Medicines damage kidneys

Whatever we eat, drink or inject into our body circulates via blood through our kidneys. This tenet holds true for medicines as well.

All of you know that prescription medicines come with specific dose instructions. These comply with dosing protocols found “safe & effective” after rigorous clinical trials for that drug. The purpose of such fixed dosing is to ensure maximum benefit from the drug & minimize the chances of harmful side effects.

If such medicines are not taken following your healthcare provider’s instructions, or if it is an illegal substance, it can end up harming your kidneys!

Technically, such medicines are termed “Nephrotoxic”.

This article aims to provide an overview of which drugs can cause nephrotoxicity (kidney damage), when and how, plus how to protect yourself against it.

1. Why do certain drugs damage kidneys?

2. When can a certain medicine commonly cause Kidney Damage?

3. In what ways can medicines damage kidneys?

4. List of Nephrotoxic (kidney-damaging) medicines

5. Best practices to protect your kidneys from any medicine-induced damage

Why do certain drugs impact kidneys?

Our Kidneys work tirelessly 24 X 7 to filter & balance 100% of our blood. This literally allows all organs to carry out all their normal activities. Of this, 20% of the cleansed blood is used up by kidney filters themselves. Wondering why? That’s because these kidney filters are made of billions of living, breathing & actively metabolizing cells themselves, that require nourishment just like cells in all other organs.

Such heavy exposure of kidney cells to our bloodstream also makes these cells more prone to be adversely impacted by unwanted changes in blood composition.

Overdose or long-term intake of certain medications, or substance abuse (illegal drugs) as detailed in the section below can cause buildup of harmful chemicals in the blood & alter its composition unfavourably. These chemicals can injure your kidneys.

When can medicines damage kidneys?

Many of the known kidney harming medications are actually safe in their clinically approved “therapeutic” dosage & duration, provided the kidney function is normal. It is the following four approaches by which medicines can commonly end up damaging your kidneys:

Drug Overdose with normal initial kidney function.

Chronic use of a prescription-drug meant for shorter time periods (eg: Painkillers, Acidity medication) without consulting your physician.

Taking any medication without doctor consultation if you already have Kidney Disease

Illegal drugs / substance abuse

How exactly do such medicines impact your kidneys?

Kidneys are made of billions of cells that can be categorized into 26 different types! And it’s all organized into over 1 million delicate kidney filters (Nephrons), blood vessels & supportive tissue. There are more ways than one that medicines can impact your kidneys adversely.

This is how a Kidney-filter (Nephron) looks:

Now that you have some perspective on the appearance of a Nephron, let’s take up one by one, how Kidney-harming drugs can affect your kidneys:

GFR Alteration

GFR stands for Glomerular Filtration Rate. It directly translates as the filtration capacity of your kidneys. Read more about GFR here
Some kidney-harming chemicals can adversely affect the ability of kidneys to regulate how efficiently your kidney filters separate out wastes from your bloodstream at the Glomerulus.
This can make your GFR number go abnormally low (below 90ml/min).

Glomerulonephritis

Inflammation & damage of the Glomerulus — the tiny blood vessel tufts at the entrance of each delicate kidney filter directly responsible for filtering your blood to purge out wastes.

Tubular Cell Toxicity

The inner surfaces of delicate kidney filter tubes responsible for urine production are lined with specialized cells called Tubular Cells.
Some kidney harming medications can directly impact these cells while passing out through urine. As a result, kidney functioning takes a direct hit.
We observe three ways in which drug-related tubular cell damage presents in the clinic:

I. Renal Tubular Acidosis

While passing out of the body via urine, certain drug metabolites can hamper the ability of Tubular cells to remove excess acid load from a person’s bloodstream.

As a result, patients present with high blood acidity (metabolic acidosis) which can harm nerves & heart plus worsen kidney function further.

