CHRONIC KIDNEY
DISEASE
DR MOSES KAZEVU
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WARM UP: TRUE/FALSE
• The kidney produces the following
substances
A. Erythropoietin
B. 25 hydroxyoholecalciferol
C. Prostaglandins PGE and PGI
D. Angiotensin-converting enzyme
E. Aldosterone
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CHRONIC KIDNEY DISEASE
• This is progressive and irreversible reduction of the renal function, over a period of more than 3
months.
• It is defined as GFR <60ml/min per 1.73 m2 for 3months or
• Urinary albumin to creatinine ratio >65mg/mmol or
• Protein creatinine ratio of 100mg/mol
• End-stage renal disease (ESRD) refers to a clinical state or condition in which there has been an
irreversible loss of endogenous renal function, of a degree sufficient to render the patient
permanently dependent upon renal replacement therapy (dialysis or transplantation) in order to
avoid life-threatening uremia.
• Recall the difference between uremia (with symptoms) and azotemia (without symptoms)
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ETIOLOGY
• Congenital and inherited disease: • Vascular disease
➢ Polycystic kidney disease (infantile and adult forms) ➢ Hypertensive nephrosclerosis (common cause)
➢ Medullary cystic disease ➢ Diabetic nephropathy (common cause)
➢ Tuberous sclerosis ➢ Renovascular
➢ Oxalosis
➢ Small and medium-sized vessel vasculitis
➢ Cystinosis
• Tubulointerstitial disease
➢ Congenital obstructive uropathy
• Glomerular disease ➢ Tubulointerstitial nephritis- idiopathic due to drugs (especially
➢ Primary glomerulonephritides including focal nephrotoxic analgesics), immunologically mediated
glomerulosclerosis ➢ Tuberculosis
➢ Secondary glomerular disease: ➢ Schistosomiasis
o SLE ➢ Reflux nephropathy
o Polyangiitis ➢ Nephrocalcinosis
o Wegener’s granulomatosis ➢ Multiple myeloma (myeloma kidney)
o Amyloidosis ➢ Renal papillary necrosis (diabetes, sickle cell disease and trait,
o Diabetic glomerulosclerosis
analgesic nephropathy)
o Accelerated hypertension
➢ Chinese herb nephropathy
o Hemolytic uremic syndrome
o Thrombotic thrombocytopenic purpura • Urinary tract obstruction
o Systemic sclerosis ➢ Calculus disease
o Sickle cells disease ➢ Prostatic disease
➢ Pelvic tumors
➢ Retroperitoneal fibrosis
➢ Schistosomiasis
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CLASSIFICATION OF CHRONIC
KIDNEY DISEASE
• Note:
Stage GFR (ml/min/1.73 m2) Description
1 ≥90 • No impairment ➢ Stage 1 and 2 also require the
• Normal or increased GFR with other presence of kidney damage
evidence of kidney damage (persistent proteinuria or
2 60-89 • Mild impairment
• Slight decrease in GFR with other unexplained hematuria,
evidence of kidney damage structural disease or
3 3A 45-59 • Moderate impairment glomerulonephritis)
3B 30-44 • Moderate decrease in GFR with or without
other evidence of kidney damage
➢ The suffix ‘P’ can be applied on
4 15-29 • Severe impairment the stage of CKD if the patient
• Severe decrease in GFR with or without has significant proteinuria
other evidence of kidney damage
5 <15 or on dialysis • Established kidney failure (End-stage
defined as urinary
kidney disease) albumin:creatinine ratio
>65mg/mol or protein:creatinine
ratio >100mg/mmol
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PATHOPHYSIOLOGY
• Uremic manifestations occur mainly due to accumulation of nitrogenous wastes and the reason for
accumulation of these wastes is decreased renal excretion and reduced catabolizing capacity of
the kidney.
• Most toxins in uremia are by products of proteins and amino acid metabolism, because unlike
carbohydrates and fats which are metabolized to carbon dioxide and water which can be excreted
through the lungs and skin, byproducts of protein are non-volatile organic acids.
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CLINICAL FEATURES-SYMPTOMS
• Early stages of CKD are often completely asymptomatic.
• A rough correlation exists between urea and creatinine concentrations and symptoms.
