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Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial

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posted on 27.01.2021, 16:28 by Frederik Persson, Stephen C Bain, Ofri Mosenzon, Hiddo J.L. Heerspink, Johannes F. E. Mann, Richard Pratley, Itamar Raz, Thomas Idorn, Søren Rasmussen, Bernt Johan von Scholten, Peter Rossing, the LEADER Trial Investigators
OBJECTIVE

A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events.

RESEARCH DESIGN AND METHODS

LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years, in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (N=2,928), 30–0% reduction N=1,218) or any increase in UACR (N=4,124) irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes.

RESULTS

For MACE, hazard ratios (HRs) for those with >30% and 30%–0% UACR reduction were 0.82 (95% CI 0.71–0.94; P=0.006) and 0.99 (0.82–1.19; P=0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs (95% CI) were 0.67 (0.49–0.93; P=0.02) and 0.97 (0.66–1.43; P=0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria.

CONCLUSIONS

A reduction in albuminuria during the first year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.

Funding

This analysis was supported by Novo Nordisk A/S.

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