• 1.

    Bakris GL, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383:22192229. doi: 10.1056/NEJMoa2025845

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  • 2.

    Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med [published online ahead of print August 28, 2021]. doi: 10.1056/NEJMoa2110956; https://www.nejm.org/doi/full/10.1056/NEJMoa2110956

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  • 3.

    Agarwal R, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: The FIDELITY pooled analysis. Eur Heart J [published online November 22, 2021]. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab777/6433104

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  • 4.

    Agarwal R, et al. Effects of canagliflozin versus finerenone on cardiorenal outcomes: Exploratory post-hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrol Dial Transpl [published online November 25, 2021]. https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfab336/6440169

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Diabetic Kidney Disease: The Future Is Now

  • 1 Edgar V. Lerma is Clinical Professor of Medicine at the University of Illinois at Chicago/Advocate Christ Medical Center. Michelle G.A. Lim, MBChB, MRCP, is consultant nephrologist at the James Cook University Hospital, Middlesbrough, UK.
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Diabetic kidney disease (DKD) has been in the forefront of industry publications during these challenging yet exciting times. With the advent of recognition of sodium glucose co-transporter 2 (SGLT2) inhibitors and their particular outcome benefits in patients with type 2 diabetes who are particularly prone to developing complications related to cardiovascular (CV) disease, there has been revitalization of our understanding of the mineralocorticoid receptor and the central role it plays in inflammation and fibrosis involving the kidneys.

A nonsteroidal mineralocorticoid antagonist—finerenone—was highlighted in several major randomized controlled trials (1, 2) that enrolled adult patients with chronic kidney disease (CKD) and type 2 diabetes with moderately to severely increased albuminuria (FIDELIO-DKD (1): urine albumin-creatinine ratio [UACR] 30–300 mg/g with estimated glomerular filtration rate [eGFR] 25–60 mL/min/1.73 m2 and diabetic retinopathy or UACR ≥300 mg/g with eGFR 25–75 mL/min/1.73 m2; FIGARO-DKD (2): UACR 30 to <300 mg/g with eGFR 25–90 mL/min/1.73 m2 or UACR 30–5000 mg/g with eGFR ≥60 mL/min/1.73 m2). During a dose-optimization period of 4–16 weeks, all patients received standard-of-care background therapy, including a maximum-tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

In a prespecified, individual-level pooled analysis of FIDELIO-DKD (Figure 1) (1) and FIGARO-DKD (Figure 2) (2), the FIDELITY analysis (3) was presented during the European Society of Cardiology Congress, which was conducted virtually in August 2021. It included 13,171 patients (with CKD and type 2 diabetes) from 48 countries randomized 1:1 to receive finerenone (10 mg or 20 mg daily) versus placebo and a median duration of 3 years’ follow-up. It was demonstrated that on top of an optimized renin-angiotensin system (RAS) blockade, finerenone significantly reduced the risk of the composite CV outcome (time to CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for heart failure) by 14%, whereas it significantly reduced the risk of the composite kidney outcome (time to kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney death) by 23%. About 40% of the 13,026 patients in FIDELITY had an eGFR of >60 mL/min/1.73 m2 and qualified for treatment because of moderately or severely elevated albuminuria.

Although hyperkalemia-related adverse events occurred more frequently with finerenone (14.0%) versus placebo (6.9%), no hyperkalemia-related adverse events were fatal, with 1.7% (incidence rate 0.66 per 100 patient-years) versus 0.6% (incidence rate 0.22 per 100 patient-years) leading to permanent treatment discontinuation or hospitalization (0.9% vs. 0.2%, respectively).

In another recent publication (4), while taking different trial designs into consideration, an analysis of FIDELIO-DKD and CREDENCE (UACR >300–500 mg/g with eGFR 30 to <90 mL/min/1.73 m2 at screening) showed a cardiorenal composite endpoint of 43.9 per 1000 patient-years with finerenone (vs. 59.5 per 1000 patient-years with placebo), with a 26% relative risk reduction (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63–0.87). In CREDENCE, there was a cardiorenal composite endpoint of 43.2 per 1000 patient-years with canagliflozin (vs. 61.2 per 1000 patient-years with placebo), with a 30% relative risk reduction (HR 0.70; 95% CI 0.59–0.82).

So where does this agent fit in to our current landscape of management of DKD? It has been suggested that a four-pillar approach to DKD management in 2021 (akin to cardiology's goal medical-directed therapy) is needed (Figure 3).

Figure 3.
Figure 3.

Four Pillars of Diabetic Kidney Disease Management in 2021

Citation: Kidney News 14, 1

Where does the current evidence bring us? We are of the opinion that the time is now to acknowledge the published data and use the drug. Should finerenone be used in combination with SGLT2 inhibitors? Should finerenone be used with novel oral potassium binders, etc.? It is prudent to pay close attention to the evidence that we have now as well as forthcoming information. Based on these results, we formulate regimens that serve our patients best.

References

  • 1.

    Bakris GL, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383:22192229. doi: 10.1056/NEJMoa2025845

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med [published online ahead of print August 28, 2021]. doi: 10.1056/NEJMoa2110956; https://www.nejm.org/doi/full/10.1056/NEJMoa2110956

    • Search Google Scholar
    • Export Citation
  • 3.

    Agarwal R, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: The FIDELITY pooled analysis. Eur Heart J [published online November 22, 2021]. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab777/6433104

    • Search Google Scholar
    • Export Citation
  • 4.

    Agarwal R, et al. Effects of canagliflozin versus finerenone on cardiorenal outcomes: Exploratory post-hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrol Dial Transpl [published online November 25, 2021]. https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfab336/6440169

    • Search Google Scholar
    • Export Citation
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