• Symptoms are common when the serum urea concentration exceeds 40mmol/L but many patients develop uremic symptoms at
lower levels of serum urea including:
➢ Insomnia
➢ Symptoms due to salt and water retention- peripheral or pulmonary edema
➢ Symptoms due to anemia
➢ Loss of appetite
➢ Malaise, loss of energy
➢ Nausea, vomiting and diarrhea
➢ Nocturia and polyuria due to impaired concentrating ability
➢ Amenorrhea in women, erectile dysfunction in men
➢ Itching
➢ Paresthesia due to polyneuropathy
➢ ‘Restless legs’ syndrome (overwhelming need to frequently alter position of lower limbs)
➢ Bone pain due to metabolic bone disease
• In more advanced uremia CKD stage 5 these symptoms become more severe and include:
➢ Mental slowing, clouding of consciousness and seizures
➢ Myoclonic twitching
• Severe depression of glomerular filtration can result in oliguria. This can occur with either AKI or in terminal stages of CKD.
However, even if the GFR is profoundly depressed failure of tubular reabsorption may lead to very high urine volumes, the urine
output is therefore not a useful guide to renal function.
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SIGNS
• There are few physical signs of uremia per se.
• Findings include:
➢ Short status (in patients who have had CKD in childhood)
➢ Pallor (due to anemia)
➢ Increased photosensitive pigmentation (which may make the patient look misleadingly healthy)
➢ Brown discoloration of nails
➢ Scratch marks due to uremic pruritus
➢ Signs of fluid overload
➢ Pericardial friction rub
➢ Flow murmurs (mitral regurgitation due to mitral annular calcification, aortic and pulmonary regurgitant murmurs
due to volume overload)
➢ Glove and stocking peripheral sensory loss (rare)
➢ The kidneys are usually impalpable unless grossly enlarged as a result of polycystic disease, obstruction or
tumor.
• In addition to these findings, there may be signs of any underlying disease that may have caused the CKD.
➢ Cutaneous vasculitic lesions in systemic vasculitides
➢ Retinopathy in diabetes and hypertension
➢ Evidence of peripheral vascular disease and associated renal artery stenosis
➢ Evidence of spina bifida or other causes of neurogenic bladder.
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COMPLICATIONS
• CNS ABNORMALITIES
• Confusion, coma, fits (severe uremia)
• CARDIOVASCULAR COMPLICATIONS
• Pericarditis: metabolic toxins are responsible for pericarditis
• The finding of a multicomponent friction rub strongly supports the diagnosis
• The pericardial effusion is often hemorrhagic
• Hypertension
• Is the most common complication of end stage renal disease
• It results from fluid overload
• Sometimes severe form of hypertension may occur
• Congestive heart failure and/or pulmonary edema due to:
• Volume over load
• Increased pulmonary capillary permeability
• Peripheral vascular disease
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• HEMATOLOGIC ABNORMALITIES
• Normocytic normochromic anemia: which may be severe (Hb 4-6g/dl) and caused by
• Decreased synthesis of erythropoietin (the most important factor)
• Toxins suppressing bone marrow function
• Bone marrow fibrosis secondary to hyperparathyroidism
• Hematinic deficiency- iron, vitamin B12, folate
• Blood loss (mainly GI blood loss)-occult gastrointestinal bleeding, blood sampling, blood loss during hemodialysis or
because platelet dysfunction.
• Decreased life span of RBC (increased red-cell destruction)
• Abnormal red-cell membranes causing increased osmotic fragility
• ACE inhibitors (may cause anemia in CKD, probably by interfering with the control of endogenous erythropoietin
release).
• Red-cell survival is reduced in CKD. Increased red-cell destruction may occur during hemodialysis owing to
mechanical, oxidant and thermal damage.
• Bleeding tendency: attributed to platelet dysfunction
• Patients may manifest with bleeding and easily bruiseability.
• GI bleeding
• Intracranial hemorrhage
• Susceptibility to infection
• Change in leukocyte formation and function
• Lymphocytopenia and atrophy of lymphoid tissue
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• GASTROINTESTINAL ABNORMALITIES
• Decreased gastric emptying
• Increased risk for reflux esophatitis, peptic ulceration, acute pancreatitis, GI bleeding and constipation.
• FLUID, ELECTROLYTE AND ACID BASE DISTURBANCES
• Volume expansion and contractions (Edema, dehydration)
• ECF expansion is isotonic and patient is normonatremic. Hyponatremia will be the consequence of
excessive water ingestion.
• Patients with chronic renal failure also have impaired renal mechanisms for conserving sodium and water.
When an extra renal cause for fluid loss is present (e.g. vomiting, diarrhea, sweating, fever) these patients
are prone to volume depletion and dehydration
• In the face of sodium intake patients may retain sodium and water which may lead to congestive heart
failure, peripheral edema and ascites.
