Renin-angiotensin-aldosterone-system inhibitors increase the serum level of complement component 4 in patients with immunoglobulin A nephropathy

Objective: To investigate the impact of renin-angiotensin-aldosterone-system (RAAS) inhibitors on complement component 4 (C4) serum levels in patients with immunoglobulin A nephropathy (IgAN). Methods: A total of 423 patients diagnosed with IgAN at Shanxi Provincial People's Hospital, China, between 1 January 2017 and 31 December 2021 were divided into two groups, a RAAS inhibitor group and a non-RAAS inhibitor group, for comparative analysis. Results: The RAAS inhibitor group exhibited significantly increased C4 and eGFR levels and had a higher proportion of patients with hypertension compared with the non-RAAS inhibitor group. Serum C4 levels were positively correlated with 24-hour urine protein, serum C3 levels and blood uric acid levels but negatively correlated with eGFR levels. In addition, serum C4 levels were positively correlated with the severity of mesangial hypercellularity and interstitial/tubular injury. Through prognostic analysis, serum C4 was identified as an independent risk factor for the progression of IgAN. Conclusion: Renin-angiotensin-aldosterone-system inhibitors can increase serum C4 levels in patients with IgAN and may represent an independent risk factor for disease progression.