange with longer dwell time).

2. NIPD (Nocturnal intermittent Peritoneal Dialysis)/ “Day Dry” APD: Multiple

exchanges in night time using a “cycler” and no exchange (dry abdomen) in day
time.

3. CCPD (Continuous Cycled Peritoneal Dialysis): It involves doing 5-7 exchanges

over 9 hrs at night time using a cycler. A manual cycle is done using 7.5% is left in
50
 at the end of the cycling period and is drained out again before the next cycling
period starts after about 15 hrs.

4. High Dose APD (APD with 2-day dwells): It is also known as or PD plus. It involves,
doing two additional exchanges along with night APD.

5. Tidal PD: In Tidal PD, PD fluid is incompletely drained and next cycle PD fluid is
instilled. It is useful in cases of a poorly draining PD catheter or patient is
experiencing pain during draining fluid.

Figure 5 - Showing the various PD modalities.

PET (Peritoneum Equilibration Test)

The functioning efficacy of peritoneal dialysis and the membrane characteristics of

the peritoneal membrane may be evaluated using the PET test. In this process, in
which the dialysate fluid drained after a 4-hour dwell time is analyzed and compared
with the serum to determine solute clearance rates. This peritoneal equilibrium test

51
helps determine the patient’s peritoneal transport characteristics, the dose of dialysis
required, and the most appropriate technique. A peritoneal equilibration test is usually
performed 4 weeks after the initiation of PD therapy so as to assess the peritoneal
membrane characteristics, whether it is a high transporter, high average, low average
or low transporter.

Advantages of CAPD

Peritoneal dialysis offers a “home based” RRT. There is no requirement of a

permanent vascular access. It avoids any chances of blood borne or cross infections.
It is particularly useful in infants and young children requiring maintenance dialysis.
Studies have shown that even though the overall mortality of patients on PD compared
with HD is not significantly different. However, the risk for death in patients treated with
PD during the initial 3 years of treatment is lower when compared with those treated
with HD. Also, it is very important to preserve the residual kidney function due to its
strong association with patient survival.

Suggested References

1. Blake PG, Daugirdas JT. Physiology of Peritoneal Dialysis. In: Handbook of

Dialysis, 5th edition, edited by Daugirdas JT, Blake PG, Ing TS, Lippincott
Williams & Wilkins, Philadelphia. 2015:392-407.

2. Figueiredo A, Goh BL, Jenkins S, Johnson DW, Mactier R, Ramalakshmi S, et

al. Clinical practice guidelines for peritoneal access. Perit Dial Int.
2010;30(4):424-9.

3. Bansal S, Teitelbaum I. Causes, Diagnosis, and Treatment of Peritoneal

Membrane Failure. In: Principles and Practice of Dialysis, 5th edition, edited by
Lerma EV, Weir MR, Lippincott Williams & Wilkins, Philadelphia.2017:194-219

52
4. Dombros N, Dratwa M, Feriani M, Gokal R, Heimburger O, Krediet R, et al.
European best practice guidelines for peritoneal dialysis. 2 The initiation of
dialysis. Nephrol Dial Transplant. 2005;20 Suppl 9:ix3-ix7

5. Peritoneal Dialysis Adequacy Work Group. National Kidney Foundation Kidney

Disease Outcomes Quality Initiative: NKF-K/DOQI Clinical practice guidelines for
peritoneal dialysis adequacy. Am J Kidney Dis. 2006;48(Suppl 1):S98–129.

53
 5
Complications of Peritoneal Dialysis
----------------------------------------------------------------------------------------------------------------

Vineet Behera, Sachin Srivastava, Rakesh JP Yadav

Introduction

There is significant morbidity and mortality as a result of infectious complications from

peritoneal dialysis. Episodes of peritonitis can cause damage to peritoneal membrane,
thus reducing its efficacy. A motivated team, proper training, appropriate culture
procedures, appropriate empiric antibiotics and frequent audits are all essential
components of a successful PD programme. Hospitals and dialysis units should follow
their PD infections rates audit their practices in case infections rates are substantially
high or increase over time.

The commonly encountered complications of peritoneal dialysis are related to PD

catheters which include exit site infection, tunnel infection, impaired flow, external cuff
extrusion, dialysate leaks and infusion pain. This chapter will highlight key concepts of
commonly encountered PD complications and their management.

PD Peritonitis

Defining Peritonitis

PD Peritonitis is diagnosed when at least 2 of the 3 features are present: typical clinical
features of peritonitis that include fever, pain abdominal, turbid PD fluid; PD fluid
effluent WBC count > 100/L (with > 50% PMN leucocytes); and a positive culture
from dialysis effluent. For diagnosing peritonitis in APD, percentage of PMN exceeding
50% is strong evidence suggestive of PD peritonitis.

54
Pathogenesis of Infection

Infection occurs when pathogenic organisms gain access to peritoneal cavity, either
due to technical errors or some form of contamination during transfer set–to-bag or
catheter-to–transfer set connection leading to micro-organisms from skin surface or
intestinal flora entering the peritoneal cavity.

Etiology

The common organisms causing PD peritonitis are gram positive organisms like
Staphylococcus aureus, coagulase- neg Staphylococcus; gram negative organisms
like pseudomonas, E Coli, and other rarer organisms like fungi or mycobacteria.

Clinical Presentation

Majority of the patients present with abdominal pain during a peritonitis episode
associated with complains of nausea, vomiting, fever and constipation or diarrhea.
Classically the dialysate fluid will appear “cloudy” due to increase in cellular
components as shown in Figure1. However, it is important to note, other reasons of
“cloudy PD fluid” apart from infection. Cloudy can be seen in cases of pancreatitis,
superior vena cava syndrome, malignancy, chemical peritonitis, lymphatic obstruction,
after prolonged dwell time, presence of blood or fibrin, drugs (calcium channel
blockers). Physical examination may reveal generalized abdominal tenderness.

Figure 1. Shows cloudy CAPD fluid.

