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 <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 mg/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 mg/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 ¼ 0.039), but not UAE (P ¼ 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 ¼ 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.