Acute kidney Injury

Acute Kidney Injury
a.k.a.
Acute Renal Failure
Rajanna Sreedhara, MD, FACP
American Board Certified in Internal Medicine & Nephrology
Formerly Associate Professor of Clinical Medicine SUNY Brooklyn, USA
Formerly Associate Professor of Nephrology, INU, Bangalore

Outline of Presentation
 Definition of AKI
 Epidemiology
 Clinical Classification
 Evaluation
 Principles of Management
Topics to be covered include: ATN & AIN

Acute Renal Failure:
Definition
Acute renal failure (ARF) has
traditionally been defined as the
abrupt loss of kidney function (over
hours to days) resulting in the
retention of urea and other
nitrogenous waste products and in the
dysregulation of extracellular volume
and electrolytes.
Urine volume can be variable –
Anuria < 100 ml/day
Oliguria 100 – 400 ml/day
Non-oliguria > 400 ml/day

ARF – Operational definition
 Over a period of 24 to 72 hours, rise in
creatinine by > 0.5 mg/dL,
or,
 relative rise in creatinine by 25 – 50% over
baseline level (AoCKD).

RIFLE classification scheme for
ARF
A patient can fulfill the
criteria through changes
in serum creatinine
(SCreat) or changes in
urinary output, or both.
The criteria that lead to
the worst possible
classification should be
used.
Bellomo R, Ronco C, Kellum JA, et al:
Acute renal failure—definition,
outcome measures, animal models,
fluid therapy and information
technology needs: the Second
International Consensus Conference of
the Acute Dialysis Quality Initiative
(ADQI) Group. Crit Care 8:R204–R212,
2004.)

Classification/staging system for Acute Kidney
Injury*
Stage
Serum creatinine (S.Cr) criteria
(Change within 48 hours)
Urine output (UO)
criteria
1
Increase in S.Cr of ≥ 0.3 mg/dL or
increase to 1.5- to 2-fold from baseline
UO < 0.5 mL/kg/hr
x 6 hours
2
Increase in S.Cr to >2- to 3-fold from
baseline
UO < 0.5 mL/kg/hr
x 12 hours
3
Increase in S.Cr to >3-fold from
baseline,
or
S.Cr of ≥ 4.0 mg/dL with an acute
increase of at least 0.5 mg/dL
UO < 0.3 mL/kg/hr
x 24 hours
or
Anuria for 12 hours
•The diagnostic criteria should only be applied after volume status has been optimized.
•Urinary tract obstruction needs to be excluded if oliguria is used as the sole criterion.
•Only one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.
Modified from RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria.
Mehta, RL, Kellum, JA, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11:R31.

AKI: Incidence
 Varies depending on the setting.
 Community hospitals: 0.9%
 Tertiary care hospitals: 5 – 7%
 Incidence in ICUs: 13 – 30%
Prerenal azotemia accounts for 60% to 70%,
intrinsic renal disease accounts for 25% to 40%, and
postrenal causes account for 5% to 10% of cases of ARF in
hospitalized patients.

The highest pooled AKI rate was observed in
Critical care settings (31.7%; 95% CI, 28.6 to 35.0), followed by
cardiac surgery (24.3%; 95% CI, 20.4 to 28.8).

Pooled AKI-associated all-cause mortality rate was
23.0%
(95% CI, 21.3 to 24.8) and increased with higher stages of severity.
23.9% in adults (95% CI, 22.1 to 25.7) and

Pooled unadjusted OR for all-cause mortality in patients with
AKI was 4.95 (95% CI, 4.13 to 5.92) relative to patients without AKI

Frequency of AKI in selected Hospital
settings
0
5
10
15
20
25
30
35
40
45
50
All Hospit al
Admissions
Cardiac Care
Unit
Post -CABG All I CU
Admissions
Severe
Trauma/ Burns
Post Liver Tx Post Bone
Marrow Tx

Fernando Liaño
Mortality in AKI has remained very high

Mortality in pre-renal ARF is < 10%

APACHE II Score & Survival
All Patients
Blue, nonoperative; Green, postoperative.

