Chronic Tubulointerstitial Nephritis

Chronic tubulointerstitial nephritis (CTIN) is chronic interstitial fibrosis, tubular atrophy and inflammation that cause progressive CKD, with relatively preserved glomeruli.

Accounts for 20 to 30% of CKD of unknown origin.

Causes: analgesic and NSAID overuse, lithium, calcineurin inhibitors, cisplatin, Chinese herbs (aristolochic acid, Balkan endemic nephropathy), lead, cadmium, uric acid and calcium disorders (hypercalcaemia, hypokalaemia), obstruction and reflux, sickle cell disease, myeloma, sarcoidosis, Sjögren syndrome, IgG4 related disease, chronic untreated AIN, radiation, Mesoamerican nephropathy (heat stress, agrochemicals).

Mechanism: tubular injury triggering fibroblast activation and progressive fibrosis.

Complications: tubular acidosis, polyuria, hyperkalaemia, anaemia (early, out of proportion to GFR), urothelial cancer with aristolochic acid.

• Insidious, often asymptomatic; nocturia and polyuria from concentrating defects.
• Hypertension is late and mild; oedema is uncommon.
• Anaemia early, bone disease, salt wasting.
• Exposure history (analgesics, herbal medicines, lithium, lead, occupation).
• Associated features: sicca symptoms, uveitis, hypercalcaemia.

• Bland urine, low grade proteinuria (under 1 to 2 g/day, mostly tubular, with raised beta-2 microglobulin and retinol-binding protein), sterile pyuria.
• Tubular acidosis (normal anion gap), hyperkalaemia or hypokalaemia, glycosuria, phosphaturia, impaired urine concentration.
• Ultrasound: small kidneys with irregular cortical scarring (papillary necrosis in analgesic nephropathy, with calcifications).
• Biopsy: interstitial fibrosis, tubular atrophy, mononuclear infiltrate with relatively spared glomeruli.
• Aetiological tests: serum and urine electrophoresis with free light chains, ACE, calcium, urate, lead level, ANA, anti-Ro/La, IgG4, sickle screen, CT for papillary necrosis, voiding cystourethrogram in reflux.

• Remove the cause: stop analgesics, NSAIDs, lithium (with psychiatric input), herbal remedies; correct hypercalcaemia or hypokalaemia; relieve obstruction; chelate lead (succimer or EDTA).
• Control blood pressure below 130/80 mmHg with an ACE inhibitor or ARB (ramipril 5 to 10 mg) when proteinuria is present; monitor potassium and creatinine.
• Correct acidosis: sodium bicarbonate 0.5 to 1 mmol/kg/day (500 mg to 1 g two to three times daily) to keep serum bicarbonate at 22 mmol/L or more.
• Manage hyperkalaemia (patiromer 8.4 g daily, dietary restriction), anaemia (iron, erythropoiesis stimulating agents when haemoglobin under 10 g/dL), mineral bone disease, salt supplementation for salt-wasting.
• Corticosteroids for immune mediated disease: prednisolone 0.5 to 1 mg/kg for sarcoidosis, IgG4 disease, Sjögren, TINU; add azathioprine, mycophenolate or rituximab for steroid dependence.
• SGLT2 inhibitor (dapagliflozin 10 mg) for proteinuric CKD.
• Surveillance for urothelial cancer in aristolochic acid nephropathy.
• Prepare for dialysis or transplantation when eGFR falls below 20 mL/min.