Abstract Body (Do not enter title and authors here): Background: The nsMRA finerenone, has been shown to reduce the risk of kidney disease progression and CV events in patients with T2D and CKD. Diuretics are widely used in the management of patients with CKD, yet there are limited data on the prognostic relevance of diuretic intensification in this population.

Methods: This was a post hoc analysis of FIDELITY, a participant-level pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials, which enrolled patients with T2D and CKD. We evaluated the association between the need for new loop diuretic (LD) initiation and rates of subsequent all-cause mortality. We then assessed the treatment effect of finerenone relative to placebo on new LD initiation among diuretic-naïve individuals overall and according to baseline eGFR and UACR. We finally examined the effects of finerenone on an expanded composite CV endpoint adding new diuretic initiation to the prespecified FIDELITY endpoint of CV death, non-fatal MI, non-fatal stroke, and hospitalization for HF.


Results: Among 12, 990 participants in FIDELITY, 10,194 (78%) were not treated with a LD at baseline and new diuretic initiation occurred in 2,107(22%) in follow up. New LD requirement was more frequent among those with lower eGFR and higher UACR at baseline (Figure 1). Patients requiring new diuretic initiation experienced rates of subsequent mortality that were nearly quadruple (8.8 [7.8-9.9] per 100 patient-years) that of those not requiring diuretic initiation (1.9 [1.7-2.0] per 100 patient-years). Treatment with finerenone reduced new initiations of LDs by 17% (HR 0.83; 95% CI: 0.76-0.91, p<0.001) in FIDELITY (Figure 1A). Relative to placebo, the reduction in the incidence of new LD initiations with finerenone was also consistent across the spectrum of both eGFR (Figure 1B) and UACR (Figure 1C). Adding new LD initiation to the prespecified FIDELITY CV composite endpoint nearly doubled the number of events from 1,764 to 3,286 and underscored the cardiovascular benefits of finerenone (HR 0.85; 95% CI: 0.80-0.91, p<0.001).

Conclusions: In patients with T2D and CKD, new requirement for diuretic initiation occurred in ~1 in 5 patients and was associated with higher rates of subsequent mortality. Treatment with finerenone significantly reduced new LD initiation, an effect that was consistent across the kidney function spectrum. These data highlight the diuretic-sparing potential of finerenone in patients with T2D and CKD.