A proteomic marker of diabetic nephropathy is associated with mortality in patients with type 2 diabetes

Abstract

BackgroundThe urinary proteomic classifier CKD273 has been found to predict diabetic nephropathy development in advance of microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown.MethodsWe studied 155 subjects with T2D, albuminuria (geometrical mean [IQR]: 85 [34;194] mg/24 hrs), controlled blood pressure (129 ± 16/ 74 ± 11 mmHg) and preserved renal function (eGFR 88 ± 17ml/min/ 1.73 m2). 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) 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.ResultsCKD273 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.ConclusionsA 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.