Prof BOBBY CHACKO1
1John Hunter Hospital, New Lambton Heights, Australia
Biography:
Professor Chacko is Director of Renal Services and Senior Staff Specialist in Nephrology and Transplantation at John Hunter Hospital, and Professor of Medicine at the University of Newcastle, Australia. His expertise is in diabetic kidney disease, IgA nephropathy, hypertension, cardio-renal syndrome, and transplantation. As National Scientific Leader for clinical trials in IgA nephropathy and diabetic kidney disease, he is a prolific researcher and influential voice in nephrology. He chairs the NSW/ACT Renal Advanced Training Recruitment Committee and is a sought-after speaker at national and international forums, recognized for his commitment to excellence in clinical care, education, and research.
Aim:
To investigate effects of empagliflozin on chronic kidney disease progression in a range of at-risk patients.
Background:
Sodium glucose co-transporter-2 (SGLT2) inhibitors reduce risk of kidney outcomes in at-risk populations, but there is uncertainty regarding benefits at different levels of albuminuria and use when there are large initial dips in estimated glomerular filtration rate (eGFR).
Method:
Meta-analysis of EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, and EMPA-KIDNEY trials. Kidney disease progression was defined as sustained ≥40% decrease in eGFR from randomisation, sustained eGFR <10ml/min/1.73m2, kidney replacement therapy, or death from kidney failure. Categorical outcomes and chronic eGFR slope analysis were assessed using Cox and shared parameter models, respectively.
Results:
23,340 participants were included (mean±SD eGFR 59±24ml/min/1.73m2; median [Q1-Q3] urinary albumin-to-creatinine ratio [uACR] 34mg/g [9-236]). Empagliflozin reduced the risk of kidney disease progression by 30% (hazard ratio 0.70, 95% confidence interval
0.63-0.78) versus placebo, with similar effects by diabetes status (phet=0.09), across uACR subgroups (ptrend=0.64), and by predicted acute eGFR dip (ptrend=0.65). Empagliflozin slowed chronic annual rate of eGFR decline by 64% (59-69%) overall; 74% in participants with diabetes and 42% without (phet<0.0001). After stratification by diabetes status, there was evidence for larger effects at low levels of uACR in participants with diabetes (phet<0.0001), but effects in patients without diabetes were similar among those with uACR <200mg/g versus ≥200mg/g (phet=0.31).
Conclusion:
Empagliflozin reduces risk of kidney disease progression in patients with type 2 diabetes, heart failure and/or chronic kidney disease irrespective of size of acute dip in eGFR, primary kidney disease, and markers of these diseases’ severity. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor.