Association between anti-complement factor H antibodies and renal outcome in primary membranous nephropathy.

Yu Kagaya,Hitoshi Yokoyama,Kengo Furuichi,Norifumi Hayashi,Keiji Fujimoto,Hiroki Adachi

doi:10.5414/cn110479

Abstract

The complement factor H (CFH) is a regulator for the alternative complement pathway. The prevalence and roles of anti-CFH antibodies in the clinical outcome of primary membranous nephropathy (MN) patients remain unclear. A total of 106 biopsy-proven kidney disease patients and 18 healthy controls were retrospectively investigated in this study. 36 patients had primary MN and 70 patients were diseased controls (31 minimal change nephrotic syndrome (MCNS), 19 rapidly progressive glomerulonephritis (RPGN), and 20 IgA glomerulonephritis (IgAGN)). Serum anti-CFH antibody titers were measured by enzyme-linked immunosorbent assay. 77.8% of MN patients were positive for anti-CFH antibodies. However, only 27.1% of diseased control patients and 5.6% of healthy controls were positive for anti-CFH antibodies. Moreover, median anti-CFH antibody titers were significantly higher in MN patients (4.69 AU/mL) than in diseased control patients (MCNS patients (0 AU/mL, p<0.01), RPGN patients (0 AU/mL, p<0.05), IgAGN patients (0 AU/mL, p<0.01)), and healthy controls (0 AU/mL, p<0.01). Anti-CFH antibody titer was selected as an independent unfavorable predictor of renal dysfunction by Cox proportional hazards analysis. These data suggest that anti-CFH antibodies may be involved in the deterioration of renal function in primary MN.

Highlights

The complement factor H (CFH) regulates activation of the alternative complement pathway
Anti-CFH antibody titers were significantly higher in membranous nephropathy (MN) patients than in normal controls (4.69 [3.69-6.38] AU/mL vs. 0 [0-0] AU/mL, p
No significant difference was observed in the remission rate of proteinuria and the incidence of 30% reduction of estimated glomerular filtration rate or 50% elevation of serum creatinine (Cr) levels between both groups

Summary

Introduction

The complement factor H (CFH) regulates activation of the alternative complement pathway. Autoantibodies against CFH are involved in progressive renal dysfunction in cases with primary membranous nephropathy (MN). Membranous nephropathy (MN) is one of the major causes of nephrotic syndrome in adults. Reactive changes such as thickening of the glomerular basement membrane, spike formation, and stippling images are observed, and it is characterized by no associated proliferative changes. Approximately 75% of cases are primary, the most common form, and approximately 25% are secondary to various causes such as tumors, infections, autoimmunity, and drugs. The poor prognostic factors were no immunosuppressive therapy including steroid monotherapy, male, age (60 years or older), renal dysfunction at onset (Cr ≥ 1.5 mg/dL), severe proteinuria at onset, focal glomerulosclerotic lesions, and advanced interstitial fibrosis.[3]

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Conclusion