Drug-Induced Nephrotoxicity

ATN, AIN, crystal nephropathy, and the drugs behind each one. Know the casts, know the answer.

CLINICAL VIGNETTE

A 42-year-old man presents to his PCP 10 days after being discharged from the hospital for a severe pneumonia. He reports a noticeable reduction in urine output over the past 3 days.

Cr: 2.9 mg/dL (baseline 0.9)
UA: 2+ proteinuria, brownish granular casts
Biopsy: patchy necrosis of proximal tubule, sloughing of epithelial cells, preserved basement membrane

Which drug most likely caused this patient's renal injury?

A. Acyclovir
B. Captopril
C. Aspirin
D. Gentamicin
E. Omeprazole

Sort the Nephrotoxins

Drag each drug into its injury category. Some drugs have more than one mechanism; sort by the PRIMARY board-tested mechanism.

Gentamicin
Amphotericin B
Cisplatin
Contrast dye
Myoglobin (rhabdo)
Omeprazole
NSAIDs (chronic)
Methicillin
Acyclovir
Indinavir
Methotrexate
Captopril (ACEi)
Ibuprofen (acute)
Losartan (ARB)
ATN (Toxic)
Direct tubular cell death. Muddy brown casts.
AIN (Allergic)
Immune reaction. Fever, rash, WBC casts.
Crystal Nephropathy
Drug crystals block tubules. Crystals in urine.
Prerenal AKI
Reduced perfusion. No structural damage.
Cast cheat sheet: Muddy brown castsDead tubular epithelial cells and cell debris. Pathognomonic for ATN. = ATN · WBC castsWhite blood cells packed into a tubular cast. Seen in AIN, pyelonephritis, and lupus nephritis. = AIN / pyelonephritis · RBC castsRed blood cells trapped in a cast. Classic for glomerulonephritis: the RBCs leaked through a damaged glomerular basement membrane. = glomerulonephritis · Waxy castsBroad, waxy-looking casts from very slow urine flow. Seen in advanced CKD (end-stage kidneys). = advanced CKD

Memory hooks: ATN drugs "AA CC M" 🔑Aminoglycosides, Amphotericin B, Cisplatin, Contrast dye, Myoglobin. "Angry ATN drugs can cause massive necrosis." · AIN = "NSAIDs, Methicillin, PPIsThe AIN triad drugs. All cause fever + rash + eosinophiluria. NSAIDs = analgesic AIN. Methicillin = the original AIN drug. PPIs = most common culprit today." 🔑"No More Pain" = NSAIDs, Methicillin, PPIs. All cause the AIN triad (fever + rash + eosinophiluria). · Crystal drugs: "AIM" 🔑Acyclovir, Indinavir, Methotrexate. Crystals block the pipe physically. Hydration dissolves them.
Category Trace It Urine Findings Classic Drugs
ATN (Toxic) Direct tubular cell death Muddy brown granular casts, epithelial cell casts Aminoglycosides, amphotericin B, cisplatin, contrast, myoglobin
AIN (Allergic) Type IV hypersensitivity in interstitium WBC casts, eosinophiluria, sterile pyuria NSAIDs, methicillin, PPIs, sulfonamides, rifampin
Crystal Drug crystals precipitate in tubules Crystalluria, hematuria Acyclovir, indinavir, methotrexate, sulfonamides
Prerenal Reduced renal perfusion (no structural damage) Bland sediment, FeNa <1%, BUN:Cr >20:1 ACEi/ARBs (efferent), NSAIDs (afferent)

Elimination Round

A biopsy shows patchy proximal tubule necrosis, sloughed epithelial cells, and a preserved basement membrane. Tap to eliminate drugs that did NOT cause this.

ATN biopsy findings. Eliminate non-ATN drugs one at a time. The last drug standing is your answer.
Acyclovir
Crystal nephropathy
Captopril
Prerenal (ACEi)
Gentamicin
Aminoglycoside
Aspirin
NSAID
Omeprazole
PPI
Indinavir
Protease inhibitor

The Villains

Tap any card to flip it. Front = the drug. Back = mechanism, cast finding, and final rule.

