Background: In primary membranous nephropathy (MN), partial remission (PR) (≥50% reduction of proteinuria to <3.5 g/d) is associated with a greater risk of relapse and end-stage kidney disease (ESKD) compared with complete remission (CR). We aimed to determine factors associated with relapse or renal failure in patients who attain the standard definition of PR. Methods: We captured PR, CR, relapse, and the composite of doubling of serum creatinine or ESKD in a cohort of 267 patients with MN, nephrotic syndrome, and >12 months of follow-up. Characteristics at the time of PR associated with the composite outcome or relapse were evaluated using a time-to-event analysis. Results: A total of 192 patients attained PR and 86 attained CR. Serum albumin at PR (hazard ratio [HR]: 1.58 per 0.5 g/dl decrease from 4.0 g/dl; 95% confidence interval [CI]: 1.03–2.43) and duration of nephrotic proteinuria (HR: 1.01 per month increase; 95% CI: 1.00–1.03) were independent risk factors for the composite endpoint. Serum albumin at PR was associated with an increased risk of relapse (HR: 1.58 per 0.5 g/dl decrease below 4.0 g/dl; 95% CI: 1.24–2.01). A cutoff for serum albumin ≤3.5 g/dl at PR performed best in predicting relapse and composite outcome. Conclusions: Patients with serum albumin >3.5 g/dl at PR have decreased risk of composite outcome or relapse compared with PR with low albumin. A definition of PR that includes normalization of serum albumin may be a more robust surrogate endpoint in MN than the traditional definition of PR.
Bibliographical noteFunding Information:
This work was supported by the University of North Carolina Kidney Center.
National Institutes of Health (NIH): VKD, SLH, CJP, RJF, and PHN; NIH, NephCure Kidney International, and University of Michigan via the Nephrotic Syndrome Study Network Consortium (NEPTUNE): VKD, PHN, and HNR; Food and Drug Administration: VKD and PHN; Kidney Foundation of Canada and Canadian Institutes of Health Research Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE) Network: HNR; RTI International: VKD; and honoraria from the American Society of Nephrology: PHN and HNR. HNR holds the University of Toronto Gabor Zellerman Chair in Nephrology Research. RJF is the Nan and Hugh Cullman Eminent Professor of Medicine.
© 2020 International Society of Nephrology
- membranous nephropathy
- nephrotic syndrome
- surrogate endpoint