Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term Treatment of Chronic Hepatitis B: A Cross-Sectional Study

Abstract

Background. There have been few reports of nucleotide analogue-related renal tubular dysfunction (RTD) in CHB patients. We assessed the prevalence and presentation of nucleotide analogue-related proximal RTD. Methods. A cross-sectional study was performed in CHB patients taking nucleotide analogues. Inclusion criteria were patients who were on adefovir or tenofovir as mono- or add-on therapy with lamivudine (LAM) >1 year. Serum and urine were collected. Fractional excretion of phosphate (FEPO4), uric acid (FEUA), and potassium was calculated. Renal losses were defined based on the criteria: protein (24-hour urine protein >150 mg), glucose (glycosuria with normoglycemia), phosphate (FEPO4 >18%), uric acid (FEUA >15%), potassium (renal potassium losses with hypokalemia), and bicarbonate (normal gap acidosis). Subclinical and overt proximal RTD were defined when 2 and ≥3 criteria presented. Results. Ninety-two patients were enrolled. The mean duration of nucleotide analogue taking was 55.1 ± 29.6 months. Proximal RTD was found in 24 (26.1%) patients (subclinical 15 (16.3%) and overt 9 (9.8%)). The severity of RTD was associated with the duration of nucleotide analogue (P = 0.01). Conclusions. The prevalence of proximal RTD in CHB patients taking nucleotide analogues was 26%. The severity of RTD was associated with the treatment duration. Comprehensive testing is necessary for early detecting nucleotide analogue-related nephrotoxicity.

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

“…A recent meta-analysis study revealed no significant differences between ETV and TDF treatment in CHB patients in terms of renal safety profiles and hypophosphatemia; however, the short duration of the study limited the power of the conclusions [4][5][6]17]. In contrast to these studies [4][5][6]17], PRTD and impaired phosphate renal tubular reabsorption were seen in 15-48% of CHB patients receiving long-term ADV and TDF therapy as in real world clinical experience [8,10,[18][19][20]. Reversibility of renal dysfunction has been shown in HIV-infected patients after cessation of TDF [21][22][23][24][25].…”

“…Written inform consent was obtained from the study subjects before recruitment. Out of 92 CHB patients who had been treated with nucleotide analogue, 24 patients were found to have nucleotide analoguerelated PRTD from our previous study [20]. Renal loss of protein, glucose, phosphate, uric acid, potassium, and bicarbonate was defined via laboratory assays.…”

“…Renal loss of protein, glucose, phosphate, uric acid, potassium, and bicarbonate was defined via laboratory assays. PRTD was diagnosed when at least two of these criteria were present [10,16,20,27]. Subclinical PRTD was defined at two criteria present, and overt PRTD was defined with ≥3 criteria [20].…”

“…PRTD was diagnosed when at least two of these criteria were present [10,16,20,27]. Subclinical PRTD was defined at two criteria present, and overt PRTD was defined with ≥3 criteria [20]. Seven patients with subclinical PRTD chose to continue ADV or TDF taking and have renal tubular function monitored periodically at the liver clinics.…”

“…The next challenging task is to find new antiviral therapies that can replace ADV or TDF for long-term suppression of HBV replication with high efficacy without causing adverse effects of PRTD and nephrotoxicity. The benefit of tenofovir alafenamide for the reduction of nucleotide analogue-related nephrotoxicity remains to be proven [20,39].…”