Gilbert Deray

Telbivudine Improves Renal Function in Patients With Chronic Hepatitis B

BACKGROUND & AIMSnThere is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of telbivudine treatment of patients with chronic hepatitis B virus infection.nnnMETHODSnWe used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4-6 years), as well as in patients with decompensated cirrhosis (2 years).nnnRESULTSneGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4-6 years. Increased eGFR with telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60-89 mL/min/1.73 m(2) (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5-6). In decompensated patients with high renal risk, eGFR was also improved on telbivudine (+2.0%).nnnCONCLUSIONSnIn global trials of patients with compensated and decompensated cirrhosis, long-term telbivudine therapy was associated with a sustained improvement of renal function-particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined.

Hepatitis B Virus Infection and the Kidney: Renal Abnormalities in HBV Patients, Antiviral Drugs Handling, and Specific Follow-Up

Chronic hepatitis B virus (CHB) infection is one of the most common causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. Many patients with CHB have variable degrees of functional renal impairment, and approximately 2 to 15% of patients on hemodialysis have CHB. Several therapeutic regimens have been developed in the past years, among which oral nucleoside and nucleotide analogues have been demonstrated to be efficient and well tolerated. However, they all are excreted in the urine and may thus require dosage adjustment in patients with decreased renal function. Furthermore, a number of them may in addition be toxic to the kidneys, especially in those patients presenting with renal insufficiency.

La physiologie rénale

Les reins sont responsables de l’elimination urinaire des toxines uremiques et de la regulation de plusieurs systemes de l’organisme comme la volemie intra- et extracellulaire, l’etat acido-basique, le metabolisme phosphocalcique ou l’erythropoiese. Ils adaptent quantitativement et qualitativement la composition de l’urine afin de garder ces systemes en equilibre. Le debit de plasma filtre est de l’ordre de 120 mL/min, et depend de l’hemodynamique systemique et renale qui est soumise a une autoregulation. L’urine primitive va alors subir des modifications dans les differents segments successifs du nephron. La partie proximale du nephron a pour role principal la reabsorption massive de l’eau et des elements essentiels comme le sodium, les bicarbonates, les acides amines et le glucose. Le nephron distal comprend le tube contourne distal, le tube connecteur et le canal collecteur. Il a pour role d’adapter qualitativement la composition de l’urine aux besoins de l’organisme.