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.


METHODS
Retrospective analysis of prospective randomized clinical trial.


METHODS
We analyzed 4,038 individuals with anemia and diabetic CKD from TREAT, a randomized trial comparing darbepoetin alfa and placebo.


METHODS
Baseline estimated glomerular filtration rate (eGFR) and protein-creatinine ratio (PCR).


RESULTS
Cause of death as adjudicated by a blinded committee.


RESULTS
Median eGFR and PCR ranged from 20.6 mL/min/1.73 m(2) and 4.1 g/g in quartile 1 (Q1) to 47.0 mL/min/1.73 m(2) 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.


CONCLUSIONS
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.
Renal Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
David M
DM
Charytan
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Eldrin F
EF
Lewis
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Akshay S
AS
Desai
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Larry A
LA
Weinrauch
Renal Division, Northwestern University, Chicago, IL.
Peter
P
Ivanovich
Renal Division, University of Texas Southwestern, Dallas, TX.
Robert D
RD
Toto
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Brian
B
Claggett
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Jiankang
J
Liu
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
L Howard
LH
Hartley
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Peter
P
Finn
Renal Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Ajay K
AK
Singh
Nephrology Division, Tufts University School of Medicine, Boston, MA.
Andrew S
AS
Levey
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA.
Marc A
MA
Pfeffer
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
John J V
JJ
McMurray
Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA. Electronic address: ssolomon@rics.bwh.harvard.edu.
Scott D
SD
Solomon
D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D002423:Cause of Death; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000068256:Darbepoetin alfa; D003925:Diabetic Angiopathies / Q000150:complications / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000150:complications / Q000401:mortality* / Q000503:physiopathology; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000401:mortality* / Q000503:physiopathology; D012189:Retrospective Studies; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006397:Hematinics; D014280:Triglycerides; D004921:Erythropoietin; D000068256:Darbepoetin alfa
Chronic kidney disease (CKD); Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT); anemia; cardiovascular (CV) disease; diabetic CKD; estimated glomerular filtration rate (eGFR); infection; mortality; protein-creatinine ratio (PCR); proteinuria; renal function; sudden death