title: Serum soluble tumour necrosis factor receptor-2 (sTNFR2) as a biomarker of kidney tissue damage and long-term renal outcome in lupus nephritis.
abstract: OBJECTIVE
  We investigated the performance of soluble tumour necrosis factor receptor-2 (sTNFR2) as a biomarker of renal activity, damage, treatment response, and long-term outcome in lupus nephritis (LN).
  
  
  METHODS
  Serum sTNFR2 levels were assessed in 64 LN patients (52 proliferative, 12 membranous) before and after induction treatment, and in 314 non-lupus controls. In LN patients, renal biopsies were performed at baseline and post-treatment. Patients with ≥ 50% reduced proteinuria, normal or improved estimated glomerular filtration rate (eGFR) by ≥ 25%, and inactive urinary sediment were considered clinical responders (CRs). Patients with ≥ 50% improved renal activity index were considered histopathological responders (HRs). Long-term renal outcome was determined using the chronic kidney disease (CKD) stage after a median follow-up of 11.3 years.
  
  
  RESULTS
  sTNFR2 levels were elevated in LN patients versus controls both at baseline (p < 0.001) and post-treatment (p < 0.001), and decreased following treatment (p < 0.001). Baseline sTNFR2 correlated with Chronicity Index scores in both baseline (r = 0.34, p = 0.006) and post-treatment (r = 0.43, p < 0.001) biopsies. In membranous LN, baseline sTNFR2 levels were higher in CRs (p = 0.048) and HRs (p = 0.03) than in non-responders, and decreased only in CRs (p = 0.03). Both baseline (p = 0.02) and post-treatment (p = 0.03) sTNFR2 levels were associated with decreasing eGFR throughout long-term follow-up, and post-treatment levels were higher in patients with long-term follow-up CKD stage ≥ 3 versus 1-2 (p = 0.008).
  
  
  CONCLUSIONS
  Our data suggest serum sTNFR2 as a marker of kidney tissue damage and a predictor of long-term prognosis in LN, and merit further evaluation of sTNFR2 as a predictor of clinical and histopathological treatment outcomes in membranous LN.
authors.affiliation: a Department of Medicine, Rheumatology Unit, Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: I
authors.identifier: http://orcid.org/0000-0002-4875-5395
authors.initials: I
authors.lastname: Parodis
authors.affiliation: b Department of Biomedical Engineering , University of Houston , Houston , Texas , USA.
authors.forename: H
authors.initials: H
authors.lastname: Ding
authors.affiliation: a Department of Medicine, Rheumatology Unit, Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Zickert
authors.affiliation: a Department of Medicine, Rheumatology Unit, Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: c Department of Medical Sciences/Clinical Chemistry , Uppsala University , Uppsala , Sweden .
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: a Department of Medicine, Rheumatology Unit, Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Svenungsson
authors.affiliation: b Department of Biomedical Engineering , University of Houston , Houston , Texas , USA.
authors.forename: C
authors.initials: C
authors.lastname: Mohan
authors.affiliation: a Department of Medicine, Rheumatology Unit, Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Gunnarsson
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008181:Lupus Nephritis / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000378:metabolism; D000069283:Rituximab / Q000627:therapeutic use; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D007166:Immunosuppressive Agents; D047889:Receptors, Tumor Necrosis Factor, Type II; D000069283:Rituximab; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine