The temporal relationship between urinary C5b-9 and C3dg and clinical parameters in human membranous nephropathy

We have previously reported that urinary excretion of the complementactivation products C3dg and C5b–9 in human membranousnephropathy (MN) correlated with clinical outcome in a cross-sectionalanalysis. We report here the results of a retrospective longitudinalstudy of the temporal relationship between urinary C3dg andC5b–9 excretion and clinical parameters. A group of 23adult patients with biopsyproven MN were studied over a meantime period per patient of 3.5 years. Freshly voided urine sampleswere collected regularly; C3dg and C5b–9 were measuredby ELISA (mean number of samples per patient=13). During the period of the study, nine patients with decliningrenal function (group A) were treated with a standard steroidregimen. Serum creatinine had improved or stabilized in sevenof these patients at the end of treatment. All nine patientswere excreting C3dg and C5b–9 before treatment. Six otherpatients with declining renal function (group B) were not treatedwith steroids because of clinical contraindications. Serum creatininecontinued to increase during the study in four of these sixpatients. C3dg and C5b–9 were present in the urine samplesof these six patients on the majority of dates tested. Eight patients maintained stable renal function during the study(group C), either normal (6 patients) or impaired (2 patients).Of these patients, six were consistently negative for urinaryC3dg and C5b–9 despite persistent proteinuria, and onepatient who was initially positive became negative within 15months, and remained negative for the rest of the study period.One patient was positive on one of 12 occasions tested. Theseresults suggest that urinary complement activation productsindicate ongoing active glomerular damage and may prove to beimportant determinants for the introduction and monitoring oftherapy.