Is a reduction in albuminuria associated with renal and cardiovascular protection? A post-hoc analysis of the ALTITUDE trial

Heerspink, H.J.L. et al. (2016) Is a reduction in albuminuria associated with renal and cardiovascular protection? A post-hoc analysis of the ALTITUDE trial. Diabetes, Obesity and Metabolism, 18(2), pp. 169-177. (doi:10.1111/dom.12600) (PMID:26511599)

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Abstract

Aims: In the ALTITUDE trial, direct renin inhibition with aliskiren on top of ACEi_or_ARB therapy decreased albuminuria by 14% while this did not lead to cardiorenal protection. Prior studies have demonstrated that the renoprotective effect of single RAAS blockade is associated with approximately 30% albuminuria reduction. . We therefore firstly investigated whether the degree of albuminuria reduction is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria in ALTITUDE 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 month-6 albuminuria changes on renal and cardiovascular outcomes by Cox proportional_hazard_regression. Results: The median change in albuminuria in the first 6 months in the aliskiren group was -12%( 25th to 75th Percentile: -48.7_to_+41.9%) and 0.0[-40.2_to_55%] in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: >30% reduction in albuminuria in the first 6 months was associated with 62% renal and 25% cardiovascular risk reduction compared to an increase in albuminuria. The association between month-6 changes in albuminuria and renal or cardiovascular endpoints was similar in both treatment groups (p for interaction >0.1 for both endpoints). Conclusions: Addition of aliskiren to ACEi/ARB therapy shows albuminuria changes that are associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection since the overall albuminuria reduction in the aliskiren arm was too small and nearly similar to placebo.

Item Type:Articles
Additional Information:Funded by: VIDI and Novartis Pharmaceuticals.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Heerspink, H.J.L., Ninomiya, T., Persson, F., Brenner, B.M., Brunel, P., Chaturvedi, N., Desai, A.S., Haffner, S.M., McMurray, J.J.V., Solomon, S.D., Pfeffer, M.A., Parving, H.-H., and de Zeeuw, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetes, Obesity and Metabolism
Publisher:Wiley
ISSN:1462-8902
ISSN (Online):1463-1326
Published Online:29 October 2015

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