Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan

Abstract

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (<3.5 g/day), however, has not been well described.

Methods: This multicenter, retrospective cohort study included 171 patients with IMN from 10 nephrology centers in Japan. The relationship between urinary protein over time and a decrease of 30% in estimated glomerular filtration rate (eGFR) was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors.

Results: During the observation period (median, 37 months; interquartile range, 16–71 months), 37 (21.6%) patients developed a 30% decline in eGFR, and 2 (1.2%) progressed to end-stage renal disease. Time-dependent multivariate Cox regression models revealed that lower proteinuria over time were significantly associated with a lower risk for a decrease of 30% in eGFR (primary outcome), adjusted for clinically relevant factors. Complete remission (adjusted hazard ratio [HR], 0.005 [95%CI, 0.0–0.09], p < .001), incomplete remission with <1.0 g/day of urine protein (ICR I) (adjusted HR, 0.01 [95%CI, 0.001–0.20], p = .002), and 1.0 to 3.5 g/day (ICR II) (adjusted HR, 0.12 [95%CI, 0.02–0.64], p = .013) were significantly associated with avoiding a 30% decrease in eGFR, compared to that at no remission.

Conclusions: Attaining lower proteinuria predicts good renal survival in Japanese patients with IMN. This study quantifies the impact of proteinuria reduction in IMN and the clinical relevance of achieving subnephrotic proteinuria in IMN as a valuable prognostic indicator for both the clinician and patient.

Keywords:

• Idiopathic membranous nephropathy
• urinary protein
• renal prognosis
• remission

Acknowledgements

We are grateful for the time and efforts of the nephrologists who supported the present study: Dr Shizunori Ichida, Dr Hideaki Shimizu, Dr Junichiro Yamamoto, Dr Tomohiko Naruse, Dr Hirofumi Tamai, Dr Kei Kurata, Dr Hirotake Kasuga, Dr Arimasa Shirasaki, and Dr Makoto Mizutani.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported in part by a Grant-in-Aid for Progressive Renal Diseases Research, Research on Rare and Intractable Disease, from the Ministry of Health, Labour, and Welfare of Japan [Grant number: H26-Nanchi-Ippan-042].