Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1326
Peer-review started: June 11, 2020
First decision: September 18, 2020
Revised: October 7, 2020
Accepted: October 28, 2020
Article in press: October 28, 2020
Published online: December 27, 2020
Processing time: 189 Days and 14.9 Hours
The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use.
To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients.
A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors.
Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naïve group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo.
The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
Core Tip: The objective of this prospective, multicenter study was to determine the 24 mo prevalence and incidence of subclinical proximal tubulopathy (SPT) in hepatitis B virus (HBV)-monoinfected patients that were either treatment-naïve or treated with nucleot(s)ide analogues. Data on early SPT markers, the estimated glomerular filtration rate and phosphatemia, were collected quarterly from 196 patients. The prevalence and incidence of SPT was higher in tenofovir disoproxil-treated patients compared to naïve patients. The median survival time without SPT (time during which more than 50% of the patients remained SPT-free), evaluated only in the tenofovir disoproxil-treated group, was 5.9 mo. SPT was detected in the naïve population, indicating possible HBV-induced toxicity in renal tubules.