55
Diagnosis PD Peritonitis

Whenever there is a suspicion of PD peritonitis, PD effluent, should be evaluated for

total cell count, differential count, gram stain, and culture. The PD fluid sample should
be sent to Lab as fast as possible and processed within 6 hrs of collection. In cases
where patient resides at a far-off place from hospital, the effluent bag should be kept
refrigerated till the sample is brought for analysis. Staining of PD effluent should be
performed, preferably after centrifugation, and the sediment should then be plated
onto solid culture media or regular blood culture media for inoculation. Bedside
inoculation of 5–10 mL effluent in two (aerobic and anaerobic) blood-culture bottles
has a reasonable sensitivity.
The most common causes of culture negative peritonitis are inadequate culture
methods, recent use of antibiotics, atypical organisms like mycobacteria, fungi. ISPD
guidelines recommend that culture-negative peritonitis should be less than 15% of all
peritonitis episodes.

Treatment of PD Peritonitis

Early administration of antibiotics is associated with better outcome of peritonitis

treatment. Empirical antibiotics choice may be based on the center’s culture positivity
reports. The recommended duration of therapy is for 2 weeks, except in the case of
staphylococcus, enterococcus species, pseudomonas, or multi organism peritonitis,
which require longer duration of therapy.

Empirical antibiotic therapy be initiated as soon as possible, using either

intraperitoneal (IP) or systemic route, after appropriate microbiological specimens
have been obtained. IP antibiotics be the preferred route of administration as long as
the compatibility and stability of the IP antibiotics allow, unless the patient has features
of systemic sepsis. Gram-positive organisms be covered by a first-generation
cephalosporin or vancomycin and gram-negative organisms by a third-generation
cephalosporin or an aminoglycoside. The common antibiotic IP doses are given in
Table 1.

56
 Antibiotic Dosing Intermittent exchange for CAPD (daily for at
least 6 hr)
Amikacin 2 mg/kg/daily
Gentamycin 0.6 mg/kg/daily
Netilmicin 0.6 mg/kg/daily
Cefepime 1gm daily
Cefotaxime 500 to 1000 mg daily
Ceftazidime 1000–1500 mg daily
Imipenem/cilastatin 500 mg in alternate exchange
Meropenem 1000 mg daily (for short dwell in CAPD)
Teicoplanin 15 mg/kg every 5 days
Vancomycin 15–30 mg/kg every 5–7 days for CAPD and 15 mg/kg
every 4 days for APD
Fluconazole IP 150–200 mg every 24 to 48 h(*oral route is preferred)

Table 1 - Showing intraperitoneal dosages of antibiotics used in PD peritonitis

When to Remove Catheter
PD catheter should be removed for refractory peritonitis (refractory is defined by failure
of resolution of peritonitis after 5 days of appropriate antibiotics), relapsing, tubercular
and fungal peritonitis. Before labelling an infection as refractory, a trial of a higher/more
susceptible antibiotic is advised for a further two days if it fails to respond to an empiric
antibiotic in culture-negative peritonitis. Relapsing peritonitis is defined as infection
caused by the same organism as the original infection occurring within 4 weeks.

Exit Site Infection

Exit site infection (ESI) is a significant long-term PD complication. Clinical evidence

supporting the diagnosis is typically seen in the form of obvious erythema or discharge
coming from the exit site. S. aureus is the most prevalent infection-causing agent. A
minimum of two weeks of treatment with gram positive coverage is advised, with three
weeks being advised in case of Pseudomonas infections.

57
Figure 2 - Shows CAPD exit site infection

Ultrafiltration Failure

Ultrafiltration failure is defined as fluid overload resulting in association with

ultrafiltration volume < 400 mL after a PD cycle using a modified peritoneal equilibrium
test. This leads to reduced ultrafiltration after PD cycles.

The various types of ultrafiltration failure are discussed in Figure 3. In patients on long
term PD, peritoneum undergoes both structural and functional changes with time,
owing to exposure of hyperosmolar glucose solution. This often leads to alteration in
transport rate of small solutes and decrease in osmotic conductance (efficiency of
ultrafiltration given a particular osmotic gradient). The two main factors for ultrafiltration
failure can be due to “fast solute transport rates” or poor membrane UF efficiency
(reduced osmotic conductance). Patients with fast solute transport status causes more
rapid diffusion of small solute across the membrane, thus causing early dissipation of
the osmotic gradient driving UF.

Management of Ultrafiltration failure consists alteration of PD prescriptions, Use of

Automated PD cyclers or ultimately shifting the patients to hemodialysis

58
 Large effective Hyperpermeahl High Solute Transport
Type 1 peritoneal
surface area
e peritoneal
membrane (D/P'Creat > 0.81)

Low osmotic High avg transport

Aquaporin
Type 2 conductance to
glucose
dysfunction D/P'Creat 0.5-0.8

Abdominal
Low effective adhesions Low-Solute
Type 3 peritoneal
surface area
Encapsul ating Transport (D/P
Creatinine < 0.5
peritonealsclero
sis

High effective
Increased
lymphatic High avg or Low avg
Type 4 absorption
lymphatic
absorption
transport
rate.

Figure 3. Summarizing various types/mechanisms of Ultrafiltration Failure

Encapsulating Peritoneal Sclerosis

It is a rare but serious PD complication, in which in which the bowel and intraperitoneal
contents are covered by a thick cocoon of fibrous tissue, causing intestinal obstruction
as shown in Figure 4. It takes both clinical evidence of intestinal obstruction causing
weight loss and malnutrition (with or without markers of systemic inflammation) and
either typical imaging characteristics (CT scanning) or confirmation via laparotomy to
make the diagnosis of EPS. Risk factors include high glucose exposure, younger age,
ultrafiltration failure, inflammation/peritonitis, discontinuation of PD therapy. Surgical
management with adhesion-o-lysis is most effective.

Figure 4. Shows encapsulating peritoneal sclerosis

59
Mechanical Problems

Mechanical complications of PD include peri catheter leaks and hernias, infusion and
drain pain, flow failure, catheter tip migration, and superficial cuff extrusion. Catheter
tip migration leads to movement of tip to right or left upper quadrants of abdomen
leading to poor causing poor inflow or outflow. In rare cases especially in children,
omentum may wrap the CAPD catheter leading to mechanical obstruction and floor
CAPD flow as shown in Figure 5. These mechanical problems often require surgical
management by open or laparoscopic repair and repositioning of PD catheter.

Figure 5. Shows Encapsulating peritoneal sclerosis

Metabolic Complications of PD

Peritoneal dialysis using glucose-based solution leads to significant daily glucose

absorption causing weight gain, deranged glycemic and lipid profile. Dialysis
exchanges leads to protein loss via peritoneum almost up to 7-8 gm/day, which gets
compounded during episodes of peritonitis leading to hypoalbuminemia and protein
malnutrition. Therefore, it has been recommended that PD patients should consume
daily at least 1.2 to 1.3 g of protein per kilogram of body weight.

60
Suggested References

1. Tanratananon D, Deekae S, Raksasuk S, Srithongkul T. Evaluation of different

methods to improve culture-negative peritoneal dialysis-related peritonitis: a single-
center study. Annals of Medicine and Surgery. 2021 Mar 1;63:102139.

2. Li PKT, Chow KM, Cho Y, Fan S, Figueiredo AE, Harris T, et al. ISPD peritonitis
guideline recommendations: 2022 update on prevention and treatment. Peritoneal
Dialysis Int. 2022;42(2):110–53.

3. Muthucumarana K, Howson P, Crawford D, Burrows S, Swaminathan R, Irish

A. The relationship between presentation and the time of initial administration of
antibiotics with outcomes of peritonitis in peritoneal dialysis patients: The PROMPT
study. Kidney International Reports. 2016 Jul 1;1(2):65-72.

4. Lam E, Lien YT, Kraft WK, Piraino B, Vozmediano V, Schmidt S, Zhang J.

Vancomycin in peritoneal dialysis: Clinical pharmacology considerations in therapy.
Peritoneal Dialysis International. 2020 Jul;40(4):384-93.

5. Rutkowski B, Tam P, van der Sande FM, Vychytil A, Schwenger V, Himmele R,

Gauly A, Schwenger V, Vychytil A, Kopriva G, van der Sande FM. Low-sodium versus
standard-sodium peritoneal dialysis solution in hypertensive patients: a randomized
controlled trial. American Journal of Kidney Diseases. 2016 May 1;67(5):753-61.

61
 6
Renal Transplant - Basics
--------------------------------------------------------------------------------------------------------------------------

Dinesh Khullar, Abhishek Singh

Introduction

The prevalence of chronic kidney disease (CKD) worldwide is rapidly rising and is
currently estimated to be between 8 – 17%. In India the annual incidence of CKD is
about 232 per million population. Unfortunately, over 50% of patients with CKD at
presentation have stage V disease i.e., an estimated GFR of less than 15 ml/min per
1.73 m2.

Patients may either opt for kidney replacement therapy (KRT) or conservative care.
The various modalities of KRT are Hemodialysis (HD), Peritoneal dialysis (PD) and
Transplantation. HD was introduced in India in 1962 and is by far the most common
modality of KRT with about 1,75,000 patients currently being on HD. PD was
introduced in India in the year 1991, and about 5000 patients use this as the KRT
modality of choice. Transplantation was first performed in India in 1971.Annually 8000-
10,000 kidney transplants are performed in India, with approximately 90% being living
donor and 10% being deceased donor transplants.

As per the United States Renal Data System (USRDS) 2018 report, the adjusted five-
year survival is 42% for those on HD, 52% for patients on PD It was 90% in patients
who received deceased donor transplants and 95% for those who received living
donor transplants. When compared with maintenance dialysis, a successful kidney
transplant offers better survival and a superior quality of life. Hence, Kidney
transplantation is now the preferred treatment for those with end-stage kidney disease.

Dr. Joseph Murray performed the first successful kidney transplant in 1954. Since
then, there have been major advancements in the science of transplantation and

62
immunology. This has encouraged a wider selection of acceptable donors and
recipients.

Transplantation of Human Organs Act (THOA), 1994 established the legal framework
for transplantation in India. Subsequently, the Transplantation of Human Organs
(Amendment) Act, 2011 and the establishment of the National Organ transplant
programme (NOTP) have further regularised kidney transplant programme in our
country.

National Organ and Tissue Transplant Organization (NOTTO) is the apex body
overseeing transplantations in India. It has two divisions: 1) The National Human
Organ and Tissue Removal and Storage Network and 2) National Biomaterial Centre.
NOTTO is further supplemented by five Regional Organ and Tissue Transplant
Organizations (ROTTO) and five State Organ and Tissue Transplant Organizations.
The Indian Society of Organ Transplantation (ISOT) is a non-profit society which
promotes the ethical science of organ transplantation in India. The ISOT is a signatory
of the Declaration of Istanbul on Organ trafficking and transplant tourism, 2008.

Types of Kidney transplantation

Based on the donor status, kidney transplant may either be a living donor transplant
or deceased donor transplant. Deceased donor transplant can further be classified as
donation after cardiac death (DCD) or donation after brain death (DBD). Innovative
transplant modalities include ABO incompatible transplants, transplants in highly
sensitized recipients and paired kidney donation. Allocation of deceased donor
kidneys is modelled on the twin principles of ‘Justice’ and ‘Utility’. Many countries use
sophisticated kidney allocation systems for deceased donor transplants matching
marginal donors, sensitized patients.

Transplant Candidate

All patients of CKD stages IV/V with anticipated dialysis initiation within 6 to 12 months
should be counselled and worked-up for transplantation. If a living donor is available,
63
a pre-emptive transplantation should be advised as it provides the best outcomes of
transplantation. Dialysis vintage is an adverse prognostic marker for transplantation.
In India, patients with CKD V on maintenance dialysis for at least 3 months are eligible
for registration into the transplant waitlist. Absolute contraindications include terminal
debilitating illness, active infection, active malignancy (with few exceptions), active
symptomatic cardiovascular disease, ongoing psychiatric disorder, substance abuse,
non-adherent behaviour, or a positive T-Cell CDC crossmatch.

Transplant candidates and potential living donors should undergo pre-surgical

evaluation to assess and minimize risks of perioperative cardiovascular, pulmonary,
bleeding or anaesthesia-related complications. Other pertinent pre-operative
evaluations include gastroenterology, gynaecology and psychological.

Prior to surgery, the following interventions are recommended:

 Cessation of smoking / tobacco use at least 1 month prior to living donor

transplantation or to waitlisting for deceased donor program.

 Weight loss interventions for morbid obesity, prior to transplantation.


