BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial.
OBJECTIVE
Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease.


METHODS
BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on-treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured.


RESULTS
The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P<0.001) with the primary end point. After multivariate adjustment, the hazard of developing the primary end point became progressively higher as mean systolic BP rose from <120 to ≥ 150 mmHg (P=0.02), with a significantly higher hazard ratio for 140-149 versus 120-129 mmHg (1.51 [1.06, 2.15]; P=0.02). There was also a significant association of mean diastolic BP with the hazard of developing the primary end point (P<0.01), with a significantly higher hazard ratio when mean diastolic BP was 80-89 versus 70-79 mmHg (1.54 [1.05, 2.25]; P=0.03); there was also a strong trend when mean diastolic BP was <60 mmHg. Associations between BP and both renal end point and rate of eGFR decline were similar to those with the primary end point. No association of BP with mortality was observed, possibly because of the limited number of mortality events.


CONCLUSIONS
In patients with proteinuric diabetic kidney disease, mean systolic BP ≥ 140 mmHg and mean diastolic BP ≥ 80 mmHg were associated with worse renal outcomes.
Department of Medicine, Veterans Affairs Hospital, Hines Illinois; Loyola University Medical Center, Maywood, Illinois; david.leehey@va.gov.
David J
DJ
Leehey
Cooperative Studies Program Coordinating Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut;
Jane H
JH
Zhang
Department of Medicine, Veterans Affairs Hospital, Hines Illinois; Loyola University Medical Center, Maywood, Illinois;
Nicholas V
NV
Emanuele
Department of Medicine, Harry S. Truman Memorial Veterans Affairs Hospital and University of Missouri-Columbia School of Medicine, Columbia, Missouri;
Adam
A
Whaley-Connell
Department of Medicine Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
Paul M
PM
Palevsky
Department of Medicine Veterans Affairs North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, Texas.
Robert F
RF
Reilly
Cooperative Studies Program Coordinating Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut;
Peter
P
Guarino
Department of Medicine Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
Linda F
LF
Fried
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control; D017706:Lisinopril / Q000627:therapeutic use*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014493:United States Department of Veterans Affairs
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D017706:Lisinopril; D019808:Losartan
blood pressure; diabetes mellitus; diabetic nephropathies; end-stage renal disease; follow-up studies; glomerular filtration rate; humans; kidney failure, chronic; progression of chronic kidney disease; proteinuria