🫀 HFpEF as Renal Disease: Roundtable Preparation

Comprehensive preparation for nephrology roundtable discussion on HFpEF

December 2025 | Bayer-Sponsored Expert Roundtable

🏠 Main Nephrology Index 📚 UDPA Lectures Home ❤️ Cardiorenal Lecture

📋 Executive Summary

This document provides comprehensive preparation for a nephrology roundtable discussion on heart failure with preserved ejection fraction (HFpEF) as a fundamentally renal disease. Key themes include:

🔬 Pathophysiology

The central role of the kidney in HFpEF pathogenesis through MR overactivation, galectin-3 mediation, and hemodynamic interactions

📊 CKM Framework

The emerging cardiovascular-kidney-metabolic syndrome framework integrated with KDIGO staging

💊 GDMT Evidence

Guideline-directed medical therapy evidence including FINEARTS-HF and CONFIDENCE

🩺 Clinical Implementation

Practical strategies and positioning of finerenone across the HFpEF spectrum

Part I: HFpEF as Fundamentally Renal Disease

🔬 The Paulus-Tschöpe Paradigm

The Paulus-Tschöpe paradigm establishes comorbidity-driven coronary microvascular endothelial inflammation—rather than ischemic cardiomyocyte death—as the central mechanism of HFpEF.

The Mechanism Chain:

Comorbidities → IL-6, TNF-α, CRP → Endothelial dysfunction → ↓NO/cGMP → Titin hypophosphorylation → Diastolic dysfunction

🫘 The Kidney's Central Role

1. MR Overactivation

Mineralocorticoid receptor overactivation occurs simultaneously in cardiomyocytes, fibroblasts, endothelial cells, and immune cells, stimulating TGF-β, IL-6, and PAI-1 production.

Key insight: Obesity and hyperglycemia cause ligand-independent MR activation even without elevated aldosterone levels.

2. Galectin-3 Mediation

Galectin-3 functions as a bidirectional mediator linking kidney injury to cardiac fibrosis. It amplifies TGF-β signaling by stabilizing TGFBR2.

Serum galectin-3 correlates with diastolic dysfunction severity (E/e' ratio): severe HFpEF 19.4 ± 12.4 ng/mL vs mild HFpEF 6.8 ± 5.3 ng/mL (p < 0.001)

3. Hemodynamic Interactions

A self-perpetuating cycle: reduced GFR → ↓sodium filtration → RAAS activation → volume expansion → hypertension → LVH → elevated CVP → "renal tamponade" → ↓GFR

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🧬 Galectin-3: The Molecular Bridge

Molecular Architecture

Galectin-3 is a 30-kDa protein encoded by the LGALS3 gene—the only chimeric member of the galectin family. It consists of:

C-terminal CRD: Binds β-galactoside moieties on cell surface glycoproteins
N-terminal domain: Mediates oligomerization, enabling extracellular lattice formation

The Adoptive Transfer Evidence

Landmark experiments: In unilateral ureteral obstruction models, galectin-3 knockout mice developed markedly less fibrosis despite normal macrophage recruitment. Adoptive transfer of wild-type macrophages into galectin-3 null mice fully restored the fibrotic phenotype. This proves macrophage-derived galectin-3 is the critical mediator.

2025 Mechanistic Update

Recent research has elucidated the molecular mechanism: extracellular galectin-3 binds directly to TGF-β receptor 2 (TGFBR2) through its CRD, inhibiting receptor ubiquitination and proteasomal degradation—prolonging receptor half-life and amplifying TGF-β signaling.

Clinical Correlations

r = −0.71

Correlation between reduced GFR and elevated galectin-3

OR 3.21

Galectin-3 predicts type 1 cardiorenal syndrome

HR 1.97

Per doubling of galectin-3 levels (FDA validated)

Clinical Pearl: Unlike natriuretic peptides (confounded by reduced clearance in CKD), galectin-3's prognostic value for cardiac outcomes is preserved in patients with renal impairment—reflecting its role as a mechanistic mediator rather than a clearance marker.
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📈 Albuminuria as Cardiovascular Risk Indicator

Albuminuria serves as both a kidney injury marker and an independent cardiovascular risk indicator, reflecting systemic endothelial injury affecting both the glomerular barrier and coronary microcirculation.

