# Nephrotoxic Drugs

> Nephrotoxic drugs for NEET-PG Medicine: aminoglycosides, amphotericin B, cisplatin, lithium, NSAIDs and contrast, with the pattern of kidney injury each causes.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/nephrotoxic-drugs
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Harrison's Principles of Internal Medicine; Brenner and Rector's The Kidney; Goodman and Gilman's The Pharmacological Basis of Therapeutics
- How to cite: "Nephrotoxic Drugs", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/nephrotoxic-drugs

## Direct answer

Nephrotoxic drugs injure the kidney through tubular toxicity, haemodynamic change or interstitial inflammation, and each class produces a recognisable pattern. Aminoglycosides and cisplatin cause proximal tubular injury, amphotericin B causes distal tubular dysfunction with potassium wasting, and NSAIDs cause haemodynamic acute kidney injury in volume depletion. Stopping the offending drug is the first and most important step.

## What you must remember

- **Aminoglycosides:** accumulate in proximal tubular cells, causing acute tubular necrosis, with hypomagnesaemia and hypokalaemia as common associated features.
- **Amphotericin B:** conventional deoxycholate formulation causes afferent vasoconstriction and distal renal tubular acidosis with potassium and magnesium wasting.
- **Cisplatin:** dose-limiting proximal tubular toxicity, reduced by saline hydration and magnesium supplementation.
- **Lithium:** causes nephrogenic diabetes insipidus, producing polyuria with low urine osmolality despite raised antidiuretic hormone.
- **NSAIDs:** block prostaglandin-mediated afferent dilation, so the glomerular filtration rate falls in volume depletion or with ACE inhibitors.
- **Iodinated contrast:** causes tubular injury through medullary hypoxia, with the greatest risk in diabetes and pre-existing chronic kidney disease.
- **Calcineurin inhibitors:** cyclosporine and tacrolimus cause afferent vasoconstriction and chronic tubulointerstitial damage.
- **Acyclovir and methotrexate:** intratubular crystal precipitation is the mechanism, which is reduced by hydration.

## Matching each drug to its pattern of injury

Nephrotoxicity is best organised by the part of the kidney the drug attacks, because the pattern predicts the biochemistry. A proximal tubular injury causes a Fanconi-type picture, a distal injury causes acidosis with potassium loss, and a haemodynamic injury causes a rise in creatinine with a low fractional excretion of sodium.

| Drug | Pattern of injury | Classic clue |
|---|---|---|
| Aminoglycosides | Proximal tubular necrosis | Muddy-brown casts, hypomagnesaemia |
| Amphotericin B | Distal tubular and vasoconstrictive | Hypokalaemic distal renal tubular acidosis |
| Cisplatin | Proximal tubular toxicity | Dose-limiting, prevented by saline and magnesium |
| Lithium | Nephrogenic diabetes insipidus | Polyuria, low urine osmolality |
| NSAIDs | Haemodynamic, interstitial nephritis | Worse with volume depletion and ACE inhibitors |
| Iodinated contrast | Tubular and medullary hypoxia | Risk in diabetes and existing CKD |

Recognising the pattern lets the student choose the right investigation and the right prevention. Aminoglycoside injury is typically dose and duration dependent, so trough levels guide prolonged courses. Lithium-induced polyuria is not treated with the same measures as ADH-deficient diabetes insipidus.

## Where the examiner tries to catch you

Nephrotoxicity questions often hinge on the drug-specific electrolyte or urinary clue rather than on creatinine alone.

- **Trap:** assuming lithium causes only tremor and toxicity. — **Correct:** lithium causes nephrogenic diabetes insipidus, and long-term exposure can cause interstitial nephritis and nephrotic-range proteinuria.
- **Trap:** attributing amphotericin-related hypokalaemia to gastrointestinal loss alone. — **Correct:** amphotericin B causes distal renal tubular acidosis with renal potassium wasting, and lipid formulations are less nephrotoxic.
- **Trap:** choosing NSAIDs for pain in a dehydrated patient with CKD. — **Correct:** NSAIDs reduce prostaglandin-dependent renal perfusion, so volume status and renal function must be checked before any prescription.

## Frequently asked questions

### Which antibiotic classically causes proximal tubular necrosis?

Aminoglycosides such as gentamicin are the classic antibiotics causing proximal tubular necrosis, because they accumulate in proximal tubular cells. The injury is dose and duration dependent, which is why trough levels are monitored during prolonged courses.

### Why does lithium cause polyuria?

Lithium causes nephrogenic diabetes insipidus by impairing the response of the collecting duct to antidiuretic hormone, so the urine stays dilute despite a raised hormone level. Management includes amiloride or a thiazide where appropriate, alongside review of the lithium dose.

### What is the mechanism of NSAID-induced acute kidney injury?

NSAIDs block prostaglandin synthesis, which normally dilates the afferent arteriole, so in volume depletion or with ACE inhibitors the glomerular filtration rate falls. Acute interstitial nephritis from NSAIDs is a separate hypersensitivity pattern, not a haemodynamic one.

### Why does amphotericin B cause hypokalaemia?

Amphotericin B causes distal renal tubular acidosis with potassium wasting, and it can also cause hypomagnesaemia. Lipid formulations reduce this toxicity, and serum potassium and magnesium are checked regularly during amphotericin therapy.

### How is cisplatin nephrotoxicity reduced in practice?

Cisplatin nephrotoxicity is reduced by saline hydration and magnesium supplementation, because proximal tubular injury is the dose-limiting toxicity of cisplatin. Monitoring creatinine and magnesium before each cycle helps detect the injury early.