Determination Of Estimated Glomerular Filtration Rate(eGFR) And Relationship Of EGFR And Antiviral Treatments In Patients With Chronic Hepatitis B Infection

BackgroundHepatitis B virus (HBV) infection is a major health problem in China. China is a high incidence of HBV infection. Currently, there are about ninety three million people with chronic HBV infection in China. HBV infection can cause liver damage, such as chronic hepatitis and liver cirrhosis, through infecting liver cells. In addition, HBV infection can also result in renal dysfunction through immune complex-mediated injury and/or infecting kidney cells directly. A close relationship exists between HBV infection and renal dysfunction. The different stages of chronic HBV infection, the degree of liver function decompensation and comorbidities of HBV patients may also impact renal function. Nevertheless, these aspects are lack of systematic research. Antiviral therapy is the key to the treatment of chronic HBV infection. Oral antiviral drugs—nucleos(t)ide analogues (NAs) are widely used. But these antiviral agents are all primarily eliminated unchanged through renal route. Long-term use of NAs may influence renal function. Therefore, the safety of long-term treatment with NAs and the appropriateness of choosing antiviral drugs have gradually gained more attention.ObjectiveTo assess the renal function in patients with chronic HBV infection without any antiviral treatment and to explore the risk factors for renal dysfunction. To evaluate renal function changes in chronic HBV infected patients receiving long-term NA therapy. To research the similarity and difference among different eGFR calculation equations.MethodsThe prospective analysis involved 206 patients with CHB(including 151 cases of CHB and 55 cases of liver cirrhosis) receiving telbivudine(LdT)、entecavir(ETV) or adefovir dipivoxil(ADV) monotherapy for 52 weeks. The renal function with estimated glomerular filtration rate (eGFR) were mainly calculated by serum creatinine (SCr)-cystatin C (CysC) combined Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We evaluated the prevalence of renal impairment (eGFR<90 ml/min/1.73 m2) among enrolled patients at baseline and explored the risk factors for renal abnormalities. Serum creatinine(Cr),cystatin C(CysC),eGFR and the percentage of patients with eGFR≥90 ml/min/1.73 m2at week 52 were compared with the baseline data between the three antiviral drugs.The renal function with eGFR at baseline and week 52 were calculated by Cockcroft-Gault(CG),Modification of Diet in Renal Disease (MDRD),serum creatinine(SCr)-based Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)and SCr-CysC combined CKD-EPI equation.We also compared the similarities and differences of different equations.Results1. The incidence of renal impairment among the enrolled patients was 21.85% (45/206). The incidence of renal impairment was 17.88%(27/151) among CHB patients and 32.73%(18/55) among liver cirrhosis patients, and the latter was significantly higher than the former (x2-5.205, P=0.023). The incidence of renal impairment was 17.39% (4/23)、29.41%(5/17) and 60.00%(9/15) among Child-Pugh stage A、B、C patients, respectively. At baseline, the eGFR of liver cirrhosis patients was lower than CHB patients (P=0.000) and the eGFR of Child-Pugh stage C patients was lower than Child-Pugh stage A patients (P=0.034) significantly.2. Univariate analysis showed that age (≥50 years), history of diabetes mellitus and history of hypertension were associated with renal dysfunction. Multivariate analysis indicated that age (≥50 years) and history of hypertension were identified as the risk factors for renal impairment.3. Compared with week 52 and the baseline period, SCr and Cys C decreased and eGFR increased significantly(P=0.000) in LdT group; SCr was unchanged, Cys C decreased and eGFR increased (P=0.002) in ETV group; SCr and Cys C increased and eGFR decreased significantly (P=0.000) in ADV group.4. Compared with week 52 and the baseline period, the rate of patients whose renal function returned to be normal in LdT groups and ETV groups was 88.89%(8/9) and 83.33%(20/24), respectively. The rate of ADV groups decreased 10%.5. After antiviral therapy for 52 weeks, the eGFR of patients with normal renal function at baseline increased by 16.61(P=0.000) and decreased by 2.01(P=0.902)、 10.92 ml/min/1.73m2(P=0.000) in LdT、ETV and ADV groups, respectively. After an average 52-week follow-up, the eGFR of patients with mild renal impairment(60≤eGFR<90 ml/min/1.73m2)at baseline increased by 37.51(P=0.000)、 23.87(P=0.000) and 2.68 ml/min/1.73m2(P=0.260).6. CKD-EPI(SCr) equation and CKD-EPI(SCr-CysC) equation reflected the changes of renal function better than CG equation and MDRD equation. ConclusionsRenal abnormalities pre-exist in parts of patients with chronic HBV infection before the initiation of any antiviral treatment. Age and history of hypertension are identified as the risk factors for renal impairment. LdT treatment shows a renoprotective effect in patients with chronic hepatitis B infection. The effect of ETV treatment on renal function needs further study. Adefovir therapy is associated with decreased eGFR. eGFR calculated by CKD-EPI(SCr) and CKD-EPI(SCr-CysC) equation are concordant and they can reflect the changes of renal function better.