Journal Article

Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy

Sigrid Lundberg, Joachim Lundahl, Iva Gunnarsson, Birgitta Sundelin and Stefan H. Jacobson

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 5, pages 1916-1923
Published in print May 2012 | ISSN: 0931-0509
Published online September 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr554
Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy

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Background.

Both systemic and mucosal IgA production are controlled by T lymphocytes and infiltrating T lymphocytes are involved in the progression of interstitial fibrosis in chronic kidney disease (CKD). Since the concentration of soluble interleukin-2 receptor alfa (sIL-2Ra) reflects the degree of T cell activation over time, we studied the impact of interleukin-2 receptor alfa levels on disease progression in patients with biopsy-proven IgA nephropathy (IgAN), a disease in which 20–30% of the patients progress to end-stage renal failure.

Methods.

sIL-2Ra plasma levels were measured in 194 patients (median age 39 years, 70% men) and 84 matched controls. One hundred and seventy-nine of the patients, with an estimated glomerular filtration rate (GFR) of ≥15 mL/min/1.73m2 at baseline (CKD Stages 1–4), were followed for up to 15 years (median 52 months; range 12–188). sIL-2Ra was evaluated as a risk marker for severe renal progression, here defined by the development of CKD Stage 5 (GFR <15 mL/min/1.73m2), a 50% decline in GFR during the follow-up period or a 30% GFR decline within 5 years of follow-up. In 51 patients, upon whom a renal biopsy had been performed within 2 years of IL2-Ra measurement, the biopsies were scored according to the Oxford classification. The correlations between the histopathological findings and the sIL-2Ra levels were examined.

Results.

sIL2-Ra levels were significantly higher in patients than in controls (P < 0.001). sIL-2Ra levels in the upper third tertile predicted a severe renal outcome, even after adjustment for the main clinical risk factors: time average albuminuria and GFR at baseline (Relative risk 5.35, P < 0.001). sIL-2Ra levels also correlated significantly to the yearly GFR slope (β = −0.24, P = 0.01). According to the Oxford classification, the presence of >25% tubular atrophy/interstitial fibrosis (T1–2) was associated with higher sIL-2Ra levels, after adjustment for serum creatinine levels, if analysed within 4 months [n = 24, odds ratio (OR) 1.0, P = 0.044] or within 2 years from the kidney biopsy (n = 51, OR 1.0, P = 0.017).

Conclusions.

The plasma levels of sIL-2Ra were predictive of long-term renal disease progression in a large cohort of patients with biopsy-proven IgAN. Further studies are warranted to evaluate if sIL-2Ra levels can feasibly contribute in the monitoring of effects of treatment, aimed to prevent the progression of interstitial fibrosis and progressive glomerulosclerosis in IgAN.

Keywords: disease progression; IgA nephropathy; IL-2Ra; risk markers; T-cells

Journal Article.  5100 words.  Illustrated.

Subjects: Nephrology

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