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Cited by 2,935Chronic Kidney Disease and DiabetesHormonal Regulation and HypertensionAcute Kidney Injury Research

Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes

Open access
Bakris, George L., Agarwal, Rajiv, Anker, Stefan D., Pitt, Bertram, Ruilope, Luis M., Rossing, Peter, Kolkhof, Peter, Nowack, Christina +3 more·2020·New England Journal of Medicine
DOI 10.1056/nejmoa2025845
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Abstract

BACKGROUND: Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown. METHODS: . All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. RESULTS: During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively). CONCLUSIONS: In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.).

Integrity signals

Registry

Crossref · 10.1056/nejmoa2025845

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 18 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Premisereasoning

    The patient populations in this trial and the CREDENCE trial differed.

    “First, the patient populations differed in the two trials”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] 4. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source

      The introduction (page not supplied) describes CREDENCE patients as having type 2 diabetes and albuminuric chronic kidney disease, and contrasts them with patients in earlier trials who were at low risk for kidney failure. The Patients section gives CREDENCE baseline characteristics. But the cited paper does not identify or describe the citing document’s “this trial,” so it cannot establish that those two specific patient populations differed. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The magnitude of the between-group difference in the risk of a primary outcome event in this trial was smaller than that shown for canagliflozin in the CREDENCE trial.

    “The magnitude of the between-group difference in the risk of a primary outcome event was smaller than that shown for the SGLT2 inhibitor canagliflozin in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial.4”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] 4. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
  • Findingcitation

    Discontinuation of the trial regimen due to hyperkalemia in this trial was markedly lower than in trials of dual RAS blockade (4.8% with combination therapy with a direct renin inhibitor and an ACE inhibitor or ARB and 9.2% with dual ACE inhibitor and ARB therapy).

    “markedly lower than in trials of dual RAS blockade (4.8% with combination therapy with a direct renin inhibitor and an ACE inhibitor or ARB 20 and 9.2% with dual ACE inhibitor and ARB therapy 22 )”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [20] 20. Parving H-H, Brenner BM, McMurray JJV, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367: 2204-13. source
    • cites [22] 22. Imai E, Chan JCN, Ito S, et al. Effects of olmesartan on renal and cardiovascu- lar outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 2011; 54: 2978-86. source

      The Discussion section, “Safety of olmesartan in patients treated with ACEI” (page unavailable), reports hyperkalaemia in 9.2% of the olmesartan group versus 5.3% of the placebo group. It separately says approximately 20% discontinued because of adverse events. It does not identify 9.2% as the rate of discontinuation due to hyperkalaemia or as a rate specifically among patients receiving both an ACE inhibitor and an ARB. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    The CREDENCE trial excluded patients treated with mineralocorticoid receptor antagonists.

    “the CREDENCE trial excluded patients treated with mineralocorticoid receptor antagonists”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] 4. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
  • Premisecitation

    Preclinical data showed that the kidney and cardiovascular benefits of finerenone were associated with potent antiinflammatory and antifibrotic effects through inhibition of overactivation of the mineralocorticoid receptor.

    “Preclinical data showed that the kidney and cardiovascular benefits of finerenone were associated with potent antiinflammatory and antifibrotic effects through inhibition of overactivation of the mineralocorticoid receptor.6,[10][11][12][13]23”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [6] 6. Barrera-Chimal J, Estrela GR, Lechner SM, et al. The myeloid mineralocorticoid receptor controls inf lammatory and fi- brotic responses after renal injury via mac- rophage interleukin-4 receptor signaling. Kidney Int 2018; 93: 1344-55. source
    • cites [10] 10. Grune J, Beyhoff N, Smeir E, et al. Se- lective mineralocorticoid receptor cofactor modulation as molecular basis for finere- none's antifibrotic activity. Hypertension 2018; 71: 599-608. source

      The Abstract reports that finerenone blocked cardiac fibrosis and macrophage invasion in mice, and the Discussion describes its cardiac antifibrotic and anti-inflammatory effects. The paper links these findings to mineralocorticoid receptor modulation, but treats a corresponding mechanism for renal benefit as a possibility rather than demonstrating that kidney benefits arise through those same effects. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [11] 11. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonste- roidal mineralocorticoid receptor antago- nist protects from rat cardiorenal injury. J Cardiovasc Pharmacol 2014; 64: 69-78. source
  • Classified as probably not a substantial claim. 20
  • May combine two claims. 20
  • The quote only partly states this claim. 1

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    To account for multiple testing, the weighted Bonferroni-Holm procedure was used for the primary outcome and the key secondary outcome, followed by a hierarchical testing procedure of additional secondary outcomes.

