Claudio Bazzi1, Tomoko Usui2, Virginia Rizza3, Daniela Casellato4, Maurizio Gallieni4, Masaomi Nangaku2. 1. D'Amico Foundation for Renal Disease Research, San Carlo Borromeo Hospital, Milan, Italy. 2. Division of Nephrology and Endocrinology, the University of Tokyo School of Medicine, Tokyo, Japan. 3. Biochemical Laboratory, San Carlo Borromeo Hospital, Milan, Italy. 4. Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy.
Abstract
AIM: 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. CONCLUSION: Idiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.
AIM: 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. CONCLUSION:Idiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.