ARIC Study Evidence (n=10,975)

Continuous graded relationship even within "normal" range:

UACR Category HF Hazard Ratio
Optimal (<5 mg/g)Reference
Intermediate-normal (5-9 mg/g)HR 1.54
High-normal (10-29 mg/g)HR 1.91
Microalbuminuria (30-299 mg/g)HR 2.49
Macroalbuminuria (≥300 mg/g)HR 3.47

Each doubling of UACR = 15% increased HF risk (HR 1.15), independent of eGFR

CHARM HFpEF Subset

Microalbuminuria vs Normoalbuminuria
HR 1.43

(95% CI 1.21-1.69, p<0.0001)

Macroalbuminuria vs Normoalbuminuria
HR 1.75

(95% CI 1.39-2.20, p<0.0001)

TOPCAT Finding: 50% albuminuria reduction corresponded to 30-70% lower heart failure hospitalization risk. Albuminuria precedes eGFR decline as an earlier warning signal.
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🗺️ HFpEF Phenomapping: The CKD-Dominant Phenotype

Shah Phenogroups (Circulation 2016)

Hierarchical clustering on 397 HFpEF patients using 67 phenotypic variables identified three distinct phenogroups:

Phenogroup 3: CKD-Dominant (Highest Risk)

Characteristics:
  • Older age (median 75 years)
  • CKD as defining feature
  • 43% atrial fibrillation
  • Pulmonary hypertension
  • RV dysfunction
  • Overt diastolic dysfunction
HR 4.2

(95% CI 2.0-9.1, p<0.001)

for HF hospitalization vs other phenogroups

Key Finding: TOPCAT phenogroup analysis revealed that the cluster characterized by obesity, diabetes, high renin, renal injury markers, and liver fibrosis showed the best response to spironolactone with NNT of 14.
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Part II: Interactive CKM-KDIGO Risk Heat Map

🎯 Integrated KDIGO-CKM Risk Stratification: The Visual Guide

This interactive heat map combines KDIGO CKD staging with AHA CKM syndrome classification. Click any cell to see detailed risk profiles and therapeutic recommendations.

Critical insight: Albuminuria is the dominant driver of cardiovascular risk—often more predictive than eGFR decline alone. A patient with eGFR 85 and UACR 400 faces higher CV risk than one with eGFR 35 and UACR 15.

Albuminuria Categories (UACR mg/g) — PRIMARY RISK DRIVER
A1
<30
Normal-mild
A2
30-300
Mod increased
A3
>300
Severely increased

Risk Profile

    Therapeutic Recommendations

      🎨 Risk Color Legend

      Low Risk (CKM 0-1)
      Moderate Risk (CKM 2)
      High Risk (CKM 2)
      Very High Risk (CKM 2-3)
      Very High Risk (CKM 3)
      Highest Risk (CKM 3-4b)
      CV≡ = Cardiovascular Risk Equivalent (eGFR <30)

      ⚠️ Albuminuria Dominance: The Key Insight

      • G1A3 (eGFR ≥90, UACR >300): HF risk 3.47× — similar to G3b/A1!

      • CKD progression steepens MORE across A categories than G categories

      • CV risk exceeds kidney failure risk in early albuminuric CKD

      • eGFR <30 = automatic CV risk equivalent regardless of UACR

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      ⚠️ Albuminuria: The Dominant Driver of Risk Progression

      The Critical Principle:

      Albuminuria is a more powerful predictor of adverse outcomes than eGFR decline, and the risk gradient steepens dramatically with increasing albuminuria severity.

      The Clinical Comparison

      Patient A

      eGFR 85 mL/min/1.73m² + UACR 400 mg/g

      (G2A3)

      HF Risk: 3.47×

      HIGHER CV risk despite excellent eGFR

      Patient B

      eGFR 35 mL/min/1.73m² + UACR 15 mg/g

      (G3bA1)

      HF Risk: 1.91×

      LOWER CV risk despite poor eGFR

      The Albuminuria Paradox

      In adults with albuminuria and preserved eGFR, the absolute risk of cardiovascular events substantially exceeds the risk of progressing to dialysis. A patient with eGFR 75 and UACR 200 faces low short-term risk of kidney failure but substantially elevated cardiovascular risk.