    “To account for multiple testing, the weighted Bonferroni-Holm procedure was used for the primary outcome and the key secondary outcome, followed by a hierarchical testing procedure of additional secondary outcomes, as described previously.16”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] 16. Bakris GL, Agarwal R, Anker SD, et al. Design and baseline characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kid- ney Disease trial. Am J Nephrol 2019; 50: 333-44. source

      The Statistical Considerations—Statistical Analyses section specifies the weighted Bonferroni-Holm procedure for the primary renal and key secondary cardiovascular endpoints, followed by hierarchical testing of further secondary endpoints. As a design paper, however, it says these procedures “will be used”; it does not establish that they were actually used. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Hemodynamic effects were also seen in trials of dual RAS blockade that did not show efficacy, which implicates other mechanisms.

    “hemodynamic effects were also seen in trials of dual RAS blockade that did not show efficacy, [20][21][22] which implicates other mechanisms.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [20] 20. Parving H-H, Brenner BM, McMurray JJV, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367: 2204-13. source
    • cites [21] 21. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013; 369: 1892-903. source
    • cites [22] 22. Imai E, Chan JCN, Ito S, et al. Effects of olmesartan on renal and cardiovascu- lar outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 2011; 54: 2978-86. source

  • May combine two claims.

    Premisecitation

    Previous kidney-outcome trials involving patients with CKD and type 2 diabetes targeting dual RAS blockade have shown a lack of efficacy and increased risk, including increased incidences of acute kidney injury, hypotension, and hyperkalemia.

    “Previous kidney-outcome trials that involved patients with CKD and type 2 diabetes targeting dual RAS blockade have shown a lack of efficacy and increased risk (including increased incidences of acute kidney injury, hypotension, and hyperkalemia) [20][21][22]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [20] 20. Parving H-H, Brenner BM, McMurray JJV, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367: 2204-13. source
    • cites [21] 21. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013; 369: 1892-903. source
    • cites [22] 22. Imai E, Chan JCN, Ito S, et al. Effects of olmesartan on renal and cardiovascu- lar outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 2011; 54: 2978-86. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The incidences of serum potassium levels >5.5 mmol/L and >6.0 mmol/L were 21.7% and 4.5% in the finerenone group and 9.8% and 1.4% in the placebo group.

    “The incidences of serum potassium levels of more than 5.5 mmol per liter and more than 6.0 mmol per liter were 21.7% and 4.5%, respectively, in the finerenone group and 9.8% and 1.4%, respectively, in the placebo group.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    A lower mean urinary albumin-to-creatinine ratio with finerenone than with placebo was maintained after month 4.

    “and a lower mean urinary albumin-to-creatinine ratio with finerenone than with placebo was maintained thereafter (Fig. 3A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Acute kidney injury-related adverse events and serious adverse events were balanced between the two groups.

    “Acute kidney injury-related adverse events and serious adverse events were balanced between the two groups (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In prespecified on-treatment sensitivity analyses, the risk of a primary outcome event and the risk of a key secondary outcome event were both lower by 22% with finerenone than with placebo.

    “In prespecified “on-treatment” sensitivity analyses that included all events from randomization to 30 days after the last dose of finerenone or placebo, the risk of a primary outcome event and the risk of a key secondary outcome event were both lower by 22% with finerenone than with placebo (Table S4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The incidences of the key secondary outcome components were lower with finerenone than with placebo except for nonfatal stroke, which had a similar incidence in the two groups.

    “The incidences of the components were lower with finerenone than with placebo except for nonfatal stroke, which had a similar incidence in the two groups (Fig. 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Glycated hemoglobin levels and body weight were similar in the two groups.

    “Glycated hemoglobin levels (Fig. S8) and body weight (Fig. S9) were similar in the two groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Patients who received finerenone had a higher mean serum potassium level than those who received placebo; a maximal difference of 0.23 mmol/L was observed at month 4, and the difference remained largely stable thereafter.

