HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy.
BACKGROUND
Hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) is an important cause of childhood nephrotic syndrome in regions endemic for the virus, but little is understood of the biosocial context in which the disease develops. We evaluated HBV status and proteinuria in family members and household contacts of index children with HBVMN to test the hypothesis that HBV carriage and asymptomatic proteinuria are closely linked and may be causally associated.


METHODS
Thirty-one black children with biopsy-proven HBVMN were the index cases. One hundred and fifty-two family members and 43 black household contacts were the subjects of the study. We assessed HBV carrier status by testing for HBV antigens and antibodies using enzyme-linked immunosorbent assays (ELISA) and for HBV DNA by using slot-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 urinary protein/creatinine ratio.


RESULTS
Seventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a protein/creatinine ratio greater than the physiological limit. The frequency of abnormal proteinuria was not significantly different in those with [22 out of 72 (30.5%)] or without [33 out of 104 (32%)] HBV carriage. This lack of association remained when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/or HBeAg and/or HBV DNA; P = 0.01). Family members were more predisposed to HBV carriage than household contacts, but abnormal proteinuria was present with equal frequency (P = 0.48). Age had a significant impact on proteinuria, with children less than five years being more likely to have abnormal proteinuria (P = 0.008). The prevalence of abnormal proteinuria in family members and household contacts of the index cases was more than that in community-based controls. The 10 index HBVMN cases and the 14 family members and household contacts who were tested all had HBV of genotype A.


CONCLUSIONS
These results suggest that the family members and household contacts of children with HBVMN are at very high risk of HBV carriage; they also have asymptomatic proteinuria at a significantly higher rate than community-based controls. The HBV carrier status was not associated with proteinuria, a finding supported by peak prevalences of proteinuria in those under five years but no corresponding peak for HBV carriage. Proteinuria may indicate glomerular basement membrane dysfunction. Environmental and social factors may underpin development of these two covert disorders, but are insufficient to account for the index cases of HBVMN. The emergence of children with HBVMN from such households additionally depends on unidentified and possibly genetic factors.
Bhimma
R
R
Department of Paediatrics, University of Natal, Durban, South Africa. bhimma@med.und.ac.za
Coovadia
H M
HM
Kramvis
A
A
Adhikari
M
M
Kew
M C
MC
Connolly
C A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002353:Carrier State / Q000821:virology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016358:Contact Tracing; D003404:Creatinine / Q000652:urine; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005190:Family; D005260:Female; D005838:Genotype; D015433:Glomerulonephritis, Membranous / Q000209:etiology* / Q000821:virology; D006509:Hepatitis B / Q000150:complications* / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006511:Hepatitis B Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology* / Q000821:virology; D012307:Risk Factors
D017931:DNA Primers; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D003404:Creatinine