What Drugs Cause Kidney and Liver Damage?

Dozens of widely used medications, from over-the-counter painkillers to prescription antibiotics and chemotherapy agents, can injure the kidneys, the liver, or both. Acetaminophen remains the single most recognized cause of acute drug-induced liver failure, while nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common culprits behind drug-related kidney injury. The risk, though, extends well beyond the medicine cabinet and into prescription-only territory, including certain antibiotics, cancer drugs, antivirals, and even diagnostic contrast dyes.

Acetaminophen and the Liver

Acetaminophen (known as paracetamol outside North America) is safe for most people at recommended doses, but it has an unusually narrow margin between a therapeutic dose and a toxic one. When you take more than your liver can handle, the normal detoxification pathways become overwhelmed. The liver produces a reactive byproduct called NAPQI, which under normal circumstances gets neutralized by a protective molecule called glutathione. In overdose situations, glutathione stores run out, and NAPQI starts binding to liver cell proteins, particularly inside mitochondria. That binding disrupts the cell’s energy production and triggers oxidative damage, which can cascade into widespread liver cell death.¹

What makes acetaminophen especially dangerous is how easily people exceed safe limits without realizing it. The drug appears in hundreds of combination products for cold, flu, and pain relief, so doubling up on products can push the total dose into risky territory. Chronic alcohol use makes things worse because alcohol ramps up the enzyme that produces NAPQI while simultaneously depleting glutathione. The standard antidote is N-acetylcysteine (NAC), which replenishes glutathione stores when given early enough. In severe poisoning cases with organ failure, hemodialysis can physically remove acetaminophen from the bloodstream, and international guidelines now recommend it in those scenarios.² One clinical study confirmed that both acetaminophen and the NAC antidote are highly dialyzable, though the NAC infusion rate needs to be more than doubled during dialysis to keep blood levels adequate.³

NSAIDs and the Kidneys

Ibuprofen, naproxen, diclofenac, and other NSAIDs work by blocking enzymes that produce prostaglandins, the signaling molecules responsible for inflammation and pain. The problem is that prostaglandins also help regulate blood flow to the kidneys. When those protective prostaglandins drop, blood vessels in the kidneys constrict, reducing filtration. For a healthy, well-hydrated person taking an occasional dose, this usually doesn’t matter. But in people who are dehydrated, elderly, or already have reduced kidney function, the loss of prostaglandin protection can tip the kidneys into acute injury.⁴

The most common pattern is a sudden drop in kidney function driven by reduced blood flow. A second, less frequent pattern is acute interstitial nephritis, an inflammatory reaction in the kidney tissue that can show up with significant protein in the urine.⁴ Long-term NSAID use carries its own concern: progressive chronic kidney disease in susceptible individuals. That susceptible group is larger than many people think. It includes older adults, people with heart failure, anyone already on blood pressure medications or diuretics, and those taking multiple drugs at once.⁵ The damage mechanism involves inhibition of prostaglandins that keep the kidneys’ blood supply open, particularly PGE2 and PGI2, and in the interstitial form, changes to the filtering structures including damage to the basement membrane and the cells that maintain the kidney’s filtration barrier.⁶

Antibiotics That Affect the Liver or Kidneys

Amoxicillin-clavulanate, one of the most commonly prescribed antibiotic combinations, is a well-documented cause of drug-induced liver injury. The liver damage it causes tends to be cholestatic, meaning bile flow is disrupted rather than liver cells being directly destroyed. Biopsies in affected patients nearly always show prominent cholestatic features.⁷ The reaction is thought to be immunoallergic in nature and is linked to specific immune-system gene variants, meaning some people are genetically predisposed to it while most are not.⁸ The injury sometimes doesn’t appear until weeks after the antibiotic course is finished, which makes it easy to miss the connection.

On the kidney side, vancomycin is a major offender. Used for serious infections like MRSA, vancomycin can cause acute kidney injury through interstitial nephritis, direct tubular damage, or both.⁹ Because vancomycin is typically given in hospitals for severe infections, kidney function is monitored during treatment, but the risk is real and sometimes requires stopping the drug.

