Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B

AIMS: Proximal renal tubular dysfunction (PRTD) is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB). METHODS: A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO(4)), uric acid (UA), and potassium and tubular maximal reabsorption rate of PO(4) to glomerular filtration rate (TmPO(4)/GFR) were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. RESULTS: Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO(4), and UA. Renal loss of PO(4), UA, protein, and β2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%). Improvements in PRTD were seen in all but one patient. CONCLUSION: One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO(4)/GFR, urinary protein, and β2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.