      Reframe the conversation: In early-stage albuminuric CKD, we are primarily preventing cardiovascular events, with kidney protection as an important co-benefit.

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      Part III: CKM Syndrome Framework

      📋 AHA Presidential Advisory (2023)

      CKM syndrome is defined as a "systemic disorder with pathophysiological interactions among metabolic risk factors, CKD, and cardiovascular system leading to multiorgan dysfunction and high adverse cardiovascular outcomes."

      Rationale: One in three US adults have 3+ CKM risk factors. Emerging therapies (SGLT2i, GLP-1 RA, finerenone) provide simultaneous CV and kidney benefits. Siloed subspecialty care fails to address integrated disease.

      🖼️ CKM Staging Framework (AHA 2023)

      AHA CKM Staging Framework showing stages 0-4 with KDIGO integration

      Figure 1: Stages of the American Heart Association CKM Health Syndrome.
      Source: Bansal N, Weiner D, Sarnak M. JASN 2024;35(5):649-652. PMC11149035

      🔢 CKM Staging with KDIGO Integration

      Stage 0-1: No/Low Risk

      KDIGO: G1-G2/A1 without metabolic disease

      Action: Lifestyle modification, annual screening

      Screen: UACR even at Stage 1 (adiposity)

      Stage 2: Metabolic Risk or Mod-High CKD

      KDIGO: G3a/A1, G1-G2/A2-A3, or metabolic risk factors

      Key insight: Stage 2 can be triggered by albuminuria alone

      Action: SGLT2i (eGFR ≥20), optimize RAASi, consider finerenone

      Stage 3: CV Risk Equivalent

      KDIGO: G4-G5 (any albuminuria), G3a-G3b/A3, or PREVENT ≥20%

      Critical: eGFR <30 = automatic CKM Stage 3

      Action: All four pillars, cardiology referral

      Stage 4: Clinical CVD + CKM

      4a: CKD without ESKD

      4b: ESKD (10-20× mortality vs general population)

      Action: Multidisciplinary, maximize tolerated therapy, RRT planning

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      Part IV: Guideline-Directed Medical Therapy Evidence

      💊 SGLT2 Inhibitors: Class I, Level A for HFpEF

      EMPEROR-Preserved (n=5,988)

      Empagliflozin vs placebo in LVEF >40%

      Primary endpoint (CV death + HF hospitalization):

      HR 0.79 (p<0.001)

      NNT = 30 over 26.2 months

      Benefit consistent regardless of diabetes status

      DELIVER (n=6,263)

      Dapagliflozin vs placebo in LVEF >40%

      Primary endpoint:

      HR 0.82 (p<0.001)

      Benefit maintained even in LVEF ≥60%

      2023 ESC Focused Update: SGLT2 inhibitors elevated to Class I, Level A recommendation for HFmrEF and HFpEF—the only treatments with this strength of recommendation in HFpEF.
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      🎯 Finerenone: FINEARTS-HF (September 2024)

      6,001 patients with symptomatic HF and LVEF ≥40% across 634 sites in 37 countries

      16%

      Relative risk reduction in CV death + worsening HF events

      RR 0.84 (95% CI 0.74-0.95, p=0.007)

      18%

      Reduction in worsening HF events alone

      RR 0.82 (p=0.007)

      Consistent Across LVEF Spectrum (p-interaction 0.75)

      LVEF <50%
      RR 0.83
      LVEF 50-60%
      RR 0.79
      LVEF >60% (True HFpEF)
      RR 0.82

      Hyperkalemia Profile

      K+ >5.5 mmol/L: 14.3% finerenone vs 6.9% placebo (2.6× increase)

      Hyperkalemia hospitalizations: 0.5% vs 0.2% (uncommon)

      No deaths attributable to hyperkalemia

      FDA Expansion (July 2025): Finerenone indication expanded to include reducing CV death, HF hospitalization, and urgent HF visits in adults with HF and LVEF ≥40%.
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      ⚖️ Finerenone vs Steroidal MRAs

      Finerenone Advantages

      • Non-steroidal structure: no affinity for androgen/progesterone receptors
      • Eliminates gynecomastia, breast pain, menstrual irregularities
      • Lower hyperkalemia risk (ARTS trial: 5% vs 12% with spironolactone)
      • Balanced heart-kidney tissue distribution

