Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes.
The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.
Milner
L S
LS
Department of Pediatrics, University of Nebraska Medical Center, Omaha 68198-2165.
Houser
M T
MT
Kolbeck
P C
PC
Antonson
D L
DL
McDonald
T L
TL
Markin
R S
RS
Shaw
B W
BW
D000936:Antigen-Antibody Complex / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003404:Creatinine / Q000652:urine; D005455:Fluorescent Antibody Technique; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology; D006417:Hematuria / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007223:Infant; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000473:pathology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D008107:Liver Diseases / Q000097:blood / Q000150:complications / Q000473:pathology*; D011507:Proteinuria / Q000473:pathology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003404:Creatinine