 Completion of vaccination series prior to transplant (Hepatitis B,
Pneumococcal, Influenza and Varicella Zoster vaccine).

 Screening for infections - Tuberculosis, Viral infections –HIV, HCV, HBV,

EBV, CMV, Periodontal disease.

The cause of CKD should be determined, where possible to advise candidates about
the:
a) Risk of recurrence and resultant of graft loss,
b) Timing of transplantation,
c) Management of systemic manifestations.
Immunologic assessment of transplant candidate includes H/O sensitization, HLA
genotyping of both donor and recipient, panel reactive antibodies (PRA) for deceased
donor waitlisted candidates, Donor Specific Antibodies (DSA) - solid phase assays,

64
Donor-recipient Crossmatch analysis through cell dependent cytotoxicity (CDC) and
flowcytometric assays.

Potential living donors should also undergo assessment of psychosocial function,

renal anatomy and vasculature, transmissible infections, donor kidney function
(acceptable GFR > 90 ml/min per 1.73m2, selection with GFR between 60-90 -
individualized), proteinuria, inherited kidney diseases, and metabolic parameters.
Contraindications for donation include albuminuria > 100 mg/day, morbid obesity,
poorly controlled hypertension with end organ damage, poor glycemic control or
current and future risk of end organ damage in patients with diabetes mellitus, active
malignancy. Deceased donors are selected after consent from family and assessment
of brain death by a team of intensivists, neurologists and neurosurgeons.

Transplant surgery involves two surgeries, donor nephrectomy and heterotopic

implantation in the recipient. The approach for donor nephrectomy can be open,
laparoscopic or robot assisted. The left kidney is preferably selected for living donor
transplantation because of easier dissection and longer length of left renal vein.
Implantation in the recipient is performed either in an open fashion or robot assisted,
where the kidney is placed heterotopically in the pelvis, anastomosing the vessels to
the external iliac vessels and the ureter to the bladder. The iliac vessels are
preferentially exposed retroperitoneally as the peritoneum is retracted medially.
However, intra-peritoneal placement is also acceptable.

Organ Preservation

Once the kidneys are procured, they are preserved before eventual implantation.
During this process of transplantation, the kidneys experience ischemia. The organs
are perfused with cold physiological solutions prior to anastomosis with the recipient
vessels to diminish metabolic demand and minimize the injury. Kidneys are
alternatively placed on machine perfusion for preservation. Warm ischemia time refers
to the period between circulatory arrest/application of clamp to initiation of cold
perfusion. Cold ischemia time is the period of cold storage/perfusion. Rewarm time is
described as the “sew-in” time i.e., time from the removal of organ from cold storage
65
until reperfusion following vascular anastomosis. The longer the ischemia time, the
greater the chance of adverse graft outcomes.

The Renal Transplant Operation

The transplant surgery involves three anastomoses:

1) The donor renal artery and the recipient external/internal/common iliac
artery (end-to-side)
2) The donor renal vein and the recipient external/internal/common iliac vein
(end-to-side)
3) The donor ureteric reimplantation to the recipient’s bladder forming a
ureteroneocystostomy with a Double - J ureteric stent left in situ.

The double J stent is removed 2–12 weeks postoperatively via flexible cystoscopy,
based on evaluation by the surgical team.
Immunosuppressive therapy requires a fine balance between preservation of allograft
rejection and minimizing adverse drug effects. The following table depicts the
commonly used immunosuppressive drugs for induction and maintenance
immunosuppression with their mechanisms of action and common adverse effects.

AGENT MECHANISM OF ACTION ADVERSE EFFECTS

Anti-Thymocyte Rapid lymphocytopenia through First dose reaction,

Globulin complement-dependent Serum sickness,
cytolysis, cell-dependent Risk for infection and Malignant
phagocytosis, and apoptosis neoplasms.

Basiliximab Chimeric monoclonal antibody Risk for infection

against CD25 (alpha subunit of
IL-2 receptor)

Corticosteroids Inhibits cytokine production Diabetes, Osteoporosis, Weight gain,

Hypertension

66
 Cyclosporin Calcineurin inhibitor Cosmetic - Hirsutism, Gum
hypertrophy
Metabolic - Hypertension, Diabetes,
Nephrotoxicity

Tacrolimus Calcineurin inhibitor Diabetes, Nephrotoxicity,

Neurotoxicity (Tremors)

Mycophenolate Inosine-monophosphate GI disturbances (diarrhoea),

mofetil dehydrogenase inhibitor Haematological (leukopenia,
anemia),
Mouth ulcers

Azathioprine Purine synthesis inhibitor Myelosuppression

Sirolimus Mammalian target of raptamycin Peripheral edema, Poor wound

(mTOR) inhibitor healing, Hypertriglyceridemia,
Anemia, Proteinuria

Transplant patients are closely monitored post-operatively for graft function, infection
and any surgical complications. Usual duration of stay is between five to ten days with
early removal of urethral catheter. The usual protocol for post-transplant follow-up is
twice weekly for the four weeks post-transplant followed by weekly for one month,
every two weeks for one month and then every three months for the first year after
transplantation. The following parameters are evaluated on follow-up – Blood
pressure, hemogram, serum creatinine, electrolytes, urinalysis, CNI levels.

Post-donation follow-up care is done at least annually and includes blood pressure
monitoring, BMI evaluation, estimation of serum creatinine, GFR and albuminuria
measurements. Donors should be reviewed regularly. A healthy lifestyle including
regular exercise, healthy diet and reinforced abstinence from tobacco along with
review and support of psychosocial health and well-being. Donors are counselled
about pregnancy post donation which may have a higher possibility of gestational
hypertension or preeclampsia.

67
 7
Complications of Renal Transplant
----------------------------------------------------------------------------------------------------------------

Dinesh Khullar, Abhishek Singh

Introduction

A successful transplant gives the best outcomes for a patient with CKD. However,
knowledge about complications and swift action on the same work a long way in
prolonging the life of a transplanted kidney and the patient.

Surgical complications associated with transplant include:

1) Wound infection
2) Wound dehiscence
3) Anastamotic-hemorrhages
4) Vascular complications
i) Renal artery thrombosis
ii) Transplant renal artery stenosis
iii) Renal Vein thrombosis
5) Lymphocele
6) Urinary leaks
7) Ureteral obstruction
Surgical intervention is guided by the acuity and nature of presentation and the risk of
graft loss.

