title: Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy.
abstract: 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/1.73m(2) 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/1.73m(2)), 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.
authors.affiliation: Nephrology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. sigrid.lundberg@karolinska.se
authors.forename: Sigrid
authors.initials: S
authors.lastname: Lundberg
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sundelin
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D015415:Biomarkers; D053645:Interleukin-2 Receptor alpha Subunit