Common Medications That Can Be Harmful to Your Kidneys

1. Ibuprofen

Ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs) for relieving pain, reducing inflammation, and lowering fever. While generally safe when taken as directed, ibuprofen can significantly impair kidney function, especially when used frequently or in high doses. The kidneys rely on a delicate balance of blood flow to function properly, and ibuprofen can disrupt this balance by blocking the production of prostaglandins—compounds that help regulate blood flow within the kidneys. This disruption may lead to acute kidney injury, particularly in those with pre-existing kidney disease, heart conditions, or dehydration.

Cases of kidney damage have been reported from over-the-counter misuse, such as taking more than the recommended dosage or using ibuprofen for extended periods without medical supervision. For example, someone using ibuprofen daily for chronic headaches or back pain, believing it to be harmless, may unknowingly put their kidneys at risk. To use ibuprofen safely, always follow dosing instructions, avoid long-term use unless prescribed, and consult your healthcare provider if you have other risk factors. For more details, visit the National Kidney Foundation’s ibuprofen and kidneys resource.

2. Naproxen

Naproxen is another popular NSAID, commonly available under brand names such as Aleve, and is often used for pain management and inflammation. Like ibuprofen, naproxen can interfere with the kidneys’ ability to maintain healthy blood flow, increasing the risk of acute kidney injury (AKI) or worsening chronic kidney disease. Naproxen works by inhibiting the production of prostaglandins, which are essential for maintaining kidney blood flow, especially during states of dehydration or stress. People with pre-existing kidney conditions, those over 65, or those taking diuretics are particularly vulnerable to naproxen’s harmful effects.

Compared to other NSAIDs, naproxen carries similar risks for kidney injury, especially when used at high doses or for extended periods. Signs of potential kidney trouble include changes in urination, swelling in the legs or ankles, fatigue, and unexplained increases in blood pressure. If you experience any of these symptoms while taking naproxen, seek medical advice promptly. To minimize risk, use the lowest effective dose for the shortest time possible and avoid combining naproxen with other NSAIDs. For more information, see the National Kidney Foundation’s guide to NSAIDs and kidney health.

3. Aspirin (High Doses)

Aspirin is often used for pain relief, inflammation, and heart health in low doses. However, at high doses, aspirin can pose significant risks to kidney health. Prolonged or excessive use can impair the kidneys’ ability to filter waste, potentially leading to chronic kidney disease or acute kidney injury. High-dose aspirin, like other NSAIDs, inhibits prostaglandin synthesis, which can decrease blood flow to the kidneys and compromise their function, especially in those who are elderly or have pre-existing kidney or heart conditions.

Historically, “analgesic nephropathy” was a well-known condition resulting from the chronic use of combination pain medications, often containing aspirin. This condition involved progressive kidney damage and, in severe cases, kidney failure. While less common today due to changes in medication formulations, high-dose aspirin can still be harmful if misused. Warning signs of kidney trouble include reduced urine output, swelling, and unexplained fatigue. If you are taking aspirin at high doses or for extended periods, it is crucial to consult a healthcare provider for monitoring and guidance. For more details, visit the National Kidney Foundation’s page on analgesics and kidney health.

4. Acetaminophen (Paracetamol)

Acetaminophen, also known as paracetamol, is a widely used over-the-counter pain and fever reliever. While generally considered safer for the kidneys than NSAIDs, chronic or excessive use can still pose risks, particularly in individuals with pre-existing kidney disease or those who consume high doses over time. Acetaminophen is primarily metabolized by the liver, but its byproducts are eliminated through the kidneys. Prolonged use or overdose can lead to the accumulation of toxic metabolites, which may contribute to kidney damage and, in rare cases, acute renal failure.

Compared to NSAIDs like ibuprofen and naproxen, acetaminophen is less likely to cause direct kidney injury in healthy individuals. However, studies have shown that habitual, long-term use, especially in combination with other medications or alcohol, can elevate the risk of kidney impairment. It is important to monitor your total daily intake, as acetaminophen is a common ingredient in many prescription and over-the-counter products. Always follow dosing recommendations and seek medical advice if you require regular pain management. For more information, visit the National Kidney Foundation’s acetaminophen information page.

5. Celecoxib

Celecoxib, a selective COX-2 inhibitor commonly prescribed for arthritis and pain management, was developed to reduce gastrointestinal side effects associated with traditional NSAIDs. However, celecoxib can still adversely affect kidney function. By selectively inhibiting the COX-2 enzyme, celecoxib decreases the synthesis of prostaglandins that help maintain adequate blood flow to the kidneys. This effect can result in reduced renal perfusion, potentially leading to acute kidney injury—particularly in individuals with underlying kidney disease, heart failure, or dehydration.

An example reported in clinical literature involved an elderly patient with hypertension who developed acute kidney injury after starting celecoxib for osteoarthritis. The patient’s kidney function improved upon discontinuation of the drug, highlighting the need for careful monitoring. Other risk factors for celecoxib-induced kidney damage include advanced age, concurrent use of diuretics or ACE inhibitors, and medical conditions such as diabetes or liver disease. Patients with these risk factors should use celecoxib with caution and under medical supervision. For more detailed information, refer to the National Institutes of Health article on COX-2 inhibitors and renal effects.

6. Diclofenac

Diclofenac is a potent NSAID frequently prescribed for treating pain and inflammation associated with conditions like arthritis. Similar to other NSAIDs, diclofenac works by inhibiting cyclooxygenase (COX) enzymes, which reduces the production of prostaglandins necessary for maintaining healthy kidney blood flow. This interference can decrease blood supply to the kidneys, potentially resulting in acute kidney injury or exacerbating chronic kidney disease, especially in susceptible individuals such as the elderly or those with pre-existing kidney problems.

Compared to ibuprofen, diclofenac is often considered more potent and carries a higher risk of cardiovascular and renal side effects, particularly when used at high doses or over a prolonged period. Clinical studies have shown that chronic use of diclofenac is associated with a higher incidence of kidney-related complications. To minimize the risks, it is advised to use diclofenac at the lowest effective dose and for the shortest possible duration. Patients should avoid combining diclofenac with other NSAIDs and always consult a healthcare professional before starting therapy. For more guidance, visit the National Kidney Foundation’s resource on diclofenac and kidney health.

7. Indomethacin

Indomethacin is a powerful NSAID prescribed for moderate to severe pain, particularly in conditions such as gout, arthritis, and ankylosing spondylitis. Like other NSAIDs, indomethacin inhibits the synthesis of prostaglandins, which are vital for maintaining optimal kidney blood flow. This suppression can lead to reduced renal perfusion, raising the risk of acute kidney injury or worsening pre-existing chronic kidney disease. The risk is especially pronounced in elderly patients, who often have diminished kidney function and may be taking multiple medications that further strain renal health.

