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

Claudia Pontillo; Zhen-Yu Zhang; Joost P. Schanstra; Lotte Jacobs; Petra Zuerbig; Lutgarde Thijs; Adela Ramirez-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 Zuerbig, Lutgarde Thijs, Adela Ramirez-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

^*Corresponding author for this work

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Research output: Contribution to journal › Article › Academic › peer-review

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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

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 mu g/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 m(2); P <0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by >= 10 to = 1.23; P = 1.20; P = 20 mu g/min) and CKD273 (>= 0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P

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

Keywords

biomarker
chronic kidney disease
clinical science
glomerular filtration rate
peptidomics
proteomics
GLOMERULAR-FILTRATION-RATE
PROGRESSION
FIBROSIS
TRIAL
RECLASSIFICATION
MICROALBUMINURIA
CANDESARTAN
RETINOPATHY
PREVENTION
FIBRINOGEN

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Pontillo, C., Zhang, Z-Y., Schanstra, J. P., Jacobs, L., Zuerbig, P., Thijs, L., Ramirez-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

@article{253736bdf32f49daa08970e6212604c8,

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) toMethods: 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 mu g/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 m(2); P <0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by >= 10 to = 1.23; P = 1.20; P = 20 mu g/min) and CKD273 (>= 0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (PDiscussion: 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.",

keywords = "biomarker, chronic kidney disease, clinical science, glomerular filtration rate, peptidomics, proteomics, GLOMERULAR-FILTRATION-RATE, PROGRESSION, FIBROSIS, TRIAL, RECLASSIFICATION, MICROALBUMINURIA, CANDESARTAN, RETINOPATHY, PREVENTION, FIBRINOGEN",

author = "Claudia Pontillo and Zhen-Yu Zhang and Schanstra, {Joost P.} and Lotte Jacobs and Petra Zuerbig and Lutgarde Thijs and Adela Ramirez-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 Science",

number = "6",

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Pontillo, C, Zhang, Z-Y, Schanstra, JP, Jacobs, L, Zuerbig, P, Thijs, L, Ramirez-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

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 - Zuerbig, Petra

AU - Thijs, Lutgarde

AU - Ramirez-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) toMethods: 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 mu g/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 m(2); P <0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by >= 10 to = 1.23; P = 1.20; P = 20 mu g/min) and CKD273 (>= 0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (PDiscussion: 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) toMethods: 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 mu g/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 m(2); P <0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by >= 10 to = 1.23; P = 1.20; P = 20 mu g/min) and CKD273 (>= 0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (PDiscussion: 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.

KW - biomarker

KW - chronic kidney disease

KW - clinical science

KW - glomerular filtration rate

KW - peptidomics

KW - proteomics

KW - GLOMERULAR-FILTRATION-RATE

KW - PROGRESSION

KW - FIBROSIS

KW - TRIAL

KW - RECLASSIFICATION

KW - MICROALBUMINURIA

KW - CANDESARTAN

KW - RETINOPATHY

KW - PREVENTION

KW - FIBRINOGEN

U2 - 10.1016/j.ekir.2017.06.004

DO - 10.1016/j.ekir.2017.06.004

M3 - Article

VL - 2

SP - 1066

EP - 1075

JO - Kidney International Reports

JF - Kidney International Reports

SN - 2468-0249

IS - 6

ER -