Coupon Accepted Successfully!



Chronic renal failure (CRF)


Note: The New term for CRF is Chronic Kidney Disease (CKD)


Definition-CRF refers to the permanent loss of renal function, which culminates in signs and symptoms termed uremia.
Common Causes
  1. Diabetic nephropathy (M/C of CRF)
  2. Hypertension
  3. Chronic glomerulonephritis
  4. Polycystic kidney disease
  5. Chronic pyelonephritis
  6. Interstitial nephritis. 
  7. Alport syndrome
(Minimal change GN is the least common cause)
Cockcroft-Gault equation (Recommended Equations for estimation of GFR using serum creatinine concentration (Pcr), Age, Sex, Race and body weight.)
(Ref. Hari. 18th ed., pg - 2309, Table 280-2)
Estimated creatinine clearance (mL/min)
(Multiply by 0.85 for women)


Extra Edge Signs and symptoms of CRF appear when GFR goes down below 50% (LQ 2012)


Clinical Action Plan (Ref. Hari. 18th ed., Pg - 2319, table 280.6)
Stage Description GFR, mL/min per 1.73 m2 Action
1 Kidney damage with normal or ­GFR ≥90 Diagnosis and treatment, treatment of comorbid conditions, slowing progression, CVD risk reduction
2 Kidney damage with mild GFR 60–89 Estimating progression
3 Moderate GFR 30–59 Evaluating and treating complications
4 Severe ↓GFR 15–29 Preparation for kidney replacement therapy
5 Kidney failure <15 (or dialysis) Kidney replacement (if uremia present)


Extra Edge The best initial test to know about CRF is GFR (LQ 2012)

Signs and symptoms of CRF may be due to the following consequences
(Ref. Hari. 18th ed., pg - 2314)
  1. Changes in body fluid volume or composition
    Na retention
    1. Hyponatremia (dilutional)
    2. Hyperkalemia or hypokalemia (Hypokalemia is more common in salt loosing nephropathy) (LQ 2012)
    3. Metabolic acidosis
    4. Hyperphosphatemia (LQ 2012)
    5. Hypocalcemia (LQ 2012)
    6. Hypermagnesemia
    7. Hyperuricemia
Hyperphosphatemia and hypocalcemia develop when GFR falls to < 25% of normal (< 30 ml/min). Prolonged hypocalcemia leads to secondary hyperparathyroidism (Increased PTH, Increased phosphate & Reduced Calcium) 


Important Points
  1. In CRF hyperkalemia or hypokalemia both can happen, hypophosphatemia is not a feature.
  2. In nutritional osteodystrophy there is hypocalcemia and hypo phosphatemia. 


Extra Edge Multiple Myeloma is the only condition where patient may have CRF with hypercalcemia.


  1. Cardiopulmonary
    1. CCF Volume over load can lead to CCF however pulmonary edema may be due to increased capillary permeability in the absence of volume overload.
    2. Hypertension
    3. Painless Pericarditis
    4. Accelerated atherosclerosis
    5. Pneumonitis
    6. Pleuritis
  2. Hematologic. (Fatigue is the commonest symptom which occurs due to anemia). 
Causes of Anemia in CKD (Ref. Hari. 18th ed., Page – 2316, Table 280-5)
  1. Relative deficiency of erythropoietin
  2. Diminished red blood cell survival
  3. Bleeding diathesis
  4. Iron deficiency
  5. Hyperparathyroidism/bone marrow fibrosis
  6. Folate or vitamin B12 deficiency

Extra Edge

  1. Anaemia (normochromic, normocytic due to diminished erythropoiesis, shortened RBC survival, and in some cases, blood loss) (S. Fe, TIBC, S. Ferritin all are normal)
  2. Poor hemostasis (prolonged bleeding time, lower platelet factor III activity, mild thrombocytopenia and platelet function abnormalities)
  3. Leukocyte abnormalities. (P/S reveals Burr cells and hyper segmentation of Neutrophill nucleus)


Important Points

Hyper segmentation of Neutrophil nucleus is also seen in

  1. Chronic liver disease
  2. Burns
  3. Microangiopathic hemolytic anemia.
  4. Megaloblastic anemia


Recent Advances



  1. It is used for the treatment of anemia due to chronic kidney disease, 
  2. It is a erythropoiesis stimulating agent (ESA).


  1. Neuromuscular features
    1. Encephalopathy
    2. Peripheral neuropathy
    3. Dialysis dementia
    4. Restless leg syndrome
    5. Impotency
CNS features in CRF are due to
  1. Increase BUN
  2. Increase Creatinine
  3. Acidosis
  4. Decrease Na
  5. Hyperosmolarity
Treatment of restless leg syndrome: (LQ 2012)
  1. Dopamine Agonists & Gabapentin as first line drugs for daily restless legs syndrome
  2. Opioids are for treatment of resistant cases
  1. Endocrine
    1. Secondary hyperparathyroidism (due to decreased phosphate excretion by the kidney)
    2. Glucose intolerance (due to resistance to insulin) or hypoglycemia because of impaired insulin metabolism.
    3. AmenorrheaQ
    4. Impaired testicular function
    5. Impotence
      In nutritional osteodystrophy both Ca nd PO4 are reduced but in CRF, Ca is reduced and phosphate is increased
  2. Skin
    1. Pruritus (due to uremia)Q
    2. Ecchymosis
    3. Hyperpigmentation (yellow hyperpigmentation due to retention of urochrome and discoloration due to hemochromatosis) 
    4. Nail & Half nail (also known as Lindsay Nail) occur due to Increased capillary density at the distal half of nails (LQ 2012)
Important Points (Ref. Hari. 18th ed., pg - 2317)
  1. A fatal skin condition called nephrogenic systemic fibrosis (fibrosing dermopathy) in which progressive subcutaneous induration, especially on the arms and legs occurs
  2. It is seen in patients with CKD, most commonly on dialysis.
  3. Exposure to the magnetic resonance contrast agent, gadolinium, may precipitate this syndrome.

