What medications can cause intrinsic Renal (Kidney) disease, specifically Impaired Renal Function?

From the Guidelines

Medications that can cause intrinsic renal disease include nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics such as aminoglycosides, certain chemotherapeutic agents, ACE inhibitors, ARBs, calcineurin inhibitors, and contrast media, as these can directly damage kidney structures or alter renal hemodynamics, leading to acute or chronic nephrotoxicity. The most recent and highest quality study, 1, highlights the importance of careful medication management in patients with chronic kidney disease (CKD) to minimize the risk of nephrotoxic effects. Key points to consider include:

• NSAIDs like ibuprofen, naproxen, and diclofenac can cause acute interstitial nephritis and papillary necrosis with prolonged use.
• Antibiotics such as aminoglycosides (gentamicin, tobramycin), vancomycin, and amphotericin B can cause acute tubular necrosis.
• Certain chemotherapeutic agents like cisplatin and methotrexate are directly toxic to kidney tubules.
• ACE inhibitors (lisinopril, enalapril) and ARBs (losartan, valsartan) can cause acute kidney injury in patients with bilateral renal artery stenosis or volume depletion.
• Calcineurin inhibitors (cyclosporine, tacrolimus) used in transplant patients can cause both acute and chronic nephrotoxicity.
• Contrast media used in imaging studies can lead to contrast-induced nephropathy, particularly in patients with pre-existing kidney disease or diabetes. Risk factors for medication-induced kidney injury include older age, pre-existing kidney disease, dehydration, and concurrent use of multiple nephrotoxic agents, as noted in 1. It is essential to weigh the benefits and risks of medications in patients with CKD and to consider alternative treatments or dose adjustments to minimize nephrotoxic effects, as recommended in 1. Comprehensive medication management, including the involvement of clinical pharmacists, can help improve outcomes in patients with CKD by ensuring that medications are individually assessed for appropriateness, effectiveness, safety, and potential interactions, as emphasized in 1.

From the FDA Drug Label

Since tenofovir is primarily eliminated by the kidneys [See Clinical Pharmacology (12. 3)], coadministration of tenofovir disoproxil fumarate with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs. Some examples include, but are not limited to, cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [See Warnings and Precautions (5.2)]. Naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function

Medications that can cause intrinsic renal disease include:

• NSAIDs (e.g., naproxen) which can reduce renal function and increase the risk of renal toxicity
• Aminoglycosides (e.g., gentamicin) which can compete for active tubular secretion and increase serum concentrations of tenofovir
• Antiviral medications (e.g., cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir) which can increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs 2 3

From the Research

Medications Causing Intrinsic Renal Disease

• Non-steroidal anti-inflammatory drugs (NSAIDs) are a common class of medications that can cause intrinsic renal disease, including acute kidney injury (AKI) and chronic kidney disease (CKD) 4, 5, 6, 7.
• The mechanism of NSAID-induced renal disease is associated with the inhibition of prostaglandin synthesis, which can lead to decreased renal blood flow and glomerular filtration rate 5, 6.
• Selective NSAID cyclooxygenase-2 inhibitors also possess risks and can cause renal disease, particularly with long-term use 4.
• Other factors that increase the risk of NSAID-induced renal disease include:
  • Advanced age 4, 5
  • Hypovolemia 4, 5
  • High-dose exposure 4, 5
  • Use of vasoconstrictors such as calcineurin inhibitors 4
  • Use of renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics 4
• The risk of CKD occurrence and progression is significantly associated with chronic NSAID use, particularly in individuals with pre-existing CKD 7.
• Other renal complications of NSAID use include:
  • Acute interstitial nephritis 5, 6
  • Nephrotic syndrome 5, 6
  • Papillary necrosis 5
  • Sodium retention and edema formation 5
  • Hyperkalemia 5