HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy

Background. Hepatitis B virus (HBV)-associated membraConclusion. These results suggest that the family members nous nephropathy (HBVMN) is an important cause of childand household contacts of children with HBVMN are at very hood nephrotic syndrome in regions endemic for the virus, but high risk of HBV carriage; they also have asymptomatic prolittle is understood of the biosocial context in which the disease teinuria at a significantly higher rate than community-based develops. We evaluated HBV status and proteinuria in family controls. The HBV carrier status was not associated with promembers and household contacts of index children with teinuria, a finding supported by peak prevalences of proteinuria HBVMN to test the hypothesis that HBV carriage and asympin those under five years but no corresponding peak for HBV tomatic proteinuria are closely linked and may be causally associated. carriage. Proteinuria may indicate glomerular basement memMethods. Thirty-one black children with biopsy-proven brane dysfunction. Environmental and social factors may unHBVMN were the index cases. One hundred and fifty-two derpin development of these two covert disorders, but are family members and 43 black household contacts were the insufficient to account for the index cases of HBVMN. The subjects of the study. We assessed HBV carrier status by testing emergence of children with HBVMN from such households for HBV antigens and antibodies using enzyme-linked immu- additionally depends on unidentified and possibly genetic facnosorbent assays (ELISA) and for HBV DNA by using slot- tors. blot hybridization and the polymerase chain reaction. Sequencing of the precore region of HBV was done in a subset of both index cases and subjects. Proteinuria was assessed by measuring The available information indicates that genetic, sothe urinary protein/creatinine ratio. cial, economic, infectious, nutritional, and climatic facResults. Seventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a tors make differing contributions to pediatric renal disorprotein/creatinine ratio greater than the physiological limit. ders [1]. Genetic causes may predominate in indusThe frequency of abnormal proteinuria was not significantly trialized countries, whereas exposure to pathogens may different in those with [22 out of 72 (30.5%)] or without [33 out be more important in the third world [1, 2]. In order to of 104 (32%)] HBV carriage. This lack of association remained explore this subject further, we chose to study the settings when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/ in which the hepatitis B virus (HBV)-associated memor HBeAg and/or HBV DNA; P 5 0.01). Family members branous nephropathy (HBVMN) emerges. were more predisposed to HBV carriage than household con- Epidemiological, clinical, and immunological evidence tacts, but abnormal proteinuria was present with equal fre- suggests a causal association between HBV carriage and quency (P 5 0.48). Age had a significant impact on proteinuria, the development of HBVMN [2, 3], although some inveswith children less than five years being more likely to have abnormal proteinuria (P 5 0.008). The prevalence of abnormal tigators dispute this interpretation [3]. The pathogenetic proteinuria in family members and household contacts of the mechanisms by which individuals with chronic HBV inindex cases was more than that in community-based controls. fection develop MN remain enigmatic, although a number of immunologic processes related to immune complex deposition have been implicated [4, 5]. Genetic