Cardiorenal prognosis by residual proteinuria level in diabetic chronic kidney disease: pooled analysis of four cohort studies

Background. No study has assessed whether the prognosis of coexisting diabetes mellitus and chronic kidney disease (DM-CKD) is dictated byDMper se or by the extent of proteinuria. Methods. In this pooled analysis of four prospective studies in CKD patients treated with drugs inhibiting the reninangiotensin system, we compared the risk of all-cause mortality, fatal and non-fatal cardiovascular (CV) events and end-stage renal disease (ESRD) between patients with (n = 693) and without diabetes (n = 1481) stratified by proteinuria level (<0.15, 0.15-0.49, 0.5-1 and >1g/day). Results. The group with DM-CKD was older (69 +/- 11 versus 65 +/- 15 years), had a higher body mass index (29.6 +/- 5.4 versus 27.5 +/- 4.8 kg/m(2)) and systolic blood pressure (143 +/- 19 versus 136 +/- 18mmHg), prevalent CV disease (48% versus 29%) and lower estimated glomerular filtration rate (34.5 +/- 17.9 versus 36.6 +/- 19.0mL/min/1.73 m(2)). During 4.07 years of follow-up, there were 466 patients with ESRD, 334 deaths and 401 CV events occurred. In the subgroup with urine protein < 0.15 g/day (N = 662), the risks of ESRD, CV events and mortality were similar in diabetic and non-diabetic patients. Conversely, in DM-CKD patients, the mortality risk was higher in proteinuric patients {hazard ratio 1.92 [95% confidence interval (CI) 1.25-2.95); 1.99 (1.26-3.15) and 1.98 (1.28-3.06) for proteinuria 0.15-0.49, 0.5-1 and > 1 g/day, respectively}, whereas in non-diabetics the mortality risk increased only for proteinuria 0.5-1 g/day [HR 1.60 (95% CI 1.07-2.40)] and > 1 g/day [HR 1.69 (95% CI1.20-2.55)]. In both groups, CV risk had a trend similar to that of mortality. ESRD risk increased progressively across strata > 0.5 g/day independent of diabetic status. Conclusions. We provide evidence that patients with non-proteinuric DM-CKD are not exposed to higher cardiorenal risk. In contrast, in the presence ofmoderate proteinuria and diabetes per se is associated with a higher risk ofmortality and CV events, whereas the entity of abnormal proteinuria modulates ESRD risk independent of diabetes.