Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with immunoglobulin A nephropathy: a retrospective study

Background: An association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy (IgAN) remains controversial. Methods: We conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN. Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from the Second Affiliated Hospital of Wenzhou Medical College, China, and various parameters were documented during follow-up until 2015. The definition of the primary endpoint was a decrease of estimated glomerular filtration rate (eGFR) more than 30% from their baseline levels. Results: A total of 403 patients (55.3% female, average 33.7 months of follow-up) were identified and enrolled, with the primary endpoint occurring in 39 (9.8%) patients. Among the patients selected, 202 (50.1%) received corticosteroid treatment alone or in combination with another immunosuppressant (GS group), while others did not receive immunosuppressive treatment (non-GS group). The incidence of the primary endpoint was slightly lower in the GS group compared to the non-GS group (7.0% versus 12.6%, p = 0.06). Multivariate Cox proportional-hazard regression analyses, adjusting for age, systolic and diastolic blood pressure, 24-h urine protein, and immunosuppressive therapy, showed that serum complement 4 (C4) levels (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.8, p < 0.001) and serum complement 3 (C3) levels (HR 0.6, 95% CI 0.2-0.6, p < 0.001) were significantly associated with a poor prognosis among patients with IgAN. Conclusions: We demonstrated that an increase in serum C4, as well as a decrease in C3, was an important outcome determinant for patients with IgAN. Testing serum C3 and C4 levels might assist in predicting renal outcomes among these patients.