Drug-Induced Kidney Disease

What is Nephrotoxicity?

Nephrotoxicity means damage to kidney function, as a result of which kidney-specific function like excretion of waste does not happen. Nephro comes from Greek and means ‘kidney’.

Approximately 20% of damage to kidney or nephrotoxicity happens due to drugs and this is more common in patients admitted to the hospital.

This damage can be caused by external or internal toxicants. If not addressed or treated in time, it can lead to chronic kidney disease or acute renal failure (ARF) and severe renal disease.

Acute kidney failure also known as acute renal failure can occur suddenly since the kidneys are unable to filter the toxic products from blood. This results in high levels of toxins in blood. It can be fatal in some conditions.

What is Drug-induced Nephrotoxicity?

Some drugs used for treatment are known to cause nephrotoxicity, i.e. impair the functioning of kidney. These could be prescription or over-the -counter medications.

Drug induced nephrotoxicity occurs in patients with certain clinical conditions.

Nephrotoxic drugs generally induce inflammation in glomerulus and proximal tubules which disturbs the kidney functions and leads to toxicity known as glomerulonephritis and intestinal nephritis.

Which Drugs Cause Nephrotoxicity?

Drugs which could cause nephrotoxicity include:

Chemotherapeutic agents to treat cancer

• Cisplatin
• Methotrexate
• Doxorubicin

Antibiotics

• Beta lactums like Penicillins and Cephalosporins
• Rifampin
• Sulfonamides
• Tetracyclines
• Aminoglycosides antibiotics to treat Gram-negative infections like Gentamicin. Amikacin, Kanamycin, Tobramycin, Streptomycin and Neomycin
• Anti-fungal antibiotics like -
• Amphotericin B

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Immunosuppressants to treat Rejection or Auto-immune disease

• Azathioprine
• Cyclosporine
• Tacrolimus

Analgesics

• Acetaminophen
• Non-Steroidal-inflammatory drugs (NSAID) like – Aspirin, Celecoxib, Diclofenac, Diflunisal, Etodolac, Ibuprofen, Indomethacin, Ketoprofen, Ketorolac Nabumetone, Naproxen, Oxaprozin, Piroxicam, Salsalate, Sulindac, Tolmetin

Antidepressants and Mood stabilizers

• Fluoxetine
• Doxepin
• Amitriptyline
• Antiretrovirals
• Tenofovir
• Indinavir

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Cardiovascular agents

• ACE inhibitors like Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril
• Clopidogrel
• Statins like - Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin and Pitavastatin

Other medications

• Cimetidine
• Allopurinol
• Contrast dye
• Drugs of abuse like Cocaine
• Streptokinase inhibitors
• Some herbal drugs

What is mechanism of action of nephrotoxicity?

The mechanism of drug-induced nephrotoxicity varies with the class of drugs. The drugs exhibit their toxic effect by affecting various microscopic components of the kidney.

The nephrotoxic antibiotics induce their effects by two different mechanisms:

• Penicillin and Cephalosporin type antibiotics show their effect by indirect action, which is due to antigen and antibody formation and is due to mechanism involving the immune system
• The Polymyxin and Sulfonamide type antibiotics have a direct effect on kidneys. They show significant nephrotoxicity, the clinical diagnosis is characterized by proteinuria, decreased clearance of creatinine, and cellular casts in urine

The drug-related renal syndromes include:

• Acute renal failure
• Nephrotoxic syndrome
• Renal tubular dysfunction
• Chronic renal failure
• Glomerulonephritis
• Cytotoxicity of renal tubular cells