    “Patients who received finerenone had a higher mean serum potassium level than those who received placebo; a maximal difference of 0.23 mmol per liter was observed at month 4, and the difference remained largely stable thereafter (Fig. 3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In a patient population with multiple coexisting conditions and advanced CKD (almost 55% had baseline eGFR <45 ml/min/1.73 m2) who were at high risk for kidney and cardiovascular events, the benefits of finerenone were observed after 12 months for the kidney outcome and as early as 1 month for the cardiovascular outcome, and these benefits persisted throughout the trial.

    “In a patient population with multiple coexisting conditions and advanced CKD (almost 55% of the patients had a baseline eGFR of <45 ml per minute per 1.73 m 2 ) who were at high risk for kidney and cardiovascular events, the benefits of finerenone were observed after 12 months for the kidney outcome and as early as 1 month for the cardiovascular outcome, and these benefits persisted throughout the”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Patients with CKD and type 2 diabetes and advanced CKD are at high risk for kidney and cardiovascular events.

  • May combine two claims.

    Findingown data

    In this trial involving patients with type 2 diabetes and advanced CKD, finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo.

    “In our trial involving patients with type 2 diabetes and advanced CKD, finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this trial, there was modest blood-pressure reduction in the absence of effects on glycated hemoglobin levels and body weight.

    “modest blood-pressure reduction (in the absence of effects on glycated hemoglobin levels and body weight)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The trial was designed to have 90% power to detect a 20% lower risk of a primary outcome event with finerenone than with placebo, on the basis of 1068 patients with a primary outcome event.

    “This event-driven trial was designed to have 90% power to detect a 20% lower risk of a primary outcome event with finerenone than with placebo, on the basis of 1068 patients with a primary outcome event.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Safety analyses were performed in the safety analysis set (all randomly assigned patients without critical Good Clinical Practice violations who received at least one dose of finerenone or placebo).

    “Safety analyses were performed in the safety analysis set (all randomly assigned patients without critical Good Clinical Practice violations who received at least one dose of finerenone or placebo).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Efficacy analyses were performed in the full analysis set (all randomly assigned patients without critical Good Clinical Practice violations).

    “Efficacy analyses were performed in the full analysis set (all randomly assigned patients without critical Good Clinical Practice violations).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Mean adherence to the trial regimen was 92.1% in the finerenone group and 92.6% in the placebo group.

    “The mean adherence to the trial regimen (the percentage of administered doses relative to the number of planned doses) was 92.1% in the finerenone group and 92.6% in the placebo group”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because of the formal interim analysis, significance levels for the multiple-testing procedure in the final analysis were adjusted from 1.6667%, 3.3333%, and 5% to 1.5762%, 3.2827%, and 4.9674%, respectively.

    “Because of the formal interim analysis, significance levels for the multipletesting procedure in the final analysis were adjusted from 1.6667%, 3.3333%, and 5% to 1.5762%, 3.2827%, and 4.9674%, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In time-to-event analyses, superiority of finerenone over placebo was tested by means of a stratified log-rank test, with stratification factors of geographic region, eGFR category at screening, and albuminuria category at screening.

    “In time-to-event analyses, the superiority of finerenone over placebo was tested by means of a stratified log-rank test; stratification factors were geographic region (North America, Latin America, Europe, Asia, or other), eGFR category (25 to <45, 45 to <60, or ≥60 ml per minute per 1.73 m 2 ) at screening, and albuminuria category (moderately or severely elevated) at screening.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial.

    “Our trial was a phase 3, randomized, doubleblind, placebo-controlled, multicenter clinical trial.”
    • Also stated in: § METHODS · plain
      “In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    At trial conclusion, 822 patients (29.0%) in the finerenone group and 801 patients (28.2%) in the placebo group had discontinued the trial regimen.

    “At the trial conclusion, after a median followup of 2.6 years, 822 patients (29.0%) in the finerenone group and 801 patients (28.2%) in the placebo group had discontinued the trial regimen”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The observed benefits of finerenone were clinically significant and were obtained on a background of guideline-directed therapy, including RAS blockade at a maximum labeled dose that did not cause unacceptable side effects plus well-controlled glycated hemoglobin and blood-pressure levels.

    “The observed benefits of finerenone were clinically significant and were obtained on a background of guideline-directed therapy, including RAS blockade at a maximum labeled dose that did not cause unacceptable side effects plus well-controlled glycated hemoglobin and bloodpressure levels.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A clinical event committee whose members were unaware of trial-group assignments independently reviewed and adjudicated all reported outcome events.