Fernando Liaño
Higher mortality in AKI is associated with

Etiologic Classification of ARF

Etiology of Anuria
 Bilateral Renal Artery Occlusion
 Bilateral Renal Vein Occlusion
 Complete Obstruction of both Ureters
 Complete Obstruction of the Urethra
 Rare Causes:
 Cortical Necrosis due to severe ischemia
 Rapidly Progressive Glomerulonephritis

Who are at risk for AKI?
NSAIDs
ACE inhibitor

Michael S. Goligorsky & Wilfred Lieberthal
Mechanism of AKI: Ischemic or Toxic

Marc E. De Broe
NSAIDs predispose to AKI
X
XX

Marc E. De Broe
Acute Tubular Necrosis

Lorraine C. Racusen & Cynthia C. Nast
ATN: Course

Pathophysiological Mechanisms of Ischemic Acute Tubular Necrosis
Abuelo J. N Engl J Med 2007;357:797-805

Frank necrosis is not prominent in human ATN. Tends to be
patchy, involving individual cells or small clusters of cells.
Less obvious injury includes loss of brush borders, flattening of
the epithelium, detachment of cells, formation of intra-tubular
casts, and dilatation of the lumen.
Observed predominantly in proximal tubules.

Intrarenal vasoconstriction
is the dominant mechanism
for the reduced GFR in
patients with ARF. The
mediators of this
vasoconstriction are
unknown, but tubule injury
seems to be an important
concomitant finding.
Prolonged vasoconstriction may
evolve into intrinsic ARF

Apoptosis differs from necrosis
because it requires the activation
of a regulated program that leads
to DNA fragmentation,
cytoplasmic condensation, and
cell loss, without precipitating an
inflammatory response.
In contrast to necrosis, the
principal site of apoptotic cell
death is the distal nephron.
During the initial phase of
ischemic injury, loss of integrity
of the actin cytoskeleton leads to
flattening of the epithelium, with
loss of the brush border, loss of
focal cell contacts, and
subsequent disengagement of
the cell from the underlying
substratum.

Acute tubular necrosis
A light photomicrograph showing patchy tubular necrosis from a nephrotoxin. Note loss of brush
border, desquamated cells in tubular lumina, and mild interstitial edema. These lesions can be seen
after ischemia or nephrotoxicity.
Source: Brun C, Olsen S. Atlas of Renal Biopsy Philadelphia: WB Saunders; 1981;135-171

Degeneration and frank necrosis, or flattened,
regenerating type epithelium with degenerated
cells in the lumen (H&E, x 200)
Acute Tubular Necrosis (ATN)
Regenerating flattened
tubular epithelium
without frank necrosis
of individual tubular
cells, by bleebbing and
individual cell
degenration (top left), or
by frank necrosis
( middle). There is
minimal accompanying
interstitial infiltrate
(periodic acid Schiff
stain, x 100).
Vacuolated cells and sloughed, necrotic cells in
tubular lumina, with some tubules lined by
flattened epithelium and some showing frank
necrosis (PAS, x 400)

Urine sediment in a patient with
acute renal failure, illustrating
fine (A) and coarse (B) granular
casts typical of acute tubular
necrosis.

Marc E. De Broe
Localization of damage in ATN

The medulla, whose meager blood supply optimizes the concentration of the urine, is poorly oxygenated.
Medullary hypoxia results both from countercurrent exchange of oxygen within the vasa recta and from
the consumption of oxygen by the mdedullary thick ascending limbs. Renal medullary hypoxia is an
obligatory part of the process of urinary concentration. PO2 denotes partial pressure of oxygen.
From Brezis M, Rosen S: Hypoxia of the renal medulla—its implications for disease. N Engl J Med 332:647–655, 1995.
Anatomic and physiologic
features of the renal cortex and
medulla. The cortex, whose
ample blood supply optimizes
glomerular filtration, is
generally well oxygenated,
except for the medullary-ray
areas devoid of glomeruli,
which are supplied by venous
blood ascending from the
medulla.