Studies have shown that elderly individuals are more susceptible to indomethacin-induced kidney complications, including fluid retention, increased blood pressure, and electrolyte imbalances. These adverse effects may present as swelling in the legs, reduced urine output, or unexplained fatigue. If indomethacin is necessary, regular monitoring of kidney function through blood tests and attention to fluid balance is essential. Patients and caregivers should be vigilant for early warning signs of kidney dysfunction. For more detailed information about indomethacin’s impact on kidney health, visit the National Center for Biotechnology Information (NCBI) page on indomethacin.

8. Lithium

Lithium is a mood stabilizer commonly prescribed for managing bipolar disorder and other psychiatric conditions. While effective for mental health, lithium carries a well-documented risk of causing chronic kidney disease (CKD) with long-term use. Lithium can accumulate in the kidneys, leading to a condition known as nephrogenic diabetes insipidus, where the kidneys lose their ability to concentrate urine. Over time, this may progress to interstitial nephritis or chronic renal impairment, especially if blood lithium levels exceed the therapeutic range.

Real-world cases highlight the risk: one patient, treated with lithium for over a decade, developed persistent thirst and excessive urination, symptoms of nephrogenic diabetes insipidus. Despite dose adjustments, kidney function gradually declined, underscoring the need for vigilant monitoring. Routine blood tests to check lithium levels and kidney function, including measurements of creatinine and glomerular filtration rate (GFR), are strongly recommended for all patients on lithium. Early detection of kidney changes can allow for timely intervention and potential medication adjustments. For more detailed guidance, visit the National Kidney Foundation’s resource on lithium and kidney health.

9. Methotrexate

Methotrexate is a widely used immunosuppressant and chemotherapy agent prescribed for conditions such as rheumatoid arthritis, psoriasis, and various cancers. While effective, methotrexate can pose risks of kidney toxicity, particularly at high doses used in cancer treatment. Methotrexate is eliminated through the kidneys, and impaired renal function can lead to dangerous accumulation of the drug and its toxic metabolites. This may result in acute kidney injury, which in turn can further reduce methotrexate clearance, creating a harmful cycle.

Compared to other immunosuppressants, methotrexate has a specific risk for renal toxicity due to its renal excretion. Other drugs, such as cyclosporine or azathioprine, have different toxicity profiles but can also affect the kidneys in susceptible individuals. To minimize risk, hydration is critical while on methotrexate, and regular kidney function monitoring through blood tests is advised. Patients should also avoid NSAIDs during methotrexate therapy, as they can further increase the risk of kidney injury. Promptly report any signs of reduced urine output, swelling, or fatigue to your healthcare provider. For more safety information, consult the NCBI overview of methotrexate toxicity.

10. Cyclosporine

Cyclosporine is an immunosuppressant frequently prescribed to prevent organ rejection in transplant patients and to treat certain autoimmune diseases. While highly effective for these purposes, cyclosporine can cause significant kidney damage by constricting blood vessels within the kidneys, reducing blood flow and impairing filtration. This vasoconstriction can lead to increased blood pressure and a decrease in glomerular filtration rate (GFR), raising the risk for both acute and chronic kidney injury.

Transplant patients are particularly susceptible, as they typically require long-term cyclosporine therapy to maintain organ function. Studies and patient experiences have shown that even therapeutic doses can result in a gradual decline in kidney function over time. Regular monitoring is essential; healthcare providers routinely order blood tests to measure cyclosporine levels, kidney function (creatinine and GFR), and blood pressure. Early detection of rising creatinine or declining GFR allows for timely dose adjustments or the consideration of alternative therapies. For more information about cyclosporine’s kidney risks and monitoring protocols, visit the National Kidney Foundation’s guide to cyclosporine and kidney health.

11. Tacrolimus

Tacrolimus is a potent immunosuppressive medication widely used to prevent organ rejection in transplant recipients and to manage certain autoimmune disorders. Like cyclosporine, tacrolimus can harm the kidneys by affecting the glomeruli, the tiny filtering units responsible for removing waste from the blood. Tacrolimus causes constriction of blood vessels within the kidneys, reducing blood flow and filtration efficiency. Over time, this can result in acute kidney injury or, with prolonged use, chronic kidney disease due to scarring and damage to the glomeruli.

When comparing tacrolimus with cyclosporine, both drugs have similar nephrotoxic effects, though some studies suggest tacrolimus may be slightly less likely to cause high blood pressure but can still lead to significant kidney impairment at therapeutic doses. Given these risks, regular laboratory monitoring is essential. Blood tests to measure tacrolimus levels, serum creatinine, and estimated glomerular filtration rate (eGFR) should be performed frequently, especially in the early months after transplantation or dosage changes. Close oversight enables healthcare providers to adjust doses promptly and minimize kidney damage. For further reading, visit the National Kidney Foundation’s tacrolimus information page.

12. Gentamicin

Gentamicin is an aminoglycoside antibiotic often used in hospitals to treat severe bacterial infections. While effective, gentamicin is known for its potential to cause nephrotoxicity by damaging the kidney tubules, specifically the proximal tubular cells responsible for filtering waste and reabsorbing essential substances. The drug accumulates in these cells, leading to cellular dysfunction, acute tubular necrosis, and, in severe cases, acute kidney injury. This risk increases with higher doses, prolonged therapy, or concurrent use of other nephrotoxic medications.

Hospital-related cases of gentamicin-induced kidney injury are well documented, particularly among critically ill patients or those with pre-existing kidney impairment. Symptoms can include reduced urine output, swelling, and increases in serum creatinine. To prevent harm, clinicians employ strategies such as dosing adjustments based on kidney function, therapeutic drug monitoring, and limiting the duration of therapy. Adequate hydration and avoiding simultaneous use of other nephrotoxic drugs further reduce risk. For more on gentamicin nephrotoxicity and prevention, see the NCBI review on aminoglycoside-induced nephrotoxicity.

13. Amikacin

Amikacin is a potent aminoglycoside antibiotic used to treat serious, often drug-resistant bacterial infections. Although lifesaving, amikacin carries a significant risk of causing acute kidney injury (AKI). Like other drugs in its class, amikacin accumulates in the proximal tubules of the kidneys, disrupting cellular function and leading to tubular necrosis. The risk of toxicity increases with higher cumulative doses, prolonged treatment, or pre-existing kidney dysfunction. Elderly patients and those with dehydration are especially vulnerable.

Compared to other aminoglycosides such as gentamicin and tobramycin, amikacin has a similar nephrotoxic profile. However, it may be preferred in certain infections due to its effectiveness against resistant bacteria. Clinically, the onset of kidney injury may be subtle. Early signs include rising blood creatinine levels, decreased urine output, and swelling in the lower limbs. Monitoring kidney function with regular blood tests and adjusting dosing based on renal function are essential strategies for minimizing risk. Reporting symptoms promptly helps prevent further damage. For more information, refer to the NCBI article on amikacin safety and toxicity.

14. Vancomycin

Vancomycin is a powerful antibiotic primarily used to treat severe infections caused by resistant bacteria, such as MRSA. However, it is known to cause kidney problems, particularly acute kidney injury, when used in high doses or for prolonged periods. Vancomycin-induced nephrotoxicity is thought to result from direct toxicity to the renal tubules, leading to cellular injury and impaired filtration. The risk increases when vancomycin is combined with other nephrotoxic drugs or given to patients with pre-existing kidney issues.

In intensive care settings, vancomycin-associated kidney problems are frequently observed. For instance, a critically ill patient receiving vancomycin and aminoglycosides for a resistant infection developed rising creatinine levels and reduced urine output, indicating acute kidney injury. Such cases underscore the importance of careful dosing and regular monitoring. Healthcare providers routinely adjust vancomycin doses based on blood levels and kidney function tests, aiming to balance effective infection control with minimal renal risk. For more details on vancomycin nephrotoxicity and dose adjustment strategies, visit the NCBI review on vancomycin-induced kidney injury.

15. Amphotericin B

Amphotericin B is a potent antifungal medication reserved for severe, life-threatening fungal infections. Despite its effectiveness, it is notorious for causing kidney toxicity, commonly leading to acute kidney injury. Amphotericin B damages kidney cells by increasing the permeability of cell membranes, resulting in the loss of essential electrolytes and impaired kidney function. The risk is particularly high with the traditional “deoxycholate” formulation, though lipid-based versions are somewhat less toxic but still require caution.

A clinical example involves a patient treated with amphotericin B for invasive aspergillosis who developed abrupt increases in creatinine and electrolyte abnormalities, necessitating discontinuation of the drug and supportive therapies. Such cases are not uncommon, especially in critically ill or immunocompromised patients. To minimize harm, clinicians often use the lowest effective dose, switch to lipid-based formulations when possible, ensure adequate hydration, and monitor kidney function and electrolytes closely throughout treatment. Early identification and intervention are crucial for preventing permanent damage. For further information, see the NCBI review on amphotericin B nephrotoxicity.

16. Acyclovir

Acyclovir is an antiviral medication widely used to treat infections caused by herpes viruses, including herpes simplex and varicella-zoster. While generally considered safe, acyclovir can cause a specific type of kidney injury known as crystal-induced nephropathy, particularly when administered intravenously (IV) at high doses. The drug can precipitate in the renal tubules, forming crystals that obstruct urine flow and damage kidney tissues. This risk is much lower with oral forms due to lower peak blood concentrations, though dehydration or pre-existing kidney problems can still increase susceptibility.

Clinical evidence shows that IV acyclovir is more commonly associated with acute kidney injury, especially in hospitalized patients who may be receiving high doses rapidly. Symptoms can include flank pain, reduced urine output, and elevated creatinine levels. To minimize risk, aggressive hydration before and during acyclovir therapy is recommended, as it helps dilute the urine and promotes the excretion of drug crystals. Monitoring kidney function throughout treatment is also crucial. For more information on acyclovir-induced kidney injury and prevention strategies, refer to the NCBI overview on acyclovir nephrotoxicity.

17. Tenofovir

Tenofovir is a widely used antiretroviral medication prescribed for the treatment and prevention of HIV and hepatitis B infections. While generally well-tolerated, tenofovir can cause damage to the kidney tubules, specifically the proximal tubules responsible for reabsorbing essential substances. This injury may lead to a condition known as Fanconi syndrome, characterized by the loss of phosphate, glucose, and other electrolytes in the urine. Over time, long-term use of tenofovir has been associated with chronic kidney disease and decreases in bone mineral density due to phosphate loss.

Patients on tenofovir, especially those with additional risk factors such as pre-existing kidney disease, diabetes, or concurrent use of other nephrotoxic medications, require careful monitoring. Routine laboratory tests including serum creatinine, estimated glomerular filtration rate (eGFR), and urine analysis are recommended to detect early signs of kidney impairment. Adjustments in dosing or switching to alternative antiretroviral drugs may be necessary if kidney function declines. For more information about tenofovir’s renal effects and guidelines for monitoring, visit the NCBI review on tenofovir nephrotoxicity.

18. Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used to treat urinary tract infections, pneumonia, and other bacterial infections. While usually well-tolerated, TMP-SMX can, in rare cases, cause serious kidney side effects, including acute interstitial nephritis, crystalluria, and hyperkalemia (elevated potassium levels). These complications are more likely in patients with pre-existing kidney disease or those receiving high doses for extended periods.

Compared to other antibiotics, TMP-SMX’s risk of kidney injury is relatively rare but significant, especially when compared to aminoglycosides or vancomycin, which are more commonly associated with nephrotoxicity. Symptoms of TMP-SMX-induced kidney injury may include sudden decreases in urine output, blood in the urine, fatigue, and swelling. Routine blood test monitoring, including serum creatinine and electrolyte levels, is recommended during therapy, particularly in patients with additional risk factors. If kidney dysfunction is detected, prompt discontinuation of the drug and medical evaluation are necessary. For more information on TMP-SMX and its renal side effects, see the NCBI review on sulfonamides and kidney toxicity.

19. Penicillins (High Doses)

Penicillins are among the most commonly prescribed antibiotics, valued for their broad safety profile. However, at high doses or with prolonged use, penicillins can cause a rare but serious kidney condition known as acute interstitial nephritis (AIN). This immune-mediated reaction leads to inflammation of the kidney’s interstitial tissue, impairing its ability to filter blood and excrete waste products. The risk is heightened when penicillins are administered in large doses or to individuals with a history of allergies or autoimmune conditions.

A notable case study involved a patient treated with high-dose intravenous penicillin for bacterial endocarditis who developed sudden renal impairment, accompanied by fever, rash, and eosinophilia—a classic triad suggestive of AIN. Discontinuation of the drug and administration of corticosteroids resulted in gradual improvement of kidney function. Warning symptoms of penicillin-induced interstitial nephritis include fever, rash, joint pain, blood in the urine, and sudden changes in urine output. Early recognition and prompt withdrawal of the offending drug are crucial for recovery. For more details on penicillin-induced nephritis, visit the NCBI review on drug-induced interstitial nephritis.

