Mesangial C4d deposition: a new prognostic factor in IgA nephropathy

• Published in: Nephrology, dialysis, transplantation Vol. 24; no. 3; pp. 886 - 891
• Main Authors: Espinosa, Mario, Ortega, Rosa, Gómez-Carrasco, Jose Manuel, López-Rubio, Fernando, López-Andreu, María, López-Oliva, María Ovidia, Aljama, Pedro
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-03-2009; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; C4d; Cohort Studies; complement; Complement C4b - metabolism; Disease-Free Survival; Emergency and intensive care: renal failure. Dialysis management; Female; Glomerular Filtration Rate; Glomerular Mesangium - metabolism; Glomerular Mesangium - pathology; Glomerulonephritis; Glomerulonephritis, IGA - complications; Glomerulonephritis, IGA - metabolism; Glomerulonephritis, IGA - pathology; Humans; IgA nephropathy; Intensive care medicine; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - pathology; lectin; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Peptide Fragments - metabolism; Retrospective Studies; Risk Factors; Young Adult; C4d; IgA nephropathy; complement; lectin; Kidney disease; Extrarenal dialysis; Lectin; IgA; Urinary system disease; Nephropathy; Prognosis; Hemodialysis; Renal failure; Complement
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfn563

Background. It has been shown that patients with IgA nephropathy can be divided into two groups on the basis of the pattern of complement activation. Activation of the lectin pathway of complement is associated with more severe renal disease. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. The aim of our study was to determine whether C4d staining at the time of the renal biopsy could identify patients with a different long-term prognosis in IgA nephropathy. Methods. This retrospective cohort study included all patients with IgA nephropathy who underwent renal biopsy at our centre from January 1992 to December 2006. We evaluated baseline age, sex, presence of macroscopic haematuria, hypertension, serum creatinine and glomerular filtration rate (GFR), urine protein, mesangial C4d staining, glomerulosclerosis, interstitial fibrosis and extracapillary proliferation. Kaplan–Meier survival and Cox proportional hazards analyses were performed, with end-stage renal disease (ESRD) being defined as onset of dialysis or transplantation. Results. Nineteen patients (32.2%) were C4d positive and 40 patients (67.8%) C4d negative. Age, hypertension, absence of macroscopic haematuria, serum creatinine levels, GFR, glomerular sclerosis, interstitial fibrosis and C4d-positive staining were all univariately associated with evolution to ESRD. Renal survival at 10 years was 43.9% in C4d-positive patients versus 90.9% in C4d-negative patients (log-rank, P = 0.0005). Conclusion. Negative mesangial C4d staining in glomeruli in patients with IgA nephropathy helps to identify patients with a good long-term prognostic for whom aggressive treatments are not justified.