Vancouver IM LMR

Thanks for joining us!

Here are the presentation slides for our review of EMPA-KIDNEY

Credit to NephJC/Freely Filtered Podcast/ACP Journal Club who I borrowed some insights from for this discussion. Thanks to Dr. Claire Harris of Nephrology for her input as well.

Key takeaways:

This study extends evidence for renoprotection with SGLT2i to non-diabetic patients and those with eGFR 20-30. More pronounced benefits in those with higher levels of proteinuria and patients with diabetes.

1. Large sample size (n=6609) across 241 centres in Europe, North America and East Asia capturing CKD patients with high risk of kidney disease progression. Specific focus on inclusion of non-diabetic patients and those with lower levels of albuminuria (limitations of CREDENCE and DAPA-CKD).
2. Composite primary outcome of kidney disease progression or cardiovascular death occurred in 432/3304 (13.1%) patients in the empagliflozin group vs 558/3305 (16.9%) patients in the placebo group (HR = 0.72, 95% CI 0.64-0.82, P<0.001)
   • Effect preserved in non-diabetics, down to eGFRs under 30, but with less convincing effect with lower albuminuria
3. Empagliflozin associated with initial GFR drop (related to release of tubuloglomerular feedback -> afferent arteriolar vasodilation -> reduction in intraglomerular pressure, decreased GFR) with improved GFR decline slope subsequently (less hyperfiltration)
4. CV mortality not an impressive outcome in this study, maybe unsurprising as only ~25% of this sample had CV disease history.
5. Good safety profile – do need to counsel patients around urinary tract infections. Very small rates of ketoacidosis.
6. Low albuminuria group difficult to sort out as the trial was stopped early for efficacy, and these patients have lower baseline rate of renal function decline – it will be more difficult to confidently show improvements in progression of kidney disease without a longer trial.