20. Angiotensin-Converting Enzyme Inhibitors (ACE inhibitors)

Angiotensin-converting enzyme inhibitors (ACE inhibitors) are widely prescribed to treat high blood pressure, heart failure, and kidney protection in diabetes. While generally beneficial for kidney health, ACE inhibitors can sometimes worsen kidney function, particularly in patients with certain underlying conditions. In individuals with bilateral renal artery stenosis, severe dehydration, or pre-existing advanced kidney disease, ACE inhibitors may reduce blood flow to the kidneys too much, resulting in a sudden decline in kidney function or acute kidney injury.

When initiating or adjusting ACE inhibitor therapy, it is essential to monitor kidney function closely with regular blood tests, including serum creatinine and potassium levels. Early detection of rising creatinine or hyperkalemia allows for timely intervention, such as dose modification or discontinuation. Most patients tolerate ACE inhibitors well and experience stabilization or improvement in kidney function over time, but those at risk must be monitored carefully. For further information on ACE inhibitors and their impact on the kidneys, see the National Kidney Foundation’s resource on ACE inhibitors.

21. Angiotensin Receptor Blockers (ARBs)

Angiotensin receptor blockers (ARBs) are commonly used to manage high blood pressure, heart failure, and chronic kidney disease, often as an alternative to ACE inhibitors. While ARBs generally protect kidney health, they can impair kidney filtration in certain situations. Like ACE inhibitors, ARBs lower blood pressure by relaxing blood vessels and reducing pressure within the glomeruli—the filtering units of the kidneys. However, when kidney blood flow is already compromised, such as in cases of bilateral renal artery stenosis or advanced chronic kidney disease, ARBs may further decrease filtration, leading to acute kidney injury.

Compared to ACE inhibitors, ARBs have a similar mechanism of action but are less likely to cause cough or angioedema. Both drug classes require careful monitoring of kidney function and potassium levels, especially after starting therapy or increasing the dose. Dose adjustments or discontinuation may be necessary if serum creatinine rises significantly or if hyperkalemia develops. Most patients benefit from ARBs, but those at elevated risk should have regular laboratory evaluations. For more information about ARBs and kidney health, visit the National Kidney Foundation’s ARB resource.

22. Diuretics (Water Pills)

Diuretics, commonly called “water pills,” are prescribed to treat conditions such as high blood pressure, heart failure, and fluid retention. These medications work by increasing urine output, which helps remove excess fluid and lower blood pressure. However, excessive diuresis can lead to dehydration, electrolyte imbalances, and, in some cases, acute kidney injury. When the body loses too much water and essential minerals like potassium and sodium, the kidneys may become stressed and unable to maintain proper filtration.

There are several types of diuretics, with loop diuretics (such as furosemide) often used for more severe fluid overload, while thiazide diuretics (such as hydrochlorothiazide) are commonly prescribed for high blood pressure. Loop diuretics tend to be more potent and carry a higher risk of causing dehydration and electrolyte disturbances compared to thiazides. To prevent kidney injury, it is important to maintain adequate hydration and follow your healthcare provider’s dosing instructions. Monitoring for signs of dehydration—such as dry mouth, dizziness, or reduced urine output—is crucial. For more on safe use of diuretics and kidney health, see the National Kidney Foundation’s guide to diuretics.

23. Proton Pump Inhibitors (PPIs)

Proton pump inhibitors (PPIs) are widely prescribed for acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Although generally considered safe for short-term use, recent studies have linked long-term PPI therapy to an increased risk of chronic kidney disease (CKD) and acute interstitial nephritis. Research published in journals such as JAMA and Kidney International has found that people taking PPIs for extended periods have a higher likelihood of developing kidney problems compared to those using alternative acid-suppressing medications.

The exact mechanism by which PPIs contribute to kidney injury is not fully understood, but it may involve immune-mediated inflammation and damage to the kidney’s filtering structures. Given these risks, patients on PPIs for more than a few weeks should regularly review the need for continued therapy with their healthcare provider. Alternative approaches for managing reflux include lifestyle changes, such as weight loss, dietary adjustments, and using H2 blockers, which may carry a lower risk for kidney complications. For more scientific details and practical advice, visit the National Kidney Foundation’s information page on PPIs and kidney disease.

24. H2 Blockers

H2 blockers, such as ranitidine and famotidine, are commonly used to reduce stomach acid and treat conditions like heartburn and ulcers. While generally considered safer than proton pump inhibitors (PPIs) regarding kidney health, H2 blockers can still rarely cause kidney issues, including acute interstitial nephritis. This immune-mediated reaction leads to inflammation of the kidney’s filtering tissue and, if undetected, may result in impaired renal function.

Compared to PPIs, H2 blockers have a lower risk of causing chronic kidney disease, but cases of kidney injury have been reported, especially with long-term use or in patients with pre-existing kidney problems. Warning signs that may indicate a kidney problem while taking H2 blockers include unexplained fatigue, swelling, sudden changes in urination, or blood in the urine. If such symptoms occur, prompt discontinuation of the medication and consultation with a healthcare provider are essential. For patients requiring ongoing acid suppression, regular monitoring and periodic reassessment of therapy are advised. For further information, refer to the NCBI article on H2 blockers and renal adverse effects.

25. Allopurinol

Allopurinol is a medication commonly prescribed to lower uric acid levels in patients with gout and certain types of kidney stones. While generally safe and effective, allopurinol can rarely cause a serious reaction known as allopurinol hypersensitivity syndrome, which may include acute interstitial nephritis—an inflammation of the kidney’s filtering tissues. This can lead to impaired kidney function, particularly in individuals with pre-existing renal disease or those on higher doses.

A documented case involved a patient who developed rash, fever, and reduced urine output shortly after starting allopurinol therapy. Laboratory tests revealed acute kidney injury and eosinophilia, prompting immediate discontinuation of allopurinol and initiation of corticosteroid treatment. The patient’s kidney function gradually recovered. For those taking allopurinol, it is important to monitor for early warning signs such as skin rash, fever, joint pain, or changes in urination. Routine blood tests to assess uric acid, creatinine, and kidney function are recommended, especially after starting therapy or adjusting the dose. For more details about allopurinol and kidney risks, visit the NCBI review on allopurinol hypersensitivity and renal complications.

26. Metformin

Metformin is a widely prescribed oral medication for type 2 diabetes, favored for its effectiveness and low risk of causing low blood sugar. However, metformin can be harmful in patients with significantly reduced kidney function. When kidney filtration is impaired, metformin and its byproducts can accumulate in the body, increasing the risk of a rare but potentially life-threatening condition called lactic acidosis. Lactic acidosis is characterized by the buildup of lactic acid in the bloodstream, leading to symptoms such as rapid breathing, abdominal pain, muscle cramps, and confusion.

