Analgesic Nephropathy

Analgesic nephropathy is chronic tubulointerstitial nephritis with renal papillary necrosis caused by prolonged heavy use of combination analgesics.

• Classic cause: phenacetin-containing mixtures (withdrawn); now chronic use of paracetamol with aspirin or NSAIDs, with caffeine or codeine, with cumulative intake over 2 to 3 kg.
• Endemic in Australia, Belgium, Switzerland, Germany historically.
• Mechanism: medullary ischaemia (prostaglandin inhibition) and oxidative injury from reactive metabolites concentrated in the papilla.
• Women over 40 and patients with chronic pain or headache disorders are affected.
• Complications: papillary necrosis, ureteric obstruction by sloughed papillae, recurrent urinary infection, urothelial cancer (risk 10 fold), hypertension, ESKD.

• Chronic headache or musculoskeletal pain with daily analgesic use, often denied.
• Polyuria, nocturia (concentrating defect), sterile pyuria, mild proteinuria, hypertension.
• Renal colic or gross haematuria from sloughed papillae.
• Anaemia (early, gastrointestinal blood loss), peptic ulcer, premature atherosclerosis, psychological dependence.
• Salt-wasting, tubular acidosis.

• History of cumulative analgesic intake.
• Urinalysis: sterile pyuria, mild proteinuria (under 2 g/day), haematuria; urine concentrating defect; reduced eGFR.
• Non-contrast CT: reduced renal size, irregular contours, papillary calcification (ring or "bean" shapes), the strongest diagnostic criterion (sensitivity and specificity over 90% when combined with small kidneys).
• Intravenous urography shows "club-shaped" calyces and ring shadows (rarely used).
• Biopsy not needed; shows chronic interstitial fibrosis.
• Urine cytology and cystoscopy for haematuria; surveillance for urothelial cancer.
• Exclude other chronic tubulointerstitial disease, obstruction, sickle cell, diabetes.

• Stop all analgesic combinations and NSAIDs; this slows or halts progression, with improvement of eGFR in some patients.
• Alternative pain control: paracetamol alone at 1 g up to four times daily (cautiously), physiotherapy, neuromodulators (amitriptyline 10 to 50 mg, gabapentin), treat headache disorder (migraine prophylaxis with propranolol 40 to 80 mg), manage dependence.
• Blood pressure control with ACE inhibitor or ARB; treat anaemia (iron, ESA), acidosis (sodium bicarbonate 1 to 3 g daily), hyperkalaemia.
• Papillary necrosis with obstruction: hydration, analgesia, stenting or ureteroscopic stone/papilla removal; treat infection (culture-directed antibiotics).
• Urothelial cancer surveillance: urine cytology, cystoscopy, imaging when haematuria.
• Dialysis or transplantation for ESKD; encourage avoidance of nephrotoxins thereafter.
• Education and addiction support; follow up eGFR every 3 to 6 months.