Calciphylaxis (Ref. Hari. 18th ed., pg - 2313)

  1. Calciphylaxis is one type of extraskeletal calcification.
  2. Calciphylaxis is a devastating condition seen almost exclusively in patients with advanced CKD.
  3. It is heralded by livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts.
  4. Pathologically, there is evidence of vascular occlusion in association with extensive vascular calcification.


  1. Eye: Band shape keratopathy. 
Important Points

Causes of Band shaped keratopathy.

  1. Ocular trauma
  2. Uveitis
  3. Prolong Hypercalcemia
  4. Chronic glaucoma
  5. Chronic keratitis.


  1. Gastrointestinal
    1. Anorexia, nausea, vomiting (especially early in the morning)
    2. Peptic ulcer
    3. Ascites
    4. Viral hepatitis

Extra Edge In CRF, GIT symptoms occurs because of Renogastric reflex

  1. Urine analysis – Broad cast in urine
  2. Isosthenuria: A state in chronic renal disease in which the kidney cannot form urine with a higher or a lower specific gravity than that of protein-free plasma; specific gravity of the urine becomes fixed around 1.010, irrespective of the fluid intake.
  3. Blood biochemistry
  4. Ultra sonography to assess the size of kidneys.
In CRF, both the kidneys are small and contracted (< 8 cm length is taken as contracted kidney). (FAQ)

B/L contracted kidney is the surest sign of CRF. But there are few exceptions where patient may have CRF but with normal or enlarge kidney size.

Causes of CRF with enlarged kidneys (FAQ)
  1. Diabetes mellitusQ
  2. Polycystic kidney diseaseQ
  3. Amyloid kidneyQ 
  4. Bilateral obstruction (hydronephrosis)Q
  5. Myeloma kidneyQ
Dialysis (Ref. Hari. 18th ed., pg - 2322)
  1. Hemodialysis (HD)
    Blood flows opposite to the dialysis fluid, and substances are exchanged down a concentration gradient across a semipermeable membrane, between the two compartments.
    Indications of hemodialysis
    1. ARF
    2. Toxins (Methanol poisoning)
    3. Drugs (Salicylate poisoning)
    4. CRF patients awaiting renal transplantation
Important Points

Dialysis is not effective in following poisoning:

  1. Digoxin
  2. Barbiturate
  3. Kerosene
  4. Copper sulphate
  5. Organo phosphorus poisoning

Many manifestation of uremia persist with chronic hemodialysis, although they are less severe. 
  1. Anaemia may be aggravated by blood loss and folate deficiency
  2. Accelerated atherosclerosis is common.
  3. Diverticulosis, hepatitis
  4. Renal osteodystrophy may progress or appear in the form of osteomalacia with bone pain and fractures. 
  5. Secondary hyperparathyroidism
  6. Reduce libido
  7. Stunted Growth
  8. Pruritus
  9. Acquired renal cysts.
  10. Peripheral neuritis
Features which develop after start of Hemodialysis (HD) 
  1. Hypotension (most common)
  2. Hepatitis
  3. Adynamic osteomalacia
  4. Idiopathic ascites
  5. Leukopenia
  6. Hypocomplementemia
  7. Disequilibrium refers to CNS symptoms ranging from nausea to seizures related to volume depletion and osmolar shifts,  usually occurring with initiation of treatment.
  8. Dialysis Dementia occurs after few years of dialysis It is due to  aluminium intoxication. Syndrome of speech dysfunction,dyspraxia, seizures and myoclonus. 
Important Point

Hypotension is the most common complication of HD


  1. Continues ambulatory (CAPD/APD)
    In this, a permanent catheter is inserted into the peritoneum via a subcutaneous tunnel. Up to 2 liters of dialysate (rich in dextrose) is introduced and exchanged up to 5 times a day. Peritoneal membrane itself acts like filtration membrane.
Complications of Peritoneal Dialysis
  1. Peritonitis (usually Staphylococcus, Streptococcus, or coliforms) 
  2. Catheter blockage
  3. Weight gain and poor diabetic control (dialysate fluid has high sugar content)
  4. Pleural effusion. 
In SCUF (Slow Continuous Ultrafiltration) type of dialyses
  1. SCUF is the removal of water from the patient’s blood as it travels through the filter. 
  2. Water removal is referred to as ultrafiltration. 
  3. SCUF is a therapy designed to only remove surplus water. The amount of water removed is not sufficient to remove wastes. 
  4. SCUF does not require the use of replacement fluid, and fluid removal is 300ml to 500ml per hour.
Kidney Transplant (Ref. Hari. 18th ed., Pg - 2331)

Immunology of Rejection
  1. Both cellular and humoral (antibody-mediated) effector mechanisms can play roles in kidney transplant rejection. 
  2. Antibodies can also initiate a form of antibody-dependent but cell-mediated cytotoxicity by recipient cells that bear receptors for the Fc portion of immunoglobulin.
Immunosuppressive Treatment
  1. Glucocorticoids
  2. Cyclosporine (CsA)
  3. Tacrolimus (Previously known as FK506)
  4. Azathioprine
  5. Mycophenolate mofetil (MMF)
  6. Sirolimus (Previously known as rapamycin)
Antibodies to Lymphocytes (Recent Advances)
  1. OKT3  
  2. Antibodies to IL-2 receptor
    1. Basiliximab
    2. Daclizumab
  3. Agents depleting T cell antibody (alemtuzumab)
  4. Fusion protein (Belatacept).

Test Your Skills Now!
Take a Quiz now
Reviewer Name