Current guidelines recommend avoiding metformin in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m² and exercising caution when eGFR is between 30 and 45. Regular monitoring of kidney function is advised for all patients on metformin, particularly those with risk factors for kidney disease or those experiencing dehydration or acute illness. Promptly report symptoms such as unusual fatigue, muscle pain, or trouble breathing to a healthcare provider. For more information on metformin safety and lactic acidosis, see the National Kidney Foundation’s guide to metformin and kidney disease.

27. Sulfonylureas

Sulfonylureas, such as glipizide, glyburide, and glimepiride, are oral medications used to help control blood sugar levels in people with type 2 diabetes. Unlike metformin, which is generally safer for the kidneys, sulfonylureas can accumulate in the body if kidney function is impaired, increasing the risk of serious side effects such as hypoglycemia (dangerously low blood sugar). The kidneys play a significant role in eliminating these drugs, so reduced renal function can lead to prolonged drug action and greater risk of adverse events.

Compared to metformin, sulfonylureas do not directly cause kidney injury but can become hazardous in patients with chronic kidney disease due to their risk of hypoglycemia and, for some agents, the formation of potentially toxic metabolites. Dose adjustments or selecting sulfonylureas with safer profiles in renal impairment (like glipizide) are often necessary. Patients with declining kidney function should have their sulfonylurea regimen reviewed regularly and may require more frequent blood glucose monitoring. For more details on sulfonylureas and kidney safety, see the NCBI review on oral diabetes medications and renal impairment.

28. Statins (High Doses)

Statins are cholesterol-lowering medications widely used to reduce the risk of heart attacks and strokes. While statins are generally safe, high-dose statin therapy can rarely cause muscle breakdown, a condition known as rhabdomyolysis. In rhabdomyolysis, muscle fibers break down and release myoglobin, a protein that can overwhelm the kidneys’ filtration system and lead to acute kidney injury or even kidney failure if not recognized and treated promptly.

Compared to lower or moderate doses, high-dose statins—such as high-dose simvastatin or atorvastatin—carry a greater risk of muscle toxicity and subsequent kidney complications. Patients taking other medications that interact with statins, or those with pre-existing kidney disease, are at heightened risk. Warning signs of statin-induced muscle injury include unexplained muscle pain or weakness, dark-colored urine, and severe fatigue. Immediate medical evaluation is necessary if these symptoms appear. For more information about statin safety and kidney risks, visit the National Kidney Foundation’s statin and kidney health resource.

29. Chemotherapy Drugs (Cisplatin)

Cisplatin is a platinum-based chemotherapy drug commonly used to treat a variety of cancers, including lung, ovarian, and testicular cancers. Despite its effectiveness, cisplatin is notorious for its nephrotoxicity, which can manifest as acute kidney injury or even chronic kidney disease with repeated exposure. Cisplatin concentrates in the kidney tubules, causing direct cellular damage, inflammation, and impaired filtration. The risk is particularly high in patients receiving high doses, those with pre-existing kidney dysfunction, or when combined with other nephrotoxic agents.

A case example involves a cancer patient who, after several cycles of cisplatin, developed rising creatinine levels and decreased urine output—hallmarks of acute kidney injury. Prompt recognition and intervention, including discontinuation or dose reduction and supportive care, helped prevent further decline in kidney function. Preventive strategies include intensive intravenous hydration before and after cisplatin administration to flush the kidneys, as well as the use of protective agents like amifostine in select cases. Close monitoring of kidney function is essential throughout therapy. For more details on cisplatin nephrotoxicity and prevention protocols, visit the NCBI review on cisplatin and kidney injury.

30. Ifosfamide

Ifosfamide is an alkylating chemotherapy agent used to treat various cancers, including sarcomas and lymphomas. A significant concern with ifosfamide is its potential to cause tubular damage within the kidneys, specifically targeting the proximal and distal tubules. This injury can result in a range of kidney problems, including Fanconi syndrome, characterized by the loss of vital electrolytes and nutrients in the urine, and may lead to chronic kidney disease if not managed appropriately.

Compared to cisplatin, which primarily causes glomerular and tubular injury through direct toxicity, ifosfamide’s effects are more pronounced in the kidney tubules and are often cumulative with repeated cycles. Children are particularly vulnerable, as their developing kidneys are more susceptible to toxic insults. Monitoring for kidney impairment in pediatric patients receiving ifosfamide includes frequent blood and urine tests to check for electrolyte imbalances, proteinuria, and changes in creatinine. Early identification and intervention are critical to limiting long-term kidney damage. For more information on ifosfamide-induced nephrotoxicity and pediatric monitoring recommendations, visit the NCBI review of ifosfamide nephrotoxicity.

31. Methicillin

Methicillin, once a widely used penicillin-class antibiotic, is historically notable for its association with drug-induced acute interstitial nephritis (AIN). This immune-mediated inflammation of the kidney’s interstitial tissue became so well recognized that the term “methicillin-induced interstitial nephritis” was often used to describe the condition. Common symptoms included fever, rash, eosinophilia, and a rapid decline in kidney function, typically occurring days to weeks after starting the drug. Methicillin’s nephrotoxic potential led to its diminished use and eventual discontinuation in many countries.

Historically, the increased incidence of AIN with methicillin prompted clinicians to reconsider its safety profile, especially as safer and equally effective alternatives became available. Today, methicillin is no longer in clinical use, but its legacy persists in the naming of methicillin-resistant Staphylococcus aureus (MRSA). Current practices focus on avoiding antibiotics with higher nephrotoxic risk and monitoring renal function closely when administering any beta-lactam antibiotic. For more historical background and an overview of methicillin’s impact on kidney health, see the NCBI article on methicillin and interstitial nephritis.

32. Amphotericin B Lipid Formulations

Lipid formulations of amphotericin B, including liposomal amphotericin B and amphotericin B lipid complex, were developed to reduce the significant kidney toxicity seen with the traditional deoxycholate form. While these newer formulations are generally less nephrotoxic, they still carry a risk of kidney injury, particularly at high doses or with prolonged use. These lipid-based drugs are designed to alter the distribution of amphotericin B in the body, lowering the concentration that reaches the kidneys and thus reducing—but not eliminating—the risk of tubular damage and electrolyte disturbances.

