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Observational Study
. 2023 Aug 10;24(1):235.
doi: 10.1186/s12882-023-03288-x.

Clinical covariates influencing clinical outcomes in primary membranous nephropathy

Lukas Westermann  1 , Felix A Rottmann  1 , Martin J Hug  2 , Dawid L Staudacher  3   4 , Rika Wobser  1 , Frederic Arnold #  5   6 , Thomas Welte #  7
Affiliations
Observational Study

Clinical covariates influencing clinical outcomes in primary membranous nephropathy

Lukas Westermann et al. BMC Nephrol. .

Erratum in

Abstract

Background: Primary membranous nephropathy (PMN) frequently causes nephrotic syndrome and declining kidney function. Disease progression is likely modulated by patient-specific and therapy-associated factors awaiting characterization. These cofactors may facilitate identification of risk groups and could result in more individualized therapy recommendations.

Methods: In this single-center retrospective observational study, we analyze the effect of patient-specific and therapy-associated covariates on proteinuria, hypoalbuminemia, and estimated glomerular filtration rate (eGFR) in 74 patients diagnosed with antibody positive PMN and nephrotic-range proteinuria (urine-protein-creatinine-ratio [UPCR] ≥ 3.5 g/g), treated at the University of Freiburg Medical Center between January 2000 - November 2022. The primary endpoint was defined as time to proteinuria / serum-albumin response (UPCR ≤ 0.5 g/g or serum-albumin ≥ 3.5 g/dl), the secondary endpoint as time to permanent eGFR decline (≥ 40% relative to baseline).

Results: The primary endpoint was reached after 167 days. The secondary endpoint was reached after 2413 days. Multivariate time-to-event analyses showed significantly faster proteinuria / serum-albumin response for higher serum-albumin levels (HR 2.7 [95% CI: 1.5 - 4.8]) and cyclophosphamide treatment (HR 3.6 [95% CI: 1.3 - 10.3]). eGFR decline was significantly faster in subjects with old age at baseline (HR 1.04 [95% CI: 1 - 1.1]).

Conclusion: High serum-albumin levels, and treatment with cyclophosphamide are associated with faster proteinuria reduction and/or serum-albumin normalization. Old age constitutes a risk factor for eGFR decline in subjects with PMN.

Keywords: Chronic kidney disease; Immunosuppression; Nephrotic syndrome; PLA2-R; Primary membranous nephropathy; Rituximab; THSD7A.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Change of outcome variables over time. Plots indicating median eGFR (A), UPCR (B), serum-albumin (C) levels per year in the study population in the first 6 years of follow-up. Error bars indicate 25% and 75% quartiles. A generalized additive regression model was fitted to the data (red lines). Grey shades indicate 95% confidence intervals of the regressions
Fig. 2
Fig. 2
Univariate time-to-event analysis of primary and secondary outcome. A, B Time-to-event estimates fitted on interval-censored data for the primary endpoint (time to proteinuria/serum-albumin response; (A)) and the secondary endpoint (time to permanent eGFR decline (B)). Shading indicates 95% confidence intervals. Data are shown as global time to respective endpoints
Fig. 3
Fig. 3
Multivariate endpoint analysis. Parametric regression models were fitted to interval-censored data. Endpoints: Primary endpoint (time to proteinuria/serum-albumin response; left panel), secondary endpoint (time to permanent eGFR decline; right panel). Abbreviations: eGFR, estimated glomerular filtration rate; inclusion year, year of inclusion in the study; UPCR, urine protein to creatinine ratio
See this image and copyright information in PMC

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