II. Acute & Chronic Tubular Necrosis

Here, toxic drug metabolites in the urine can viciously cut off adequate nutrient delivery to Tubular cells in kidney filters and literally cause them to partially rot & slough out with urine. This is called Tubular Necrosis.
Depending on the drug, its quantity & duration of intake, this process could take shape over a few days (Acute) or over months to years (Chronic).

III. Crystal Nephropathy

Metabolites of some drugs end up forming sharp micro-crystals within the urine.

These can block the urine outflow to put a back-pressure on kidney cells. These crystals can also forcibly “push into the kidney cell mass & settle-in” to inflame kidney tissue.

Nephrotic Syndrome

Certain drugs can affect kidney filter surfaces adversely such that they start leaking huge quantities of plasma proteins like Albumin, in urine.
This can raise your blood pressure, cause fluid buildup in your limbs & damage your kidney filters. However, timely diagnosis can reverse this condition completely.

Acute & Chronic Interstitial Nephritis

This is a direct toxic effect of kidney-harming medicines on kidney “interstitium” i. e. kidney cells apart from those that line filtration tubes.
Such damage is often distributed in patches across the kidney. The cells in the affected area shrink down and are unable to function optimally.
This can decline your kidney filtration function. It can show up as pain during urination, lower back pain, protein in urine, rise in blood pressure, increased blood acidity or even frank kidney failure.

Rhabdomyolysis

Breakdown of proteins forming skeletal muscles.
This is a dangerous complication that greatly weakens your limb and trunk muscles.
In addition, the breakdown products of such muscle proteins like Myoglobin can cause sudden, severe damage to your kidneys while being let out via urine. Such kidney damage qualifies as Acute Kidney Injury.

Thrombotic Micro-angiopathy

This mouthful of a phrase literally means disease of small blood vessels caused due to blockage to normal blood flow by abnormal clumps of platelets – a type of blood cells.
Certain medicines can cause such abnormal platelet clumping.
As a result, the reduced blood flow can directly cut off nutrition supply to kidney cells, and cause Kidney Damage.

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List of Medicines that can harm your Kidneys

Find below, the list of drugs that can cause kidney injury & damage categorized according to their medical use.

The list includes generic names of medicines with common brand names in the bracket.

However these medicines are marketed in many other brand names worldwide.

To see if your brand of medicines could cause kidney injury, look for its “composition” printed on the medicine packaging / container and cross-check with the list below.

NEPHROTOXIC MEDICINES

I. PAIN-KILLER MEDICINES

Painkillers commonly belong to the NSAID class. With normal kidney function, these medicines must not be taken any more than 10 days for pain & 3 days for fever.

In the scenario of kidney disease, painkillers are best avoided.

Else they can damage kidneys with Acute Tubular Necrosis, Acute Kidney Injury, Glomerulonephritis, Chronic Interstitial Nephritis or even Rhabdomyolysis. Such painkillers include, but are not limited to:

1. Aceclofenac

2. Acemetacin

3. Acetaminophen (paracetamol) acute overdose

4. Acetylsalicylic Acid (Aspirin)

5. Acetylsalicylic Acid + Ascorbic Acid (Aspirin + Vitamin C)

6. Celecoxib

7. Dexibuprofen

8. Diclofenac

9. Diclofenac sodium + Misoprostol combination

10. Etodolac

11. Etoricoxib

12. Ibuprofen

13. Ketorolac

14. Lornoxicam

15. Meloxicam

16. Methadone (narcotic analgesic)

17. Naproxen

18. Naproxen + Esomeprazole combination therapy

19. Nimesulide

20. Niflumic Acid

21. Piroxicam

22. Phenacetin

23. Tenoxicam

24. Tiaprofenic Acid

II. BLOOD PRESSURE MEDICATION

Some blood pressure medication used for kidney conditions itself are, ironically, harmful to kidneys if doses are not adjusted accordingly.

The medicine classes listed below help control your blood pressure by modifying the blood flow to kidneys. If their blood levels increase abnormally due to long term use or poor excretion (as in kidney disease), these meds may cause Acute Kidney Injury (AKI).

