Activation of the acute phase response and complement C3 in patients with IgA nephropathy

Recently we showed systemic complement activation in patients with immunogl obulin A (IgA) nephropathy (measured by "activated C3" [actC3], in other wo rds, neoantigens developing on breakdown products after C3 activation) and reported that plasma levels of actC3 can indicate disease activity and rena l outcome. In this study we investigated whether plasma C3a and C-reactive protein (CRP), which require tests that are more readily available, have a similar diagnostic and predictive value. CRP was measured using a highly se nsitive enzyme-linked immunosorbent assay and C3a using a specific immunoas say, CRP and C3a levels were significantly higher in 56 patients with IgA n ephropathy as compared with 55 healthy controls. C3a levels in IgA nephropa thy patients were also significantly increased in comparison with 42 patien ts with hypertension or nonimmune renal diseases, Neither C3a nor CRP level s correlated with those of actC3 in IgA nephropathy patients, We also compa red 10 IgA nephropathy patients with stable, normal renal function with eig ht IgA nephropathy patients progressing from normal to impaired renal funct ion during mean follow-ups of 7.1 and 5.1 years, respectively. Mean CRP but not C3a levels during the observation period were significantly higher in IgA nephropathy patients with disease progression than in those with stable renal function. Conclusion: Systemic complement activation can be detected by measurement of plasma C3a in IgA nephropathy, but C3a levels cannot sub stitute for actC3 in predicting renal prognosis. Subclinical induction of t he acute phase response is also present in patients with progressive IgA ne phropathy, but again its prognostic value is limited. Repeated determinatio ns performed over prolonged time courses may possibly improve the prognosti c value of CRP levels. (C) 2000 by the National Kidney Foundation, Inc.