Anti-tuberculosis drugs deserve special mention because they can damage the liver through a different route. Drugs like isoniazid and rifampicin produce reactive metabolites during liver processing, and genetic differences in how quickly people metabolize these drugs can substantially raise or lower the risk of toxicity. Factors like pre-existing liver disease, older age, and enzyme interactions between the drugs themselves all compound the problem.¹⁰ One pharmacogenomic study of over 600 TB patients found that a specific genetic variant in the CYP2D6 gene more than doubled the risk of liver toxicity from the treatment regimen.¹¹

Chemotherapy Drugs

Cancer treatment is hard on organs by nature, since many chemotherapy agents work by damaging rapidly dividing cells. Cisplatin, one of the most effective and widely used platinum-based drugs, is a well-known kidney toxin. The risk of kidney damage in patients taking cisplatin runs between about 20% and 35%.¹² The drug injures the proximal tubules of the kidney through a combination of direct cell death, oxidative stress, and an inflammatory response. Animal research has shown that a specific inflammatory signal, TNF-α, plays a central role; blocking it significantly reduces kidney damage in experimental models.¹²

Methotrexate is another drug that hits both organs. Originally a chemotherapy agent, it’s now widely used at lower doses for autoimmune conditions like rheumatoid arthritis. A large pharmacovigilance analysis of over 10,000 adverse event reports found that kidney reactions accounted for about 3.5% of cases and liver reactions for about 10.5%. The kidney cases tended to occur in older patients after longer use, and fatal outcomes were far more common in kidney-related reactions than liver-related ones (roughly 21% versus 6%).¹³ When given in high doses for cancer treatment, the liver risk is amplified further, especially in patients who have underlying fatty liver disease that may not have been diagnosed. One pediatric case demonstrated how high-dose methotrexate led to acute kidney injury within 24 hours, which then progressed to liver failure, confirmed on biopsy to be methotrexate toxicity compounded by undiagnosed fatty liver disease.¹⁴

Antiviral Medications

Tenofovir, a cornerstone drug in HIV treatment and hepatitis B therapy, has a well-characterized effect on the kidneys. The drug accumulates in the cells of the kidney’s proximal tubules and damages their mitochondria. Electron microscopy in animal studies has shown that tenofovir-treated kidneys contain abnormal mitochondria with fragmented internal structures, and the amount of mitochondrial DNA in those cells drops significantly.¹⁵ Animal studies using therapeutic doses have confirmed mild but real histological changes in both kidneys and liver, including widening of kidney structures and small vacuolations in liver cells.¹⁶ Newer formulations of tenofovir (tenofovir alafenamide) were developed in part to reduce kidney exposure.

Other antivirals carry kidney risk through different mechanisms. Acyclovir, used for herpes infections, and certain HIV protease inhibitors can form crystals inside the kidney’s tubules, physically blocking them. Atazanavir, another HIV drug, can trigger a rapid-onset inflammatory reaction in the kidneys that sometimes requires dialysis.¹⁷ These aren’t reasons to avoid antiviral therapy when it’s needed. But they do explain why doctors order regular kidney function tests during treatment.

Herbal Supplements and Recreational Drugs

Herbal and dietary supplements occupy a risky gray area because they aren’t regulated with the same rigor as prescription drugs, and people often don’t mention them to their doctors. Some of the most dangerous kidney toxins come from plants. Aristolochic acids, found in certain traditional herbal preparations, are potent nephrotoxins that can cause irreversible kidney damage and have been linked to a specific form of kidney disease seen in patients using Chinese herbal medicines.¹⁸ Other plant alkaloids also carry kidney risk, and contamination or mislabeling of herbal products can mean people are exposed to toxins they never intended to take.

Cocaine stands out among recreational drugs for its ability to damage multiple organs simultaneously. Through its sympathomimetic effects, cocaine causes widespread vasoconstriction, meaning blood vessels clamp down. This can starve muscles of oxygen, triggering massive muscle breakdown (rhabdomyolysis) that floods the kidneys with toxic proteins. The same vasoconstriction can produce “shock liver” from ischemia. Case reports describe cocaine-induced injury involving the kidneys, liver, lungs, and muscles all at once, sometimes with muscle damage markers exceeding 100,000 U/L, a staggeringly high number.¹⁹

Contrast Dyes Used in Medical Imaging

Iodinated contrast media, the dyes injected during CT scans and certain cardiac procedures, have long been considered a cause of acute kidney injury. The picture is more complicated than it once seemed. Some retrospective studies have questioned whether the dye itself is truly to blame, since rates of kidney injury looked similar in patients who received contrast and matched patients who didn’t. Still, experimental evidence clearly shows that contrast agents constrict blood vessels in the kidneys, increase oxygen demand in certain segments, and can be directly toxic to tubular cells.²⁰