      TOPCAT Issues

      Americas cohort: HR 0.82 (31.8% placebo event rate)

      Russia/Georgia: HR 1.10 (8.4% placebo event rate)

      2017 NEJM analysis: Canrenone undetectable in large proportions of Eastern European participants

      AMBER Trial Comparison

      K+ ≥5.5 in CKD with resistant HTN:

      Spironolactone without K+ binder: 64.2%

      Finerenone (FIDELITY): 11.6%

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      Part V: Clinical Implementation

      🌟 KEY TRIAL FOR ROUNDTABLE

      🔬 CONFIDENCE Trial (NEJM 2025): Practice-Changing Evidence

      First prospective evidence supporting simultaneous finerenone + SGLT2i initiation in diabetic kidney disease

      "Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes"
      N Engl J Med 2025;393:533-43. DOI: 10.1056/NEJMoa2410659

      52%

      UACR Reduction

      with combination therapy at Day 180

      29%

      Greater Than Finerenone Alone

      Additive benefit demonstrated

      32%

      Greater Than Empagliflozin Alone

      Complementary mechanisms

      8.1%

      Hyperkalemia with SGLT2i

      vs 18.7% without SGLT2i (FIDELITY)

      📋 Roundtable Talking Points

      1. Safety Signal: SGLT2i co-administration substantially reduces finerenone-associated hyperkalemia through natriuretic and kaliuretic effects.

      2. Efficacy Signal: The 52% UACR reduction with combination therapy exceeds what would be expected from simple addition of effects—suggesting synergistic mechanisms.

      3. Practical Implications: In patients with stable K+ (<4.5), eGFR ≥45, and significant albuminuria, simultaneous initiation is now evidence-supported.

      4. Clinical Integration: This supports the "four-pillar" approach to cardiorenal protection rather than sequential addition of therapies.

      Bottom Line: CONFIDENCE transforms our approach from "add one at a time and wait" to "initiate comprehensive protection early." For appropriate patients, the combination of SGLT2i + finerenone is now the evidence-based standard.
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      🔍 HFpEF Screening in Nephrology Practice

      NT-proBNP Thresholds

      Outpatient (eGFR ≥60): <125 pg/mL rules out HF
      CKD (eGFR <60): Use 200-400 pg/mL threshold

      H2FPEF Score (Simpler Alternative)

      FeaturePoints
      BMI >302
      Multiple antihypertensives (≥2)1
      Atrial fibrillation3
      Pulmonary hypertension (PA systolic >35)1
      Age >601
      Elevated E/e' (>9)1

      Score ≥6: High probability of HFpEF

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      💊 Finerenone Dosing and Monitoring

      Dosing by Baseline eGFR

      eGFR ≥60: Start 20mg daily, target 20-40mg
      eGFR 25-<60: Start 10mg daily, target 20mg
      eGFR <25: Not recommended

      Critical Monitoring Protocol

      4 weeks post-initiation: K+ and eGFR (mandatory)

      Uptitrate if: K+ ≤4.8 mEq/L with stable eGFR

      Ongoing: Every 4 months

      If K+ >5.5 mEq/L:

      Hold finerenone until K+ ≤5.0, then restart at lower dose. Consider potassium binders (patiromer, SZC) for recurrent hyperkalemia.

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      Part VI: Roundtable Question Responses

      Q: Are you aware of the CKM concept? How do you prioritize comorbidity management in CKD plus type 2 diabetes?

      CKM syndrome (AHA 2023) formalizes the pathophysiological interconnections nephrologists observe clinically. The staging system (0-4) provides actionable structure:

      • Stage 2 (metabolic risk or moderate-to-high-risk CKD) → SGLT2i initiation
      • Stage 3 (subclinical CVD or eGFR <30) → Add finerenone if UACR >30 on ACEi/ARB

      Prioritization follows KDIGO 2024: Optimize RAASi → Add SGLT2i (eGFR ≥20) → Add finerenone if persistent albuminuria (UACR ≥30, eGFR ≥25, K+ ≤5.0) → Consider GLP-1 RA.

      Q: Do you screen diabetic patients for heart failure?

      Yes. The ADA 2024 Standards now recommend screening for asymptomatic HF in diabetes using BNP or NT-proBNP.

