What are the management guidelines for a patient with chronic kidney disease (CKD) and heart failure (HF) with a reduced ejection fraction (EF) of 34%?

Management of Chronic Kidney Disease with Heart Failure and Ejection Fraction 34%

Core Pharmacological Therapy

For a patient with HFrEF (EF 34%) and CKD, initiate quadruple therapy with an SGLT2 inhibitor, beta-blocker, ARNI (or ACE inhibitor/ARB if ARNI not tolerated), and mineralocorticoid receptor antagonist, with diuretics added only if congestion is present. 1

First-Line Therapy Foundation

• SGLT2 Inhibitor (Dapagliflozin or Empagliflozin): Start immediately as foundational therapy regardless of diabetes status 1, 2

  • Can be initiated at eGFR as low as 20 mL/min/1.73 m² with dapagliflozin or empagliflozin 1
  • Reduces cardiovascular death and HF hospitalization while protecting kidney function 1, 3
  • Expect modest eGFR decrease of 3-10% initially—do not discontinue unless acute kidney injury suspected 1
  • Lowers hyperkalemia risk when combined with MRA 1

• Beta-Blocker (Carvedilol, Metoprolol Succinate, or Bisoprolol): Initiate at low dose and uptitrate to target 1, 4, 2

  • Reduces morbidity and mortality in HFrEF regardless of CKD stage 4
  • Bisoprolol may accumulate in renal impairment but still titrate to target dose (10 mg daily) based on clinical response 5

• ARNI (Sacubitril/Valsartan) or ACE Inhibitor/ARB: Replace ACE inhibitor with ARNI for superior outcomes 1, 6, 2

  • ARNI preferred over ACE inhibitor/ARB for patients with symptomatic HFrEF 1, 6
  • Start sacubitril/valsartan 24/26 mg twice daily if eGFR <30 mL/min/1.73 m² or 49/51 mg twice daily if eGFR ≥30 mL/min/1.73 m² 6, 5
  • Titrate every 2-4 weeks to target dose of 97/103 mg twice daily as tolerated 6
  • If using ACE inhibitor instead, tolerate eGFR decreases up to 30% after initiation—this is expected and beneficial 1
  • 36-hour washout required when switching from ACE inhibitor to ARNI; no washout needed from ARB 6
  • ARNI carries lower hyperkalemia risk compared to ACE inhibitors when combined with MRA 1

• Mineralocorticoid Receptor Antagonist (Spironolactone or Eplerenone): Add if eGFR ≥30 mL/min/1.73 m² 1, 2

  • Start low dose (spironolactone 6.25-12.5 mg daily or 12.5 mg every other day) 5
  • Uptitrate based on potassium and renal function monitoring 5
  • Nonsteroidal MRA (finerenone) recommended for prevention in patients with T2D and CKD 1

Diuretic Management

• Loop Diuretics: Use only if congestion present 1
  • Adjust dosage to maintain euvolemia 1
  • Monitor closely as diuretic doses may need reduction when initiating SGLT2 inhibitors or ARNI due to enhanced natriuresis 6

Critical Monitoring Parameters

Tolerating Expected Changes in Renal Function

• Accept eGFR decreases ≤30% after initiating RAS inhibitors or SGLT2 inhibitors—do not discontinue therapy prematurely 1
• If eGFR decline >30%, ensure euvolemia by adjusting diuretics, discontinue nonessential nephrotoxic agents, and evaluate alternative causes 1
• Renal function often stabilizes over time despite initial decline, and drugs maintain clinical efficacy 3

Hyperkalemia Management (K+ >5.0 mEq/L)

• Recheck elevated potassium before making therapeutic changes 1
• Consider potassium binders (patiromer or sodium zirconium cyclosilicate) to facilitate ongoing use of evidence-based therapies rather than discontinuing life-saving medications 1
• Implement low-potassium diet 1
• SGLT2 inhibitors and ARNI lower hyperkalemia risk compared to traditional RAS inhibitors with MRA 1

Disease Progression Monitoring

• Measure natriuretic peptides (NT-proBNP or BNP) regularly to assess HF status 1
• Monitor albuminuria (UACR) at least annually to track CKD progression 1
• Screen eGFR and albuminuria at least annually using creatinine-based equation (without race) or cystatin C for greater precision 1

Additional Therapeutic Considerations

Lifestyle and Risk Factor Control

• Sodium restriction is critical as sodium excretion is impaired in CKD, exacerbating hypertension and HF 1
• Optimize blood pressure, lipid, and glucose control 1
• Implement ASCVD interventions as indicated 1

GLP-1 Receptor Agonist

• Consider adding GLP-1 RA if BMI ≥30 kg/m² to improve symptoms and physical limitations 1
• Provides cardiovascular benefit and may reduce inflammation 1

Ivabradine

• Consider if patient remains symptomatic with heart rate ≥70 bpm despite maximally tolerated beta-blocker or has beta-blocker contraindication 7
• Start 5 mg twice daily with food, adjust to achieve resting heart rate 50-60 bpm 7
• Start 2.5 mg twice daily in patients with conduction defects 7

Statin Therapy

• Initiate statin for all patients with HFrEF regardless of LV dysfunction to prevent HF progression 4
• Consider lower statin doses when combined with sacubitril/valsartan due to drug interactions via OATP transporters 6

Common Pitfalls to Avoid

• Do not withhold or discontinue GDMT due to asymptomatic hypotension—mortality benefit persists even with lower blood pressure 6, 2
• Do not permanently discontinue therapies for mild creatinine elevation (<0.5 mg/dL increase)—this is expected and acceptable 6
• Do not fail to uptitrate medications to target doses—medium-range doses do not provide most benefits of target doses 6
• Do not discontinue RAS inhibitors or SGLT2 inhibitors for expected eGFR decline ≤30%—this reflects beneficial hemodynamic changes 1, 3
• Do not avoid evidence-based therapies in CKD stages 3-4—most drug classes are safe and effective up to eGFR 30 mL/min/1.73 m² 3

Special Considerations for Advanced CKD

• For eGFR <30 mL/min/1.73 m²: SGLT2 inhibitors and beta-blockers remain safe and effective 1, 3
• Sacubitril/valsartan not recommended if eGFR <30 mL/min/1.73 m² per standard guidelines 5, though emerging evidence suggests careful use may be feasible with close monitoring of eGFR and potassium 8
• MRA use requires extreme caution if eGFR <30 mL/min/1.73 m² with very low starting doses and frequent monitoring 5
• Limited data exist for any HFrEF therapies in CKD stage 5 (eGFR <15 mL/min/1.73 m² or dialysis) 3