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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • 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
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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 m(2).

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 m(2), 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 m(2); 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 m(2)), 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.

OriginalsprogEngelsk
TidsskriftKidney International Reports
Vol/bind2
Udgave nummer6
Sider (fra-til)1066-1075
Antal sider10
ISSN2468-0249
DOI
StatusUdgivet - nov. 2017

ID: 52019371