Preserving renal function: gliflozins, GLP1 agonists, and antialdosterones

Abstract

For a long time, a prognostic and therapeutic fatalism accompanied even the most motivated clinicians when they had to deal with a progressive decline in renal function; the modest successes were nullified by an increasingly aggressive syndrome whose therapy had remained the same for more than 30 years. In the meantime, the increased understanding of the physiopathological mechanisms connected to it had not been accompanied by an equal development of drugs capable of counteracting it, and this, also due to the progressive aging of the population, had rapidly made 'chronic kidney disease' (CKD) a problem of World Public Health due to its incidence, prevalence, and exponentially increasing costs in every part of the world. The progressive reduction of glomerular filtration rate, as has been known for some time, is accompanied by an increase in cardiovascular risk, understood as fatal and non-fatal heart attack, stroke, heart failure, and mortality. Therefore, every effort must be aimed at preventing or slowing the decline of renal function to reduce not only critical renal events (the need for dialysis or transplant among the most feared) but also the incidence of cardiovascular events. Since the disease is asymptomatic for a long time (it is often detected occasionally and with culpable delay), it is essential to make a correct and early assessment of renal function with appropriate methods. Once CKD was identified, clinicians, to slow its progression, could rely for a long time only on strict control of those risk factors most responsible for worsening it, such as diabetes and its complications, on the optimization of high blood pressure values and the mandatory use of drugs blocking the renin-angiotensin-aldosterone system, particularly in the presence of albuminuria. This strategy has proven to be only partially effective over time, and most patients still showed a progressive worsening of renal function. Only in the last few years have we had access to two classes of innovative drugs, such as gliflozins and incretins, that have imposed themselves on the therapeutic scene because they have shown that they can slow the progression of CKD, first in patients with Type 2 diabetes and subsequently in patients with CKD regardless of the presence or absence of diabetes. Unexpectedly and convincingly, they have also shown a significant impact on cardiovascular prognosis. Initially antidiabetic drugs, their efficacy has forced the reviewers of both cardiology and nephrology guidelines to indicate them among the drugs to use. Lately, the class of mineralocorticoid receptor antagonist drugs has been enriched by finerenone. This molecule has favourable pharmacokinetic characteristics compared with previous medications of the same class and tested in Phase 3, randomized, placebo-controlled trials (FIDELIO-DKD and FIGARO-DKD) which has been shown to significantly reduce the risk of cardiovascular and renal disease in diabetic patients compared with placebo.

Keywords: Chronic kidney disease; GLP1 agonist; Gliflozin.

Figure 1

Definition and stage classification of chronic kidney disease.

Figure 2

Primary composite outcome. The primary outcome was a composite of sustained decline in the estimated glomerular filtration rate of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.

Figure 3

Primary composite outcome FIDELIO-DKD. The primary outcome was a composite of kidney failure, end-stage kidney disease, and a sustained decrease in estimated glomerular filtration rate to <15 mL/min/1.73 m’. Primary composite outcome FIGARO-DKD. The primary outcome was a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure.