Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy

Histopathology. 2021 May;78(6):882-895. doi: 10.1111/his.14318. Epub 2021 Mar 13.

Abstract

Aims: Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression.

Methods and results: From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3high group (34 patients) and a glomerular C3low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3low group. Renal biopsies in the C3high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-γ than those in the C3low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease.

Conclusions: A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.

Keywords: IgA nephropathy; complement; glomerulonephritis; lymphocytes; pathology.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Complement C3 / metabolism*
  • Disease Progression
  • Female
  • Glomerulonephritis, IGA / metabolism
  • Glomerulonephritis, IGA / mortality
  • Glomerulonephritis, IGA / pathology*
  • Humans
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Complement C3