Rejection

Acute renal allograft rejection is defined as an acute deterioration in graft function

associated with specific pathologic changes. It can be of two types. Acute T cell-
mediated (cellular) rejection (ACR) is described morphologically as mononuclear
leukocyte infiltration in tubules, interstitium, arterial intima. Acute antibody-mediated

68
rejection (AMR) is defined as morphologic evidence of acute tissue injury, evidence
of circulating donor-specific alloantibodies, immunologic evidence of an antibody-
mediated process (such as C4d deposition in the allograft). AMR and ACR may
coexist.
It used to be reported in 50 to 60 percent of renal allograft recipients in the 1980s.
Organ Procurement and Transplantation Network (OPTN) now reports the incidence
of rejection between 8 to 10 percent among first year post-transplant patients. Living
donor transplants experience a lower rate of rejection (by 1 to 2 percent) than
deceased-donor kidney transplants, likely due to better matching in living-donor
transplants and less cold ischemia time. Risk factors for rejection include sensitization,
human leukocyte antigen (HLA) mismatches, blood group incompatibility, paediatric
recipient, prolonged cold ischemia time, delayed graft function (DGF), previous
episode of rejection, medication nonadherence.

Rejection is suspected when there is an increase in serum creatinine of ≥25 percent

from baseline and/or worsening hypertension, proteinuria >1 g/day. Patient may
present clinically with fever, graft tenderness/pain or reduced urine output. The
diagnosis requires a graft biopsy which grades the severity of rejection, differentiates
between ACR and AMR and determines the degree of irreversible kidney damage
(interstitial fibrosis/tubular atrophy [IF/TA]). The Banff criteria is used to classify graft
biopsies for uniformity of reporting and diagnosis. Non-invasive tests like the plasma
donor-derived cell-free DNA (dd-cfDNA >1 percent) are being validated as markers of
rejection.

Treatment

ACR -Methylprednisolone ± Thymoglobulin

AMR -Methylprednisolone ± Therapeutic plasma exchange ± IVIg. Rituximab,
Eculizumab, Bortezomib may be used in refractory cases.

Chronic Active Antibody Mediated Rejection (CAMR) is now established as the most
common cause of graft loss. It is caused by a repetitive pattern of graft injury
characterized by thrombotic events, inflammatory changes, endothelial cell injury and
69
allograft matrix remodelling. This leads to a slow and persistent decline in kidney
function. It is more difficult to treat than active AMR since irreversible tissue damage
has already occurred and there are no established treatment options. The approach
to management of CAMR includes optimization of immunosuppression, use of
glucocorticoids and intravenous immune globulin (IVIG). Rituximab is used if biopsy is
suggestive of active microvascular inflammation. Tocilizumab maybe used as rescue
therapy.

Infections

Infections are the bane of kidney transplantation as recipients have to endure life-long
immunosuppressive therapy. The Figure 1 below represents the timeline of common
infections post- transplant.

Figure 1 – Timeline of infections in kidney transplant

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Early post-transplant infections are related to surgery and hospitalisation. The next
phase of infections is those due to heightened immunosuppression, associated with
atypical, opportunistic infections. Kidney transplant recipients typically receive
prophylaxis against Pneumocystis carinii (Cotrimoxazole), cytomegalovirus
(valganciclovir) and candidiasis (clotrimazole, fluconazole). CMV and EBV are
immunomodulatory, not only causing systemic manifestations but also increasing the
likelihood of rejection and malignancy. BK virus nephropathy is another dreaded
infectious complication post-transplant which may lead to graft loss. High index of
suspicion, frequent monitoring and rapid, judicious tapering of immunosuppression are
required for its prevention and management. In late post-transplant period, community
acquired infections are more common, however risk of opportunistic infections is never
nullified.

Recurrence

The native kidney disease may recur post-transplant. Histological recurrence is much
more common as compared to clinical recurrence. Not all recurrences lead to graft
loss. The table below depicts the rates of histological recurrence and graft loss from
various common kidney diseases
Disease Recurrence (%) Graft loss (%)
FSGS 20 – 40 40 – 50
Membranous 30 50
Nephropathy
IgA Nephropathy 40 – 60 20 – 30
C3 Glomerulopathy 80 – 100 20
HUS/TTP 30 – 60 60 – 100
Lupus Nephritis <10 Rare
ANCA associated 10 – 20 20 – 50
vasculitis
Primary hyperoxaluria 80 – 100 80 – 100
Diabetic kidney disease 80 – 100 Uncommon
Table 1. Recurrence rates of various native kidney diseases in transplanted kidney

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Medical Complications

Transplant patients need to be monitored for various medical complications.

Cardiovascular disease (CVD) is the most common cause of mortality accounting for
50 to 60 percent of post-transplant deaths. Its risk factors need to be tackled
aggressively. Hypertension occurs in 50 to 80 percent of post-transplant patients.
KDIGO guidelines recommend target blood pressure <130/80 mmHg in transplant
recipients. Statins are recommended for cardiovascular disease prevention and
management of dyslipidemia in all transplant patients. Lifestyle modification and
weight reduction interventions should be recommended to all obese post-transplant
patients.

Post-Transplant Diabetes Mellitus (PTDM) develops most commonly within the first
few months’ post-transplant. Pre-existing risk factors include increased age, obesity,
family history of diabetes or gestational diabetes. The transplanted kidney is
gluconeogenic and metabolizes and excretes insulin more efficiently. Moreover,
immunosuppressive medications, such as glucocorticoids, calcineurin inhibitors
(CNIs), and mammalian (mechanistic) target of rapamycin (mTOR) inhibitors increase
the risk of PTDM. Glycemic targets are similar to the general population.

Risk factors for development of mineral bone disease (MBD) include pretransplant
renal osteodystrophy, drugs - glucocorticoids, CNIs, persistent hyperparathyroidism,
calcium and vitamin D deficiencies. Persistent hyperparathyroidism is seen in as many
as 50 percent of transplant recipients and is associated with increased mortality,
increased graft loss and osteoporosis.