 Initiation
 Factors known to cause ATN present
(hypotension, ischemia, sepsis,
nephrotoxins) but have not yet developed
overt parenchymal damage
 Maintenance
 Lasts 1-2 weeks (few days to 4-6 wks)
 Recovery phase
 Cellular regeneration and repair restore
tubular integrity.
ATN: Clinical Course

ATN: Exogenous Causes
 Radiocontrast agents (3 to 5%)
 Aminoglycosides (10 to 15%)
 Cyclosporine
 Cisplatin
 Amphotericin B (30%)
 Others:
 organic solvents, detergents
 heavy metals such as mercury,
cadmium, and arsenic

Michael S. Goligorsky & Wilfred Lieberthal
IV Contrast causes ATN in patients with CRF

Risk estimates for RCN in patients with
CRF
Baseline renal function Risk of RCN
Normal Negligible risk
Mild to moderate CRF 5-10%
Mild to moderate CRF
with Diabetes
10-40%
Advanced renal
insufficiency
>50%
Odds of death associated with RCN was 5.5

Marc E. De Broe
Gentamicin is a major cause of ATN
10 to 15% of
patients treated may
develop ATN.
Peak level correlates
with AKI.
Once daily dosing
may be less
nephrotoxic.

Aminoglycoside induced ATN:
Effect of decreased EABV
0
5
10
15
20
25
30
35
40
45
50
All Patient s CHF Liver Disease CKD I CU patients

 Heme-containing products
 Myoglobin in rhabdomyolysis

muscle necrosis from prolonged unconsciousness,
seizures, cocaine, alcohol abuse, statins, fibrates,
etc.
 Hemoglobinuria in massive hemolytic anemia
 Uric acid in cancer patients receiving
chemotherapy
 Paraproteins in myeloma
ATN: Endogenous Causes

ATN: Mortality
 Highly dependent on co-morbid conditions
 Uncomplicated ATN – 7 to 23%
 Associated with MSOF in post-op or critically ill – 50 to 80%
 In 16,000 patients undergoing radiocontrast procedures,
mortality in ARF was 34% (vs. 7% in control subjects, OR
=5.5)
 In 42,773 VA pts undergoing CABG, 1.1% developed ARF
requiring RRT. Overall mortality 63.7% vs. 4.3% (Odds Ratio
for death was 7.9).

AKI is an independent predictor of mortality
irrespective of APACHE-II scores.

Elevated BUN & Serum Creatinine
First Question to ask – Acute or Chronic?
If no evidence for Chronic, assume AKI.
 Evidence for chronic kidney disease
 Elevated creatinine in earlier (>3 months) reports.
Gradually rising creatinine.
 History of kidney disease, hypertension, abnormal
urinalysis.
 Small & echogenic kidneys.
 Anemia.
 Uremic Symptoms.
 Broad casts in urine.

Acute
Kidney
Injury
Pre-Renal
≈ 40-50%
Post-Renal
≈ 10-15%
Renal
≈ 30-40%
Volume Depletion
Volume Sequestration
Low Cardiac Output
Obstruction:
Bladder Outlet
Ureteric
Renal Tubular
Acute Tubular Necrosis
Ac. Interstitial Nephritis
Glomerulonephritis
Vascular dz.

Clinical Approach to patient with AKI:
Clinical History & Physical Examination
 Hypotension
 Volume contraction
 Congestive heart failure
 Nephrotoxic drug ingestion (NSAIDs, Aminoglycosides,
ACE inhibitors, etc.)
 History of exposure to contaminated water
 History of trauma or unaccustomed exertion
 Blood loss or transfusions
 Evidence of connective tissue disorders
 Exposure to toxic substances such as methyl alcohol
or ethylene glycol

Clinical Approach to patient with AKI
Step Item Evaluation process & Response
1 Evaluate volume status Physical Exam, weight, CVP, PCWP.
Fluid challenge.

Fluid challenge.
2 Rule out Obstruction Physical Exam, patency of catheters,
Renal ultrasound.
Foley catheterization.

Fluid challenge.
Renal ultrasound.
3 Renal function tests BUN, creatinine & electrolytes.
Hemoglobin, calcium & phosphorus.

Fluid challenge.
Renal ultrasound.
4 Probable cause for
renal dysfunction
Evaluate nephrotoxic (drug) exposure –
NSAIDs, aminoglycosides, hypotension,
etc.

Drugs Associated with ARF
Mechanism Drugs
Reduction in renal perfusion
through alteration of
intrarenal hemodynamics
NSAIDs, ACE-inhibitors or ARBs, CNIs, radiocontrast
agents, amphotericin B, interleukin-2
Direct tubular toxicity
Aminoglycosides, radiocontrast agents, cisplatin, CNIs,
amphotericin B, methotrexate, foscarnet,
pentamidine, organic solvents, heavy metals,
intravenous immune globulin
Rhabdomyolysis Cocaine, ethanol, lovastatin
Intratubular obstruction by
precipitation of the agent
Acyclovir, sulfonamides, ethylene glycol,
chemotherapeutic agents, methotrexate
Allergic interstitial nephritis
Penicillins, sulfonamides, ciprofloxacin, NSAIDs,
phenytoin, allopurinol
Hemolytic-uremic syndrome CNIs, mitomycin, cocaine, quinine, conjugated estrogens
CNIs, calcineurin inhibitors; NSAIDs, nonsteroidal antiinflammatory drugs
Modified from Thadhani R, Pascual M, Bonventre JV: N Engl J Med 334:1448, 1996.

Fluid challenge.
Renal ultrasound.
renal dysfunction
etc.
5 Urine Routine &
Microscopy
Specific gravity, protein, glucose, blood,
casts – granular &/or cellular, cells &
crystals.

Fluid challenge.
Renal ultrasound.
renal dysfunction
etc.
5 Urine Routine &
Microscopy
Specific gravity, protein, glucose, blood,
casts – granular &/or cellular, cells &
crystals.
6 Urinary Indices
Fractional Excreation of
sodium (FeNa)
Obtain spot urine sodium & creatinine.

Urine Osmolality in AKI
Failure to excrete concentrated urine, even
in the presence of oliguria, is a helpful
diagnostic clue to distinguish prerenal from
intrinsic renal disease.
Intrinsic Renal
Disease
< 300 mOsm/kg
Prerenal azotemia > 500 mOsm/kg

 T: Tumor, Trauma.
 C: Compression (ureteric), Clot.
 S: Stone, Surgery.
Location/Etiology: Post-renal
Always obtain a renal ultrasound to rule
out an obstructive cause.

Radiology
 Ultrasound
 Size

Small size Chronicity
(Exceptions: DM, HIVAN, Myeloma, Amyloidosis)

Asymmetry
Vascularization Potential.
 Echogenicity
 Hydronephrosis
 Mass/Cysts
 Fluid Collection

Brian G. Dwinnell & Robert J. Anderson
Urinalysis in AKI

Urinalysis in AKIUrinalysis in AKI

Granular Casts
The muddy brown granular casts,
amorphous debris, and renal tubular
epithelial cells are consistent with tubular
injury. (Original magnification, x400.)

Urine Microscopy: CellsUrine Microscopy: Cells
Squamous epithelial cells (arrows) and
leukocytes (200 X).
Convoluted renal tubule cells (200 X).

Urine Microscopy: CastsUrine Microscopy: Casts
(A) Hyaline cast (200 X); (B) erythrocyte cast (100 X); (C) leukocyte cast (100 X); (D)
granular cast (100 X).

Urine Microscopy: CrystalsUrine Microscopy: Crystals
(A) Calcium oxalate crystals (arrows; 100 X); (B) uric acid crystals (100 X); (C) triple
phosphate crystals with amorphous phosphates (400 X); (D) cystine crystals (100 X).

Significance of specific urinary casts
Type Significance
Hyaline casts
Concentrated urine, febrile disease,
strenuous exercise, diuretic therapy,
etc. (not indicative of renal disease)
Red cell casts Glomerulonephritis
White cell casts Pyelonephritis, interstitial nephritis
(indicates infection or inflammation)
Renal tubular ATN, Interstitial nephritis
Coarse, granular Nonspecific; can represent ATN
Broad, waxy Chronic renal failure (indicative of
stasis in collecting tubule)

Location/Etiology: Pre-
renal
 Cardiac Output.
 Intravascular Volume status.
 Vasodilatation (sepsis, liver failure).
 Renal artery Blockage.
 Intraglomerular hemodynamics
(ACEIs/NSAIDs).

