Hepatitis B virus infection and development of chronic kidney disease: a cohort study

Abstract

Background: The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women.

Methods: Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m² and/or proteinuria.

Results: Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m² and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03-1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m² were 1.23 (1.12-1.35; P < 0.001) and 0.89 (0.73-1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline.

Conclusion: In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD.

Keywords: Chronic kidney disease; Cohort study; Hepatitis B surface antigen; Hepatitis B virus infection; Proteinuria; Risk factors.

Fig. 1

Flowchart of study participants Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HBsAg, Hepatitis B surface antigen

Fig. 2

Adjusted cumulative incidence of chronic kidney disease by HBsAg serology at baseline Parametric cumulative incidence curves (smooth lines) were estimated from a spline-based parametric survival model allowing for non-proportional hazards between positive HBsAg and negative HBsAg groups. Nonparametric cumulative incidence curves (step functions) were estimated from Kaplan-Meier methods. Both methods were weighted by stabilized inverse probability weights and stratified by HBsAg serology status. Confounders used to estimate inverse probability weights were measured at baseline, and included age (< 30, 30–34, 35–39, 40–44, 45–49, 50–54, 55–59 or ≥ 60 years), sex (male or female), study center (Seoul or Suwon), year of health screening exam, eGFR (< 90 or ≥ 90 mL/min/1.73m²), smoking status (never, former, or current), alcohol intake (none, moderate, or high), education (less than college degree, or college degree or higher), exercise (< 3 or ≥ 3 times per week of moderate- or vigorous-intensity exercise), BMI (< 18.5, 18.5–22.9, 23–24.9, or ≥ 25 kg/m²), presence of diabetes, presence of hypertension, and presence of fatty liver disease. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HBsAg, Hepatitis B surface antigen