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Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy

View Article: PubMed Central - PubMed

ABSTRACT

Background: A 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.

Methods: We 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.

Results: The 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.

Conclusions: In 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.

No MeSH data available.


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Levels of u-PCX in each kidney disease.MCD: minimal change disease; MN: membranous nephropathy; FSGS: focal segmental glomerulosclerosis; MPGN: membranoproliferative glomerulonephritis; LN: lupus nephritis; DN: diabetic nephropathy; and amyloidosis. LN was classified into two subclass; LN (V) and LN (non-V) according to the 2003 ISN/RPS classification. Class V lesion was defined as global or segmental sub-epithelial immune deposits or their morphologic sequelae, with or without class III/IV lesion. (A) Training cohort. (B) Validation cohort.
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pone.0163507.g001: Levels of u-PCX in each kidney disease.MCD: minimal change disease; MN: membranous nephropathy; FSGS: focal segmental glomerulosclerosis; MPGN: membranoproliferative glomerulonephritis; LN: lupus nephritis; DN: diabetic nephropathy; and amyloidosis. LN was classified into two subclass; LN (V) and LN (non-V) according to the 2003 ISN/RPS classification. Class V lesion was defined as global or segmental sub-epithelial immune deposits or their morphologic sequelae, with or without class III/IV lesion. (A) Training cohort. (B) Validation cohort.

Mentions: The levels of u-PCX in each disease are shown in Fig 1. Levels of u-PCX were higher among cases of DN, LN, and MN in the training cohort. The levels of u-PCX were higher among MN cases with nephrotic range proteinuria than those without. The median value of u-PCX was 399.8μg/gCr [interquartile range (IQR); 208.5–535.3] in MN cases with nephrotic–range proteinuria, whereas the median u-PCX value was 151.1μg/gCr [IQR; 113.2–244.7] in cases without nephrotic–range proteinuria (P = 0.026). The levels of u-PCX were also higher among cases of DN, LN, MPGN, and MN in the validation cohort. The intra- and inter-assay coefficients of variation were 4.53% and 7.12%, respectively.


Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy
Levels of u-PCX in each kidney disease.MCD: minimal change disease; MN: membranous nephropathy; FSGS: focal segmental glomerulosclerosis; MPGN: membranoproliferative glomerulonephritis; LN: lupus nephritis; DN: diabetic nephropathy; and amyloidosis. LN was classified into two subclass; LN (V) and LN (non-V) according to the 2003 ISN/RPS classification. Class V lesion was defined as global or segmental sub-epithelial immune deposits or their morphologic sequelae, with or without class III/IV lesion. (A) Training cohort. (B) Validation cohort.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036798&req=5

pone.0163507.g001: Levels of u-PCX in each kidney disease.MCD: minimal change disease; MN: membranous nephropathy; FSGS: focal segmental glomerulosclerosis; MPGN: membranoproliferative glomerulonephritis; LN: lupus nephritis; DN: diabetic nephropathy; and amyloidosis. LN was classified into two subclass; LN (V) and LN (non-V) according to the 2003 ISN/RPS classification. Class V lesion was defined as global or segmental sub-epithelial immune deposits or their morphologic sequelae, with or without class III/IV lesion. (A) Training cohort. (B) Validation cohort.
Mentions: The levels of u-PCX in each disease are shown in Fig 1. Levels of u-PCX were higher among cases of DN, LN, and MN in the training cohort. The levels of u-PCX were higher among MN cases with nephrotic range proteinuria than those without. The median value of u-PCX was 399.8μg/gCr [interquartile range (IQR); 208.5–535.3] in MN cases with nephrotic–range proteinuria, whereas the median u-PCX value was 151.1μg/gCr [IQR; 113.2–244.7] in cases without nephrotic–range proteinuria (P = 0.026). The levels of u-PCX were also higher among cases of DN, LN, MPGN, and MN in the validation cohort. The intra- and inter-assay coefficients of variation were 4.53% and 7.12%, respectively.

View Article: PubMed Central - PubMed

ABSTRACT

Background: A 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.

Methods: We 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.

Results: The 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.

Conclusions: In 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.

No MeSH data available.


Related in: MedlinePlus