Cause of Death in Patients With Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Background The cause of death in patients with chronic kidney disease (CKD) varies with CKD severity, but variation has not been quantified. Study Design Retrospective analysis of prospective randomized clinical trial. Setting & Participants We analyzed 4,038 individuals with anemia and diabetic CKD from TREAT, a randomized trial comparing darbepoetin alfa and placebo. Predictors Baseline estimated glomerular filtration rate (eGFR) and protein-creatinine ratio (PCR). Outcomes Cause of death as adjudicated by a blinded committee. Results Median eGFR and PCR ranged from 20.6 mL/min/1.73 m2 and 4.1 g/g in quartile 1 (Q1) to 47.0 mL/min/1.73 m2 and 0.1 g/g in Q4 ( P < 0.01). Of 806 deaths, 441, 298, and 67 were due to cardiovascular (CV), non-CV, and unknown causes, respectively. Cumulative CV mortality at 3 years was higher with lower eGFR (Q1, 15.5%; Q2, 11.1%; Q3, 11.2%; Q4, 10.3%; P < 0.001) or higher PCR (Q1, 15.2%; Q2, 12.3%; Q3, 11.7%; Q4, 9.0%; P < 0.001). Similarly, non-CV mortality was higher with lower eGFR (Q1, 12.7%; Q2, 8.4%; Q3, 6.7%; Q4, 6.1%; P < 0.001) or higher PCR (Q1, 10.3%; Q2, 7.9%; Q3, 9.4%; Q4, 6.4%; P = 0.01). Sudden death was 1.7-fold higher with lower eGFR ( P = 0.04) and 2.1-fold higher with higher PCR ( P < 0.001). Infection-related mortality was 3.3-fold higher in the lowest eGFR quartile ( P < 0.001) and 2.8-fold higher in the highest PCR quartile ( P < 0.02). The overall proportion of CV and non-CV deaths was not significantly different across eGFR or PCR quartiles. Limitations Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Measured GFR was not available. Conclusions In diabetic CKD, both lower baseline GFR and higher PCR are associated with higher CV and non-CV mortality rates, particularly from sudden death and infection. Efforts to improve outcomes should focus on CV disease and early diagnosis and treatment of infection.