Patients are treated with prescription or over-the-counter drugs that are chemical or biological agents, some of which may be nephrotoxic when metabolized or excreted through the kidneys, causing some degree of renal impairment. Studies have shown that the incidence of drug nephrotoxicity in the adult population is about 14% to 26%. Especially in hospitalized patients, drug nephrotoxicity tends to be more common because of the severity of the condition and the variety of medications used.
In this article, we take stock of drugs that are nephrotoxic and hope that people will be aware of the possible kidney risks before taking them, weigh the pros and cons, and use them carefully!
Common nephrotoxic drugs
As shown in the table below, these are common drugs with a risk of nephrotoxicity across all disease areas, whether they are cold and flu medications or anti-cancer drugs, or even diagnostic reagents and herbal medicines that can damage kidney tissue.
Table 1. Therapeutic agents with nephrotoxicity
| Drug Type | Examples of typical drugs |
| Anti-microbial agents | |
| Aminoglycosides | Neomycin, gentamicin, tobramycin, amikacin |
| Ribavirin, adefovir, tenofovir | |
| Amphotericin B | |
| Polymyxin | Polymyxin B sulfate, Polymyxin E sulfate |
| Sulfadoxine-pyrimethamine | |
| Quinolones | Norfloxacin, ofloxacin, ciprofloxacin, gatifloxacin |
| Vancomycin | |
| Anti-cancer drugs | |
| Platinum-based drugs | Cisplatin, carboplatin |
| Isocyclophosphamide | |
| Mithramycin | |
| Gemcitabine | |
| Methotrexate | |
| Pentostatin | |
| Anti-angiogenic agents | Bevacizumab |
| Immune checkpoint inhibitors | Ipivizumab, nabumab, pembrolizumab |
| Gene reconstitution immunotherapy | Chimeric antigen receptor T-cell immunotherapy (CAR-T) therapy |
| Analgesics | |
| Nonsteroidal antiinflammatory drug (NSAID) | Acetaminophen, ibuprofen, naproxen |
| Selective COX-2 inhibitors | Celecoxib |
| Finasteride | |
| Analgesic combination compound | |
| Immunosuppressants | |
| Calcium-regulated phosphatase inhibitors | Cyclosporine, tacrolimus |
| mammalian target of rapamycin (mTOR) inhibitors | Sirolimus, everolimus |
| Antihypertensive drugs | |
| angiotensin converting enzyme inhibitors (ACEI) | Captopril, enalapril |
| Angiotensin II receptor antagonists (ARBs) | Valsartan, olmesartan, irbesartan |
| Renin inhibitors | Aliskiren |
| Other drugs | |
| SGLT-2 inhibitor class of hypoglycemic agents | Carboglitazone, daglitazone |
| Statin-based lipid-lowering drugs | Simvastatin, atorvastatin |
| Pamidronate, zolendronate | |
| Methoxyflurane (anesthetic) | |
| Topiramate, zonisamide (antiepileptic) | |
| Orlistat (weight loss drug) | |
| Mesalazine (ulcerative colitis) | |
Table 2. Diagnostic reagents with nephrotoxicity
| Reagent type | Examples of typical drugs |
| All types of hypertonic, hypotonic, or isotonic iodine-containing contrast media | Pantopamine, iodotriptan, iodinated oil |
| Gadopentetate glucosamine, gadodiamide | |
| Oral sodium phosphate solution (for colonoscopy) |
Table 3. Herbs with nephrotoxicity
| Drug Type | Examples of typical drugs |
| Drugs containing aristolochic acid | Aristolochic acid, Bonesetter, Viburnum |
| Ephedra spp. | Grass Ephedra, Miscanthus Ephedra |
| Ganja spp. | Licorice, Distended Fruit Licorice, Light Fruit Licorice |
| Mandarins | White flowered mandarins, red flowered mandarins |
| Redbud (also known as Purple Shirt) genus | Compound redbud preparation |
| Aloe vera | Spotted Aloe, Good Hope Aloe |
Table 4. Chemicals with nephrotoxicity in fake and substandard drugs
| Composition type | Examples of typical substances |
| 2,3-dimethylaniline, potassium dichromate, melamine | |
| All types of heavy metals | lead, mercury, cadmium, uranium, copper, bismuth |
| All types of organic solvents | Solvents containing benzene or hydrocarbons |
Mechanisms of drug-induced nephrotoxicity
The severity of drug nephrotoxicity is influenced by a number of factors, mainly involving 2 aspects – the drug and the patient.
Drug factors
- The drug itself is toxic to kidney tissue;
- Increased levels of drug exposure, including higher doses, longer courses of therapy, or administration by intravenous infusion;
- Interference with the body’s immune system, inducing renal inflammation;
- Concurrent use of multiple drugs with nephrotoxic effects;
- Production of insoluble urine crystals deposited in the kidney during metabolism;
- Interference with substance transport in renal cells and intracellular accumulation of the drug;
- Drug accumulation in the extracellular interstitium due to abnormal metabolic enzymes that fail to clear the drug in a timely manner;
- Drug interacts with proteins in the renal tubules and forms tubular deposits.
Patient factors
- Age >65 years;
- Female;
- with abnormal renal function or kidney disease;
- Combined with other chronic diseases;
- An allergic reaction of the immune system to certain drugs;
- Some defects in genetic genes responsible for drug metabolism and transport.
Summary
In summary, all drugs have certain toxic side effects while treating diseases, and it is necessary for patients to refer to their doctor’s advice when taking any drug, and not to change the dosing regimen or dosage without authorization to avoid increasing the risk of nephrotoxicity. Particular care should be taken not to indiscriminately abuse herbal medicines, which is one of the major causes of severe kidney injury in the Asian population. Patients with more severe disease or who have been taking medications for a long time must follow their doctor’s orders for regular follow-up visits so that the doctor can make appropriate adjustments to the medication regimen based on the actual situation.