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BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RESUMO
INTRODUCTION: Gastroparesis, or delayed gastric emptying, can be diagnosed with gastric emptying scintigraphy. Manometric studies of patients with gastroparesis show increased pyloric tone (pylorospasm). Among the recent endoscopic therapies for pylorospasm is peroral endoscopic pylorotomy (POP). In this study, we explored the effect of POP on gastric emptying in healthy pigs. MATERIAL AND METHODS: Four mini-pigs underwent POP following general anaesthesia. The mucosal entrance was situated 5âcm above the pylorus. POP was performed through a submucosal tunnel dissection. The duration of gastric emptying was assessed by scintigraphy before and after the procedure. The pigs were then euthanised for necropsy and pathologic assessment of the pylorus. RESULTS: The mean duration of the procedure was 55 (±â4 SD) min. All surgeries were performed in their entirety with 100â% feasibility. There were no cases of bleeding. The one case of perforation had no clinical significance. The duration of gastric emptying was 2.22-fold shorter after POP compared with before POP (T½ post-POPâ=â84.5 [±â35.7 SD] min vs. T½ pre-POPâ=â188.4 [±â87.3 SD] min; Pâ=â0.029). In agreement with the endoscopic observations, sectioning of the pyloric muscle in each pig was histologically complete. CONCLUSION: The efficacy of the procedure provides indirect proof of the involvement of the pyloric ring in delayed gastric emptying and suggests new therapies for patients with gastroparesis. Our protocol combining gastric emptying scintigraphy and POP validated the use of anaesthetised mini-pigs as a learning and training model for POP or other endoscopic/surgical procedures related to gastric emptying.
