Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy.

Takahiro Imaizumi,Masanori Hara,Shin’Ichi Akiyama,Yoshiaki Hirayama,Hiroyuki Kurosawa,Shoichi Maruyama,Makoto Yamaguchi,Naotake Tsuboi,Masahiro Nakatochi,Takayuki Katsuno,Benedetta Bussolati

doi:10.1371/journal.pone.0163507

Takahiro Imaizumi, Masanori Hara + Show 9 more

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https://doi.org/10.1371/journal.pone.0163507

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Abstract

BackgroundA non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters.MethodsWe performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals. Urinary (u-) PCX was measured by sandwich ELISA. We constructed 3 types of diagnostic models in 105 training samples: u-PCX univariate model, the combined model of clinical parameters other than u-PCX (clinical model), and the combined model of both u-PCX and clinical parameters (combined model). We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples.ResultsThe clinical model consisted of age, glomerular filtration rate, and diabetes mellitus. In the training cohort, the c-statistics were 0.868 [95% CI, 0.799–0.937] in the combined model. In the validation cohort, sensitivity was 80.5% and specificity was 73.5% on the cut-off value. The net benefit of the combined model was better between threshold probabilities of 40–80% in DCA.ConclusionsIn this study, we demonstrated the utility of u-PCX as a diagnostic marker for MN and the clinical usefulness of the diagnostic models, through the combination of u-PCX and clinical parameters including age, glomerular filtration rate, and diabetes mellitus.

Highlights

Membranous nephropathy (MN) is one of the major subtypes of nephrotic syndrome (NS), where the clinical course is often chronic and requires long term immunosuppressive therapy [1]
We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples
The clinical model consisted of age, glomerular filtration rate, and diabetes mellitus

Summary

Introduction

Membranous nephropathy (MN) is one of the major subtypes of nephrotic syndrome (NS), where the clinical course is often chronic and requires long term immunosuppressive therapy [1]. But it is sometimes difficult to perform kidney biopsy because of comorbidities and treatments such as anti-thrombotic therapy. A non-invasive diagnostic marker of MN is desirable. The anti-PLA2R antibody is a well-known biomarker used to diagnose idiopathic MN, and is highly specific but not so sensitive[2]. The sensitivity of anti-PLA2R antibody was reported to be 52%–78%[2,3,4,5], but only 53% among the Japanese population[6]. There are no sensitive screening markers or diagnostic models of MN

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