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Abstract: TH-OR034

Reduction in Albuminuria Is Associated with Cardiorenal Protection Independent of Baseline Albuminuria – A Post-Hoc Analysis of the LEADER Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Persson, Frederik, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Bain, Stephen, Institute of Life Science, Swansea University, Swansea, United Kingdom
  • Mosenzon, Ofri, Hadassah Hebrew University Hospital, Jerusalem, Israel
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Mann, Johannes F., KfH Kidney Center, and Friedrich Alexander University of Erlangen, Munich, Germany
  • Raz, Itamar, Hadassah Hebrew University Hospital, Jerusalem, Israel
  • Idorn, Thomas, Novo Nordisk A/S, Soborg, Denmark
  • Rasmussen, Soren, Novo Nordisk A/S, Soborg, Denmark
  • Von Scholten, Bernt Johan, Novo Nordisk A/S, Soborg, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Group or Team Name

  • The LEADER Publication Committee on behalf of the LEADER Trial Investigators
Background

We investigated association between changes in urinary albumin-to-creatinine ratio (UACR) and subsequent risk of cardiovascular (CV) and renal events in the LEADER trial according to baseline UACR.

Methods

LEADER was a randomized, double-blind, multicenter, placebo-controlled CV outcomes trial of liraglutide up to 1.8 mg/day vs placebo added to standard care for 3.5–5 years in 9340 patients with type 2 diabetes and high risk for CV disease. Using a Cox regression model including subjects with a UACR measurement at baseline and after 1 year (N=8231 [88%]) adjusted for treatment, we analyzed the risk of major adverse CV events (MACE) and adjudicated renal events (doubling of serum creatinine and estimated glomerular filtration rate ≤45 ml/min/1.73 m2; the need for continuous renal-replacement therapy; or death from renal disease) from 1 year to end of trial in subgroups defined by first-year change in UACR: >30% reduction, 30-0% reduction, any increase, and according to absolute level of baseline UACR (normo- [<30 mg/g], micro- [30 to 300 mg/g] or macroalbuminuria [>300 mg/g]).

Results

For first MACE, the hazard ratios (HRs) according to baseline UACR groups were: HR=2.49, 95%CI (2.09;2.97) for macro- vs normoalbuminuria and HR=1.38 (1.18;1.60) for micro- vs normoalbuminuria. Correspondingly for first renal event: HR=39.4 (26.3;58.9) and HR=3.57 (2.20;5.80) (Figure). Within each subgroup the risk for CV and renal events was lower in patients with >30% UACR reduction than in those with any UACR increase. There were no interactions between groups (Figure).

Conclusion

These findings highlight the benefit of UACR reduction, even in patients with normoalbuminuria at baseline.

Funding

  • Commercial Support