• Potassium homeostasis:
• Hyperkalemia occurs when GFR falls below 10ml/min
• Endogenous factors (e.g. hemolysis, trauma, infection) or exogenous factors (administration of stored blood,
potassium containing medications, potassium containing dietary salt substitute) contribute to hyperkalemia.
• Acidosis: facilitate efflux of potassium from ICF to ECF
• Drugs: potassium sparing diuretic, ACE inhibitors.
• Metabolic acidosis: common in the advancing stages. Total urinary net daily acid excretion is usually markedly
reduced.
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• RENAL OSTEODYSTROPHY AND METABOLIC BONE DISEASE
• This is due to disturbance in bone phosphate and calcium metabolism.
• Hyperphosphatemia is a feature of advanced renal failure. The serum phosphate concentration
rises in patients with a GFR< 20ml/min.
• Total serum calcium in chronic renal failure is often significantly lower than normal. These patients
tolerate hypocalcemia quite well, rarely is a patient symptomatic from the decreased calcium
concentration. Note that the low serum calcium is attributed to secondary hyperparathyroidism.
• Reduced synthesis of vitamin D during chronic renal disease plays a role in the pathogenesis of
hyperparathyroidisim (active vitamin D metabolite is normally produced in the proximal tubule), both
directly and through hypocalcemia.
• Bone abnormalities:
➢ Renal rickets (osteomalacia)
➢ Osteosclerosis: enhanced bone density in the upper and lower margins of vertebrae.
➢ Osteitis fibrosa cystica: due to osteoclastic bone resorption (due to hypocalcemia and PTH) of
especially terminal phalanges, long bones and distal end of clavicle.
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• MALIGNANCY
• The incidence of malignancy is raised in patients with CKD and with dialysis. Malignant change
can occur in multicystic kidney disease. Lymphomas, primary liver cancer and thyroid cancers
can occur.
• ENDOCRINE
• Hypogonadism is common
• In men: decreased plasma testosterone level (erectile dysfunction), impotence and
oligospermia
• In women: Olifomenorrhea/amenorrhea, inability to carry pregnancy to term,
hyperprolactinemia (galactorrhea in females as well as males), increased LH levels
• In children: impaired growth hormone secretion
• Abnormal thyroid hormone levels, partly because of altered protein binding. Measurement of
TSH is the best way to assess thyroid function. True hypothyroidism occurs with increased
frequency in CKD.
• Posterior pituitary gland function is normal in CKD.
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• METABOLIC ABNORMALITIES
• Gout: due to urate retention. Treatment is complicated by nephrotoxic potential of NSAIDs.
Colchicine is useful for the acute attack and allopurinol should be introduced under colchicine
cover to prevent further attacks. The dose of allopurinol should be reduced in CKD e.g. 100mg
on alternate days.
• Insulin: insulin is catabolized by and to some extent excreted via the kidneys. For this reason,
insulin requirements in diabetic patients decreases as CKD progresses. By contrast end-organ
resistance to insulin is a feature of advanced CKD resulting in modestly impaired glucose
tolerance. Insulin resistance may contribute to hypertension and lipid abnormalities.
• Lipid metabolism abnormalities: correction of lipid abnormalities by e.g. HMG-CoA reductase
inhibitor therapy (statins) is used in patients with CKD although without formal proof of survival
benefit.
• Impaired clearance of triglyceride-rich particles
• Hypercholesterolemia (particularly in advanced CKD)
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• DERMATOLOGIC ABNORMALITIES
• Pallor due to anemia
• Echymosis, hematoma
• Pruritus and excoriations (due to retention of nitrogenous waste products of protein catabolism
or hypercalcemia, hyperphophatemia, and secondary hyperparathyroidism which leads to
calcium deposits)
• Yellowish discoloration of skin: urochronmes
• Uremic frost: is seen in advance uremia, it is due to high concentration of urea in the sweat and
after evaporat9on of the sweat, a fine white powder can be found on the skin surface.
• Nephrogenic systemic fibrosis: due to Gadolinium-containing contrast agents which are
excreted exclusively by the kidney.
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DIAGNOSTIC APPROACH
• History:
➢ Duration of symptoms
➢ Drug ingestion, including NSAIDs, analgesics and other medications and unorthodox treatment such as herbal remedies.
➢ Past medical and surgical history:
o previous chemotherapy, multisystem disease such as SLE, malaria
o Hypertension
o Diabetes mellitus
o Systemic infectious or inflammatory diseases
o Metabolic diseases
➢ Previous occasions on which urinalysis or measurement of urea and creatinine might have been performed e.g. pre-employment
or insurance medical examinations, new patient checks.