      Practical approach: Annual NT-proBNP in all T2D + CKD patients. NT-proBNP ≥125 pg/mL (≥200 if eGFR <45) triggers echocardiography. Early detection enables SGLT2i initiation before symptomatic HF develops.

      Key stat: FIGARO demonstrated 32% new-onset HF reduction with finerenone in patients without baseline HF.

      Q: How do you communicate increased CV risk with persistently elevated UACR?

      The "smoke detector" analogy: "UACR functions as an early warning system for your kidneys and heart—like a smoke detector that detects damage before it becomes irreversible."

      Quantify risk: "Your UACR >300 mg/g increases heart failure risk by 1.7-2.7 times—but this is modifiable with treatment."

      Set concrete goals: "We're targeting at least 30% UACR reduction."

      Connect to outcomes: "TOPCAT showed that 50% UACR reduction correlates with 30-70% lower heart failure hospitalization risk."

      Q: Do you perform simultaneous initiation of pillars (SGLT2i + finerenone)?

      CONFIDENCE (NEJM 2025) provides first prospective evidence supporting simultaneous initiation: finerenone + empagliflozin achieved 52% UACR reduction (29% greater than finerenone alone) with similar safety.

      My algorithm:

      • Simultaneous initiation: Stable patients with high albuminuria, K+ <4.5, eGFR ≥45
      • Sequential initiation: Borderline K+ (4.5-4.8), uncertain volume status, or eGFR <45 → SGLT2i first, reassess K+ at 4 weeks, then add finerenone

      Key safety finding: SGLT2i co-administration reduces finerenone hyperkalemia (8.1% vs 18.7%).

      Q: Are you aware of finerenone data in HF with LVEF ≥40%?

      FINEARTS-HF (September 2024, n=6,001) demonstrated finerenone reduced CV death + worsening HF events by 16% (RR 0.84, p=0.007) in symptomatic HF with LVEF ≥40%.

      Remarkably consistent across LVEF spectrum (p-interaction 0.75):

      • HFmrEF (LVEF <50%): RR 0.83
      • LVEF 50-60%: RR 0.79
      • True HFpEF (LVEF >60%): RR 0.82

      This addresses concerns from TOPCAT about heterogeneous MRA effects in HFpEF. FDA expanded finerenone indication (July 2025) to include HF with LVEF ≥40%.

      ↑ Back to Table of Contents

      🎯 Key Clinical Pearls

      1. HFpEF is fundamentally a renal disease—the kidney plays central pathophysiological and therapeutic roles.
      2. CKD-dominant HFpEF phenotype carries highest risk (HR 4.2) yet responds best to targeted therapy including MRAs.
      3. Albuminuria is both kidney marker and CV risk indicator—routine UACR monitoring identifies high-risk patients.
      4. eGFR <30 = CV risk equivalent under CKM framework—warranting intensive prevention even without overt CVD.
      5. SGLT2i achieved Class I, Level A for HFpEF. Finerenone is the first definitively proven MRA for HFpEF.
      6. Simultaneous SGLT2i + finerenone is safe and effective (CONFIDENCE: 52% UACR reduction).
      7. SGLT2i mitigates finerenone-associated hyperkalemia (8.1% vs 18.7% in FIDELITY).
      8. Galectin-3 is a "culprit" biomarker mechanistically involved in cardiorenal fibrosis (r = −0.71 with eGFR).
      9. Four pillars (RAASi, SGLT2i, finerenone, GLP-1 RA) address complementary mechanisms for comprehensive protection.
      10. Target ≥30% UACR reduction as therapeutic goal—50% reduction correlates with 30-70% lower HF hospitalization.
      ↑ Back to Table of Contents
      📚 SUPPLEMENTAL RESOURCES

      ❤️🫘 Comprehensive Cardiorenal Disease Evidence Synthesis

      Complete evidence-based analysis of modern guideline-directed medical therapy for cardiorenal disease

      📄 Comprehensive Cardiorenal Report

      31 pages | 82 references | Complete RAAS inhibitor hierarchy, four-pillar GDMT evidence, population health impact analysis

      📄 Heart Failure Neurohormonal Report

      27 pages | 30 references | MRA phenotype specificity, natriuretic peptide resistance, therapeutic strategies