ATN: Essentials of Diagnosis
 Acute renal failure.
 Urine sediment with pigmented granular
casts and renal tubular epithelial cells.
 FENa
> 1%

Urinary diagnostic indices in AKI
<25 FE-Urea >50

Exceptions in the evaluation of
Urinary diagnostic indices in AKI
 Pre-Renal Azotemia
with High FeNa
 Diuretic therapy
 Chronic Kidney
Disease
 Glycosuria (High
osmolarity of urine)
 Alkaline urine
 Low FeNa but NOT
Pre-Renal
 Early stages of
Obstruction
 Acute
Glomerulonephritis
 Pigment Nephropathy
 Radio-contrast
Nephropathy

Drug-Induced
Allergic Interstitial Nephritis (1)
 β-Lactams
 Ampicillin
 Amoxicillin
 Carbenicillin
 Methicillin
 Nafcillin
 Oxacillin
 Penecillin G
 Cephalexin
 Cephatholin
 Cephradine
 Cefotaxime
 NSAIDs
 Aspirin
 Celecoxib
 Fenoprofen
 Ibuprofen
 Indomethacin
 Mefenamic acid
 Naproxen
 Phenazone
 Phenylbutazone
 Tolmetin
 Other Antibiotics
 Ethambutol
 p-Aminosalicylate
 Rifampin
 Sulfonamides
 Trimethoprim
 Ciprofloxacin
 Levofloxacin
 Norfloxacxin
 Vancomycin

Drug-Induced
Allergic Interstitial Nephritis (2)
 Diuretics
 Chlorthalidone
 Furosemide
 Bumetanide
 Thiazides
 Other Causes
 α-Methyldopa
 Allopurinol
 Azathioprine
 Carbamazepine
 Cimetidine
 Omeprazole
 Clofibrate
 Clozapine
 Famotidine
 Sulfinpyrazone
 Phenobarbital

Other causes of Interstitial
Nephritis:
Infections & Systemic diseases
 Bacterial
 Acute
pyelonephritis
 Leptospirosis
 Scarlet fever
 Typhoid Fever
 Legionaires
Disease
 Viral
 CMV
 Measles
 Infectious
Mononucleosis
 Rocky Mountain
Spotted fever
 Candidiasis
 other fungi
 Toxoplasmosis
 Systemic
Diseases
 SLE
 Sjögren syndrome
 TINU
 Cancer
 Lymphoma
 Leukemia
 Myeloma
 Sarcoidosis

Differential Diagnosis of AKI
Goldfarb DA, O'Hara JF: AUA Update Series 2001.

AKI: Principles of
Treatment
 Correct Underlying Cause.
 Fluid/Diuretic Challenge.
 Bladder Catheterization.
 Diet/TPN orders.
 Review Medication List.
 Monitor I/O
Daily weight.

Minimizing the risk of development of
AKI
 Identify high risk patients
 Use of volume expansion
 Pre-operative optimization of cardiovascular
hemodynamics
 Aggressive surveillance of renal function in high risk
patients
 Minimizing use of nephrotoxins
 Changing dosage schedule
 Modifying formulation of nephrotoxins
 Minimizing use and length of invasive lines/catheters to
avoid nosocomial infections

Strategies for the prevention of
RCN (1)
 Avoid the use of contrast agent if possible
 Alternative imaging modalities
 Use carbon-dioxide
(Gadolinium is no longer safe in patients with CKD)
 Correct hypovolemia
 Discontinue NSAIDS and COX-2 inhibitors for several days.
 Hold ACE inhibitors/ARBs and diuretics on the day of procedure.

Strategies for the prevention of
RCN (2)
 Proven Useful:
 IV hydration (normal saline or 0.45% saline)
 N-acetylcysteine 600 mg bid for 2 days
 Low-osmolar agents in diabetics and in pts with CRF
 Iso-osmolar agents in diabetic pts with CRF
 Not proven useful: Fenoldapam, atrial natriuretic peptide,
theophylline and “prophylactic hemodialysis”.
 Harmful: Furosemide, mannitol, and “Renal dose” dopamine.

