Urinary C4d and progression of kidney disease in IgA vasculitis

Nephrol Dial Transplant. 2024 Sep 27;39(10):1642-1648. doi: 10.1093/ndt/gfae045.

Abstract

Background: Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear.

Methods: This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines.

Results: The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101-2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135-27.035; P = .034) for the higher levels group.

Conclusions: Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN.

Keywords: IgA vasculitis nephritis; kidney disease progression; urinary C4d.

MeSH terms

  • Adult
  • Biomarkers / urine
  • Case-Control Studies
  • Complement C4b* / urine
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate*
  • Glomerulonephritis, IGA* / complications
  • Glomerulonephritis, IGA* / pathology
  • Glomerulonephritis, IGA* / urine
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glomerulosclerosis, Focal Segmental / urine
  • Humans
  • Immunoglobulin A / urine
  • Male
  • Middle Aged
  • Peptide Fragments* / urine
  • Prognosis
  • Vasculitis / etiology
  • Vasculitis / pathology
  • Vasculitis / urine

Substances

  • Complement C4b
  • Peptide Fragments
  • complement C4d
  • Immunoglobulin A
  • Biomarkers