↻ tap to flip

💊
Aminoglycosides
Gentamicin, tobramycin, amikacin
Aminoglycosides
Where: Proximal tubule (PCT)
How: Taken up by megalin receptor into PCT cells, accumulates in lysosomes, triggers cell death from inside
Cast: Muddy brown granular casts
Extras: Ototoxic (hair cell damage) · hypoMg · non-oliguric ATN
Final rule: muddy brown casts + aminoglycoside = toxic ATN. Reversible if caught early.
🔧
Cisplatin
Platinum chemo agent
Cisplatin
Where: PCT and DCT
How: Enters tubular cells, crosslinks DNA, triggers apoptosis; also causes oxidative stress
Cast: Muddy brown casts
Extras: HypoMg (tubular Mg wasting), hypoK, ototoxic · prevent with aggressive saline hydration
Final rule: testicular/ovarian cancer chemo + rising Cr + hypoMg = cisplatin ATN.
🔄
Contrast Dye
CIN / contrast-induced AKI
Contrast Dye
Where: Medullary tubules (especially TAL)
How: Direct tubular toxicity + renal vasoconstriction (decreased medullary O2 delivery)
Cast: Muddy brown casts
Extras: Cr rises 24-48h post-contrast, peaks at 3-5 days · prevent with IV saline ± NAC
Final rule: CT scan + Cr rise 48h later = contrast nephropathy. Risk up in CKD + DM.
💌
Amphotericin B
Antifungal, IV formulation
Amphotericin B
Where: PCT and DCT membranes
How: Binds cholesterol in tubular cell membranes (like ergosterol in fungi), punches holes, K+ and H+ leak out
Electrolytes: HypoK + type 1 RTA (distal RTA)
Extras: Lipid formulation (AmBisome) is less nephrotoxic
Final rule: amphotericin + hypoK + metabolic acidosis = tubular membrane pore toxicity.
🐪
NSAIDs
Aspirin, ibuprofen, naproxen
NSAIDs
Acute: Block PGE2 at afferent arteriole → vasoconstriction → prerenal AKI. Bland sediment, FeNa <1%.
Chronic (months-years): Analgesic nephropathy → papillary necrosis → sloughed papilla can obstruct ureter
Also: Can cause AIN (allergic, reversible)
Final rule: acute NSAID = prerenal (no casts). Chronic NSAID = papillary necrosis. POSTCARDS mnemonic.
💩
Acyclovir / Indinavir
Crystal nephropathy drugs
Crystal Nephropathy
Acyclovir: Needle-shaped crystals in concentrated urine → physical tubular obstruction. Treat with hydration.
Indinavir (HIV): Protease inhibitor crystals in alkaline urine → flank pain, hematuria, crystalluria
Methotrexate: Precipitates at acidic pH → give urinary alkalinization
Final rule: crystals in urine + drug exposure = crystal nephropathy. No muddy brown casts. Hydration is treatment.

Workup Algorithm

Follow the decision tree to identify the type of drug-induced kidney injury.

Drug exposure + rising creatinine
Check urine sediment
Muddy brown granular casts
→ ATN (toxic)
Aminoglycosides, cisplatin, amphotericin B, contrast, myoglobin
WBC casts + eosinophiluria
→ AIN (allergic)
Check for fever + rash triad. NSAIDs, methicillin, PPIs, sulfonamides
Crystalluria (needle or fan-shaped)
→ Crystal nephropathy
Acyclovir, indinavir, methotrexate. Hydrate aggressively.
Bland sediment + FeNa <1% + BUN:Cr >20
→ Prerenal AKI
ACEi / ARBs (efferent dilation), NSAIDs (afferent constriction)
ATN confirmed? → Was it reversible?
Yes + preserved basement membrane on biopsy
→ Toxic ATN: tubular cells regenerate from surviving basement membrane. Recovery in 1-3 weeks.
Persistent AIN despite drug removal
→ Consider steroids (prednisone). AIN can progress to CKD if untreated.

Clinical Images

Key histology and clinical concepts. Tap any image to open.

Loading images...
Small echogenic kidney ultrasound
Kidney injury contextChronic kidney disease increases nephrotoxin risk.

Which Drug Is Causing AKI?

Recent new medication + rising creatinine. Follow the culprit.

Recent new medication + rising creatinine?

clinical reference

5 random questions from a pool of 10. All original.

Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last reviewed June 2026
Bone Wizardry is an independent educational resource for visual learning in the medical sciences. It is not affiliated with, endorsed by, or sponsored by any licensing or examination board, contains no real or recalled examination questions, and does not guarantee any educational or examination outcome.

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