TY - JOUR
T1 - Cause of Death in Patients with Diabetic CKD Enrolled in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT)
AU - Charytan, David M.
AU - Lewis, Eldrin F.
AU - Desai, Akshay S.
AU - Weinrauch, Larry A.
AU - Ivanovich, Peter
AU - Toto, Robert D.
AU - Claggett, Brian
AU - Liu, Jiankang
AU - Hartley, L. Howard
AU - Finn, Peter
AU - Singh, Ajay K.
AU - Levey, Andrew S.
AU - Pfeffer, Marc A.
AU - McMurray, John J V
AU - Solomon, Scott D.
N1 - Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - Index Words Chronic kidney disease (CKD)
KW - Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)
KW - anemia
KW - cardiovascular (CV) disease
KW - diabetic CKD
KW - estimated glomerular filtration rate (eGFR)
KW - infection
KW - mortality
KW - protein-creatinine ratio (PCR)
KW - proteinuria
KW - renal function
KW - sudden death
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U2 - 10.1053/j.ajkd.2015.02.324
DO - 10.1053/j.ajkd.2015.02.324
M3 - Article
C2 - 25935581
AN - SCOPUS:84936857235
SN - 0272-6386
VL - 66
SP - 429
EP - 440
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -