Should hydrochlorothiazide (HCTZ) be held in the setting of acute kidney injury (AKI)?

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From the Guidelines

Yes, hydrochlorothiazide (HCTZ) should be held in patients with acute kidney injury (AKI). HCTZ is a thiazide diuretic that works by inhibiting sodium reabsorption in the distal convoluted tubule of the kidney, which can worsen kidney function in the setting of AKI. According to the KDIGO practice guideline on acute kidney injury, diuretics, including HCTZ, should not be used to treat AKI, except in the management of volume overload 1. Continuing HCTZ during AKI may exacerbate volume depletion, electrolyte abnormalities (particularly hyponatremia, hypokalemia, and hypercalcemia), and further reduce glomerular filtration rate.

When a patient develops AKI, it's essential to temporarily discontinue HCTZ until kidney function recovers, as determined by normalization of creatinine levels and estimated glomerular filtration rate. During this time, the patient's blood pressure should be monitored, and alternative antihypertensive medications that are less dependent on kidney function (such as certain calcium channel blockers or centrally acting agents) may be considered if blood pressure control is needed. The KDIGO guideline suggests that diuretics may actually improve outcomes in cases where volume overload complicates AKI 1. However, in the absence of volume overload, the potential benefit of HCTZ is outweighed by the risk of precipitating volume depletion, hypotension, and further renal hypoperfusion.

Key considerations in managing patients with AKI include:

  • Monitoring kidney function and electrolytes closely
  • Avoiding medications that can worsen kidney function, such as HCTZ
  • Managing volume status and blood pressure with alternative medications
  • Reintroducing HCTZ cautiously once kidney function has recovered, with close monitoring of kidney function, electrolytes, and volume status. The guideline recommendation is based on the principle that diuretics should not be used to prevent AKI, but may be used to treat volume overload in patients with AKI 1.

From the FDA Drug Label

Hydrochlorothiazide is eliminated primarily by renal pathways. Following oral doses of 12. 5 to 100 mg, 55% to 77% of the administered dose appears in urine and greater than 95% of the absorbed dose is excreted in urine as unchanged drug. In patients with renal disease, plasma concentrations of hydrochlorothiazide are increased and the elimination half-life is prolonged

Hold HCTZ with acute kidney injury. The drug is primarily eliminated by renal pathways, and its accumulation can occur in patients with renal disease, which may worsen the condition. Therefore, it is recommended to hold HCTZ in patients with acute kidney injury to avoid potential adverse effects 2.

From the Research

Holding HCTZ with Acute Kidney Injury

  • The decision to hold HCTZ (hydrochlorothiazide) in patients with acute kidney injury (AKI) should be based on the individual patient's condition and the potential risks and benefits of continuing or discontinuing the medication.
  • According to a study published in 2019 3, loop diuretics, which are similar to HCTZ, may not be beneficial for AKI treatment if kidney-related endpoints are considered.
  • Another study published in 2021 4 highlights the importance of fluid and electrolyte management in AKI patients, which may involve the use of diuretics like HCTZ.
  • A review of the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI, published in 2011 5, suggests that these medications may not have convincing benefits in clinical studies.
  • A systematic review published in 2011 6 found that the evidence for the effectiveness and safety of interventions, including diuretics like HCTZ, in preventing or treating AKI is limited.
  • A retrospective study published in 2022 7 found that loop diuretics, which are similar to HCTZ, are associated with an increased risk of hospital-acquired AKI in adult patients.

Considerations for Holding HCTZ

  • The potential risks and benefits of continuing or discontinuing HCTZ in patients with AKI should be carefully considered, taking into account the individual patient's condition and the potential impact on kidney function.
  • Patients with AKI who are taking HCTZ should be closely monitored for signs of worsening kidney function or other adverse effects.
  • The use of alternative medications or therapies may be considered in patients with AKI who are taking HCTZ, depending on the individual patient's needs and condition.
  • The study published in 2019 3 suggests that maintaining euvolemia (a state of normal fluid balance) is important when using loop diuretics, which may also apply to the use of HCTZ in patients with AKI.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute kidney injury.

Nature reviews. Disease primers, 2021

Research

Diuretics in acute kidney injury.

Seminars in nephrology, 2011

Research

Acute kidney injury.

BMJ clinical evidence, 2011

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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