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Aliskiren affects progression of albuminuria, not renal outcomes in type 2 diabetes
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Patients with type 2 diabetes and chronic kidney disease or cardiovascular disease randomly assigned aliskiren as an add-on therapy to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers saw decreased progression and increased regression across albuminuria classes vs. those assigned placebo, but no effect on renal outcomes were observed, according to a secondary analysis of the ALTITUDE trial appearing in The Lancet Diabetes & Endocrinology.
Hiddo J.L. Heerspink, PhD, of the University of Groningen and University Medical Center Groningen in the Netherlands, and colleagues analyzed data from 8,561 patients with type 2 diabetes and CKD or CVD participating in the ALTITUDE trial. Researchers randomly assigned 300 mg aliskiren daily (n = 4,274) or placebo (n = 4,287) as an adjunct to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, stratified by baseline urinary albumin-to-creatinine ratio and CVD history. The trial was stopped early due to excess hyperkalemia, acute renal impairment and insufficient efficacy (mean follow-up period, 2.6 years).
Researchers analyzed prespecified intermediate renal outcomes of transitions between normoalbuminuria, microalbuminuria and macroalbuminuria, as well as the rate of change in estimated glomerular filtration rate. The primary composite renal outcome of ALTITUDE was defined as a sustained doubling of serum creatinine, end-stage renal disease or renal death.
Aliskiren significantly decreased the progression of transitions in albuminuria classes, with 635 patients in the aliskiren group (15%) reaching the endpoint of one-step progression vs. 736 (17%) in the placebo group (HR = 0.83; 95% CI, 0.75-0.93). Within the aliskiren group, 1,354 patients (32%) experienced regression of transition in albuminuria vs. 1,128 (26%) assigned placebo (HR = 1.29; 95% CI, 1.19-1.39).
Patients assigned aliskiren saw an initial significant change in eGFR during the first 6 months vs. placebo (–2.5 mL/min/1.73 m² vs. –1.4 mL/min/1.73 m²; P < .0001); however, subsequent eGFR change did not differ between groups (–2.8 mL/min/1·73 m² per year vs. –3.1 mL/min/1.73 m² per year; P = .068). Aliskiren did not delay progression to the primary renal outcome in the overall study population or in any of the subgroups examined, according to researchers.
“Aliskiren showed beneficial effects on surrogate outcomes of renal function, but these did not translate into renoprotection in terms of clinical outcomes,” the researchers wrote.
In commentary accompanying the study, Martin Gallagher, MD, MBBS, FRACP, associate professor of medicine at Concord Hospital Clinical School and senior director of the renal and metabolic division at The George Institute for Global Health in Sydney, and colleagues wrote that the results further challenge the value of such a treatment approach.
“Heerspink and colleagues’ results ... raise further questions about the potential role of dual-agent [renin–angiotensin system] blockade, and emphasize the importance of new, safer treatment options that affect other pathways to more effectively reduce albuminuria and potentially the subsequent inexorable decline in renal function,” Gallagher and colleagues wrote. – by Regina Schaffer
Disclosure: Novartis funded the ALTITUDE trial. Heerspink reports consulting for and receiving honoraria from AbbVie, Astellas, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals and ZS Pharma, and receiving research support from AstraZeneca. Gallagher reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.
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