What medications should be held or used with caution in acute on chronic kidney injury?

From the Guidelines

In acute on chronic kidney injury, it is crucial to hold or use with caution medications that can worsen kidney function, and according to the most recent evidence 1, medications such as NSAIDs, ACE inhibitors, ARBs, and direct renin inhibitors should be temporarily discontinued. The following medications should be held or used with caution:

• Nephrotoxic medications: NSAIDs (ibuprofen, naproxen, diclofenac), ACE inhibitors (lisinopril, enalapril), ARBs (losartan, valsartan), and direct renin inhibitors (aliskiren)
• Aminoglycoside antibiotics (gentamicin, tobramycin) should be avoided or require significant dose adjustments based on renal function
• Contrast agents used in imaging studies should be minimized, with appropriate pre-hydration if absolutely necessary
• Certain chemotherapeutic agents (cisplatin, methotrexate) require dose adjustments or temporary discontinuation
• Medications requiring dose adjustments include many antibiotics (vancomycin, fluoroquinolones), antivirals (acyclovir, valacyclovir), antifungals (fluconazole), digoxin, gabapentinoids (gabapentin, pregabalin), and certain antidiabetic medications (metformin, SGLT2 inhibitors) as noted in 1. However, it's essential to consider the latest guidelines, which suggest that ACE inhibitors and ARBs should not be discontinued for minor increases in serum creatinine (<30%) in the absence of volume depletion 1. These precautions are necessary because impaired kidney function reduces drug clearance, leading to accumulation and potential toxicity, while some medications can directly worsen kidney injury through mechanisms like altered renal hemodynamics or direct tubular toxicity. Drug levels should be monitored when appropriate, and nephrology consultation is recommended for complex cases.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

1. 1 Lactic Acidosis ... Renal impairment — The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment ... In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.

Medications to hold in acute on chronic kidney injury:

• Metformin: should be held or used with caution in patients with acute on chronic kidney injury, especially if the eGFR falls below 45 mL/min/1.73 m^2 2 Other medications that may need to be held or used with caution:
• Carbonic Anhydrase Inhibitors (e.g. topiramate, zonisamide, acetazolamide or dichlorphenamide) due to increased risk of lactic acidosis 2
• Drugs that reduce metformin clearance (e.g. ranolazine, vandetanib, dolutegravir, and cimetidine) due to increased risk of lactic acidosis 2

From the Research

Medications to Hold in Acute on Chronic Kidney Injury

In the context of acute on chronic kidney injury, it is crucial to carefully manage medications to prevent further kidney damage. The following medications should be held or used with caution:

• Antibiotics and Antimicrobials: These can cause nephrotoxicity, leading to acute kidney injury (AKI) 3.
• NSAIDs: Nonsteroidal anti-inflammatory drugs have been associated with kidney disease, both acute and chronic, and should be used cautiously in patients with chronic kidney disease (CKD) 4.
• Aminoglycosides: These can cause nephrotoxicity and should be used with caution in patients with pre-existing kidney disease 5.
• Amphotericin B: This medication can cause nephrotoxicity and should be used with caution in patients with pre-existing kidney disease 5.
• Diuretics: While diuretics are often used to manage fluid overload in patients with kidney disease, they can also cause nephrotoxicity and should be used with caution 6.
• Angiotensin-Converting Enzyme (ACE) Inhibitors: These medications can cause nephrotoxicity, particularly in patients with pre-existing kidney disease, and should be used with caution 6.

Key Considerations

When managing medications in patients with acute on chronic kidney injury, it is essential to:

• Monitor kidney function closely
• Adjust medication doses according to kidney function
• Avoid using nephrotoxic medications whenever possible
• Use alternative medications that are less likely to cause kidney damage
• Consider the potential benefits and risks of each medication in the context of the patient's overall health status 7.