Fifty children with idiopathic membranoproliferative glomerulonephritis (MPGN), aged 2-14 years at apparent onset, were monitored for the presence of C3 nephritic factor (C3 NeF) and signs of complement activation in serum. In addition, C3 allotyping was performed in 32 patients. Observation time ranged from 2 to 20 (median 11) years. C3 NeF activity was detected at least once in 60% of the patients (in 11 of 26 with type I, in 15 of 17 with type II, and in four of seven with type III). C3 NeF-positive patients had significantly reduced levels of CH50 and C3 and elevated levels of C3dg/C3d. During follow-up, C3 levels were persistently normal in 62% of the patients with MPGN type I and in 43% with type III but in only 18% with type II. C3 allotype frequencies differed from those found in healthy controls with a significant shift to the C3F/C3FS variants in C3 NeF-positive patients. C3b(Bb)P as a marker for alternative pathway activation was not increased in C3 NeF-positive patients. Despite the presence of C3 NeF activity, C3 levels remained normal in six patients throughout the observation period. C3 NeF became undetectable in six patients, whereas seven developed C3 NeF activity during follow-up. There was no significant difference in renal survival probability in patients with or without C3 NeF activity. Neither C3 variants nor continuous low C3 or low CH50 levels had any prognostic value for the clinical outcome. No factor H deficiency was detected.

The aim of this multicentre study was to analyse the long-term outcome of idiopathic membranoproliferative glomerulonephritis (MPGN) according to histological type and to the presence of C3 nephritic factor. Fifty patients aged 2-14 years at the onset of the study were followed over 2-20 years; 26 patients had MPGN type I, 17 had type II and 7 had type III. Treatment was variable. At the last observation, 30 patients had reached terminal and four pre-terminal renal failure. The median survival probability until renal death was 15.3, 8.7 and 15.9 years for disease types I, II and III respectively (difference between MPGN types I + III versus type II: p = 0.013). The presence of an initial nephrotic syndrome was associated with a more rapid progression (p = 0.018). C3 nephritic factor was of no prognostic value. We conclude that the outcome of MPGN mainly depends on the histological type observed.

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