Anemia occurs in 30 to 40 percent of kidney transplant recipients and usually resolves

within first year with hematinics. On the other hand, erythrocytosis may be seen in
nearly 22 percent of kidney transplant recipients. It usually develops 8 to 24 months
after transplantation. Approximately 20 to 60 percent of patients will experience at
least one episode of leukopenia or neutropenia, typically within the first year after
transplantation. It is associated with increased risk of infections. Some patients may
also experience thrombocytopenia.

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Kidney transplant recipients are approximately three times more likely to develop
cancers than the general population. Risk factors specific to the transplant population
include type, extent, and duration of immunosuppression, viral infections, donor
transmission. Modification (reduction/ alteration/ cessation) of immunosuppression is
required based on the nature and aggressiveness of the malignancy and the ongoing
need for immunosuppression to prevent graft rejection.

Infertility is common among patients with end-stage kidney disease. Fertility is usually
improved within just a few months after kidney transplantation. Pregnancy in a
transplant recipient is considered high risk. The goal is to minimize risks to the mother
and fetus. Pregnancy should usually be planned after one year of transplantation with
stable graft function and immunosuppression. Modification of immunosuppression
may be required to avoid teratogenicity. Close monitoring of the mother, fetal well-
being and graft function is required during pregnancy.

Chronic Allograft Dysfunction is defined as irreversible and progressive loss of graft

function. It manifests morphologically as interstitial fibrosis and tubular atrophy (IFTA)
on graft biopsy. It may be caused by non-immune as well as alloimmune factors.
Management of non-immune factors includes treatment of hypertension, lifestyle
modification (stop smoking, control lipids), control of diabetes, prevention and
treatment of urinary tract infection and CNI dose reduction or replacement for CNI
toxicity. Treatment of Alloimmune factors includes early diagnosis and treatment of
acute rejection and chronic antibody-mediated rejection.

Failed Transplant
About 1 % of transplants fail annually. The balance of immunosuppressive therapy
now shifts towards increased risk of infection, malignancy and metabolic complications
of glucocorticoid therapy. Hence, a planned withdrawal of immunosuppression is
undertaken. In case of early graft failure (<1year post-transplant), pre-emptive
nephrectomy and immediate withdrawal of immunosuppression at the time of
nephrectomy is done. However, with late graft failure (>1-year post-transplant),
immunosuppression withdrawal is based on plan for re-transplantation and residual
graft function. Generally, antimetabolites are withdrawn first followed by CNIs and low
dose steroid is continued to prevent graft intolerance.
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 8
Conservative Kidney Management
----------------------------------------------------------------------------------------------------------------

Narinder Pal Singh, Sambit Sundaray Vineet Behera

Introduction

Dialysis has been the cornerstone of therapy for end stage renal disease (ESRD). The
thrust of management of advanced chronic kidney disease (CKD) has revolved around
renal replacement therapy (RRT) including hemodialysis (HD), peritoneal dialysis
(PD), or if possible renal transplant. There has been an effort to extend dialysis to
more patients over the past few decades, which has seen progressive broadening of
dialysis criteria. This has led to extending dialysis with individuals with increasing age
and with more comorbidities. Despite providing symptomatic or immediate therapy to
old age CKD patients with comorbidities, it rarely changes the long-term outcomes
and prognosis of these patients. Therefore, the intention of providing dialysis to these
patients is always considered unnecessary.

Conservative (non-dialytic) kidney management (CKM) has been a new concept in

nephrology practice. The futility or no benefit of dialysis to CKD patients with old age
or with comorbidities, has always been considered by nephrologists, and these
patients who were not suitable for (or not willing to have) dialysis were not given
dialysis and discharged back to the community. But no cognizance was given to
symptomatic relief to these patients and providing supportive medical therapy to these
patients. Conservative kidney management includes non-dialysis supportive therapy
directed at specialist symptom control, conservative measures correction of
dyselectrolytemia, fluid status correction, optimisation of anemia and terminal care.

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Definition - Conservative Kidney Management

Conservative Kidney Management is a management option for patients with CKD

stage 5 (eGFR <15 mL/min/1.73 m2) that focuses on providing kidney supportive care
to improve quality of life without doing HD/PD or renal transplantation. CKM is distinct
from the pre-dialysis care of patients with stage 5 CKD who plan to pursue kidney
replacement therapy when indicated. CKM is also distinct from withdrawal of dialysis,
which refers to discontinuation of maintenance dialysis.

The main principle is to optimize the supportive care with the patient's choices in order
to achieve their personal goals, which are directed towards enhancing the quality of
residual life. This is best delivered through a collective, collaborative, multi-speciality
team, which primarily constitutes a nephrologist, a general physician, geriatrician, a
nurse, a diet expert, a counsellor and when appropriate, the palliative therapist.

Ideal Candidates for CKM

CKM is preferred for the following category of patients:

1. Frail patients with significant functional or cognitive impairment, who have serious
functional and cognitive deterioration after dialysis.
2. Patients with multiple serious comorbidities like refractory heart failure or end-
stage liver disease.
3. Patients with severe or refractory physical or psychological manifestation.
4. Patients with irreversible mental decline or breakdown which makes them unable
to understand the various aspects and risks of dialysis.

Components of CKM

The CKM treatment plan is individualized for each patient. Specific interventions are
chosen based upon the overall prognosis and upon patients' goals and wishes as
shown in Figure1. The plan is flexible and may change over a period of time.

75
1. Medical Management
This includes medications that decelerate progression of kidney disease and
medications that treat secondary complications of ESRD.

a. Deceleration of kidney disease progression — Treatment options that

decelerate progression among patients with specific kidney diseases, such as
use of renin-angiotensin aldosterone system (RAAS) inhibitors or SGLT2
inhibitors.

b. Blood Pressure Management — Blood pressure (BP) control is vital in CKD to

slow the progression of renal disease and also to minimize the cardiovascular
morbidity. Target BP is typically kept ≤150/90 mmHg in such patients.

c. Treatment of anemia — Among patients on the CKM pathway, we continue to

administer erythropoietin analogues, iron and other hematinics to treat anemia,
as indicated.

d. Treatment of mineral bone disease — This includes management of

hyperphosphatemia, hypocalcemia, vitamin D insufficiency and other problems
associated with mineral-bone disease. Depending on type of involvement
calcium based or non-calcium-based phosphate binders, activated vitamin D
analogues, calcimimetics and others may be used.

e. Treatment of Metabolic Acidosis and Hyperkalemia - Metabolic acidosis is

treated with base-containing agents like fruits and oral sodium bicarbonate.
Among patients with hyperkalemia, we first discontinue medications that might
be culprits, such as RAAS inhibitors, and then we treat with dietary modification
and gastrointestinal cation exchangers such as potassium binders like calcium
polystyrene, or newer agents like patiromer or zirconium cyclosilicate.