N-Acetylcysteine and Contrast-Induced
Nephropathy in Primary Angioplasty
Giancarlo Marenzi et al. N Engl J Med 2006;354:2773-82.
Conclusions: Intravenous and oral N-acetylcysteine may prevent contrast-
medium–induced nephropathy with a dose-dependent effect in patients
treated with primary angioplasty and may improve hospital outcome.
N = 354 patients
undergoing primary
angioplasty
Standard dose of
NAC = 600-mg IV
bolus before primary
angioplasty and 600
mg orally twice daily
for the 48 hours
after angioplasty
(N=116)
Double dose of N-
acetylcysteine
(N=119)
Placebo: (N=119)

Indications For Kidney
Biopsy
 Massive Proteinuria (>3 g/d).
 Hematuria with Proteinuria.
 Rapidly worsening renal failure.
 Unexplained Renal Failure.
 Miscellaneous.
 Transplant, Insurance, etc.

Essentials elements in a
Nephrology Consultation
 Acute or Chronic or AoCKD.
 Identify cause(s).
 Dialysis or no Dialysis.
 Fluid/electrolyte Management.
 Diet and medication dosage adjustment.
 Biopsy or not.

Caution while using of equations
to calculate GFR
 Estimations of GFR assume steady state.
 Do not use the MDRD equation or Cockroft-
Gault equation when the serum creatinine
is fluctuating.
 As a rule, if the serum creatinine doubles in
1 day, GFR is near Zero.

Indications For
Renal Replacement Therapy in AKI
 Refractory fluid Overload.
 Severe Hyperkalemia.
 Severe Metabolic Acidosis.
 Uremic Symptoms or signs.
 Pericarditis.
 Progressive azotemia in the absence of
uremia
 Miscellaneous: Drug Overdose.

Hemodialysis
• Hemodialysis is a method for removing
waste products from the blood
– Uremic toxins
– Acid
– potassium
– free water
• It involves diffusion of solutes across a
semipermeable membrane

4008 H
dialysis
machine
(Fresenius
Medical
Care)

Hemodialysis
Artificial Kidney (Dialyzer)Out-patient Dialysis Center

Principles of Dialysis: Diffusion

Principles of Dialysis: Convection

Principles of Dialysis: Adsorption

Simplified view of peritoneal
transport

N = 1124
Iintensive treatment:
Hemodialysis/SLED: 6 times/week
and continuous venovenous
hemodiafiltration at 35 ml/kg/hr
Less-intensive treatment:
Hemodialysis/SLED: 3 times/week
CVVHDF at 20 ml/kg/hr
Conclusions:
Intensive renal support in critically ill
patients with acute kidney injury did
not decrease
mortality, improve recovery of kidney
function, or reduce the rate of
nonrenal
organ failure as compared with less-
intensive therapy
NEJM July 2008

Wilfred Druml
Increased protein degradation in uremia

Review Article
Normotensive Ischemic Acute Renal Failure
J. Gary Abuelo, M.D.
N Engl J Med
Volume 357(8):797-805
August 23, 2007

Outline
• Renal Response to Ischemia
• Factors Increasing Renal Susceptibility to Ischemia
• Low-Perfusion States in Normotensive Renal Failure
• Diagnosis of Normotensive Ischemic Acute Renal Failure
• Laboratory Findings
• Therapy and Response
• Conclusions

Factors Increasing Susceptibility to Renal Hypoperfusion

Causes of Low-Perfusion States

Daily Hemodialysis and the Outcome of Acute
Renal Failure
Helmut Schiffl, M.D., Susanne M. Lang, M.D. and Rainald Fischer, M.D.
N Engl J Med
Volume 346;5:305-310
January 31, 2002

Daily Hemodialysis and the Outcome of Acute
Renal Failure
Helmut Schiffl, M.D., Susanne M. Lang, M.D. and Rainald Fischer, M.D.
N Engl J Med. 346;5:305-310, January 31, 2002
• Morbidity and mortality among patients with acute renal failure are high,
despite the use of renal-replacement therapies
• This study investigated two regimens of intermittent hemodialysis -- a
daily regimen and an alternate-day (conventional) regimen -- in 160
patients with acute renal failure
• Survival two weeks after hemodialysis was the primary end point; the
duration of acute renal failure and the rate of complications were
secondary end points
• Daily hemodialysis was associated with better control of symptoms of
uremia and longer survival than was conventional intermittent
hemodialysis

