Differences in nephrotoxicity risk and renal effects among anti‐viral therapies against hepatitis B

Abstract

Summary Background Results are conflicting with respect to the renal effects of anti‐viral agents used for hepatitis B virus infection. Aim To compare short and long‐term renal effects in real‐life settings and to determine risk factors for renal impairment during treatment. Methods 2221 treatment‐naïve patients were enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273 tenofovir and 11 adefovir initiated patients) had ‘repeated measures’ of creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine and adefovir groups were excluded from further analysis because of the low number of patients. We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula at each time point. Hypophosphataemia was also recorded. Risk factors for renal impairment were analysed. Results Tenofovir caused a decline in GFR at each time point when compared to baseline levels. However, lamivudine and entecavir did not change GFR. GFR‐shifting from ≥90 to 60–89 mL/min/1.73 m2 was comparable among groups. The proportion of patients whose baseline creatinine increased more than 25% was comparable among all anti‐virals. GFR showed a decline in patients who switched from entecavir to tenofovir. One patient with compensated cirrhosis needed to change from tenofovir because of renal safety. Seven and three patients developed transient hypophosphataemia in the tenofovir and lamivudine groups, respectively. Conclusions Although tenofovir caused a decline in GFR, differences between the anti‐viral agents do not appear to be so impressive. In patients with and without renal risk factors at baseline, there is no impact of anti‐virals, including tenofovir.

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

“…The prevalence of nucleotide analogue-related proximal RTD in our study was higher than a previous report (15%), which may be due to the different criteria of proximal RTD in our study [17, 23, 24] and the other report [19]. On contrary, previous studies did not report significant reduction in renal function after long-term nucleotide analogue treatment in CHB [13–15, 26]. However, comprehensive laboratory testing for proximal renal tubular function was not performed in these reports.…”

“…In clinical practice, TDF has been believed to be safer in terms of nephrotoxicity than ADV [12], and this has been supported by previous studies which showed that TDF was associated with a low incidence of renal dysfunction [13–15]. On the other hand, subsequent small studies on the safety of ADV and TDF have shown that long-term treatment with ADV or TDF could potentially cause renal dysfunction, hypophosphatemia, and impaired renal tubular phosphate reabsorption [16–19].…”

“…Long-term ADV and TDF treatment were both associated with proximal RTD in 15% of patients [19]. The inadequacies of these studies were small sample size, insufficient assessment of proximal renal tubular function, or retrospective conducted studies [15–19]. Due to the limitation of previous reports in term of low-quality of data and the short duration of follow-up, the recent guideline of the American Association for the Study of Liver Diseases (AASLD) recommends no preference between ETV and TDF regarding possible long-term risks of renal and bone complications [7].…”

Efficacia e sicurezza di entecavir dopo switch da tenofovir per comparsa di effetti collaterali renali: uno studio multicentrico italiano, di pratica clinica, su 103 pazienti con epatite cronica B

“…Sebbene negli studi clinici randomizzati, controllati, in pazienti selezionati con epatite cronica B, il trattamento con TDF si sia dimostrato ben tollerato e senza segnalazioni di tossicità renale clinicamente significativa, l'esperienza clinica real life ha riportato casi di compromissione della funzione renale fino all'insufficienza renale e alla sindrome di Fanconi [6,7,[10][11][12][13][14][15][16][17][18][19][32][33][34][35][36][37][38][39]. Spesso i fattori di rischio per un peggioramento della funzione renale sono l'età avanzata, l'ipertensione arteriosa e una preesistente riduzione del filtrato glomerulare.…”

“…Tra i NUC approvati, entecavir (ETV) e tenofovir disoproxil fumarato (TDF) sono raccomandati in prima linea nel trattamento dell'epatite cronica B, poiché entrambi sono antivirali potenti e con elevata barriera alla resistenza [1][2][3]. Negli studi registrativi e negli studi clinici a lungo termine, sia ETV che TDF hanno mostrato un profilo di sicurezza favorevole [4][5][6][7][8][9][10][11], anche se recentemente sono stati segnalati nella pratica clinica eventi avversi a livello Efficacia e sicurezza di entecavir dopo switch da tenofovir per comparsa di effetti collaterali renali M. Viganò renale e osseo nei pazienti trattati per lungo tempo con TDF [6,7,[10][11][12][13][14][15][16][17][18][19]. I meccanismi alla base della potenziale tossicità dei NUC sono legati alla loro capacità di inibire la DNA polimerasi ϒ mitocondriale umana quando le concentrazioni intracellulari dei NUC superano una soglia critica [12].…”