Tenofovir-Induced Distal Renal Tubular Acidosis Presenting as Flaccid Paraparesis in Chronic Hepatitis B

Dear Editor,

A 51-year-old male with chronic hepatitis B-related cirrhosis on long-term tenofovir disoproxil fumarate (TDF) presented with progressive lower limb weakness, culminating in flaccid paraparesis. On examination, tone and power were reduced (Medical Research Council grade 2/5) with areflexia. There were no features of hepatic encephalopathy. Investigations revealed profound hypokalemia (1.3 mmol/L), normal serum magnesium (2.6 mmol/L), non-anion gap metabolic acidosis, and a urine pH of 6.5. Transtubular potassium gradient was elevated (transtubular potassium gradient = 12), consistent with renal potassium wasting. Urinalysis showed 1+ protein, 1+ glucose, 8-10 RBCs/hpf, and 6-8 WBCs/hpf. Urine osmolality was 61 mOsm/kg. Spot urinary sodium was 33 mmol/L, and urinary creatinine was 17 mg/dL. Urinary anion gap was 28 mmol/L, supporting distal RTA. The autoimmune panel was negative; the renal ultrasound was unremarkable. Distal renal tubular acidosis (dRTA) secondary to TDF was diagnosed after excluding other causes. The patient responded promptly to TDF withdrawal, potassium supplementation, and alkali therapy, with full neurological recovery within days. He has been followed up for 2 months post-discharge and has remained asymptomatic with stable potassium and bicarbonate levels.

This case highlights a rare but severe complication of TDF, isolated distal RTA, plausibly mediated by tenofovir-associated mitochondrial injury affecting distal nephron intercalated cells; while proximal tubular toxicity is well recognized with TDF,¹ distal acidification defects are under-reported.^2-4 Clinicians should maintain a high index of suspicion in patients on TDF presenting with neuromuscular symptoms, metabolic acidosis, and hypokalemia.⁵