➢ Family history of renal disease.
• Examination
➢ Blood pressure
➢ Fundoscopy
➢ Precordial examination
➢ Examination of the abdomen for bruits and palpable renal masses
➢ Extremity examination for edema
➢ Neurologic examination for the presence of asterixis, muscle weakness and neuropathy.
➢ In addition, the evaluation of prostate size in men and potential pelvic masses in women should be undertaken by appropriate
physical examination
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DIFFERENTIATING ACUTE FROM
CHRONIC RENAL FAILURE
• Reduced kidney size on ultrasound
• Longstanding nocturia and pruritus
• Finding of broad tubular casts on urine analysis
• Anemia (not always)
• Renal osteodystrophy
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• Identify aggravating factors (acute or chronic)
➢ Hypovolemia or hypotension
➢ Hypertension
➢ Congestive heart failure
➢ Sepsis
➢ Nephrotoxins
• Evaluation of reversible underlying etiology
➢ Malignant hypertension
➢ Obstructive uropathy
➢ Systemic lupus erythematosis
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INVESTIGATIONS
• Diagnostic investigations
➢ Urinalysis:
o Hematuria: may indicate glomerulonephritis, but other sources must be excluded. Hematuria should not be assumed
to be due to presence of an indwelling catheter.
o Proteinuria: if heavy, is strongly suggestive of glomerular disease. Urinary infection may also cause proteinuria.
o Glycosuria with normal blood glucose is common in CKD
➢ Urine culture: including early-morning urine samples for TB
➢ Urine microscopy:
o White cells: indicate active bacterial urinary infection but this is an uncommon cause of CKD, sterile pyuria suggests
papillary necrosis or renal TB
o Eosinophilia: allergic tubulointerstitial nephritis or cholesterol embolization
o Casts: granular casts are formed from abnormal cells within the tubular lumen and indicate active renal disease. Red
cell casts are highly suggestive of glomerulonephritis
o Red cells in the urine may be from anywhere between the glomerulus and the urethral meatus.
➢ Urine biochemistry
o Urinary electrolytes measurement not helpful in CKD.
o Urine osmolality: this is a measure of concentrating ability. A low urine osmolality is normal in the presence of a high
fluid intake but indicates renal disease when the kidney should be concentrating urine such as in hypovolemia or
hypotension.
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➢ Blood:
o Urea and creatinine (serial measurements help in determining the severity and chronicity)
o Calculation of eGFR
o Full blood count: Eosinophilia suggests vasculitis, allergic tubulointerstitial nephritis or cholesterol embolism.
o Fragmented red cells and/or thrombocytopenia suggest intravascular hemolysis due to accelerated hypertension, hemolytic uremic syndrome
or thrombotic thrombocytopenic purpura.
o ESR: markedly raised viscosity or ESR suggests myeloma or vasculitis.
o Test for:
Sickle cell disease,
Hepatitis B (polyarteritis and membranous nephropathy) and C (cryoglobulinemic renal disease)
HIV (HIV-associated renal disease)
Antibodies to streptococcal antigens (ASOT): post-streptococcal glomerulonephritis
Antibody screening for SLE, scleroderma, wegener’s granulomatosis and microscopic polyangitis and Goodpastre’s syndrome
➢ Imaging: Ultrasound of kidney
o Verifies the presence of 2 symmetric kidneys, provides an estimate of kidney size and rules out renal masses and obstructive uropathy.
o Symmetric small kidneys support the diagnosis of progressive chronic renal failure with an irreversible component of scarring. The occurrence
of normal kidney size suggests the possibility of an acute rather than chronic process. However, in some diseases, chronic renal failure may
be present with normal sized or even enlarged e.g. amyloidosis, polycystic kidney diseases, diabetic nephropathy.
➢ CT and MRI may also be useful in diagnosis.
