Abstract P142: The CKD273 Urinary Peptidomic Biomarker is Associated with Mortality in People at Early Stages of Diabetic Nephropathy Independent of Traditional Risk Factors

Abstract

Background: Mortality in type 2 diabetes (T2D) is primarily driven by cardiovascular disease. This is amplified in diabetic nephropathy (DN), even in early ‘pre-clinical’ stages. A urinary peptidomic classifier (CKD273) has been found to predict DN development in advance of detectable microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown. Methods: We studied 155 subjects with T2D, albuminuria (geometrical mean [IQR]: 85 [34;194] mg/24hrs), controlled blood pressure (129±16/74±11 mmHg) and preserved renal function (eGFR 88±17 ml/min/1.73m 2 ). Blood and urine samples were collected for measurement of estimated glomerular filtration rate (eGFR), urine albumin excretion (UAE), N-terminal pro-brain natriuretic peptide (NT-proBNP; ELISA) and urinary proteomics (capillary electrophoresis coupled to mass spectrometry). Computed tomography imaging was performed to assess coronary artery calcium (CAC) score. Outcome data were collected through national disease registries over a 6 year follow up period. Results: CKD273 correlated with UAE (r=0.481, p=<0.001), age (r=0.238, p=0.003), CAC score (r=0.236, p=0.003), NT-proBNP (r=0.190, p=0.018) and eGFR (r=0.265, p=0.001). On multiple regression only UAE (β=0.402, p<0.001) and eGFR (β=-0.184, p=0.039) were statistically significant determinants. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p=0.004), and retained significance (p=0.050) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. Neither eGFR nor UAE were determinants of mortality in this cohort. Conclusions: A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the peptidomics-based classifier CKD273 is associated with mortality in albuminuric people with T2D in even when adjusted for other established cardiovascular and renal biomarkers.