The current consensus is that the risk is minimal for anyone with reasonably normal kidney function, specifically a filtration rate above 30 mL/min. Below that threshold, the risk becomes clinically meaningful and warrants preventive hydration protocols.²¹ Gadolinium-based contrast agents used in MRI carry a different concern: in patients with very poor kidney function, older gadolinium agents were linked to a serious condition called nephrogenic systemic fibrosis. Newer “group II” agents have largely eliminated that risk, even in advanced kidney disease.²¹ A pilot study in patients with normal kidney function found that even a single MRI with gadolinium produced a measurable increase in one urinary marker of tubular stress, suggesting subclinical effects may occur even in low-risk patients, though the clinical significance remains unclear.²²

Why Some People Get Hurt and Others Don’t

Two broad categories of drug-induced liver injury help explain the unpredictability. Intrinsic toxicity, as with acetaminophen, is dose-dependent and reproducible: take enough and the damage happens. Idiosyncratic toxicity is the trickier kind. It occurs in a minority of patients, doesn’t follow a clear dose pattern, and isn’t predictable with standard animal testing.²³ Many of the drugs discussed above, like amoxicillin-clavulanate and anti-TB medications, cause idiosyncratic injury. The “why me?” question often traces back to genetics, immune activation, or both.

Genetic variations in immune-system genes (particularly HLA genes) and in the enzymes and transporters that process drugs have been identified as risk factors for drug-induced liver injury across multiple drug classes.²⁴ Research into specific gene families involved in drug metabolism, including certain cytochrome P450 enzymes, glucuronosyltransferases, and drug transporter proteins, has turned up associations with liver injury from various medications.²⁵ The field is still young, though, and genetic testing before prescribing most drugs isn’t standard practice yet. Factors like age, pre-existing liver or kidney disease, the drug’s inherent molecular properties, and local oxygen supply in the liver all modulate the threshold at which toxicity occurs.²⁶

One mechanism that has gained attention is mitochondrial damage. An analysis of the FDA’s adverse event reporting system found that drugs whose liver toxicity involves mitochondrial mechanisms had about 1.4 times higher odds of being reported for liver injury compared to drugs that harm the liver through other pathways.²⁷ This makes sense biologically: mitochondria are the cell’s power plants, and disrupting them tends to cause more severe downstream damage than many other forms of injury.

The Compounding Effect of Multiple Medications

Taking many medications at once amplifies organ risk in ways that go beyond simple addition. Drug-drug interactions can alter how quickly each drug is broken down, change the concentration that reaches the liver or kidneys, and generate unexpected toxic metabolites. In patients who already have impaired kidney function, estimates suggest that between about 57% and 89% experience drug-drug interactions, driving up hospitalizations and healthcare costs.²⁸

A longitudinal study of older adults in China found a graded relationship between the number of medications taken and the risk of chronic kidney disease. Compared to people taking no medications, those on five or more drugs had roughly 3.7 times the odds of developing CKD.²⁹ A European study of people over 65 identified specific disease-and-drug clusters that carried elevated risk for both organs. People with overlapping cardiovascular and kidney conditions who were on multiple corresponding medications had about twice the odds of abnormal kidney function, while those with digestive conditions and their associated polypharmacy had over three times the odds of abnormal liver function.³⁰

Catching Damage Early

Diagnosing drug-induced liver injury is frustratingly indirect. It remains a diagnosis of exclusion, meaning doctors have to rule out viral hepatitis, autoimmune disease, bile duct obstruction, and other causes before concluding that a drug did the damage. Blood tests measuring the ratio of two liver enzymes (ALT and ALP) help classify the injury pattern as primarily liver-cell damage, bile-flow obstruction, or a mix. The single most important treatment step is stopping the suspected drug.³¹

For kidneys, the situation is improving. Regulators in the U.S. and Europe have accepted several urinary biomarkers as highly sensitive and specific tools for detecting drug-induced kidney injury. These include kidney injury molecule-1 (KIM-1), β2-microglobulin, cystatin C, clusterin, and trefoil factor-3, among others. A commercially available test called NephroCheck was the first FDA-approved biomarker platform specifically for detecting acute kidney injury in patients.³² These newer markers can detect tubular injury before the traditional blood creatinine test budges, which matters because creatinine only rises after a meaningful amount of kidney function has already been lost. The gap between subclinical damage and a change in creatinine is where early intervention lives, and it’s where the field is moving fastest.