Drug-induced renal impairment in the elderly

Renal function declines predictably with age, so drugs and their active metabolites that are cleared by the kidney are eliminated more slowly, have longer half-lives, and accumulate to toxic steady-state concentrations.

Serum creatinine is an unreliable guide. Muscle mass and daily endogenous creatinine production both fall, so creatinine may be normal when renal function is substantially reduced. The aged kidney also shows net tubular reabsorption of creatinine, which further underestimates true GFR.

There is wide interindividual variation in the rate of decline. Applying the "average 50% fall between 20 and 90 years" to an individual patient causes over- or under-dosing.

Non-age factors are often just as important: state of hydration, cardiac output and intrinsic renal disease.

Tubular frailty means the elderly tubule progresses easily to acute tubular necrosis and recovers slowly — a small nephrotoxic insult produces a large injury.

Pharmacokinetics are altered across the board — bioavailability, volume of distribution, GFR-dependent excretion, and the time to steady state (four half-lives). With polypharmacy, older people are predisposed to drug toxicity.

Haemodynamic (functional) injury: NSAIDs block prostaglandin-mediated afferent vasodilatation; ACE inhibitors and ARBs remove efferent arteriolar tone; diuretics deplete intravascular volume. In bilateral renal artery stenosis, an ACE inhibitor can precipitate reversible renal failure. This triple combination is the classic community "triple whammy".

Acute tubular necrosis: nephrotoxins, classically aminoglycosides; also contrast, vancomycin, amphotericin, cisplatin, calcineurin inhibitors.

Acute interstitial nephritis (AIN): mainly a delayed hypersensitivity response to drugs — NSAIDs and diuretics. Most reported patients are elderly. Renal abnormalities usually improve once the drug is withdrawn, with or without steroids, but chronic kidney disease or even ESRD may follow.

Proton-pump inhibitors (omeprazole, esomeprazole, pantoprazole) are increasingly recognised as a cause of AIN. Diagnosis needs a high index of suspicion; renal biopsy shows eosinophilic infiltration, and prompt steroid therapy after confirmation restores function. For this and other reasons PPIs have become a target of deprescribing in older adults.

Chronic analgesic nephropathy: patients taking NSAIDs for months or years may develop papillary necrosis, chronic interstitial nephritis, or end-stage renal disease.

Glomerular injury: in some older people membranous nephropathy is related to drug ingestion (or to underlying malignancy in about 20%, mainly lung or colon adenocarcinoma); minimal change disease can be associated with NSAIDs.

Electrolyte and acid–base toxicity: on diuretics the elderly become hypokalaemic faster than the young; conversely they are predisposed to hyperkalaemia on NSAIDs, ACE inhibitors, beta blockers and potassium-sparing diuretics. Metformin can cause lactic acidosis — avoid in renal insufficiency and heart failure, measure creatinine clearance before starting in those aged 80 and over, and stop during volume-depleting illness and before surgery.

Perioperative nephrotoxicity: ACE inhibitors, diuretics and NSAIDs are the common culprits. Anaesthetic agents have little direct renal effect but reduce cardiac output, causing renal vasoconstriction and falling perfusion; prolonged enflurane or isoflurane generates fluoride, and sevoflurane at low fresh-gas flows generates compound A, though neither is usually a clinical problem.

Presentation is often silent or atypical — a rising creatinine, falling urine output, or a geriatric syndrome such as delirium, falls, anorexia or unexplained weight loss.

Red flag: AKI appearing shortly after introduction of a new drug — PPI, NSAID, antibiotic, diuretic or allopurinol — should be treated as drug-induced until proved otherwise.

Take a complete drug history including over-the-counter analgesics and traditional or herbal preparations, and establish the temporal relationship to drug initiation.

Estimate GFR with an eGFR equation rather than creatinine alone: CKD-EPI is regarded as most accurate, Cockcroft–Gault as most sensitive for dosing. For drugs with a narrow therapeutic-to-toxic ratio, measure actual creatinine clearance and drug blood levels.

Renal biopsy confirms interstitial nephritis when the diagnosis is uncertain and steroids are being considered.

Withdraw the offending drug — this is the single most effective intervention. Correct volume depletion, treat hyperkalaemia and acidosis, and dose all remaining drugs to the measured GFR.

Corticosteroids for biopsy-confirmed drug-induced AIN, given promptly, produce recovery of renal function; delay allows fibrosis.

Prevention is the exam answer: individualise treatment, use low and slowly increasing doses, and avoid polypharmacy. Alter dosing intervals for renally excreted drugs such as aminoglycosides and titrate to plasma levels. Stop nephrotoxic drugs before surgery and review diuretics against the patient's volume status and the planned procedure. Deprescribe PPIs and long-term NSAIDs.

Listing drugs without classifying by mechanism — the marks are in the classification.

Forgetting that a normal creatinine does not exclude significant impairment in a sarcopenic patient.

Omitting PPIs, which are the most examined "newer" cause.

Calling SGLT2 inhibitors nephrotoxic — they are renoprotective, but held during acute illness.

Forgetting herbal and over-the-counter preparations in the drug history, especially in Indian practice.

Stopping drugs and never mentioning restarting them after recovery.