Development of a Biomarker Panel to Distinguish Risk of Progressive Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) patients typically progress to kidney failure, but the rate of progression differs per patient or may not occur at all. Current CKD screening methods are sub-optimal at predicting progressive kidney function decline. This investigation develops a model for predicting progressive CKD based on a panel of biomarkers representing the pathophysiological processes of CKD, kidney function, and common CKD comorbidities. Two patient cohorts are utilised: The CKD Queensland Registry (n = 418), termed the Biomarker Discovery cohort; and the CKD Biobank (n = 62), termed the Predictive Model cohort. Progression status is assigned with a composite outcome of a ≥30% decline in eGFR from baseline, initiation of dialysis, or kidney transplantation. Baseline biomarker measurements are compared between progressive and non-progressive patients via logistic regression. In the Biomarker Discovery cohort, 13 biomarkers differed significantly between progressive and non-progressive patients, while 10 differed in the Predictive Model cohort. From this, a predictive model, based on a biomarker panel of serum creatinine, osteopontin, tryptase, urea, and eGFR, was calculated via linear discriminant analysis. This model has an accuracy of 84.3% when predicting future progressive CKD at baseline, greater than eGFR (66.1%), sCr (67.7%), albuminuria (53.2%), or albumin-creatinine ratio (53.2%).

Keywords

• chronic kidney disease
• progression
• biomarkers
• progressive