Plasma C-terminal agrin fragment and rapid kidney function decline in chronic kidney disease patients

C-terminal agrin fragment (tCAF) is a promising biomarker for glomerular filtration. Data regarding biomarkers that have the ability to predict rapid progression of chronic kidney disease (CKD) are sparse but necessary in order to identify patients at high risk for rapid progression. This study addresses the value of tCAF as a predictor of rapid kidney function decline in CKD patients. We measured plasma tCAF in a retrospective observational cohort study of 277 prevalent CKD patients stage I-V. Using multivariable Cox proportional hazards regression analysis, we evaluated the association of tCAF with end-stage-renal-disease (ESRD), ≥30%-decline of estimated glomerular filtration rate (eGFR) and the composite endpoint of both, adjusting for eGFR, age, systolic blood pressure, proteinuria and diabetes. The median age was 58 [interquartile range 47, 71] years, 36% were female. Median tCAF level was 822 [594, 1232] pM, eGFR was 32 [19, 48] ml/min/1.73 m². tCAF was correlated to eGFR and proteinuria (r = -0.76 and r = 0.49, P < .001 resp.). During a follow-up of 57.1 [42.9, 71.9] weeks, 36 (13%) patients developed ESRD and 13 (5%) had an eGFR decline of ≥30% (composite endpoint: 49 (18%)). In multivariable analysis, each 100 pM higher tCAF was independently associated with ESRD (hazard ratio (HR) 1.05 (95%-CI 1.02-1.08)), ≥30% eGFR decline (HR 1.10 (1.03–1.18)) and the composite endpoint (HR 1.07 (1.04–1.1)). Plasma tCAF may identify CKD patients at risk for rapid kidney function decline independent of eGFR and other risk factors for eGFR loss such as proteinuria. Abbreviations: ANOVA = analysis of variance, AUC-ROC = area under the receiver operating characteristic curve, BUN = blood urea nitrogen, CKD = chronic kidney disease, CKD-EPI = Chronic Kidney Disease Epidemiology Initiative, CRP = C-reactive protein, eGFR = estimated glomerular filtration rate, ELISA = enzyme-linked immunosorbent assay, ESRD = end-stage renal disease, HR = hazard ratio, pM = picomolar, SBP = systolic blood pressure, tCAF = total C-terminal agrin fragment, VIF = variance inflation factor.