Drugs and the Kidney / Toxic Nephropathies

Renal Elimination and Drug Dosing

•    Many drugs require dose adjustment in CKD to avoid toxicity due to reduced clearance:

o    Aminoglycosides – nephrotoxic, require careful therapeutic monitoring

o    Lithium – narrow therapeutic window; accumulates in CKD, ↑ risk of toxicity

o    Digoxin – renally cleared; monitor levels in CKD and with hypokalaemia

Nephrotoxic Agents

1. Aminoglycosides (e.g. gentamicin)

•    Cause acute tubular necrosis (ATN) via direct toxicity to proximal tubule cells

•    Risk factors: dehydration, prolonged use, other nephrotoxins

•    Monitor drug levels and renal function closely

2. Amphotericin B

•    Causes renal vasoconstriction and tubular damage, leading to AKI and electrolyte disturbances (↓ K⁺, ↓ Mg²⁺)

•    Liposomal formulations are less nephrotoxic

3. NSAIDs

•    Triple mechanism of nephrotoxicity:

o    Pre-renal AKI (↓ prostaglandin-mediated afferent arteriolar dilation)

o    AIN (hypersensitivity reaction)

o    Papillary necrosis (long-term use)

4. Radiocontrast agents

•    Cause contrast-induced nephropathy: ATN-like injury peaking ~48–72 hrs post-exposure

•    Risk: pre-existing CKD, diabetes, dehydration

•    Prevention: IV hydration, withhold nephrotoxins, consider N-acetylcysteine

Calcineurin Inhibitors (Ciclosporin, Tacrolimus)

•    Cause dose-dependent vasoconstriction of afferent arterioles → ↓ GFR

•    Long-term use leads to chronic interstitial fibrosis

•    Monitor drug levels and renal function; nephrotoxicity may be indistinguishable from rejection

Heavy Metal Toxicity

•    Lead, mercury, cadmium → chronic tubulointerstitial nephritis

•    Features: slowly progressive CKD, Fanconi syndrome (proximal tubule dysfunction)

•    Diagnosis: exposure history, heavy metal levels

•    Management: chelation therapy in selected cases

Ethylene Glycol Poisoning

•    Found in antifreeze; metabolised to oxalic acid → tubular damage

•    Features:

o    Severe metabolic acidosis, ↑ anion gap

o    AKI with oxalate crystal deposition in renal tubules (envelope-shaped crystals)

•    Diagnosis: osmolar gap, serum ethylene glycol (if available)

•    Management: fomepizole or ethanol, haemodialysis