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

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 [= 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

Cardiovascular and renal outcomes by baseline albuminuria status and renal function — results from the LEADER randomized trial

Aim: To assess cardiorenal outcomes by baseline urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in the contemporary LEADER cohort. Materials and methods: LEADER was a multinational, double-blind trial. Patients with type 2 diabetes and high cardiovascular (CV) risk were randomized 1:1 to the glucagon-like peptide-1 analogue liraglutide (≤1.8 mg daily; n = 4668) or placebo (n = 4672) plus standard care and followed for 3.5 to 5 years. Primary composite outcomes were time to first non-fatal myocardial infarction, non-fatal stroke or CV death. Post hoc Cox regression analyses of outcomes by baseline UACR and eGFR subgroups were conducted with adjustment for baseline variables. Results: In the LEADER population, 1598 (17.5%), 2917 (31.9%), 1200 (13.1%), 1611 (17.6%), 845 (9.2%) and 966 (10.6%) had UACR = 0, >0 to <15, 15 to <30, 30 to <100, 100 to <300 and ≥300 mg/g, respectively. Increasing UACR and decreasing eGFR were linked with higher risks of the primary outcome, heart failure hospitalization, a composite renal outcome and death (P-values for the Cochran-Armitage test for trends were all <.0001). Across UACR and eGFR subgroups, risks of cardiorenal events and death were generally lower or similar with liraglutide versus placebo. Conclusions: In a contemporary type 2 diabetes population, increasing baseline UACR and declining eGFR were linked with higher risks of cardiorenal events and death

Obesity-Related Kidney Disease: Current Understanding and Future Perspectives

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex