title: Urinary N-acetyl-β-glucosaminidase and estimated Glomerular filtration rate may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy.
abstract: OBJECTIVE
  The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). The aim of the study was baseline identification of patients with high risk of progression for which immunosuppressive therapy is mandatory.
  
  
  METHODS
  Eighty-six IMN subjects were followed for a median of 69 months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or estimated glomerular filtration rate (eGFR) reduction ≥50% of baseline.
  
  
  RESULTS
  Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-β-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24 h (0.770 and 0.637 respectively, P = 0.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (<9.4 UI/gC) or highest tertile of eGFR (≥88 mL/min per 1.73m2), the multivariable-adjusted hazard ratio of highest tertile of NAG/C (≥19.2) was 18.97 (95%CI, 1.70-211.86) and lowest tertile of eGFR (<59) was 11.58 (95%CI, 2.02-66.29). Subjects with high NAG/C or low eGFR (high-risk, n = 43) had greater progression rate compared to moderate to low NAG/C and high eGFR (low-risk, n = 43) with or without NS at baseline (Log-rank test P = 0.001 and 0.006, respectively). In NS subjects (n = 65), high-risk group progression rate was significantly higher (91% vs. 29%, P = 0.003) and remission rate significantly lower (0% vs. 42%, p < 0.001) in non-immunosuppressed compared to steroids and cyclophosphamide treated patients; no significant differences were observed in low-risk group.
  
  
  CONCLUSIONS
  Idiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.
authors.affiliation: D'Amico Foundation for Renal Disease Research, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bazzi
authors.affiliation: Division of Nephrology and Endocrinology, the University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Usui
authors.affiliation: Biochemical Laboratory, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Rizza
authors.affiliation: Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Casellato
authors.affiliation: Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy.
authors.forename: Maurizio
authors.identifier: http://orcid.org/0000-0002-2011-2160
authors.initials: M
authors.lastname: Gallieni
authors.affiliation: Division of Nephrology and Endocrinology, the University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D000066491:Clinical Decision-Making; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D000118:Acetylglucosaminidase
keywords: estimated glomerular filtration rate; idiopathic membranous nephropathy; outcome prediction; risk-stratification; urinary N-acetyl-β-glucosaminidase/creatinine