76
Figure1. Essentials of conservative kidney management.

2. Symptoms Evaluation and Management

a. Symptom Evaluation — Symptoms may result from complications of

advanced CKD or from coexisting other conditions such as diabetes mellitus,
chronic heart failure, peripheral vascular disease, and cancer. We use either
the ESAS-r scale (Renal Edmonton Symptom Assessment System-Revised) or
the IPOS-Renal (Integrated Palliative Care Outcome Scale-Renal). These are
administered at every routine patient visit (generally every three months). Once
a symptom is recognized, the impact on function and quality of life should be
assessed to better appreciate the level of distress or intrusiveness of the
symptoms.

b. Management of Symptoms — The aim of treatment is to overcome the

symptoms that are compromising the patient's quality of life. To optimize patient
safety and reduce polypharmacy, the management of all symptoms should follow
a similar stepwise approach in the following order - exclude contributing or
reversible factors, use of nonpharmacologic interventions and use of use
pharmacologic interventions

77
i. Fatigue — Fatigue is a common manifestation among patients with ESRD.
Nonpharmacologic interventions to mitigate fatigue include improving
nutrition and hydration, encouraging gentle exercise as tolerated, optimizing
sleep hygiene, and identifying energy conservation strategies.

ii. Pruritus — Pruritus often seen and can be extremely troublesome to

patients with ESKD. We first treat pruritus with topical treatments. For
resistant symptoms, we initiate antihistaminics, low-
dose gabapentin or pregabalin.

iii. Pain — Pain is frequent, disturbing symptom and requires a comprehensive

assessment in all patients with advanced CKD, including those being cared
for conservatively. The treatment of pain in advanced CKD, including
patients being cared for with CKM, is very essential.

iv. Dyspnea — Nonpharmacologic interventions to relieve the sensation of

breathlessness include sitting in an upright position (eg, 45 degrees), pursed
lip breathing, and supplemental oxygen. Dyspnea and accompanying
anxiety can be addressed with low-dose opiates and benzodiazepines.
Safer opioids include methadone and fentanyl.

v. Nausea and vomiting — Nonpharmacologic management includes

strategies, such as eating smaller but frequent meals, eating slowly, and
attempting to avoid alcohol or foods that are oily, spicy, or excessively sweet
as far as possible. For persistent nausea or vomiting, low dose ondansetron,
low-dose haloperidol, 0.5 mg every eight hours or metoclopramide may be
used.

vi. Psychological symptoms — chronic kidney disease is in itself a

predisposing risk factor for psychological conditions such as depression and
anxiety. These psychological symptoms can often worsen physical
symptoms, negatively impact the quality of life, and are associated with
increased rates of hospitalization. Appropriate therapy is important.

78
3. Crisis Planning

Crisis planning is the process of planning for future clinical setbacks, such as symptom
crises, that may occur among patients who choose CKM. Crisis planning involves
Advanced Care Planning (ACP), by virtue of which patients, their family, and care
givers reflect upon the patient's goals and values to tackle medical care plans. Despite
optimized ACP and crisis management, patients may change their mind and request
for dialysis. For seriously ill patients who are near the terminal stage of life, this
approach may also require skills to manage conflict and consideration of palliative care
consultation.

4. End-of-Life Care

Symptom burden appears to be relatively stable for patients being cared for
conservatively until the last two months before death. Patients and their caregivers
experience lots of psychological concerns, confusion, depression, and other concerns.
A multi-modality palliative care team may assist with such tough symptoms. Patients
on CKM and their caregivers may also benefit from hospice services.
References
1. Brown MA, Collett GK, Josland EA, et al. CKD in elderly patients managed
without dialysis: survival, symptoms, and quality of life. Clin J Am Soc Nephrol 2015;
10:260.
2. Foote C, Kotwal S, Gallagher M, et al. Survival outcomes of supportive care
versus dialysis therapies for elderly patients with end-stage kidney disease: A
systematic review and meta-analysis. Nephrology (Carlton) 2016; 21:241.
3. Buur LE, Madsen JK, Eidemak I, et al. Does conservative kidney management
offer a quantity or quality of life benefit compared to dialysis? A systematic review.
BMC Nephrol 2021; 22:307.
4. Weisbord SD. Symptoms and their correlates in chronic kidney disease. Adv
Chronic Kidney Dis 2007; 14:319.
5. Wong SPY, Yu MK, Green PK, et al. End-of-Life Care for Patients with
Advanced Kidney Disease in the US Veterans Affairs Health Care System, 2000-2011.
Am J Kidney Dis 2018; 72:42.

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 9
Renal Replacement Therapy in Acute Kidney Injury
----------------------------------------------------------------------------------------------------------------

Vineet Behera, Prabhat Chuahan

Introduction

Acute kidney injury (AKI) is acute onset deterioration of kidney functions. It is usually
diagnosed and staged based on the urine output and serum creatinine levels. KDIGO
defines AKI as rise in serum creatinine by 0.3 mg/dl within 48 hours or more than 1.5
times within 7 days or urine output of < 0.5 ml/kg /hour for 6 hours. Based on the level
of involvement it can be further divided into pre-renal (haemodynamic), intrinsic renal
and post renal causes.

AKI is associated with a retention of metabolic end products. These accumulated

toxins lead to the harmful effects of AKI. The more well characterized abnormalities
include fluid overload, electrolyte abnormalities and metabolic acidosis. The severity
of these derangements is mainly determined by the severity of renal injury however
the precipitating cause and presence of sepsis are also important determinants. If not
treated these abnormalities can rapidly lead to death of the patient. Mortality in ICU
patients with AKI can be as high as 80%.

