4.6 Article

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

Journal

HISTOPATHOLOGY
Volume 78, Issue 6, Pages 882-895

Publisher

WILEY
DOI: 10.1111/his.14318

Keywords

complement; glomerulonephritis; IgA nephropathy; lymphocytes; pathology

Funding

  1. National Natural Science Foundation of China for Young Scholars [81600556, 81700653]
  2. Major Research Plan of the National Natural Science Foundation of China [91742204]
  3. international (regional) cooperation and exchange projects (NSFC-DFG) [81761138041]
  4. National Natural Sciences Foundation of China [81470948, 81670633, 81570669, 81570615]
  5. National Key Research and Development Programme [2016YFC0906103]
  6. National Key Technology RD Programme [2013BAI09B06, 2015BAI12B07]
  7. third project for the young and middle-aged excellent medical talents of Wuhan

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High intensity of glomerular C3 deposition is associated with the severity of renal lesions and predicts long-term poor renal survival for IgAN patients.
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 C3(high) group (34 patients) and a glomerular C3(low) 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 C3(high) 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 C3(low) group. Renal biopsies in the C3(high) group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-gamma than those in the C3(low) 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.

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