Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease. Issue 8 (26th August 2021)

• Record Type: Journal Article
• Authors: Martin, William P.; Conroy, Chloe; Naicker, Serika D.; Cormican, Sarah; Griffin, Tomás P.; Islam, Md Nahidul; McCole, Eibhlin M.; McConnell, Ivan; Lamont, John; FitzGerald, Peter; Ferguson, John P.; Richardson, Ciarán; Logue, Susan E.; Griffin, Matthew D.
• Is Part Of: Kidney360. Volume 2:Issue 8(2021)
• Page Start: 1225
• Page End: 1239
• Publication Date: 2021-08-26
• Subjects: chronic kidney disease -- biomarkers -- C3a-desArg -- end stage renal disease -- machine learning -- mortality -- multiplex assays -- neutrophil gelatinase-associated lipocalin -- renal function decline -- soluble tumor necrosis factor receptor; 616.61
• DOI: 10.34067/KID.0007552020
• Languages: English
• ISSNs: 2641-7650

Abstract

Visual Abstract: Abstract: Key Points: Incorporation of 11 serum biomarkers alongside clinical variables improved prediction of adverse CKD outcomes over 5-year follow-up. Patients with the triad of high sTNFR1 and NGAL coupled with low C3a-desArg had particularly high adverse event rates during follow-up. Biomarkers were quantified on a single, clinical-grade analyzer, with potential for improved translatability to the CKD outpatient setting. Background: We investigated the predictive value of 11 serum biomarkers for renal and mortality end points in people with CKD. Methods: Adults with CKD ( n =139) were enrolled from outpatient clinics between February 2014 and November 2016. Biomarker quantification was performed using two multiplex arrays on a clinical-grade analyzer. Relationships between biomarkers and renal and mortality end points were investigated by random forests and Cox proportional hazards regression. Results: The cohort was 56% male. The mean age was 63 years and median (IQR) CKD-EPI eGFR was 33 (24–51) ml/min per BSA. A total of 56 (40%) people developed a composite end point defined as ≥40% decline in eGFR, doubling of serum creatinine, RRT, or death over median (IQR) follow-up of 5.4 (4.7–5.7) years. Prediction of the composite end point was better with random forests trained on serum biomarkers compared with clinical variables (area under the curve of 0.81 versus 0.78). The predictive performance of biomarkers was further enhanced when considered alongside clinical variables (area under the curve of 0.83 versus 0.81 for biomarkers alone). Patients ( n =27, 19%) with high soluble TNF receptor-1 (≥3 ng/ml) and neutrophil gelatinase-associated lipocalin (≥156 ng/ml), coupled with low complement 3a des-arginine (<2368 ng/ml), almost universally (96%) developed the composite renal and mortality end point. C-reactive protein (adjusted hazard ratio, 1.4; 95% CI, 1.1 to 1.8), neutrophil gelatinase-associated lipocalin (adjusted hazard ratio, 2.8; 95% CI, 1.3 to 6.1) and complement 3a des-arginine (adjusted hazard ratio, 0.6; 95% CI, 0.4 to 0.96) independently predicted time to the composite end point. Conclusions: Outpatients with the triad of high soluble TNF receptor-1 and neutrophil gelatinase-associated lipocalin coupled with low complement 3a des-arginine had high adverse event rates over 5-year follow-up. Incorporation of serum biomarkers alongside clinical variables improved prediction of CKD progression and mortality. Our findings require confirmation in larger, more diverse patient cohorts.