Renal Failure

Renal failure can present as either acute renal failure (ARF) or chronic renal failure (CRF). Acute exacerbations with sudden and often reversible deterioration in renal function may occur in patients with chronic renal failure (acute on chronic renal failure).

• A significant deterioration in renal function occurring over hours or days.
• Clinically, there may be no symptoms or signs, but oliguria (urine volume less than 400 mL/24 hour) is common.
• Biochemically, ARF is detected by rising plasma urea and creatinine.
• ARF may arise as an isolated problem; more commonly it occurs in the setting of circulatory disturbance, e.g. severe illness, sepsis, trauma, or surgery-or in the context of nephrotoxic drugs.

Recognition of ARF

• ARF is characterised by rapid deterioration of renal function over a period of hours or days.
• ARF should be suspected in the context of an acute illness in the presence of:
  • A 50% rise in serum creatinine concentration.
  • A fall in estimated GFR of greater than 25% (if baseline unknown assume 75 mL/min/1.73m²) but GFR must be interpreted with caution as formulae rely on a stable creatinine concentration.
  • Oliguria (urinary output less than 0.5 mL/kg/hour).
• Because it requires emergency treatment, all patients with newly detected abnormal renal function should be assumed to have ARF until proven otherwise, although the majority will turn out to have chronic kidney disease (CKD).

Kidney function should be assessed by estimated GFR, and CKD is classified on this basis. The GFR should be estimated from serum creatinine using the 4-variable MDRD equation:¹

• Stage 1: normal; GFR >90 mL/min/1.73 m² with other evidence of chronic kidney damage (see below).
• Stage 2: mild impairment; GFR 60-89 mL/min/1.73 m² with other evidence of chronic kidney damage.
  

  Patients with a GFR of >60 mL/min/1.73 m2 without evidence of chronic kidney damage should NOT be classified as having CKD and do not necessarily need further investigation; (ie other evidence of kidney damage is necessary before labelling a patient as having CKD1 or CKD2).

• Stage 3: moderate impairment; GFR 30-59 mL/min/1.73 m².
• Stage 4: severe impairment; GFR 15-29 mL/min/1.73 m².
• Stage 5: established renal failure (ERF); GFR less than 15 mL/min/1.73 m² or on dialysis.

Other evidence of chronic kidney damage may include:

• Persistent microalbuminuria
• Persistent proteinuria
• Persistent haematuria (after exclusion of other causes, e.g. urological disease)
• Structural abnormalities of the kidneys demonstrated on ultrasound scanning or other radiological tests, e.g. polycystic kidney disease, reflux nephropathy
• Biopsy-proven chronic glomerulonephritis

Serum creatinine concentration should be measured at initial assessment and then at least annually in all adult patients with:²

• Previously diagnosed CKD including:
  • Identified renal pathology (e.g. polycystic kidney, biopsy proven glomerulonephritis, reflux nephropathy)
  • Persistent proteinuria
  • Haematuria with no urological cause
• Conditions associated with a high risk of silent development of obstructive kidney disease:
  • Bladder voiding dysfunction (outflow obstruction, neurogenic bladder)
  • Urinary diversion surgery
  • Urinary stone disease (more than one episode per year)
• Conditions associated with a high risk of silent development of parenchymal kidney disease:
  • Hypertension, diabetes mellitus, heart failure
  • Atherosclerotic coronary, cerebral, or peripheral vascular disease
• Conditions requiring long-term treatment with potentially nephrotoxic drugs: examples of potentially nephrotoxic drugs include: ACE inhibitors, angiotensin receptor blockers, NSAIDs, lithium, mesalazine, cyclosporin, tacrolimus
• Multi-system diseases that may involve the kidney, e.g. systemic lupus erythematosus, vasculitis, myeloma, rheumatoid arthritis

See separate article Drug Prescribing in Renal Impairment.

Great care is required with all drugs used by patients with renal failure, including over the counter drugs. Current and proposed medications should be carefully checked before prescribing:

• Drugs that have been reported to cause glomerulonephritis include penicillamine, gold, captopril, phenytoin and some antibiotics, including penicillins, sulphonamides and rifampicin.
• Penicillins, cephalosporins, sulphonamides, thiazide diuretics, frusemide, NSAIDs and rifampicin are among the many drugs that have been implicated in causing interstitial nephritis.
• Drugs that can cause renal damage and/or accumulate in renal insufficiency include:
  • Antibiotics:
    • Aminoglycosides: may cause renal tubular necrosis and accumulation may cause ototoxicity and further renal damage.
    • Nutrofurantoin: may cause renal tubular necrosis and accumulation may cause peripheral neuropathy.
    • Penicillins: may cause interstitial nephritis and accumulation may cause convulsions and haemolytic anaemia.
    • Cephalosporins: cefaloridine, one of the first generation cephalosporins, was associated with direct renal toxicity and is no longer in clinical use. Other cephalosporins are much less likely to produce renal damage but care is needed when prescribing cephalosporins to patients with impaired renal function, especially if they are also receiving loop diuretics. The third-generation cephalosporins, e.g. cefixime, have very rarely been reported to cause nephrotoxicity.
    • Quinolones and sulphonamides: may cause renal tubular obstruction due to crystalluria.
    • Tetracyclines: accumulation may cause nausea, vomiting and diarrhoea, and further renal damage.
  • Other drugs:
    • ACE inhibitors: can worsen pre-existing renal insufficiency and cause hyperkalaemia.
    • NSAIDs: may cause interstitial nephritis and reduce glomerular filtration rate.
    • Diuretics, especially loop diuretics, may causes volume depletion and underperfusion of the kidneys, especially if co-prescribed with an ACE inhibitor.

Dose modification

• Dose modification should be related to creatinine clearance, and the extent to which a drug is renally excreted.
• This is significant for aminoglycosides, some antibiotics including cephalosporins, lithium, opiates and digoxin.
• Loading doses should not be changed.
• If the patient is on dialysis, dose modification depends on how well it is eliminated by dialysis. Dosing should be timed around dialysis sessions.