Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy

Taewoo Lee; Yunro Chung; Caroline J. Poulton; Vimal K. Derebail; Susan L. Hogan; Heather N. Reich; Ronald J. Falk; Patrick H. Nachman

doi:10.1016/j.ekir.2020.02.1030

Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy

Taewoo Lee, Yunro Chung, Caroline J. Poulton, Vimal K. Derebail, Susan L. Hogan, Heather N. Reich, Ronald J. Falk, Patrick H. Nachman

Medicine - Renal and Hypertension Division

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	706-717
Number of pages	12
Journal	Kidney International Reports
Volume	5
Issue number	5
DOIs	https://doi.org/10.1016/j.ekir.2020.02.1030
State	Published - May 2020

Bibliographical note

Funding Information:
This work was supported by the University of North Carolina Kidney Center.

Funding Information:
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.

Publisher Copyright:
© 2020 International Society of Nephrology

Keywords

albuminemia
membranous nephropathy
nephrotic syndrome
proteinuria
remission
surrogate endpoint

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10.1016/j.ekir.2020.02.1030

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@article{5b98fa9eaffb4a7183851442d2e9368d,

title = "Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy",

abstract = "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.",

keywords = "albuminemia, membranous nephropathy, nephrotic syndrome, proteinuria, remission, surrogate endpoint",

author = "Taewoo Lee and Yunro Chung and Poulton, {Caroline J.} and Derebail, {Vimal K.} and Hogan, {Susan L.} and Reich, {Heather N.} and Falk, {Ronald J.} and Nachman, {Patrick H.}",

note = "Funding Information: This work was supported by the University of North Carolina Kidney Center. Funding Information: 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. Publisher Copyright: {\textcopyright} 2020 International Society of Nephrology",

year = "2020",

month = may,

doi = "10.1016/j.ekir.2020.02.1030",

language = "English (US)",

volume = "5",

pages = "706--717",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "5",

}

TY - JOUR

T1 - Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy

AU - Lee, Taewoo

AU - Chung, Yunro

AU - Poulton, Caroline J.

AU - Derebail, Vimal K.

AU - Hogan, Susan L.

AU - Reich, Heather N.

AU - Falk, Ronald J.

AU - Nachman, Patrick H.

N1 - Funding Information: This work was supported by the University of North Carolina Kidney Center. Funding Information: 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. Publisher Copyright: © 2020 International Society of Nephrology

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - albuminemia

KW - membranous nephropathy

KW - nephrotic syndrome

KW - proteinuria

KW - remission

KW - surrogate endpoint

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U2 - 10.1016/j.ekir.2020.02.1030

DO - 10.1016/j.ekir.2020.02.1030

M3 - Article

C2 - 32405591

AN - SCOPUS:85083337191

VL - 5

SP - 706

EP - 717

JO - Kidney International Reports

JF - Kidney International Reports

SN - 2468-0249

IS - 5

ER -

Serum Albumin at Partial Remission Predicts Outcomes in Membranous Nephropathy

Abstract

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