    “A clinical event committee whose members were unaware of the trial-group assignments independently reviewed and adjudicated all reported outcome events.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    An independent data monitoring committee conducted one planned interim efficacy analysis and oversaw patient safety.

    “an independent data monitoring committee con-ducted one planned interim efficacy analysis and oversaw patient safety.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Mean daily dose was 15.1 mg in the finerenone group and 16.5 mg in the placebo group.

    “the mean daily dose was 15.1 mg and 16.5 mg in the respective groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A total of 98.1% and 98.8% of patients were treated with an ACE inhibitor or ARB, respectively, at a maximum labeled dose that did not cause unacceptable side effects.

    “A total of 98.1% and 98.8% of the patients were treated with an ACE inhibitor or ARB, respectively, at a maximum labeled dose that did not cause unacceptable side effects (Table S2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Vital status was ascertained for all but 18 patients (99.7%).

    “vital status was ascertained for all but 18 patients (5656 patients [99.7%])”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Owing to critical Good Clinical Practice violations, 60 patients were prospectively excluded from all analyses, leaving 5674 patients included in the statistical analyses.

    “Owing to critical Good Clinical Practice violations (including violations that led to the closure of one site and other violations related to patient misconduct), 60 patients were prospectively excluded from all analyses (further details are provided in the Supplementary Appendix), leaving 5674 patients who were included in the statistical analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All eGFR outcome events required confirmation with a second consecutive central laboratory measurement at least 4 weeks after the initial measurement.

    “All eGFR outcome events required confirmation with a second consecutive central laboratory measurement at least 4 weeks after the initial measurement.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Baseline characteristics and concomitant medications were balanced between the two groups.

    “Baseline characteristics and concomitant medications were balanced between the two groups (Table 1 and Table S1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The trial was performed in accordance with the principles of the Declaration of Helsinki.

    “The trial was performed in accordance with the principles of the Declaration of Helsinki.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    This trial excluded patients with nonalbuminuric CKD and CKD not due to type 2 diabetes.

    “we excluded patients with nonalbuminuric CKD and CKD not due to type 2 diabetes”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The factors of advanced CKD, exclusion of nonalbuminuric CKD and CKD not due to type 2 diabetes, and low proportion of Black patients may restrict the generalizability of the findings.

    “These factors may restrict the generalizability of the findings.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    The present trial had no protocol recommendations to restrict dietary potassium or potassium supplements, including in patients with hyperkalemia.

    “the present trial had no protocol recommendations to restrict dietary potassium or potassium supplements, including in patients with hyperkalemia”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premiseown data

    This trial allowed SGLT2 inhibitor treatment.

    “our trial allowed SGLT2 inhibitor treatment”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premiseown data

    This trial had a run-in period that allowed background medical therapies to be adjusted, including adjustment of ACE inhibitor or ARB therapy to a maximum labeled dose that did not cause unacceptable side effects.

    “our trial had a run-in period that allowed background medical therapies to be adjusted, including adjustment of ACE inhibitor or ARB therapy to a maximum labeled dose that did not cause unacceptable side effects.”
    Quote in the paperNot a substantial claim
36 of 36

  • The paper relies on this without support.

    The long-term effects of finerenone on kidney and cardiovascular outcomes in patients with CKD and type 2 diabetes are unknown.

    “However, its long-term effects on kidney and cardiovascular outcomes are unknown.”

  • The paper relies on this without support.

    Finerenone reduced albuminuria in short-term trials.

    “Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials”

  • The paper relies on this without support.

    Patients with CKD and type 2 diabetes and advanced CKD are at high risk for kidney and cardiovascular events.

    “who were at high risk for kidney and cardiovascular events”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Nonsteroidal mineralocorticoid receptor antagonists do not increase the risk of AKI when used to slow kidney disease progression.

    “It is also noteworthy that the nonsteroidal mineralocorticoid receptor antagonists (MRAs) do not increase the risk of AKI when used to slow kidney disease progression (33).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [33]

    The Safety Outcomes and Vital Signs section reports that acute kidney injury–related adverse events were balanced between finerenone and placebo. The trial studied finerenone in patients with chronic kidney disease and type 2 diabetes; it does not establish the same risk profile for nonsteroidal mineralocorticoid receptor antagonists as a class. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The FIDELIO-DKD trial included participants with (i) eGFR 25-60 ml/min per 1.73 m2, ACR 30-<300 mg/g, and diabetic retinopathy or (ii) ACR 300-5000 mg/g and eGFR 25-75 ml/min per 1.73 m2.

