What medications are associated with impaired renal (kidney) function?

From the Guidelines

When managing medications with kidney concerns, it's essential to adjust dosages or avoid certain drugs based on kidney function, as recommended by the most recent guidelines 1. Medications that require special attention include:

• NSAIDs (ibuprofen, naproxen), which should be avoided or used cautiously as they can worsen kidney function
• ACE inhibitors and ARBs (lisinopril, losartan) that need dose adjustments and careful monitoring, especially in patients with a GFR < 60 ml/min/1.73 m2 (GFR categories G3a-G5) who have serious intercurrent illness that increases the risk of AKI 1
• Metformin, which should be avoided when eGFR falls below 30 ml/min
• Certain antibiotics like gentamicin that require reduced dosing and drug level monitoring
• Contrast dyes used in imaging studies that may need to be avoided or require pre-hydration protocols

Always ensure medication dosages are adjusted based on creatinine clearance or eGFR values. Patients with kidney disease should maintain proper hydration, avoid nephrotoxic combinations, and have regular kidney function monitoring. These precautions are necessary because impaired kidneys have reduced ability to filter and eliminate medications, leading to drug accumulation and potential toxicity if doses aren't appropriately adjusted.

Some key considerations for specific medications include:

• Lithium, which can cause renal tubular dysfunction with prolonged use and requires monitoring of GFR, electrolytes, and lithium levels 1
• Diuretics, which should be used with caution in patients with kidney disease
• RAAS blockers, including ACE-Is, ARBs, aldosterone inhibitors, and direct renin inhibitors, which should be temporarily discontinued in people with a GFR < 60 ml/min/1.73 m2 (GFR categories G3a-G5) who have serious intercurrent illness that increases the risk of AKI 1

It's also important to note that the use of certain medications, such as ACE inhibitors and ARBs, can be beneficial in patients with kidney disease, but requires careful monitoring and dose adjustment 1. Additionally, the use of isosmolar contrast material can help reduce the risk of contrast-induced nephropathy in patients with CKD or CKD and diabetes 1.

From the FDA Drug Label

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance < 30 mL/min) Given that naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment

Naproxen is not recommended for patients with moderate to severe renal impairment due to the potential for metabolite accumulation and decreased elimination. This is a key concern for patients with renal insufficiency.

• Renal impairment may lead to increased risk of adverse effects.
• Dose selection should be careful in patients with impaired renal function.
• It may be useful to monitor renal function in these patients 2.

From the Research

Medication Concerns in Kidney Disease

• Medications can be a significant source of medical errors in patients with kidney disease, with almost half of all medications being eliminated via the kidney 3.
• Patients with kidney disease are susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease 3, 4.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension 5, 6.

NSAID Use in Kidney Disease

• The use of NSAIDs in patients with chronic kidney disease (CKD) is challenging due to their risk of nephrotoxicity 5, 6.
• However, alternatives such as opioids, tramadol, gabapentin, and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD 6.
• The evidence directly examining the impact of NSAIDs on long-term outcomes in end-stage kidney disease (ESKD) is limited, and further study is warranted 7.

Medication Safety in Kidney Disease

• Ensuring patient safety is a priority of medical care, and medications are an important source of medical errors 3.
• Improved prescribing practices can decrease the risk for the development of acute kidney injury and the progression to end-stage kidney disease 4.
• KDIGO Clinical Practice Guidelines recommend the use of caution when prescribing potentially nephrotoxic medications for patients with kidney disease 4.