From the Guidelines
Nephrotoxic drugs should be used with caution, and the lowest effective dose for the shortest duration necessary should be prescribed, especially in patients with pre-existing kidney disease, diabetes, heart failure, advanced age, or dehydration, as recommended by the most recent study 1. When prescribing potentially nephrotoxic medications, it's essential to consider the benefits versus potential harms, as people with chronic kidney disease (CKD) may be more susceptible to the nephrotoxic effects of medications 1. Some common nephrotoxic drugs include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen
- Aminoglycoside antibiotics such as gentamicin and tobramycin
- Certain chemotherapy agents like cisplatin
- Contrast media used in imaging studies
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Some antiviral medications including acyclovir and tenofovir These medications cause kidney damage through various mechanisms, including direct tubular toxicity, altered hemodynamics, crystal formation, or immune-mediated injury 1. To minimize the risk of nephrotoxicity, it's crucial to:
- Ensure adequate hydration
- Monitor kidney function through blood tests (creatinine, BUN)
- Adjust dosages based on kidney function
- Consider alternative medications in high-risk patients If signs of kidney injury develop (decreased urine output, elevated creatinine, fluid retention), the offending drug should be promptly discontinued, and appropriate supportive care initiated 1. Comprehensive medication management is vital in patients with CKD, and pharmacists play a key role in ensuring that each patient's medications are individually assessed to determine that each medication is appropriate, effective, safe, and able to be taken by the patient as intended 1. The use of drugs associated with kidney injury or dysfunction is common, and it's essential to be aware of the potential risks and benefits of these medications, as well as the importance of monitoring kidney function and adjusting dosages accordingly 1.
From the FDA Drug Label
Systemic exposure to Tobramycin for Injection and other aminoglycosides can cause nephrotoxicity, primarily manifested as acute tubular necrosis. As with other aminoglycosides, gentamicin injection is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage of prolonged therapy
Nephrotoxic drugs mentioned in the labels are:
- Tobramycin
- Gentamicin
- Cisplatin
- Cephaloridine
- Kanamycin
- Amikacin
- Neomycin
- Polymyxin B
- Colistin
- Paromomycin
- Streptomycin
- Vancomycin
- Viomycin
These drugs can cause nephrotoxicity, which may be manifested as:
- Rising blood urea nitrogen (BUN) and creatinine (Cr)
- Decreased urinary output
- Sodium, potassium, bicarbonate, magnesium, phosphate, and calcium urinary losses
- Acute tubular necrosis
The risk of nephrotoxicity increases with:
- Accumulation of the drug (indicated by rising trough levels)
- Excessive peak concentrations
- Total cumulative dose
- Advanced age
- Volume depletion
- Concurrent or sequential use of other nephrotoxic drugs
- Patients with diabetes 2
- Impaired renal function 3
- Dehydration 3
From the Research
Nephrotoxic Drugs
- Nephrotoxicity can manifest itself in several forms depending on the specific site involved as well as the underlying pathophysiological mechanisms 4
- A variety of marketed drugs belonging to various therapeutic classes are known to cause nephrotoxicity, including:
- Bisphosphonates and hypnotics, which increase the progression of chronic kidney disease (CKD) 5
- Tenofovir disoproxil fumarate (TDF), which increases the risk of renal tubular toxicity and adverse effects on bone 5
- Nonsteroidal anti-inflammatory drugs (NSAIDs), which increase the risk of acute kidney injury or progression of CKD 6, 7
- Aminoglycoside antibiotics, such as gentamicin, tobramycin, and amikacin, which can cause nephrotoxicity due to their mechanism of action 8
- Prior knowledge of risk factors associated with special patient populations and specific classes of drugs, combined with early diagnosis, therapeutic drug monitoring with dose adjustments, as well as timely prospective treatments are essential to prevent and manage nephrotoxicity 4
- Community prescribing of potential nephrotoxins, such as angiotensin-converting-enzyme inhibitors/angiotensin-receptor blockers, diuretics, or NSAIDs, increases the risk of renal replacement therapy and early acute kidney injury in ICU populations 7
Management and Prevention
- Early diagnosis and treatment are crucial to prevent and manage nephrotoxicity, as most incident drug-induced renal toxicity is reversible only if diagnosed at an early stage and treated promptly 4
- Mathematical modeling and simulation (M&S) approaches may help to better understand and predict toxicities in a clinical setting 4
- Close attention is needed to select the appropriate dose or safer alternatives to reduce the risk of drug-induced harm in patients with CKD 5
- Timely cessation of potential nephrotoxins in acute illness may help to reduce the risk of renal replacement therapy and early acute kidney injury 7