TO017PROGNOSTIC ROLE OF PROTEINURIA IN DIABETIC VERSUS NON-DIABETIC CKD PATIENTS: A MULTICOHORT PROSPECTIVE STUDY IN ITALIAN RENAL CLINICS

Abstract

Introduction and Aims: Diabetic Chronic kidney disease (DM-CKD) is leading cause of end-stage renal disease (ESRD) worldwide. Proteinuria (Uprot) has a central role in the screening, diagnosis and management of DM-CKD as in non diabetic CKD (nonDM-CKD). However, recent studies have shown normal or minimal Uprot in a significant portion of diabetic patients with progressive disease. To evaluate whether the role of Uprot is similar in the two groups, we compared the excess risk of DM-CKD vs non-DM-CKD patients stratified by same cutoff values of Uprot. Methods: We studied 2619 patients (805 DM-CKD and 1814 non-DM-CKD) derived from three prospective cohorts that in 2000-2010 enrolled CKD patients stage I-V under stable care from ≥6 months in 40 Italian renal clinics. Patients were stratified into four categories of Uprot (g/24h): <0.15 (normal), 0.15-0.49 (mild), 0.5-1 (moderate), >1 (severe). GFR was estimated by CKD-EPI equation. Endpoints were ESRD (chronic dialysis-transplant), fatal and non fatal cardiovascular (CV) events, and all-cause mortality. Multivariable Cox proportional hazards models adjusted for age, gender, BMI, smoking, history of CV disease, LVH, calcium, phosphorus, albumin, total cholesterol, LDL-C, triglycerides, hemoglobin, eGFR, systolic BP and use of RAS inhibitors and stratified by cohort were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Mean age was 67±14 y, males 58%, history of CV disease 35%, BP 138±18/79 ±11 mmHg, BMI 27.8±4.9 kg/m2, cholesterol 194±43 mg/dL Hb 12.6±1.7 g/dL and eGFR 34.2±18.4 mL/min/1.73m2. Median Uprot [IQR] was 0.07 [0-0.10], 0.25 [0.19-0.35], 0.72 [0.58-0.83], 1.91 [1.43-3.46], in the four categories of DM-CKD and 0.05 [0-0.10], 0.26 [0.20-0.38], 0.72 [0.60-0.81], 1.79 [1.29-2.85], in nonDM-CKD. Across proteinuria categories, age, BP, BMI, phosphorus, cholesterol and triglycerides increased while, calcium, albumin, eGFR and hemoglobin levels declined (P<0.05 for all comparisons) in DM-CKD and in nonDM-CKD. As compared with nonDM-CKD, diabetic patients were characterized by older age, higher BMI, higher prevalence of prior CV disease and less pronounced dyslipidemia. In diabetic patients, antihypertensive drugs (2.8±1.3 vs 2.3±1.2, P<0.001), use of RAS (79% vs 74%, P=0.009) and statin (42% vs 31%, P<0.001) were higher. Over a median follow-up of 45.3 months, 582 ESRD, 406 all cause-deaths and 458 CV events occurred in the whole cohort. In particular, in DM-CKD, incidence rate (n/100 pts/year) for ESRD, death and CV events was 5.85, 5.16 and 6.31, respectively. In nonDM-CKD, incidence rate (n/100 pts/year) for ESRD, death and CV events was 5.68, 3.50 and 4.19, respectively. Conclusions: Cardiorenal prognosis worsens with increasing Uprot in DM as nonDM CKD; however, at mild and moderate Uprot, the excess risk for CV events and mortality is higher in diabetics. These data suggest that in renal clinics Uprot has a similar etiologic role on ESRD onset in DM and non DM patients while other factors dictate the poor CV outcome and survival in DM-CKD. (Table Presented).