A urinary proteome-based classifier for the early detection of decline in glomerular filtration

Claudia Pontillo; Lotte Jacobs; Jan A Staessen; Joost P Schanstra; Peter Rossing; Hiddo J L Heerspink; Justyna Siwy; William Mullen; Antonia Vlahou; Harald Mischak; Ray Vanholder; Petra Zürbig; Joachim Jankowski

doi:10.1093/ndt/gfw239

A urinary proteome-based classifier for the early detection of decline in glomerular filtration

Claudia Pontillo, Lotte Jacobs, Jan A Staessen, Joost P Schanstra, Peter Rossing, Hiddo J L Heerspink, Justyna Siwy, William Mullen, Antonia Vlahou, Harald Mischak, Ray Vanholder, Petra Zürbig, Joachim Jankowski

61 Citations (Scopus)

Abstract

Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m2. Methods. A total of 2672 patients with different CKD stages were included in the study. Of these 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m2/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of 80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m2. In addition, areas under the curve for CKD273 and UAE were calculated. Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.

Original language	English
Article number	gfw239
Journal	Nephrology, Dialysis, Transplantation
Volume	32
Issue number	9
Pages (from-to)	1510-1516
Number of pages	7
ISSN	0931-0509
DOIs	https://doi.org/10.1093/ndt/gfw239
Publication status	Published - 1 Sept 2017

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Pontillo, C., Jacobs, L., Staessen, J. A., Schanstra, J. P., Rossing, P., Heerspink, H. J. L., Siwy, J., Mullen, W., Vlahou, A., Mischak, H., Vanholder, R., Zürbig, P., & Jankowski, J. (2017). A urinary proteome-based classifier for the early detection of decline in glomerular filtration. Nephrology, Dialysis, Transplantation, 32(9), 1510-1516. [gfw239]. https://doi.org/10.1093/ndt/gfw239

Pontillo, C, Jacobs, L, Staessen, JA, Schanstra, JP, Rossing, P, Heerspink, HJL, Siwy, J, Mullen, W, Vlahou, A, Mischak, H, Vanholder, R, Zürbig, P & Jankowski, J 2017, 'A urinary proteome-based classifier for the early detection of decline in glomerular filtration', Nephrology, Dialysis, Transplantation, vol. 32, no. 9, gfw239, pp. 1510-1516. https://doi.org/10.1093/ndt/gfw239

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title = "A urinary proteome-based classifier for the early detection of decline in glomerular filtration",

abstract = "Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m2. Methods. A total of 2672 patients with different CKD stages were included in the study. Of these 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m2/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of 80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m2. In addition, areas under the curve for CKD273 and UAE were calculated. Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.",

author = "Claudia Pontillo and Lotte Jacobs and Staessen, {Jan A} and Schanstra, {Joost P} and Peter Rossing and Heerspink, {Hiddo J L} and Justyna Siwy and William Mullen and Antonia Vlahou and Harald Mischak and Ray Vanholder and Petra Z{\"u}rbig and Joachim Jankowski",

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T1 - A urinary proteome-based classifier for the early detection of decline in glomerular filtration

AU - Pontillo, Claudia

AU - Jacobs, Lotte

AU - Staessen, Jan A

AU - Schanstra, Joost P

AU - Rossing, Peter

AU - Heerspink, Hiddo J L

AU - Siwy, Justyna

AU - Mullen, William

AU - Vlahou, Antonia

AU - Mischak, Harald

AU - Vanholder, Ray

AU - Zürbig, Petra

AU - Jankowski, Joachim

PY - 2017/9/1

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N2 - Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m2. Methods. A total of 2672 patients with different CKD stages were included in the study. Of these 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m2/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of 80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m2. In addition, areas under the curve for CKD273 and UAE were calculated. Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.

AB - Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m2. Methods. A total of 2672 patients with different CKD stages were included in the study. Of these 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m2/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of 80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m2. In addition, areas under the curve for CKD273 and UAE were calculated. Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.

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JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

IS - 9

M1 - gfw239

ER -

A urinary proteome-based classifier for the early detection of decline in glomerular filtration

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