Patients Enrolled in the Study, Assigned to Daily or Alternate-Day Hemodialysis, and Included
in the Analysis
Schiffl, H. et al. N Engl J Med 2002;346:305-310

Characteristics of the Patients at Enrollment

Characteristics of Hemodialysis Sessions

Outcomes According to Treatment Group

Odds Ratios for Death According to Selected Variables, from the Multiple Logistic-
Regression Analysis

Conclusions
• Conclusions The high mortality rate among critically ill patients with acute
renal failure who require renal-replacement therapy is related to both
coexisting conditions and uremic damage to other organ systems
• Intensive hemodialysis reduces mortality without increasing
hemodynamically induced morbidity

Original Article
Intensity of Renal Support in Critically Ill Patients
with Acute Kidney Injury
The VA/NIH Acute Renal Failure Trial Network
N Engl J Med
Volume 359(1):7-20
July 3, 2008

Study Overview
• This randomized, controlled trial compared standard renal-replacement
therapy with more intensive therapy in critically ill patients with acute
kidney injury and failure of at least one nonrenal organ or sepsis
• Intensive renal support did not decrease mortality, improve recovery of
kidney function, or reduce the rate of nonrenal organ failure as compared
with thrice-weekly intermittent hemodialysis

Enrollment, Randomization, and Follow-up of Study Patients
The VA/NIH Acute Renal Failure Trial Network. N Engl J
Med 2008;359:7-20

Baseline Characteristics of the Study Patients
Med 2008;359:7-20

Management of Renal-Replacement Therapy (RRT) during the Therapy Phase
Med 2008;359:7-20

Primary and Secondary Outcomes
Med 2008;359:7-20

Kaplan-Meier Plot of Cumulative Probabilities of Death (Panel A) and Odds Ratios for Death
at 60 Days, According to Baseline Characteristics (Panel B)
Med 2008;359:7-20

Summary of Complications Associated with Study Therapy
Med 2008;359:7-20

Conclusion
• Intensive renal support in critically ill patients with acute kidney injury did
not decrease mortality, improve recovery of kidney function, or reduce
the rate of nonrenal organ failure as compared with less-intensive
therapy involving a defined dose of intermittent hemodialysis three times
per week and continuous renal-replacement therapy at 20 ml per
kilogram per hour

 The development of ARF in hospitalized patients increases
mortality sixfold.
 Indications for acute dialysis include severe metabolic acidosis,
severe hyperkalemia, certain toxic ingestions, volume overload,
and signs of uremia.
 For unstable patients needing emergent hemodialysis, the
following temporizing measures can be used until renal
replacement therapy is available:
 For volume overload, intravenous nitroglycerin and high-dose
intravenous diuretics can be used.
 For hyperkalemia, calcium gluconate can be used to stabilize the
cardiac cell membrane; intravenous insulin, glucose, and nebulized
albuterol can be used to temporarily shift potassium into cells; and
intravenous diuretics or sodium polystyrene sulfonate can be used
to remove potassium.
 For metabolic acidosis, bicarbonate infusion can be used.

 Because serum creatinine does not accurately reflect
glomerular filtration rate (GFR), especially in older patients and
those with preserved renal function, an estimated GFR should
be calculated in all inpatients using the Modification of Diet in
Renal Disease (MDRD) Study equations. Note that this formula
cannot be used with a serum creatinine that is rising or falling.
 Acute renal failure (ARF) may be defined as a rise in
creatinine of more than 0.5 mg/dl over baseline or a decrease in
GFR by 50% over a period of days to weeks.
 The differential diagnosis of ARF can be divided into prerenal,
intrinsic renal, and postrenal causes. A thorough history and
physical examination, urinalysis, blood work, and renal
ultrasonography may help to quickly differentiate the different
causes.

Normal and Impaired Autoregulation of the Glomerular Filtration Rate during Reduction of
Mean Arterial Pressure

Acute kidney Injury

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