    “The FIDELIO-DKD trial included participants with (i) eGFR 25 -60 ml/min per 1.73 m 2 , ACR 30 -&lt; 300 mg/g [3 -&lt; 30 mg/mmol], and diabetic retinopathy or (ii) ACR 300 -5000 mg/g [30 -500 mg/mmol] and eGFR 25 -75 ml/min per 1.73 m 2”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [162]

    The Patients and Methods passages give the two albuminuria, eGFR, and retinopathy eligibility groups described in the claim. The upper eGFR limits are stated as *less than* 60 and *less than* 75 ml/min per 1.73 m², whereas the claim’s “25–60” and “25–75” ranges could be read as including those endpoints. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Finerenone had no effect on HbA1c, no increase in hypo- or hyperglycemia, and no sexual side effects due to the specificity for the MRA.

    “and no effect on HbA1c, no increase in hypo- or hyperglycemia, and no sexual side effects due to the speci fi city for the MRA.”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [162]

    The Safety Outcomes and Vital Signs section reports similar glycated hemoglobin (HbA1c) levels in the finerenone and placebo groups, and Table 2 reports hypoglycemia in 5.3% versus 6.9%, respectively. The copy does not establish that hyperglycemia did not increase or report an absence of sexual side effects attributable to receptor specificity. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Finerenone reduced the risk of kidney and cardiovascular outcomes in 2 pivotal outcome trials.

    “and fi nerenone reduced the risk of kidney and cardiovascular outcomes in 2 pivotal outcome trials.”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [162]

    The Results report lower risks of kidney and cardiovascular composite outcomes with finerenone in this trial. The discussion describes FIGARO-DKD, the other trial, as ongoing; this paper therefore does not support the claim that reductions had been shown in two pivotal outcome trials. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • The FIDELIO-DKD and FIGARO-DKD trials demonstrated that finerenone reduced CKD progression and heart failure among patients with T2D and albuminuria.

    “Patients with T2D and albuminuria are known to be at high risk of CKD progression and cardiovascular events, and the FIDELIO-DKD and FIGARO-DKD trials demonstrated that fi nerenone reduced these events (particularly CKD progression and heart failure) among such patients.”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [162]

    The Results and Discussion report that finerenone reduced the composite kidney and cardiovascular outcomes in FIDELIO-DKD patients with type 2 diabetes and CKD. The Discussion says FIGARO-DKD was still ongoing, so this paper cannot establish what both trials demonstrated. Hospitalization for heart failure was a component of the cardiovascular outcome; its individual estimate had a 95% confidence interval crossing 1, so the paper does not establish a reduction in that outcome specifically. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Not all patients received the stated background treatment

    Minor

    The methods say all patients received renin-angiotensin system blockade at the maximum tolerated labeled dose, but the paper also states that 14 patients received neither an ACE inhibitor nor an angiotensin-receptor blocker at baseline.

1 of 1

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Authors
Bakris, G. L., Agarwal, R., Anker, S. D., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Nowack, C., Schloemer, P., Joseph, A., & Filippatos, G.
Affiliations
  • University of Chicago (US)
  • University of Michigan (US)
  • University of Copenhagen (DK)
  • National and Kapodistrian University of Athens (GR)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2020-12-03
Volume
383
Issue
23
Pages
2219-2229
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2025845
OpenAlex
W3094429645
Semantic Scholar
44a8071f04b73823b399c19107ce7654773ab880
Cited by
2,935
References
27
Citations by year
2026: 661 · 2025: 603 · 2024: 504 · 2023: 464 · 2022: 400 · 2021: 284 · 2020: 17 · 2019: 1
FWCI
182.72
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • ABACUS. Repositorio de Producción Científica (Universidad Europea) (submittedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
  • Open Access CRIS of the University of Bern
Funders
Bayer
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
finerenone, chronic kidney disease, type 2 diabetes, mineralocorticoid receptor antagonists, renal failure, cardiovascular events, hyperkalemia, renin-angiotensin system blockade, FIDELIO-DKD, albuminuria
MeSH terms
Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Hyperkalemia, Male, Naphthyridines, Treatment Outcome, Renal Insufficiency, Chronic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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