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

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  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 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.