Baseline characteristics in PRIORITY study: Proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in type 2 diabetes

Background and aims The urinary proteomics based classifier CKD273 has been shown to retrospectively identify normoalbuminuric diabetic patients who progress to overt kidney disease. In the PRIORITY (Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria) trial, the aim is to confirm that CKD273 can predict microalbuminuria prospectively, and to test whether mineralocorticoid receptor antagonism (MRA) delays progression to microalbuminuria. Here we report the association between CKD273 and traditional risk factors for diabetic nephropathy at baseline. Materials and methods PRIORITY is an investigator-initiated, prospective, randomized, double blind, placebo-controlled multicentre clinical trial and observational study in normoalbuminuric type 2 diabetic patients. Patients are stratified into high-or low risk groups based on CKD273. Patients in the high risk group are assigned to spironolactone 25 mg once daily or placebo, whereas the low-risk group is followed on standard care. The trial continues until September 2018, following patients for up to 4.5 years. The primary endpoint is development of microalbuminuria. Results In total 2277 type 2 diabetic patients have been screened over a time period of 2.5 years and 1811 are included from 15 sites. Table 1 shows the baseline characteristics. 224 (12.4%) have the high-risk CKD273 pattern. The high- and low-risk populations differ statistically in terms of gender, age, diabetes duration, UACR and eGFR however the differences are numerically small. Univariate regression analyses of CKD273 vs each baseline variable demonstrated weak associations (R2 of 0.03, p <0.0001) for the strongest correlations with UACR and eGFR respectively. In a logistic regression model predicting CKD273 risk strata, including all baseline variables, eGFR and UACR remain statistically significant (p < 0.0003) with an AUC of 0.70 (95 % CI: 0.65, 0.74). Conclusion Classical risk factors for diabetic kidney disease differ only slightly between high and low risk patients based on the urinary proteomics based risk classifier CKD273 in type 2 diabetes, suggesting it provides additional information to the measures already available in the clinic. The potential added value will be tested in this prospective study. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 279277.