Drug Induced Renal Disease

The kidneys receive 25% of the cardiac output but only comprise about 0.5% of body weight, therefore it is quite common for drugs to damage the kidney.

Drugs can damage the kidneys by:

1)      Direct biochemical effects.

Substances that cause direct toxicity include – Heavy metals (mercury, gold, lead, iron), Antimicrobials (aminoglycosides, sulphonamides, cephalosporins), Analgesics (NSAIDs), Solvents (carbon tetrachloride, ethylene glycol), and X-ray contrast media.

2)      Indirect biochemical effects.

a)      Cytotoxic drugs and uricosurics may cause urate to be precipitated in the tubule.

b)      Calciferol may cause renal calcification by causing hypercalcaemia.

c)      Diuretic and laxative abuse can lead to tubule damage secondary to potassium and sodium depletion.

d)      Anticoagulants may cause haemorrhage into a kidney

3)      Immunological effects.

A wide range of drugs produces a wide range of injuries

Drugs include – phenytoin, gold, penicillins, sulphonamides, hydralazine, isoniazid, rifampicin, procainamide, penicillamine, probenecid.

Injuries include – arteritis, glomerulitis, interstitial nephritis, systemic lupus erythematosus.

Glomerular damage

The large surface area of the glomerular capillaries renders them susceptible to damage from circulating immune complexes eg immune response to penicillamine

Tubular damage

The renal tubule cells are exposed to greater amounts of solutes and toxins than other cells in the body. The proximal tubule experiences the greatest conc. and so suffers the most drug-induced injury. Specialised transport processes concentrate acids (aspirin), cephalosporins and bases (aminoglycosides) in renal tubular cells.

The countercurrent multiplier and exchange system can cause drugs to accumulate in the renal medulla (analgesics).

The distal tubule is the site of lithium-induced nephrotoxicity.

Tubule obstruction

Crystals can deposit within the tubular lumen. Methotrexate is insoluble at low pH and can precipitate in the distal nephron where the urine is acid.

Other drug-induced lesions

1)      Vasculitis, caused by sulphonamides, allopurinol, isoniazid.

2)      Allergic interstitial nephritis, caused by penicillins, sulphonamides, thiazides, allopurinol, phenytoin.

3)      Systemic lupus erythematosus, caused by hydralazine, procainamide.

Drugs may thus induce any of the common clinical syndromes of renal injury:

Acute renal failure – aminoglycosides (tubular toxin), NSAIDs (inhibit PG mediated vasodilataion), ACEI (reduce efferent arteriole tone), Cephalosporins (tubular toxin), Amphotericin B (vasoconstriction membrane damage), Acyclovir (precipitation in tubules), Cyclosporin/Tacrolimus (indirect vasoconstriction), Radiocontrast (vasoconstriction).

Nephrotic Syndrome – penicillamine, gold, captopril (only at very high doses)

Chronic renal failure – NSAIDs

Functional impairment – reduced ability to dilute and concentrate urine (lithium), potassium loss in urine (loop diuretics), acid base imbalance (acetazolamide).