Compared to conventional amphotericin B, lipid formulations are associated with a lower incidence of acute kidney injury and electrolyte imbalances, such as hypokalemia and hypomagnesemia. However, patients with pre-existing kidney disease or those receiving other nephrotoxic medications remain at risk. Usage tips include ensuring adequate hydration, closely monitoring renal function and electrolytes, and adjusting dosages as needed. The benefits of lipid formulations are most apparent in patients requiring prolonged antifungal therapy or those with higher vulnerability to renal side effects. For more information on the safety profile of lipid-based amphotericin B, visit the NCBI review of amphotericin B lipid formulations.

33. Foscarnet

Foscarnet is an antiviral medication used primarily to treat severe cytomegalovirus (CMV) and herpesvirus infections, especially in immunocompromised patients. A significant risk associated with foscarnet is crystal nephropathy—a form of kidney injury caused by the precipitation of drug crystals in the renal tubules. This crystallization can obstruct urine flow, damage kidney tissues, and lead to acute kidney injury, particularly in patients who are dehydrated or receive high doses.

A real-world example involves a bone marrow transplant recipient treated with foscarnet who developed rising creatinine levels and decreased urine output. Kidney biopsy revealed crystal deposits within the tubules, confirming crystal nephropathy as the cause of acute kidney injury. Prevention strategies include aggressive intravenous hydration before and during treatment, slow infusion rates, and regular monitoring of renal function and electrolytes. Prompt recognition of early symptoms—such as flank pain, reduced urine output, or sudden changes in kidney function—can help avoid permanent damage. For more details on foscarnet nephrotoxicity and prevention, refer to the NCBI review on foscarnet-induced kidney injury.

34. Zoledronic Acid

Zoledronic acid is a potent bisphosphonate used to treat osteoporosis, Paget’s disease, and bone complications in cancer patients. Although highly effective at strengthening bones and reducing fractures, zoledronic acid has been linked to kidney toxicity, especially when administered too rapidly or at high doses. The drug can cause acute tubular necrosis, leading to sudden decreases in kidney function, and is particularly risky in patients with pre-existing renal impairment or those receiving other nephrotoxic medications.

Compared to pamidronate, another bisphosphonate, zoledronic acid is considered more likely to cause acute kidney injury due to its higher potency and rapid infusion requirements. Clinical guidelines recommend careful patient selection, slowing the infusion rate, and ensuring adequate hydration before and after treatment to help minimize risk. Monitoring kidney function (serum creatinine and eGFR) before each infusion is essential, and therapy should be withheld or adjusted if kidney function declines. For more information about zoledronic acid’s renal safety and infusion protocols, visit the NCBI review on zoledronic acid and kidney toxicity.

35. Pamidronate

Pamidronate is a bisphosphonate medication commonly used to treat high blood calcium levels associated with cancer, as well as bone complications in patients with multiple myeloma or metastatic bone disease. While effective in managing bone loss and hypercalcemia, pamidronate has been associated with kidney injury, particularly when administered at high doses or rapid infusion rates. The risk is heightened in cancer patients, who may already have compromised kidney function due to their underlying disease or concurrent therapies.

Renal complications from pamidronate include both acute tubular necrosis and focal segmental glomerulosclerosis, which can manifest as a sudden rise in creatinine, proteinuria, or reduced urine output. To minimize the risk of renal toxicity, infusion rates should be kept slow, and the total dose should be adjusted based on kidney function. Regular monitoring of serum creatinine and estimated glomerular filtration rate (eGFR) is essential before each treatment cycle. Recognizing early signs of kidney impairment allows for prompt intervention, such as dose reduction or discontinuation. For more information about pamidronate and its renal safety, refer to the NCBI review on bisphosphonates and kidney toxicity.

36. Contrast Dyes (Iodinated Contrast)

Iodinated contrast dyes are frequently used in imaging procedures such as CT scans and angiography to enhance visualization of blood vessels and tissues. While generally safe for most patients, these contrast agents can cause a form of kidney injury known as contrast-induced nephropathy (CIN), particularly in individuals with pre-existing kidney disease, diabetes, or dehydration. CIN manifests as a sudden deterioration in kidney function within 48-72 hours following dye exposure.

A typical hospital example involves a patient with underlying chronic kidney disease who undergoes a contrast-enhanced CT scan. Despite no immediate symptoms, blood tests within a few days reveal an abrupt rise in serum creatinine, indicating acute kidney injury. To minimize CIN risk, preventive strategies include adequate hydration before and after the procedure, using the lowest possible dose of contrast, and selecting alternative imaging techniques when appropriate. Intravenous or oral fluids are commonly recommended, and medications that can worsen kidney function should be temporarily withheld. For more information about contrast dye and kidney safety, visit the National Kidney Foundation’s guide to contrast dyes and kidneys.

37. Mannitol

Mannitol is an osmotic diuretic often used in emergency medicine to reduce brain swelling (cerebral edema) and lower intraocular pressure. While effective in these settings, mannitol carries a risk of kidney injury, particularly if administered in excessive amounts or to patients with pre-existing renal impairment. Mannitol works by drawing water into the renal tubules, leading to increased urine output, but in high doses, it can overwhelm the kidneys’ capacity to reabsorb water, resulting in acute kidney injury or even acute tubular necrosis.

Compared to other diuretics like loop or thiazide diuretics, mannitol’s mechanism is unique, but its risk for causing kidney damage is pronounced when not carefully monitored. Overuse may lead to electrolyte disturbances, dehydration, and accumulation of the drug in the bloodstream, further stressing the kidneys. Continuous monitoring of fluid balance, electrolytes, and kidney function is essential during mannitol therapy. Signs of potential harm include reduced urine output, rising creatinine, or fluid overload. For more on mannitol’s renal risks and monitoring protocols, see the NCBI review on mannitol and acute kidney injury.

38. Pentamidine

Pentamidine is an antimicrobial medication primarily used to treat and prevent Pneumocystis jirovecii pneumonia (PJP), especially in immunocompromised patients such as those with HIV/AIDS. Despite its effectiveness, pentamidine carries a significant risk for nephrotoxicity. The drug can cause both acute tubular necrosis and interstitial nephritis, leading to impaired renal function. Risk factors include high cumulative doses, pre-existing kidney disease, and concurrent use of other nephrotoxic agents.

A notable case involves an HIV-positive patient receiving intravenous pentamidine for PJP who developed sudden increases in serum creatinine and electrolyte abnormalities, including hypokalemia and hypomagnesemia. Renal biopsy confirmed tubular injury, necessitating discontinuation of pentamidine and intensive supportive care. To minimize risks, regular laboratory monitoring is essential during therapy, including serum creatinine, blood urea nitrogen (BUN), and electrolyte levels. Early detection of renal dysfunction allows for prompt intervention, such as dose adjustment or drug discontinuation. For more details on pentamidine’s nephrotoxic effects and monitoring recommendations, visit the NCBI review on pentamidine-induced kidney injury.

39. Rifampin

Rifampin is a cornerstone antibiotic in the treatment of tuberculosis and certain other bacterial infections. While generally well-tolerated, rifampin has been linked to rare cases of acute kidney injury, most commonly in the form of acute tubular necrosis or acute interstitial nephritis. This risk is heightened during intermittent dosing regimens, re-exposure after a drug-free interval, or in patients with a history of hypersensitivity reactions to antibiotics.

An illustrative example involves a patient undergoing tuberculosis treatment who developed sudden-onset fever, nausea, and reduced urine output after several weeks on rifampin. Laboratory tests revealed elevated creatinine and characteristic findings of acute kidney injury. Prompt withdrawal of rifampin and supportive care resulted in gradual recovery of renal function. Early symptoms of rifampin-induced kidney injury include fever, rash, joint pain, dark urine, and swelling. Recognizing these warning signs and discontinuing the drug quickly can help prevent permanent renal damage. For more details on rifampin’s renal side effects and clinical recommendations, refer to the NCBI review on rifampin-induced kidney injury.

40. Nitrofurantoin

Nitrofurantoin is a commonly prescribed antibiotic for the treatment and prevention of urinary tract infections (UTIs). While effective for short-term use, nitrofurantoin carries risks for chronic kidney problems, especially with prolonged therapy or in elderly patients. The drug can accumulate in individuals with reduced renal function, leading to toxic effects such as chronic interstitial nephritis and even irreversible kidney damage over time. This is particularly concerning for older adults, who are more likely to have decreased kidney function and may be prescribed nitrofurantoin for long-term UTI prevention.

Studies have shown that elderly patients on extended nitrofurantoin therapy are at higher risk for both lung and kidney complications. Symptoms of chronic nitrofurantoin-induced kidney injury may include persistent fatigue, swelling, reduced urine output, and unexplained changes in kidney function tests. Given these risks, safer alternatives such as trimethoprim-sulfamethoxazole or fosfomycin may be considered, particularly for those with compromised kidney function. Regular monitoring of renal function is essential when long-term nitrofurantoin use is necessary. For more information, visit the NCBI review on nitrofurantoin toxicity.

41. Gold Salts

Gold salts, such as aurothiomalate and auranofin, were historically used as disease-modifying agents in the treatment of rheumatoid arthritis before the advent of modern biologics and other immunosuppressive drugs. Although these compounds provided relief for some patients, gold salts were associated with a range of adverse effects, including significant kidney problems. The most notable renal complication was membranous nephropathy, a condition characterized by protein leakage into the urine (proteinuria) and, in some cases, progressive kidney damage leading to nephrotic syndrome or even renal failure.

Patients receiving gold salt therapy often required regular urine tests to monitor for the early signs of kidney involvement, such as foamy urine, swelling, or elevated protein levels. Fortunately, with the development of safer and more effective arthritis treatments, the use of gold salts has dramatically declined and is now rare in contemporary clinical practice. Nonetheless, understanding their historical relevance underscores the importance of ongoing monitoring for drug-induced kidney injury. For further reading about gold salts and their renal complications, see the NCBI article on gold salt nephrotoxicity.

42. D-penicillamine

D-penicillamine is a chelating agent primarily used to treat conditions such as Wilson’s disease, rheumatoid arthritis, and cystinuria. While useful for reducing heavy metal toxicity and managing autoimmune disorders, D-penicillamine is known for its potential to cause kidney side effects. The most significant renal complication is membranous nephropathy, a condition marked by proteinuria and, in severe cases, progressive loss of kidney function. D-penicillamine can also trigger other glomerular diseases, such as minimal change disease or focal segmental glomerulosclerosis.

Compared to other chelators like trientine (used in Wilson’s disease), D-penicillamine carries a higher risk of nephrotoxicity and requires more frequent monitoring. Patients receiving D-penicillamine should undergo regular urine tests to check for proteinuria and periodic blood tests to assess renal function. Early detection of kidney involvement is crucial for minimizing irreversible damage, and the drug should be discontinued if significant proteinuria or a rapid decline in kidney function is detected. For more information on D-penicillamine-induced nephrotoxicity and monitoring recommendations, visit the NCBI review on D-penicillamine and renal injury.

43. Nonsteroidal Anti-Inflammatory Drug Combinations

Combining multiple nonsteroidal anti-inflammatory drugs (NSAIDs)—such as ibuprofen, naproxen, and diclofenac—greatly increases the risk of kidney injury compared to using a single NSAID. NSAIDs work by inhibiting prostaglandin synthesis, which is essential for maintaining adequate blood flow to the kidneys. When more than one NSAID is taken, their effects are compounded, further reducing renal perfusion and heightening the risk of acute kidney injury, especially in those with underlying kidney disease, dehydration, or other risk factors.

A cautionary example involves a patient with chronic back pain who alternated between over-the-counter ibuprofen and prescription naproxen, believing each provided unique benefits. After several weeks of dual therapy, the patient developed swelling, decreased urine output, and a significant rise in creatinine—signs of acute kidney injury. The combination of NSAIDs was promptly discontinued, and kidney function slowly recovered. Safer pain relief strategies include using acetaminophen for mild to moderate pain, applying topical agents, or exploring non-drug approaches such as physical therapy. Always consult a healthcare provider before combining pain medications. For more on NSAID safety and alternatives, visit the National Kidney Foundation’s NSAID resource.

44. Herbal Remedies Containing Aristolochic Acid

Herbal remedies containing aristolochic acid, derived from plants in the Aristolochia genus, are known for their potent nephrotoxic effects. Aristolochic acid can cause severe and irreversible kidney damage, leading to a condition called aristolochic acid nephropathy (AAN), which often progresses to end-stage renal disease. In addition to kidney injury, aristolochic acid is a recognized carcinogen, increasing the risk of urothelial cancers.

A real-world outbreak occurred in Belgium in the 1990s when patients seeking weight loss treatments at a herbal clinic were inadvertently exposed to Aristolochia fangchi. Many developed rapid-onset kidney failure, and a significant number progressed to terminal kidney disease or developed urinary tract cancers. This event prompted widespread regulatory scrutiny and warnings from health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), against the use of aristolochic acid-containing products. Consumers are urged to avoid unregulated herbal supplements and consult healthcare professionals before using alternative remedies. For detailed information and official warnings, visit the FDA’s advisory on aristolochic acid.

45. Chinese Herbal Medicines (Unregulated)

Unregulated Chinese herbal medicines can pose significant risks to kidney health due to contamination, adulteration, or the inclusion of toxic substances such as aristolochic acid, heavy metals, or unlisted pharmaceuticals. Without stringent quality control, the concentration and purity of ingredients can vary widely, increasing the risk of acute or chronic kidney injury. These dangers are heightened when herbal remedies are taken in high doses or for extended periods, or when combined with other nephrotoxic medications.

A notable case study involved a patient who developed acute kidney failure after using a traditional Chinese herbal product for joint pain. Laboratory analysis later revealed the presence of aristolochic acid and high levels of mercury, both known nephrotoxins. The patient required hospitalization and long-term dialysis. To reduce the risk of kidney injury, consumers should only use herbal medicines that are certified by reputable regulatory agencies, check for third-party testing, and consult healthcare professionals before starting any new supplement. For more information on the risks and safety measures related to Chinese herbal medicines, visit the NCBI review on nephrotoxicity of Chinese herbal medicines.

46. Over-the-Counter Laxatives (Magnesium-containing)

Magnesium-containing over-the-counter laxatives, such as milk of magnesia or magnesium citrate, are frequently used for constipation relief. While these medications are generally safe when used as directed, excessive or prolonged use can be dangerous, especially in people with impaired kidney function. The kidneys are responsible for excreting excess magnesium, and when they are unable to do so efficiently, magnesium can accumulate in the body, leading to hypermagnesemia. This condition may cause muscle weakness, low blood pressure, irregular heartbeat, and in severe cases, life-threatening cardiac or neurological complications.

A misuse example involves an elderly patient who used high doses of magnesium-containing laxatives daily for chronic constipation without consulting a healthcare provider. Over time, the patient developed confusion, muscle weakness, and was found to have critically elevated serum magnesium levels, requiring emergency medical intervention. For safer management of constipation, non-magnesium alternatives such as fiber supplements, stool softeners, or lifestyle modifications like increased hydration and dietary fiber are recommended. Always consult a healthcare provider before using laxatives regularly. For more information on magnesium toxicity and safe laxative use, see the National Kidney Foundation’s resource on magnesium and kidney health.

47. Phosphate-containing Enemas

Phosphate-containing enemas are often used to relieve constipation or prepare the bowel for medical procedures. However, these products can cause serious kidney injury, particularly in elderly individuals or those with pre-existing kidney problems. The kidneys must excrete excess phosphate, and when overwhelmed, this can result in a dangerous condition called acute phosphate nephropathy. This disorder is characterized by calcium-phosphate crystal deposits in the kidney tubules, leading to impaired filtration and sometimes irreversible kidney damage.

Elderly patients are especially susceptible due to age-related decline in kidney function and increased sensitivity to electrolyte imbalances. Case reports describe individuals developing acute kidney failure after using more than the recommended dose of phosphate enemas. Symptoms may include weakness, confusion, reduced urine output, and muscle cramps. To minimize risk, phosphate enemas should be used only as directed, never exceeding recommended doses, and avoided in those with kidney disease, dehydration, or on medications affecting kidney function. Always consult a healthcare provider before using these products, especially in high-risk groups. For further information, visit the National Kidney Foundation’s advisory on phosphate enema safety.

48. Aliskiren

Aliskiren is a direct renin inhibitor used to manage high blood pressure by blocking the activity of renin, an enzyme involved in the body’s regulation of blood pressure and fluid balance. By interfering with the renin-angiotensin-aldosterone system (RAAS), aliskiren can reduce blood pressure but may also impact kidney filtration, especially in patients with underlying chronic kidney disease, diabetes, or those taking other RAAS inhibitors. Like ACE inhibitors and angiotensin receptor blockers (ARBs), aliskiren can decrease glomerular filtration rate (GFR) and, in some cases, cause acute kidney injury, particularly if used in combination with these other agents.

Compared to ACE inhibitors, aliskiren offers a similar effect on blood pressure and kidney filtration but is generally not recommended for use alongside ACE inhibitors or ARBs due to a heightened risk of hyperkalemia and renal dysfunction. Regular monitoring of kidney function and serum potassium is essential when starting or adjusting aliskiren therapy. Patients should report symptoms such as reduced urine output, swelling, or muscle weakness. For more information about aliskiren’s renal effects and safety advice, visit the National Kidney Foundation’s resource on aliskiren and kidney health.

49. Methadone

Methadone is a long-acting opioid commonly prescribed for chronic pain management and opioid dependence treatment. Although methadone is primarily metabolized by the liver, rare kidney complications have been reported, particularly in cases of overdose or pre-existing renal impairment. Methadone can cause urinary retention, which may increase the risk of urinary tract infections and, in severe cases, potentially lead to acute kidney injury. In rare instances, methadone overdose has been linked to a syndrome called rhabdomyolysis—rapid breakdown of muscle tissue—which releases myoglobin into the bloodstream and can cause acute kidney damage.

Compared to other opioids, methadone does not inherently carry a higher risk of direct nephrotoxicity, but its unique long half-life and potential for drug interactions warrant caution in patients with kidney disease or those at risk for dehydration. High-risk groups, such as the elderly or those with pre-existing renal dysfunction, should be closely monitored for changes in urine output, swelling, or muscle pain. Dose adjustments may be necessary in these populations. For more information on methadone’s effects and safe opioid use in kidney disease, see the National Kidney Foundation’s opioid safety guide.

50. Certain Antidepressants (SSRIs, SNRIs)

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly prescribed antidepressants known for their favorable safety profiles. However, rare kidney-related side effects have been reported, particularly with long-term use or in patients with underlying renal dysfunction. Some studies and case reports have linked SSRIs and SNRIs—such as fluoxetine, sertraline, and venlafaxine—to conditions like hyponatremia (low sodium levels), which can indirectly affect kidney function, or to rare cases of interstitial nephritis and acute kidney injury.

Recent literature highlights that the risk of these adverse renal effects appears to be low but may increase in elderly patients, those with pre-existing kidney disease, or when antidepressants are combined with other nephrotoxic medications. Symptoms to watch for include unexplained fatigue, swelling, changes in urination, or confusion (a sign of hyponatremia). It is important to consult a healthcare provider if any of these symptoms develop or before starting new medications, especially in high-risk groups. For a comprehensive review of antidepressants and kidney effects, visit the NCBI article on SSRIs, SNRIs, and renal safety.

Conclusion

Protecting kidney health is crucial, as many common medications—when misused or overused—can lead to serious and sometimes irreversible kidney damage. It is essential for individuals to proactively communicate with healthcare providers about all medications and supplements they are taking, and to report any unusual symptoms promptly. Regular kidney screening, especially for those at higher risk or on long-term drug therapies, can help detect problems early and prevent progression. For more information on safe medication use and kidney protection, visit the National Kidney Foundation’s medication safety resource.

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