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.

Genetic effect of the NPHS2 gene variants on proteinuria in minimal change disease and immunoglobulin A nephropathy.

BACKGROUND: Proteinuria varies in different glomerular diseases and even the same one. Podocin, encoded by gene NPHS2, is important in maintaining the integrity of slit diaphragm structure and avoiding proteinuria. Presently, case-control association studies were performed to investigate the genetic effect of variants in NPHS2 in a mass proteinuric glomerulopathy, minimal change disease (MCD) at first, followed by further investigation in immunoglobulin A nephropathy (IgAN). METHODS: At first, 214 northern Chinese patients with MCD and 493 geographically-matched healthy controls were enrolled. Variants of the NPHS2 were screened. SNP-2 (rs3829795:C>T, c.-670C>T) and SNP-5 (rs3738423:C>T, c.288C>T) were selected as tagging single nucleotide polymorphisms (SNP) and haplotypes were reconstructed. Association was analyzed in MCD patients. Then, the identified SNP site was analyzed in IgAN patients with mild histological changes (Haas subclass I and II). RESULTS: The C allele and CC genotype frequencies at the SNP-2 site, as well as the frequency of haplotype CC, were significantly lower in MCD patients than in healthy controls. Furthermore, they were also associated with the degree of proteinuria in MCD patients. But in IgAN patients, no such association was identified. CONCLUSION: The study suggested the polymorphism and haplotype of NPHS2 gene were associated with the genetic susceptibility and also the degree of proteinuria to MCD. Proteinuria in MCD and IgAN might occur through different mechanisms.