Is a reduction in albuminuria associated with renal and cardiovascular protection? A post hoc analysis of the ALTITUDE trial.
OBJECTIVE
To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit.


METHODS
In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression.


RESULTS
The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints).


CONCLUSIONS
The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
H J L
HJ
Heerspink
Division of Research Management, Center for Cohort Studies Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
T
T
Ninomiya
Steno Diabetes Centre, Gentofte, Denmark.
F
F
Persson
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
B M
BM
Brenner
Novartis Pharma AB, Global Medical Affairs, Basel, Switzerland.
P
P
Brunel
Institute of Cardiovascular Sciences, University College London, London, UK.
N
N
Chaturvedi
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
A S
AS
Desai
Department of Medicine and Clinical Epidemiology, University of Texas Health Science Center, San Antonio, TX, USA.
S M
SM
Haffner
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
J J V
JJ
Mcmurray
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
S D
SD
Solomon
Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
M A
MA
Pfeffer
Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
H-H
HH
Parving
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
D
D
de Zeeuw
D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D000577:Amides / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D012307:Risk Factors; D000092502:Renin Inhibitors
D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren
albuminuria; cardiovascular disease; chronic kidney disease; direct renin inhibition; surrogate endpoint; type 2 diabetes