1. ACE-Inhibitors

Generic names of these medicines ends with -pril.

Eg: Lisinopril, Ramipril, Fosinopril, Perindopril

2. ARB

Generic names of these medicines ends with -sartan.

Eg: Telmisartan, Olmesartan, Candesartan, Losartan, Valsartan, Irbesartan etc.

III. DIURETICS (WATER PILLS)

Diuretics or “water pills” are medicines used to treat excess fluid buildup in the body. These medications could be prescribed in patients with kidney disease, high blood pressure, heart failure or even advanced liver disease.

Taking the diuretics listed below in the long term can cause kidney damage with Renal Tubular Acidosis & Acute Interstitial Nephritis.

1. Acetazolamide

2. Furosemide (Lasix)

3. Hydrochlorthiazide

4. Triampterine (Dyrenamide)

IV. HEART MEDICATION / CHOLESTEROL LOWERING MEDICINES

Some medicines under this category can cause kidney damage by Thrombotic microangiopathy & Rhabdomyolysis.

1. Clopidogrel (Plavix)

2. Ticlopidine (Ticlid)

3. Medicine generic names ending with “-statin” (Atorvastatin, Rosuvastatin, Simvastatin etc)

V. MEDICINES FOR ACIDITY AND HEARTBURN

Heartburn is a common problem worldwide. This could either be due to erratic food habits/lifestyle, conditions like Acid Reflux disease (GERD), obesity or even as a side effect of other medicines.

However, unless advised by your physician, it is best to not depend on Acidity reducing medicines in the longer term. That is because these have been found to impact kidneys with Acute Interstitial Nephritis:

1. Cimetidine

2. Lansoprazole (Prevacid)

3. Omeprazole (Prilosec)

4. Pantoprazole (Protonix)

5. Ranitidine (Rantac, Zantac, Aciloc)

VI. ANTIBIOTICS / ANTIMICROBIALS

Antibiotics or anti-microbials prescribed to cure infections have a fixed specific dose and duration. Many of these get eliminated from the body through kidneys via urine.

Patients must not take these medications without supervision, or overuse these for the long-term. Else kidneys could be severely impacted. The damage could range from Glomerulonephritis, Acute Tubular Necrosis, Crystal Nephropathy to Acute Interstitial Nephritis.

1. Aminoglycosides (Streptomycin, Gentamycin, Amikacin, Tobramycin, Netilmycin)

2. Beta-lactams (like Penicillin, Amoxicillin, Ampicillin, Carbenicillin)

3. Cephalosporins

4. Penicillin G

5. Pentamidine (Pentam)

6. Puromycin

7. Quinolones (Ciprofloxacin, Levofloxacin, Ofloxacin, Norfloxacin)

8. Rifampin (Rifadin)

9. Sulphonamide

i. Sulphamethoxazole + Trimethoprim = Cotrimoxazole

ii. Sulphametrole + Trimethoprim

iii. Sulphamazone

10. Tetracycline

11. Vancomycin (Vancocin)

VII. ANTIVIRAL MEDICATION

Some anti-viral medicines can be harsh to kidneys, especially if one has chronic kidney disease already. Your physician must know about your kidney health status.

The anti-virals listed below can damage kidneys with Crystal Nephropathy & Acute Interstitial Nephritis.

1. Acyclovir (Zovirax)

2. Gancyclovir (Cytovene)

3. Indinavir (Crixivan)

4. Afefovir (Hepsera)

5. Cidofovir (Vistide)

6. Tenofovir (Viread)

VIII. ANTI-FUNGAL MEDICINE (Taken by mouth)

“Systemic” Anti-fungal medicines taken by mouth get eliminated through kidneys via urine, after metabolism. In the process, some may harm kidneys with Acute Tubular Necrosis & raise overall blood acidity by Renal Tubular Acidosis.

