What drugs cause uremia (azotemia, impaired renal function)?

From the Guidelines

Drugs that can cause uremia include nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics such as aminoglycosides, ACE inhibitors, ARBs, contrast agents, chemotherapy drugs, calcineurin inhibitors, and lithium. The primary mechanism by which these drugs cause uremia is through impairment of kidney blood flow and function, direct kidney toxicity, or altered kidney hemodynamics. Some key points to consider when evaluating the risk of uremia with these medications include:

• The use of NSAIDs, such as ibuprofen and naproxen, can impair kidney function and increase the risk of uremia, particularly with prolonged use 1.
• Certain antibiotics, such as aminoglycosides, can cause direct kidney toxicity and increase the risk of uremia 1.
• ACE inhibitors and ARBs may precipitate uremia in patients with underlying kidney disease or bilateral renal artery stenosis 1.
• Contrast agents used in imaging studies can cause contrast-induced nephropathy leading to uremia 1.
• Other medications, such as certain chemotherapy drugs, calcineurin inhibitors, and lithium, can also increase the risk of uremia with long-term use 1. It is essential to monitor patients taking these medications for signs of uremia, particularly those with pre-existing kidney disease, dehydration, or those taking multiple nephrotoxic medications simultaneously 1. The most recent and highest quality study, published in 2018, highlights the importance of monitoring renal function in patients taking diuretics, which can also contribute to the development of uremia 1. Overall, the use of these medications should be carefully considered and monitored in patients at risk for uremia, and alternative treatments should be explored when possible.

From the FDA Drug Label

In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Advanced Renal Disease No information is available from controlled clinical studies regarding the use of ibuprofen tablets in patients with advanced renal disease. If ibuprofen tablets therapy must be initiated, close monitoring of the patients renal function is advisable. Nonteratogenic Effects ... renal dysfunction ... Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs

NSAIDs, such as ibuprofen 2 and naproxen 3 and 3, may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation and increase the risk of renal toxicity.

• Ibuprofen and naproxen may cause renal dysfunction.
• Geriatric patients may be at a greater risk for the development of renal toxicity.
• Close monitoring of the patient's renal function is advisable when initiating NSAID therapy.

From the Research

Drugs Causing Uremia

• Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), nephrotic syndrome, and chronic kidney disease (CKD) 4
• The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2 4
• Some studies suggest that certain antihypertensive drugs, such as diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers, when used concurrently with NSAIDs, may increase the risk of acute kidney injury 5
• However, other studies have found that angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers may be associated with prolonged vascular access patency in uremic patients undergoing hemodialysis 6

Specific Drug Interactions

• The concurrent use of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with NSAIDs may not be associated with an increased risk of acute kidney injury, but the use of a triple therapy combination may increase this risk 5
• Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce the incidence of new onset diabetes and have favorable effects on cardiovascular and non-cardiovascular mortality 7