➢ Renal biopsy: should be performed in every person with unexplained CKD and normal-sized kidneys, unless there are strong contraindications. If
rapidly progressive glomerulonepheitis is possible this investigation must be performed within 24 hours of presentation if at all possible
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MANAGEMENT OF CHRONIC RENAL
FAILURE
• Treat reversible causes
• Hypotension or dehydration
• Administration of nephrotoxic drugs
• Urinary tract obstruction
• Severe hypertension (Goal BP <120/80mmHg)
• Infection
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• Prevent or slow the progression of renal disease (Renoprotection)
• ACE inhibitors or angiotensin II receptor blockers slow the progression of chronic renal failure
• Patients with CKD and proteinuria >1g/24 h
• ACE inhibitor increasing to maximum dose
• Add angiotensin receptor antagonist if goals are not achieved (in type 2 diabetes start with angiotensin receptor antagonist)
• Add diuretic to prevent hyperkalemia and help to control BP
• Add calcium channel (verapamil or diltiazem) if goals not achieved
• Blood pressure control: decreases progression of chronic renal failure
• Target BP:
• With proteinuria= 125/75mmHg
• Without proteinuria= 130/85mmHg
• Additional measures:
• Statins to lower cholesterol to <4.5mmol/L
• Stop smoking (three-fold higher rate of deterioration in CKD)
• Treat diabetes (HBA1c <7%, 53mmol/mol)
• Normal protein diet (0.8-1g/kg bodyweight): The possible efficacy of dietary protein restriction, in slowing progression of renal diseases,
is less clear.
• Avoid the following drugs:
• Tetracycline (with the possible exception of doxycycline): due to anti-anabolic effect and tendency to worsen uremia
• Drugs excreted by kidneys e.g. gentamicin (should only be prescribed when there is no alternative)
• NSAIDs
• Potassium sparing agents e.g. spironolactone and amiloride
• Bardoxolone an antioxidant inflammatory modulator has shown a reduction in GFR in diabetic CKD.
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Treatment of complications of renal dysfunction
➢ Hyperkalemia:
o Potassium restriction in diet. Stop drugs that cause potassium
o Protect the heart: 10mls 10% Calcium Gluconate over 10 mins. Effect is temporary but can be repeated after 15
minutes.
o Push Potassium into cells
50mls 50% Dextrose with 10IU soluble insulin over 15-20 mins. May be given 2-4 hourly as required. Monitor
serum glucose and potassium 2-4 hourly
10-20mg Nebulized Salbutamol (or 0.5mg in 100ml of 5% glucose over 15 min-rarely used)
o Push Potassium out of the body
Furosemide 1mg/kg IV (hydrate patient first if dehydrated)
Kayexalate (polystyrene sulphonate)/sodium Resonium 15-30g in 50-100ml 20% Sorbitol or with lactulose
PO/PR
Consider hemodialysis if refractory
➢ Hypertension:
o Salt restriction
o Diuretics: loop diuretic are recommended for the treatment of hypertension and edema in patients with chronic renal
failure. Thiazide diuretics have additive effect when administered with a loop diuretic for refractory edema
o Antihypertensive drug
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➢ Volume overload- dietary sodium restriction, diuretic therapy (usually with a loop diuretic given daily)
➢ Metabolic acidosis: maintain plasma bicarbonate concentration above 22mEq/L. Give sodium bicarbonate (daily dose of 0.5 to
1 mEq/kg per day)
➢ Hyperphosphatemia: dietary phosphate restriction may limit secondary hyperparathyroidism in patients with chronic renal
failure. An intake of above 800mg/day may be desirable but can be accomplished only by limiting protein intake.
➢ Anemia: blood transfusion (selected patients), recombinant erythropoietin may be given. Target hemoglobin 11-12 g/dl. Failure
to respond may be due to iron deficiency (due to hepcidin from the liver produced in response to IL-6), bleeding, malignancy,
infection, inflammation or formation of anti-EPO neutralizing antibodies. Intravenous (rather than oral) iron supplements
optimize response to EPO treatment by repletion of iron stores.
➢ Malnutrition:
o Low protein diet, restrict intake to 0.8 to 1g/kg or high biologic value protein (plant source)
o Since this level of restriction avoids protein malnutrition and may slow progressive disease. Overall, the diet of most
patients with chronic renal failure should provide approximately 30 to 35kcal/kg per day.
➢ Male Erectile dysfunction: testosterone deficiency should be corrected. The oral phosphodiesterase inhibitors e.g. sildenafil,
tadalafill and verdenafil are effective in ESKD and are first line therapy. The use of nitrates is contraindicated to this treatment.
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Identification and adequate preparation of the patient in whom renal replacement therapy will be
required
➢ Educate patient
➢ Informed choice of renal replacement therapy:
o Chronic hemodialysis
o Kidney transplantation
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WARM UP: TRUE/FALSE
• The kidney produces the following
substances
A. Erythropoietin-True
B. 25 hydroxyoholecalciferol-False
C. Prostaglandins PGE and PGI-True
D. Angiotensin-converting enzyme-True
E. Aldosterone-False
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THANK YOU
“IT WILL ALL ADD UP IN THE END”
