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. 2023 Jan 23;38(1):10-25.
doi: 10.1093/ndt/gfab167.

Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease

Alberto Ortiz  1 , Charles J Ferro  2   3 , Olga Balafa  4 , Michel Burnier  5 , Robert Ekart  6 , Jean-Michel Halimi  7   8 , Reinhold Kreutz  9 , Patrick B Mark  10 , Alexandre Persu  11   12 , Patrick Rossignol  13   14 , Luis M Ruilope  15   16   17 , Roland E Schmieder  18 , Jose M Valdivielso  19 , Lucia Del Vecchio  20 , Carmine Zoccali  21 , Francesca Mallamaci  21 , Pantelis Sarafidis  22 ; European Renal and Cardiovascular Medicine (EURECA-m) Working Group of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney Working Group of the European Society of Hypertension (ESH)
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Free article

Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease

Alberto Ortiz et al. Nephrol Dial Transplant. .
Free article

Abstract

Diabetic kidney disease (DKD) develops in ∼40% of patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Patients with CKD, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular (CV) death. The use of renin-angiotensin system (RAS) blockers to reduce the incidence of kidney failure in patients with DKD dates back to studies that are now ≥20 years old. During the last few years, sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with RAS blockers and SGLT2is, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of CV death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists (MRAs) reduce albuminuria and surrogate markers of CV disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In the FInerenone in reducing kiDnEy faiLure and dIsease prOgression in DKD (FIDELIO-DKD) study comparing the actions of the non-steroidal MRA finerenone with placebo, finerenone reduced the progression of DKD and the incidence of CV events, with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of MRAs, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic CKD.

Keywords: cardiovascular risk; diabetic kidney disease; hyperkalaemia; mineralocorticoid antagonism; nephroprotection.

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