Nephrotoxic Medicine Review

A nephrotoxic medicine review is a structured check of every prescribed, over-the-counter and herbal product for kidney harm, done at admission, before contrast or major surgery, when creatinine rises, and at each review in chronic kidney disease. Harm is most likely when several risks combine: age over 65, chronic kidney disease, diabetes, volume depletion, sepsis, heart failure and more than one nephrotoxic drug.

Mechanisms.

• Haemodynamic: NSAIDs, ACE inhibitors, angiotensin receptor blockers, calcineurin inhibitors, diuretics.

• Tubular injury: aminoglycosides, vancomycin, amphotericin, cisplatin, tenofovir disoproxil, polymyxins, contrast.

• Interstitial nephritis: proton pump inhibitors, beta-lactams, NSAIDs, rifampicin, allopurinol.

• Crystal injury: aciclovir, high-dose methotrexate, sulphonamides.

• Thrombotic microangiopathy: gemcitabine, quinine. Rhabdomyolysis: statins with interacting drugs.

• Nephrogenic diabetes insipidus and chronic interstitial disease: lithium.

Dangerous combinations. An ACE inhibitor or angiotensin receptor blocker with a diuretic and an NSAID (the triple combination) carries the highest risk. Vancomycin with piperacillin and tazobactam is associated with more injury than vancomycin with an alternative beta-lactam.

Review steps. List all products including herbal and traditional remedies. Mark each as stop, substitute, dose-reduce or continue with monitoring. Calculate clearance by the Cockcroft-Gault equation before any dose is chosen.

Substitutions.

• NSAID: paracetamol, topical agents for localised pain, or a short opioid course.

• Tenofovir disoproxil: tenofovir alafenamide 25 mg once daily when eGFR is 30 or over, or another regimen.

• Conventional amphotericin: liposomal amphotericin 3 mg/kg once daily.

• Aminoglycoside: a beta-lactam or another class if susceptibility allows.

• Proton pump inhibitor without a clear indication: stop, or step down to the lowest effective dose.

Special groups.

• Older adults: lower muscle mass hides reduced clearance.

• Children: dose by mg/kg and avoid aminoglycoside courses longer than needed.

• Pregnancy: avoid NSAIDs, ACE inhibitors and angiotensin receptor blockers.

• East Africa: ask directly about herbal remedies, over-the-counter NSAIDs and aminoglycoside courses from other facilities, which are often unrecorded.

Contrast. Give isotonic saline for patients with eGFR under 30 or acute kidney injury before intravascular contrast, for example 1 mL/kg/h for several hours before and after; the benefit is contested. Hold NSAIDs and diuretics around the procedure.

Aminoglycosides. If unavoidable, give gentamicin 3 to 5 mg/kg as a single dose and repeat only when the pre-dose level is under 1 mg/L. Limit the course to 3 days where possible.

Vancomycin. Loading 25 mg/kg intravenously (maximum 3 g), then dose by level, aiming for a pre-dose level of 15 to 20 mg/L.

Monitoring. Check creatinine and potassium before the first dose and every 24 to 48 hours during exposure, and 48 to 72 hours after contrast. Test urine for protein and blood when interstitial nephritis is possible.

Stop rules. Stop or replace the suspected drug when creatinine rises by 26.5 micromol/L or more within 48 hours, or to 1.5 times baseline, or urine output falls under 0.5 mL/kg/h for 6 hours.

Referral and escalation. Request nephrology review for stage 2 or 3 injury, suspected interstitial nephritis (rash, fever, eosinophilia, sterile pyuria), crystal nephropathy, or when the only effective drug is nephrotoxic.

Common errors. Continuing the triple combination during illness, missing herbal products, and not repeating creatinine after starting an aminoglycoside or vancomycin.