ICU · Renal and metabolic

Drug-induced nephrotoxicity: mechanism, offending agents, and prevention in ICU

Also known as Drug-induced nephrotoxicity · Nephrotoxic AKI · Acute tubular necrosis drugs · Acute interstitial nephritis · Contrast nephropathy · Vancomycin nephrotoxicity

Drug-induced nephrotoxicity accounts for 2-15% of acute renal failure in hospital/ICU series and 28.6% of a Naranjo-adjudicated hospital AKI cohort. Five dominant mechanisms: (1) HAEMODYNAMIC (NSAIDs constrict afferent arteriole via prostaglandin inhibition; ACEi/ARB dilate efferent arteriole by blocking angiotensin II; calcineurin inhibitors constrict afferent arteriole via endothelin — the 'triple whammy' combination carries AKI odds ratio 2.01). (2) ACUTE TUBULAR NECROSIS (ATN) — direct tubular toxicity: aminoglycosides accumulate in proximal tubular cells via the megalin receptor (the only major uptake pathway); amphotericin B deoxycholate is dose-limited by nephrotoxicity (prefer lipid formulations); tenofovir causes proximal tubular injury (Fanconi syndrome); iodinated contrast causes medullary vasoconstriction/hypoxia plus direct cytotoxicity; cisplatin enters via OCT2. (3) ACUTE INTERSTITIAL NEPHRITIS (AIN) — Type IV hypersensitivity: antibiotics, PPIs (a common cause), NSAIDs, rifampicin, sulfonamides, allopurinol; biopsy is definitive; up to one-third progress to chronic dialysis. (4) CRYSTAL NEPHROPATHY — sulfadiazine, aciclovir, indinavir, triamterene, methotrexate precipitate in tubules when volume is depleted, kidney disease exists, or urinary pH shifts. (5) OSMOTIC NEPHROSIS — IV immunoglobulin (sucrose stabiliser), hydroxyethyl starch, mannitol cause tubular cell swelling. Prevention: identify high-risk patients, avoid/limit nephrotoxins, therapeutic drug monitoring (vancomycin AUC/MIC 400-600; aminoglycoside once-daily dosing lowers nephrotoxicity risk ratio to 0.74), isotonic volume expansion for contrast (PRESERVE: saline = bicarbonate, NAC no benefit), recognise and STOP offending drug early.