Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

Claudia Pontillo; Zhen-Yu Zhang; Joost P Schanstra; Lotte Jacobs; Petra Zürbig; Lutgarde Thijs; Adela Ramírez-Torres; Hiddo J L Heerspink; Morten Lindhardt; Ronald Klein; Trevor Orchard; Massimo Porta; Rudolf W Bilous; Nishi Charturvedi; Peter Rossing; Antonia Vlahou; Eva Schepers; Griet Glorieux; William Mullen; Christian Delles; Peter Verhamme; Raymond Vanholder; Jan A Staessen; Harald Mischak; Joachim Jankowski

doi:10.1016/j.ekir.2017.06.004

Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

Claudia Pontillo, Zhen-Yu Zhang, Joost P Schanstra, Lotte Jacobs, Petra Zürbig, Lutgarde Thijs, Adela Ramírez-Torres, Hiddo J L Heerspink, Morten Lindhardt, Ronald Klein, Trevor Orchard, Massimo Porta, Rudolf W Bilous, Nishi Charturvedi, Peter Rossing, Antonia Vlahou, Eva Schepers, Griet Glorieux, William Mullen, Christian DellesPeter Verhamme, Raymond Vanholder, Jan A Staessen, Harald Mischak, Joachim Jankowski

Department of Clinical Medicine

38 Citations (Scopus)

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Abstract

Introduction CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m². Methods In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m², 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers. Results Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m²; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m²), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086). Discussion In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.

Original language	English
Journal	Kidney International Reports
Volume	2
Issue number	6
Pages (from-to)	1066-1075
Number of pages	10
ISSN	2468-0249
DOIs	https://doi.org/10.1016/j.ekir.2017.06.004
Publication status	Published - Nov 2017

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Prediction of Chronic Kidney DiseaseStage 3 by CKD273, a UrinaryProteomic BiomarkerFinal published version, 664 KBLicence: CC BY-NC-ND

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Pontillo, C., Zhang, Z-Y., Schanstra, J. P., Jacobs, L., Zürbig, P., Thijs, L., Ramírez-Torres, A., Heerspink, H. J. L., Lindhardt, M., Klein, R., Orchard, T., Porta, M., Bilous, R. W., Charturvedi, N., Rossing, P., Vlahou, A., Schepers, E., Glorieux, G., Mullen, W., ... Jankowski, J. (2017). Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker. Kidney International Reports, 2(6), 1066-1075. https://doi.org/10.1016/j.ekir.2017.06.004

Pontillo, C, Zhang, Z-Y, Schanstra, JP, Jacobs, L, Zürbig, P, Thijs, L, Ramírez-Torres, A, Heerspink, HJL, Lindhardt, M, Klein, R, Orchard, T, Porta, M, Bilous, RW, Charturvedi, N, Rossing, P, Vlahou, A, Schepers, E, Glorieux, G, Mullen, W, Delles, C, Verhamme, P, Vanholder, R, Staessen, JA, Mischak, H & Jankowski, J 2017, 'Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker', Kidney International Reports, vol. 2, no. 6, pp. 1066-1075. https://doi.org/10.1016/j.ekir.2017.06.004

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title = "Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker",

abstract = "Introduction CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m2. Methods In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m2, 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers. Results Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m2; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m2), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086). Discussion In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.",

author = "Claudia Pontillo and Zhen-Yu Zhang and Schanstra, {Joost P} and Lotte Jacobs and Petra Z{\"u}rbig and Lutgarde Thijs and Adela Ram{\'i}rez-Torres and Heerspink, {Hiddo J L} and Morten Lindhardt and Ronald Klein and Trevor Orchard and Massimo Porta and Bilous, {Rudolf W} and Nishi Charturvedi and Peter Rossing and Antonia Vlahou and Eva Schepers and Griet Glorieux and William Mullen and Christian Delles and Peter Verhamme and Raymond Vanholder and Staessen, {Jan A} and Harald Mischak and Joachim Jankowski",

year = "2017",

month = nov,

doi = "10.1016/j.ekir.2017.06.004",

language = "English",

volume = "2",

pages = "1066--1075",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier",

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TY - JOUR

T1 - Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

AU - Pontillo, Claudia

AU - Zhang, Zhen-Yu

AU - Schanstra, Joost P

AU - Jacobs, Lotte

AU - Zürbig, Petra

AU - Thijs, Lutgarde

AU - Ramírez-Torres, Adela

AU - Heerspink, Hiddo J L

AU - Lindhardt, Morten

AU - Klein, Ronald

AU - Orchard, Trevor

AU - Porta, Massimo

AU - Bilous, Rudolf W

AU - Charturvedi, Nishi

AU - Rossing, Peter

AU - Vlahou, Antonia

AU - Schepers, Eva

AU - Glorieux, Griet

AU - Mullen, William

AU - Delles, Christian

AU - Verhamme, Peter

AU - Vanholder, Raymond

AU - Staessen, Jan A

AU - Mischak, Harald

AU - Jankowski, Joachim

PY - 2017/11

Y1 - 2017/11

N2 - Introduction CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m2. Methods In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m2, 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers. Results Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m2; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m2), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086). Discussion In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.

AB - Introduction CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m2. Methods In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m2, 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers. Results Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m2; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m2), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086). Discussion In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.

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DO - 10.1016/j.ekir.2017.06.004

M3 - Journal article

C2 - 29130072

SN - 2468-0249

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SP - 1066

EP - 1075

JO - Kidney International Reports

JF - Kidney International Reports

IS - 6

ER -

Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

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