Activated complement C3: a potentially novel predictor of progressive IgA nephropathy

In the search for a serologic marker of disease activity, we measured concentrations of activated C3 (actC3, that is, neoantigens developing after C3 activation on breakdown products), C4-C3 complexes and soluble C5b-9 (sC5b-9) in one or two plasma samples from adult patients with IgA nephropathy (IgAN, N = 50) or Henoch-Schönlein purpura (HSP, N = 4). As controls, 20 patients with non-immune renal disease, but comparable age, degree of proteinuria, renal dysfunction and prevalence of hypertension were studied. Compared to controls, actC3 levels were elevated in 30% of the patients with IgAN and one of the HSP patients. C4-C3 complexes were elevated in only 8% of the IgAN patients, and sC5b-9 levels were within the control range in all IgAN and HSP patients. In IgAN patients with elevated actC3 levels, proteinuria and hematuria were more pronounced than in those with normal levels. Elevated plasma concentrations of actC3 at the first presentation correlated with subsequent deterioration of renal function both in patients with initially normal and already impaired renal function (r = -0.56, N = 44, P = 0.003). The five IgAN patients with elevated actC3 on both occasions of obtaining plasma showed the most rapid loss of renal function. We conclude that mainly alternative pathway complement activation can be demonstrated in patients with IgAN and HSP. In IgAN patients the presence of complement activation is associated with more severe renal disease. Further studies are warranted to examine the clinical usefulness of actC3 as a predictor of the subsequent course of IgAN.