      🎯 Key Evidence Highlights

      • RAAS Inhibitor Hierarchy in Heart Failure: ARNIs > ACE-I > ARBs for HF mortality (NNT 36, 70, 446 respectively)
      • ACE-I Benefits: Mortality reduction attenuated when combined with comprehensive GDMT (beta-blockers, MRAs, SGLT2i)
      • MRA Phenotype Specificity: 2024 Lancet meta-analysis on steroidal vs non-steroidal selection
      • CONFIDENCE Trial: 52% UACR reduction with simultaneous SGLT2i + finerenone initiation
      • Population Impact: 253 lives saved per 100K annually, $39.4M cost savings, 4.8:1 ROI
      • Four-Pillar Synergy: 40-50% mortality reduction with comprehensive GDMT
      📥 Access Complete Evidence Synthesis & Download PDFs

      📚 Verified Sources

      Phase 2 audit (dialysis-cardiorenal-hfpef-verification.md) flagged this file as having no formal PubMed-link bibliography despite citing CONFIDENCE inline. Anchors below for the named trials and CKM framework. Effect-size claims (FINEARTS-HF 16% RRR / RR 0.84 / NNT 17, EMPEROR-Preserved HR 0.79 NNT 30, DELIVER HR 0.82, ARIC HF HRs 1.54/1.91/2.49/3.47) verified accurate against primary publications. Shah phenogroups year-correction (Circulation 2015 not 2016) noted in the per-claim audit. [Bibliography added 2026-05-03]

      1. Solomon SD, McMurray JJV, Vaduganathan M, et al; FINEARTS-HF Investigators. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2024;391(16):1475-1485. PMID: 39225278. — FINEARTS-HF: composite RR 0.84 (16% RRR, NNT 17); benefit consistent across LVEF spectrum.
      2. Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461. PMID: 34449189. — EMPEROR-Preserved: composite HR 0.79; NNT 30 over 26.2 months; N=5,988.
      3. Solomon SD, McMurray JJV, Claggett B, et al; DELIVER Trial Committees and Investigators. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-1098. PMID: 36027570. — DELIVER: composite HR 0.82; benefit maintained in LVEF ≥60% subgroup.
      4. Shah SJ, Katz DH, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015;131(3):269-279. PMID: 25398313. — Shah phenogroup analysis; HR 4.2 for adverse-phenogroup CV outcomes. [Note — Phase 2 audit identified prior version cited "Circulation 2016"; actual publication year is 2015 per PubMed metadata.]
      5. Heerspink HJL, Stefansson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID: 32970396. — DAPA-CKD primary composite HR 0.61; supports SGLT2i in cardiorenal continuum.
      6. Bakris GL, Agarwal R, Anker SD, et al; FIDELIO-DKD Trial. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. PMID: 33264825. — FIDELIO-DKD; non-steroidal MRA evidence base.
      7. Pitt B, Filippatos G, Agarwal R, et al; FIGARO-DKD Trial. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021;385(24):2252-2263. PMID: 34449181. — FIGARO-DKD CV outcomes.
      8. Agarwal R, Filippatos G, Pitt B, 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. 2022;43(6):474-484. PMID: 35023547. — FIDELITY: pooled FIDELIO + FIGARO; comprehensive cardiorenal outcomes in T2DM-CKD.
      9. Pitt B, Pfeffer MA, Assmann SF, et al; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. PMID: 24716680. — TOPCAT: spironolactone in HFpEF; primary composite no benefit overall, regional heterogeneity (Americas vs Russia/Georgia) prompted post-hoc reanalysis.
      10. Selvaraj S, Claggett B, Shah SJ, et al. Prognostic value of phenotypic responses to spironolactone in patients with heart failure with preserved ejection fraction in the TOPCAT trial. JACC Heart Fail. 2020;8(3):172-184. PMID: 32035890. — TOPCAT phenotypic responder analysis; informs the spironolactone NNT 14 claim in the lecture (specific NNT not extractable from abstract — verify against full paper).

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      🏠 Main Nephrology Index 📚 UDPA Lectures Home ❤️ Cardiorenal Lecture

      Document prepared for Bayer-sponsored HFpEF Roundtable Discussion

      December 2025