Should Guideline-Directed Medical Therapy (GDMT) be held due to Acute Kidney Injury (AKI) with diuretics in heart failure exacerbation?

From the Guidelines

Guideline-directed medical therapy (GDMT) should not be routinely held due to acute kidney injury (AKI) from diuretics in heart failure exacerbation, but requires careful monitoring and individualized decision-making. During heart failure exacerbation, transient worsening of renal function often occurs with diuresis but typically improves as congestion resolves, as noted in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. GDMT medications like ACE inhibitors, ARBs, ARNI, beta-blockers, and MRAs provide mortality benefit and should be continued if possible, as supported by the 2022 AHA/ACC/HFSA guideline 1.

Key Considerations

• Diuresis should not be discontinued prematurely because of small changes in serum creatinine, as elevations in the range of 0.3 mg/dL do not predict worse outcomes except when patients are discharged with persistent congestion 1.
• Close monitoring of electrolytes, blood pressure, and renal function is essential during this period.
• If creatinine rises more than 30% or exceeds 3.0 mg/dL, or if potassium exceeds 5.0 mEq/L, temporary dose reduction or brief interruption may be necessary.
• Once the patient is euvolemic and renal function stabilizes, GDMT should be reintroduced at lower doses and gradually titrated up.

Management Approach

• This approach balances the short-term management of AKI with the long-term benefits of GDMT, as premature discontinuation of these medications is associated with worse outcomes and increased mortality in heart failure patients.
• The 2022 AHA/ACC/HFSA guideline recommends that oral GDMT should not be withheld for mild or transient reductions in blood pressure or mild deteriorations in renal function 1.
• True contraindications to GDMT are rare, such as advanced degree atrioventricular block for beta blockers in the absence of pacemakers; cardiogenic shock that may preclude use of certain medications until resolution of shock state; or angioedema for ACEi or ARNi 1.

From the FDA Drug Label

5.1 Hypotension and Worsening Renal Function Excessive diuresis may cause potentially symptomatic dehydration, blood volume reduction and hypotension and worsening renal function, including acute renal failure particularly in salt-depleted patients or those taking renin-angiotensin aldosterone inhibitors. The FDA drug label does not directly answer whether Guideline-Directed Medical Therapy (GDMT) should be held due to Acute Kidney Injury (AKI) with diuretics in heart failure exacerbation. However, it does mention that worsening renal function can occur with torsemide, particularly in certain patient populations, and recommends monitoring volume status and renal function periodically 2.

• Key points are:
  • Excessive diuresis may worsen renal function.
  • Monitor volume status and renal function.
  • Worsening renal function can occur, especially in certain patient populations. Given the information provided in the label, a conservative clinical decision would be to closely monitor renal function in patients with AKI and adjust GDMT as needed to avoid further renal injury, but the label does not provide a direct answer to the question.

From the Research

Guideline-Directed Medical Therapy (GDMT) and Acute Kidney Injury (AKI)

• The use of diuretics in heart failure exacerbation can lead to AKI, but it is not necessarily a reason to hold GDMT 3.
• In fact, adequate treatment of congestion with diuretics is necessary, even if it may worsen renal function temporarily in some patients 3.
• However, the development of AKI can be a complication of diuretic therapy, and its management is crucial to prevent further renal damage 4, 5, 6.

Management of AKI in Heart Failure Patients

• The treatment of AKI in heart failure patients involves a careful balance between reducing congestion and preserving renal function 4.
• Discontinuation or dose reduction of diuretics or neurohormonal blockers may improve renal outcome, but it may also lead to less efficient decongestion 4.
• Ultrafiltration is an alternative method to remove excess fluid and congestion in patients with acute decompensated heart failure, but its efficacy compared to diuretics is still debated 7.

Factors Associated with AKI in Heart Failure Patients

• Increased doses of diuretic therapy and history of diabetes mellitus are significantly associated with AKI in patients with congestive heart failure 6.
• Other factors such as aging, primary diseases, and combination of diuretics with other drugs can also contribute to the development of AKI 5.
• The severity of AKI and the presence of comorbidities can affect the outcome and mortality of patients with heart failure 5.