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

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, LEADER Trial Investigators, 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, LEADER Trial Investigators

Abstract

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 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 1st 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.

Trial registration: ClinicalTrials.gov NCT01179048.

© 2021 by the American Diabetes Association.

Figures

Figure 1
Figure 1
CV (A) and renal (B) events from 1 year and onward by baseline albuminuria and change in albuminuria from baseline to 1 year (adjusted values). CV events were defined as the time from randomization to first occurrence of a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Renal events were defined as a three-component nephropathy composite (doubling of serum creatinine, eGFR <45 mL/min/1.73 m2, renal replacement therapy).

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