Complement Activation Contributes to the Injury and Outcome of Kidney in Human Anti-glomerular Basement Membrane Disease

Linear or granular deposition of complement 3 (C3) along glomerular basement membrane (GBM) is generally revealed in kidneys of human anti-GBM disease. However, the mechanism of complement activation and its association with clinical features and outcomes are less clear.

We measured the plasma and urinary levels of complement components, C1q, mannose-binding lectin (MBL), factor B (Ba), C3, C3a, C4, C4a, C5, C5a and soluble C5b-9 (SC5b-9), using ELISA in 20 patients with renal biopsy proven anti-GBM disease.

The end product of complement activation, SC5b-9, was elevated both in plasma and urine. The levels of C3 and C4 were normal in plasma, while elevated in urine. The levels of C5a and SC5b-9 were increased in plasma from 15% and 30% patients respectively, while they were raised in urine from almost all patients (100% and 92%). The levels of plasma SC5b-9 and urinary C5a were positively correlated with the serum creatinine at presentation (r = 0.56, P = 0.01; r = 0.68, P = 0.02, respectively) and the percentage of crescents in glomeruli (r = 0.60, P = 0.005; r = 0.75, P = 0.005, respectively). The plasma level of SC5b-9 was further identified as the predictor for renal failure during follow up (HR, 1.46; 95% CI, 1.12-1.90; P = 0.005).

Complement cascade goes to the end in human anti-GBM disease and resides mainly in kidney. It plays pathogenic role in renal injury, by the possible proinflammatory effect of C5a and/or cell lysis effect of C5b-9. C5a and C5b-9 may be useful in clinical monitoring and predicting.