Prognostic Value of Serum Biomarkers of Autoimmunity for Recurrence of IgA Nephropathy after Kidney Transplantation

J Am Soc Nephrol. 2017 Jun;28(6):1943-1950. doi: 10.1681/ASN.2016060670. Epub 2017 Mar 2.

Abstract

A prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor-based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1-specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (n=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1-specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; P=0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; P=0.05). Normalized Gd-IgA1-specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1-specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN.

Keywords: IgA deposition; IgA nephropathy; recurrent disease; renal transplantation; transplant outcomes.

MeSH terms

  • Autoantibodies / blood*
  • Autoimmunity*
  • Biomarkers / blood
  • Female
  • Glomerulonephritis, IGA / blood*
  • Glomerulonephritis, IGA / immunology
  • Glomerulonephritis, IGA / surgery*
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Recurrence

Substances

  • Autoantibodies
  • Biomarkers