Effect of empagliflozin on albuminuria, eGFR and serum creatinine: updated results from the ABCD nationwide empagliflozin audit

Authors

  • Thomas SJ Crabtree University Hospitals of Derby and Burton NHS Trust; Sandwell and West Birmingham Hospitals NHS Trust; University of Nottingham, UK
  • Alex Bickerton Yeovil District Hospital NHS Trust, Somerset, UK
  • Jackie Elliott Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  • Rajeev Raghavan Wolverhampton Diabetes Centre, New Cross Hospital
  • Dennis Barnes The Tunbridge Wells Hospital, UK
  • Siva Sivappriyan Maidstone Hospital, Kent, UK
  • Suzanne Phillips Cheltenham General Hospital, Cheltenham, UK
  • Alison Evans Cheltenham General Hospital, Cheltenham, UK
  • Devesh Sennik Princess Alexandra Hospital, Harlow, UK
  • Anurita Rohilla Chief Pharmacist, West Essex CCG, UK
  • Ian Gallen Royal Berkshire NHS Foundation Trust, UK
  • Robert EJ Ryder City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, UK
  • ABCD Empagliflozin Audit Contributors - ABCD

DOI:

https://doi.org/10.15277/bjd.2021.288

Keywords:

empagliflozin, real-world, urinary albumin, albuminuria, renal, eGFR

Abstract

Introduction: Evidence from phase III and the EMPA-REG OUTCOME trials have demonstrated improvements in renal endpoints with empagliflozin use. The EMPA-KIDNEY trial is currently underway and is assessing whether there are benefits of empagliflozin in improving renal outcomes in people both with and without diabetes, and the mechanism has been suggested to be similar to that of ACE inhibitors with the haemodynamic effects of sodium-glucose co-transporter-2 inhibition reducing intraglomerular pressure.

Aim: To assess the impacts of empagliflozin use on albuminuria and estimated glomerular filtration rate (eGFR) in a real-world UK-based audit.

Methods: Data were collated via the ABCD nationwide audit programme, with analyses performed using either t-tests/ ANOVA or Wilcoxon signed rank/Kruskal–Wallis tests. Pre-specified stratified subgroup analyses by baseline eGFR and baseline albuminuria levels were also performed.

Results: Our results demonstrated significant reductions in albuminuria across the population as a whole. When stratified by baseline albuminuria levels, those with microalbuminuria (30–300 μg/mg) or macroalbuminuria (>300 μg/mg) had significant improvements in urine albumin levels at 6-month (3–9-month) follow-up, with median changes of −17.7 μg/mg (p<0.0001; 95% CI −17.4 to −23.7) and 379.4 μg/mg (p=0.03; 95% CI −269.9 to −725.4), respectively. Across the population as a whole, eGFR reduced initially (at 6 months, −1.26 mL/min/1.73 m3; p<0.0001; 95% CI −0.87 to −1.64) before recovering to baseline by 24 months. When stratified by baseline eGFR, those with reduced renal function (eGFR <90) recovered quickest, with improvements in eGFR noted from baseline by 24 months.

Conclusion: In this real-world analysis, the results are comparable to those in randomised controlled trials and are likely more generalisable to UK clinical practice. Unfortunately, we do not have clinical endpoints such as end-stage renal failure, renal death or dialysis as part of our dataset. Future audits could consider including these data to establish clinical as well as biochemical outcomes.

References

Cherney D, Lund SS, Perkins BA, et al. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia 2016; 59(9):1860–70. https://doi.org/10.1007/s00125-016-4008-2

Cherney DZI, Zinman B, Inzucchi SE, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017;5(8):610–21. https://doi.org/10.1016/S2213-8587(17)30182-1

Wanner C, Heerspink HJL, Zinman B, et al. Empagliflozin and kidney function decline in patients with type 2 diabetes: a slope analysis from the EMPA-REG OUTCOME trial. J Am Soc Nephrol 2018;29(11):2755–69. https://doi.org/10.1681/ASN.2018010103

Herrington WG, Preiss D, Haynes R, et al. The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study. Clin Kidney J 2018;11(6):749–61. https://doi.org/10.1093/ckj/sfy090

Burns KD, Cherney D. Renal angiotensinogen and sodium-glucose cotransporter-2 inhibition: insights from experimental diabetic kidney disease. Am J Nephrol 2019;49(4):328–30. https://doi.org/10.1159/000499598

Perrone-Filardi P, Avogaro A, Bonora E, et al. Mechanisms linking empagliflozin to cardiovascular and renal protection. Int J Cardiol 2017; 241:450–6. https://doi.org/10.1016/j.ijcard.2017.03.089

Woods TC, Satou R, Miyata K, et al. Canagliflozin prevents intrarenal angiotensinogen augmentation and mitigates kidney injury and hypertension in mouse model of type 2 diabetes mellitus. Am J Nephrol 2019;49(4):331–42. https://doi.org/10.1159/000499597

Heerspink HJL, Brantsma AH, de Zeeuw D, et al. Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality. Am J Epidemiol 2008; 168(8):897–905. https://doi.org/10.1093/aje/kwn209

Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130(6):461–70. https://doi.org/10.7326/0003-4819-130-6-199903160-00002

Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150(9):604–12. https://doi.org/10.7326/0003-4819-150-9-200905050-00006

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Published

2021-05-28

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Original Research

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