Example:

1. Amphoptericin-B (Fungizone)

IX. DIABETES MEDICINES

Diabetes medicines work via a number of mechanisms to keep your blood glucose levels in control. Many of these mechanisms directly pertain to the kidneys.

Since these medications are meant to be taken for the long term, your kidney function may end up being hampered.

As a result, there could be excessive water retention in the bloodstream which ultimately burdens kidneys, excessive loss of Sodium – a major blood mineral – via urine, high blood acidity or even sudden, excessive protein loss due to Nephrotic Syndrome. Diabetes medicines that commonly raise such concerns are:

1. Chlorpropamide

2. Phenformin

3. Tolbutamide

X. BONE & JOINT DISORDER MEDICATION

This is another class of medicines that is prescribed for the long-term & requires patients to get monitored continuously for any adverse impact on kidneys.

If that happens, your physician will either adjust the dosage or change your medication.

Kidney damage with Bone/Joint disorder meds can range from Thrombotic Micro-angiopathy, Glomerulonephritis, Crystal Nephropathy, Acute Interstitial Nephritis, Nephrotic Syndrome to membranous nephropathy which can progress to frank Chronic Kidney Disease with time.

Most common medicines of this class that present with such scenarios include:

1. Allopurinol (Zyloprim)

2. D-penicillamine

3. Gold Na-Thiomalate, Gold Na-Thiosulphate & Auranofin

4. Methotrexate (Rheumatrex)

5. Palmidronate / Palmidronic acid (Aredia)

6. Probenecid

7. Quinine (when used as muscle relaxant) (Qualaquin)

8. Zoledronate (Zometa)

XI. ANTI-ALLERGIC

Chronic overuse of some of these medicines can cause Rhabdomyolysis that leads to Acute kidney Injury.

1. Diphenhydramine (Benadryl)

XII. MEDICINES FOR PSYCHIATRIC CONDITIONS (mental health-related)

Some medicines used to treat depression & psychosis carry kidney health concerns when continued for the long term. These can damage kidneys via Rhabdomyolysis, Glomerulonephritis & Chronic Interstitial Nephritis.

1. Amitriptyline (Elavil, Endep, Vanatrip)

2. Haloperidol (Haldol)

3. Lithium (Eskalith, Lithobid)

XIII. CANCER MEDICINES

Medicines used in cancer chemotherapy are notorious for harming kidneys. These can do so by causing Thrombotic Microangiopathy, Glomerulonephritis, Crystal Nephropathy, Chronic Interstitial Nephritis & Hemorrhagic Cystitis (inflammation of & bleeding from the urinary bladder). Most concerns come from:

1. Cisplatin (Platinol)

2. Cyclophosphamide (Cytoxan, Endoxan, Neosar)

3. Interferon-alpha (Intron)

4. Methotrexate (Otrexup, Rasuvo, Trexall)

5. Mitomycin-C (Mutamycin)

XIV. MEDICINES TO CONTROL SEIZURES / FITS (eg: Epilepsy)

Some medicines for seizure disorders (eg: epilepsy) injure kidneys via Rhabdomyolysis & Acute Interstitial Nephritis.

1. Benzodiazepines

Alprazolam (Xanax), Lorazepam, Diazepam etc.

2. Phenytoin (Dilantin)

XV. IMMUNOSUPPRESSIVE MEDICINES

Some medicines are meant to dampen your immune defences. These can help to reduce unwanted inflammation if you have autoimmune disorders or to prevent your body from rejecting an implant or have had an organ transplant.

These medications MUST be taken in the specified dosage as advised by your physician.

If possible, your physician may also order bloodwork to check the levels of these medicines in your body. This is to minimize the chances of any adverse effect.

Else, overdose or unmonitored, chronic high dose of the immunosuppressive medication listed below can cause kidney damage via Metabolic Acidosis, Acute Tubular Necrosis, Acute Interstitial Nephritis, Thrombotic Microangiopathy & High blood pressure.

Such immunosuppressive medications include:

1. Cortisone (Prednisone)

2. Cyclosporine (Neoral)

3. Tacrolimus (Prograf)

XVI. PRESCRIPTION LAXATIVES

FDA has raised a red flag on the association of Acute Kidney Injury with use of certain prescription laxatives.

Chronic overuse or high-doses before undergoing a Colonoscopy, especially if you already have kidney disease could carry kidney health risks.

Example of such laxative is:

1. Oral Sodium Phosphate

XVII. UNAPPROVED HERBAL SUPPLEMENTS

Herbal supplements sold worldwide under various traditional medicine systems do not undergo regulatory approval assessments that allopathic medicines are normally subject to. The explicit purpose of such regulations is to establish how “safe” & “effective” a drug is. Not undergoing such regulatory studies means herbal supplements are not assessed for possible side effects at all. There is no proof on how safe they are.

Some of these traditional herbal supplements can contain Aristolochic Acid. Patients who took such herbals were found to develop Chronic Interstitial Nephritis.

1. Xiaoqinglong Heji (Chinese proprietary medicine)

- Contains “Asarum” which is a source of Aristolochic Acid
- Many “herbal” slimming teas & powders contain this extract in dangerous levels. The kidney damage associated with the use of these supplements is often termed “Chinese Herb Nephropathy”.

2. Plants of Aristolochiaceae family used in Homeopathic & Traditional Chinese Medicines as painkillers and blood pressure lowering medicines:

Aristolochia contorta, Aristolochia debilis, Aristolochia clematitis, Aristolochia manshuriensis, Aristolochia fangchi, Aristolochia indica (Indian birthwort)

XVIII. RADIOCONTRAST DYE

Certain diagnostic tests called “Imaging Tests”, such as CT scan, MRI, IVP, Angiogram or Barium scans may use a “radiocontrast dye”.

The patient could be injected or fed the chemical that works as a dye.

The purpose of this dye is to enhance the quality of the medical image & help with better diagnosis & treatment planning.

However, it is important to consider use of such dyes & weigh the benefit with health risks for patients who are at risk of Kidney Damage due to contrast dyes:

1. Aged beyond 65 years

2. Have high blood pressure

3. Are Diabetic

4. Have advanced kidney disease with eGFR value below 30 ml/min.

The explicit reason is that in such high risk patients, some contrast dyes can damage kidneys via Acute Tubular Necrosis & Acute Kidney Injury.

These dyes include:

1. Gadolinium-based dyes

2. Iodine-based dyes

There is a special name for Acute Kidney Injury (AKI) caused by radiocontrast dyes. It is Contrast-induced Nephropathy (CIN).

In addition, there is a separate, more extensive side effect that may set-in from using Contrast dyes in patients with kidney disease. It is called Nephrogenic Systemic Fibrosis (NSF). Read more about these here.

XIX. ALCOHOL

Regular heavy drinking (>5 drinks daily where the standard measure of 1 drink is as illustrated here) can harm both your kidneys via Acute Tubular Necrosis or even frank Renal Shutdown.

Click on the article link below to read more:

ALCOHOL & KIDNEY DISEASE

XX. SUBSTANCE ABUSE / ILLEGAL DRUGS

Certain illegal “rave” drugs can abruptly cut down blood flow to your muscles & force muscle fibre over-activity.

The combination of these factors can cause muscle proteins to “break down”. This is called Rhabdo-myo-lysis.

Such muscle breakdown products are typically eliminated from the body through your kidneys via urine. These are extrenely harsh on your delicate kidney filters (nephrons). It can result in Acute Kidney Injury.

Such kidney-harming substances include:

1. Cocaine

2. Heroin

3. Ketamine (Ketalar)

4. Methadone

5. Methamphetamine (Ecstasy)

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Prevention of drug-induced Kidney Damage: Best Practices

1. Do not take any medicine, drug or substance unless you are under a healthcare provider’s supervision.

2. Do not take pills, powders or substances that may claim to “lift your mood” on your own or after being given to you by somebody else (even a friend!).

3. Cut down on alcohol intake if you drink frequently. Avoid binge drinking.

4. If you feel ill after taking any medication or substance, contact your healthcare provider immediately.

5. Kidney disease caused by painkillers is preventable! Follow the instructions below to keep painkiller induced kidney damage at bay:

Do not use over-the-counter pain relieving medicines for more than 10 days for pain or more than three days for fever. If your pain or fever persists, consult your physician for further assessment.

Avoid using painkillers for the long-term, especially the ones that contain a combination of ingredients, like aspirin, acetaminophen and caffeine in one pill.

If you are on pain medication, make sure you stay well-hydrated. Drink atleast 2-2.5 litres (~8 glasses) of water daily. This dilutes your blood and reduces the potential harmful impact that such drugs may have on healthy kidneys.

Painkillers don’t mix well with alcohol, because alcohol dehydrates your body. Avoid drinking alcohol when on pain medication.

If you have kidney disease, it is best that you avoid any painkiller that belongs to the NSAID class (as listed above).

Use NSAID painkillers only under your doctor’s supervision if you have heart disease, high blood pressure, kidney disease or liver disease or if you take diuretic medications(water pills) or are over 65 years of age.

If you have kidney disease, never start any new medication without consulting your doctor. This includes over-the-counter medicines as well.

Every FDA approved medicine comes with a “Warning label” printed on the medicine strip or has a separate “Drug Fact Sheet” within the packaging. Make sure you read these warning labels or the “contraindications” before using any over-the-counter drugs.

6. If you are advised to get an imaging test or colonoscopy & you have kidney disease, make sure let your healthcare provider know about it.

7. Whenever facing the prospect of getting an imaging test (CECT, CEMRI, Angiogram or IVP), keep in mind the following:

If you have Chronic Kidney Disease (CKD), make sure you know your GFR number.

If you do not know your GFR, you can calculate your GFR (kidney function) here or ask your doctor/healthcare provider. Your kidney function is estimated by the glomerular filtration rate, or eGFR.

Make sure you inform all of your healthcare professionals about your CKD & GFR number.

This is especially if an imaging test such as a CT scan, MRI, Angiogram or IVP has been ordered. The doctor ordering the diagnostic test must be aware of your kidney health status. You can also ask to talk to the radiologist, radiology technician and nurse.

Proactively ask the need for the imaging tests using Contrast agents with your healthcare professional.

- Ask about alternatives such as a test without contrast, if feasible.

If using contrast dyes is necessary in your case, ask about precautions that will be taken to ensure your kidneys are safe.

These include:

- How much water you should drink before or after the test
- If certain contrast dyes could be avoided if you are at risk developing kidney damage (NSF or CIN).
- How long the specific contrast dye is likely to circulate in your body before it is completely eliminated via urine.
- How long you should wait if you were to have a second imaging test using a Contrast dye to prevent blood levels of such dyes from shooting up.
- If repeated or higher doses of contrast dye could be adjusted in your case if you are at risk of kidney damage.
- Performing long-term monitoring for CIN or NSF after a diagnostic test.

Contact your medical team immediately if you experience any of the following symptoms after an imaging test with a contrast agent:

- Swelling of limbs
- Puffiness around eyes or face,
- Sudden extreme fatigue,
- Loss of appetite
- Skin changes (dryness, itchiness, scaly, burning, hardening, swelling, tightening or red, dark skin patches)
- New onset or worsening of joint stiffness, bone pain or muscle weakness.

CONCLUSION

This was a comprehensive overview of why, how, when & which medicines could harm kidneys or in other words, Drug-induced Nephropathy.

Unfortunately, this method of kidney damage is really common these days, especially because of unmonitored self-medication, taking unapproved health supplements or substance abuse.

The good news though, is that with proactive awareness from your side, a big section of Drug-induced Nephrotoxicity cases are completely preventable!

So go ahead, educate yourself actively on this front, be vigilant about what medication / supplements you take & stay kidney-smart!

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