Indications RRT

The established indications for RRT in critically ill patients are severe hyperkalemia,
severe metabolic acidosis, and uremic complications including encephalopathy,
pericarditis or bleeding. RRT may also be considered for severe intoxication with a
dialysable drug like lithium. However, in absence of these established indications the
decision making becomes more nuanced.

80
Timing of initiation of RRT- the Early versus Late debate

While early initiation of RRT may expose the patient to complications inherent to RRT
including bleeding, infection, thrombosis, hypotension etc. which may further
compromise an already unstable patient. Substantial proportion of patients with AKI
may spontaneously recover in absence of RRT if given sufficient time and optimal
medical support. On the other hand, delaying RRT may expose the patient to the
dangers of the toxic uremic milieu and jeopardize other organ systems with
catastrophic results. The landmark trials have tried to compare early vs late initiation
of RRT, are shown in Figure1. As there is no consensus, with regard to early vs late
initiation of RRT, we can conclude that in absence of absolute indication of RRT patient
should be carefully decided.

Figure 1. Shows Landmark trials regarding timing of renal replacement therapy in

acute kidney injury (adapted from ASN Kidney news, Behera V, Dogra PM. Early
versus Late Initiation of Dialysis in AKI, Dec 2022)

81
Modality of RRT

Once we have decided on the need for RRT, the next pertinent question is the modality
of RRT. The different modalities of RRT include – intermittent hemodialysis (IHD)
including slow low efficiency dialysis (SLED) and extended daily dialysis (EDD),
continuous renal replacement therapy (CRRT) and peritoneal dialysis. Technical
aspects of different RRT modalities are enumerated in Table 1. In resource limited
settings the major determinant of the choice of modality includes local availability and
facility expertise.

CRRT IHD SLED PD

(conventional)

Principle of Both Diffusion Diffusion Predominantly diffusion

clearance convective with small contribution
and diffusive from convective clearance

Session 24/day 3-6 6-12 24/day

duration(hr)

Blood flow rate 50-150 ml/min 300-500 ml/min 100-200 NA

(Qb) ml/min

Dialysate flow 20-50ml/min 500 ml/min 100-300 1000-2000 ml/hr

(Qd) ml/min

Replacement 10- 25 ml/min NA NA NA

fluid

Small solute 15-30 ml/min 200 ml/min 100-150 15-20 ml/min

clearance ml/min

Daily clearance 36-72 48 54-60 20-36

(in litres)

Effluent 10-80 NA NA NA
flow(ml/kg)

Table 1. Shows the comparison between different forms of RRT.

82
Continuous Renal Replacement Therapy

On the face of it CRRT is a more physiological form of RRT. The major benefits include
slower removal of fluids and toxins and lesser hemodynamic changes. However,
CRRT is limited by availability, higher costs, need for prolonged immobilization and
anticoagulation.

Intermittent Hemodialysis

IHD with its modifications is comparatively less cost intensive, need lesser technical
expertise and more easily available. There is rapid diffusive clearance with IHD which
makes it more suitable for cases of severe hyperkalemia, hypercalcemia and
hypercatabolic AKI like rhabdomyolysis and tumor lysis syndrome.

Modifications of IHD include SLED and EDD among others. In SLED the blood flow
rate and dialysate flow rate are slowed so as to make the process of clearance slower
and “gentler” which helps in maintaining the hemodynamic stability better. The only
situations in which CRRT may be preferred over IHD include hemodynamically
unstable patients, patients with raised ICT and patients with acute liver failure.
Peritoneal Dialysis

Peritoneal dialysis has its own importance especially in resource limited settings as
well as in peripheral centres which lack facilities and technical expertise. It is the most
commonly used modality in children with AKI. The major limitation being inadequate
control over fluid removal and clearance of uremic toxins.

Intensity of RRT

Once we have decided on the need and modality the other important decision is the
dialysis dosage. The intensity of IHD is calculated using clearance per session and
the frequency, while for CRRT it is quantified in terms of effluent volume. Multiple
observational studies have shown that increased intensity of RRT is associated with
83
better outcomes. However, these results have not stood the test of time. Two recent
RCTs have failed to show any benefit of more intensive RRT (defined by effluent rate
more than 20-25 ml/kg /hour for CRRT and IHD frequency more than 3/week with
target normalized urea clearance) on patient survival. In fact, a patient level meta-
analysis has shown delayed kidney recovery with more intensive RRT. Hence in
absence of hypercatabolic state the recommended intensity for IHD is 3/week and for
CRRT is effluent volume of 25ml/kg/hr.

Discontinuing RRT

RRT is discontinued once spontaneous kidney function recovers. However, factors

determining successful discontinuation haven’t been well studied. Improvement in
urine output and spontaneous decline in creatinine are the main parameters which are
used to indicate kidney function recovery. Early and intensive RRT has been
associated with delayed recovery and longer RRT dependence. It is important to
consider that RRT may act as a second hit and delay recovery of kidney function. The
postulated mechanism includes dialytic hypotension and membrane bio-
incompatibility derived inflammation.

Suggested References

1) Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin
Pract. 2012;120(4):c179-84.
2) Lobo VA. Renal Replacement Therapy in Acute Kidney Injury: Which Mode and
When? Indian J Crit Care Med. 2020 Apr;24(Suppl 3):S102-S106. doi: 10.5005/jp-
journals-10071-23383.
3) Kellum, J.A., Romagnani, P., Ashuntantang, G. et al. Acute kidney injury. Nat Rev
Dis Primers 7, 52 (2021).
4) Negi, S., Koreeda, D., Kobayashi, S. et al. Renal replacement therapy for acute
kidney injury. Ren Replace Ther 2, 31 (2016).

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5) Rajeev A. Annigeri, Marlies Ostermann, Ashita Tolwani, Armando Vazquez-
Rangel, et al. Support for Acute Kidney Injury in the Developing World,Kidney
International Reports,Volume 2, Issue 4,2017,Pages 559-578,ISSN 2468-0249.
6) Chionh, Chang Yin*, Soni, Sachin S.; Finkelstein, Fredric O.; Ronco, Claudio*;
Cruz, Dinna N.Use of Peritoneal Dialysis in AKI: A Systematic Review. Clinical
Journal of the American Society of Nephrology 8(10): 1649-1660, October 07,
2013.

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