PharmacologyTier 1Medical Sciences concept

Drug and metabolic causes of crystal nephropathy (acyclovir, ethylene glycol, tumour lysis, indinavir)

Core concept

Crystals precipitate when solubility is exceeded in the tubular lumen - three variables, all modifiable
- Concentration - determined by urine flow rate (volume status) and by dose
- Urine pH - each crystal has its own solubility curve
- Nucleation surface - pre-existing tubular injury
Consequence: intratubular obstruction + direct tubular toxicity + interstitial inflammation -> AKI, often non-oliguric
Prevention is the same for all: volume expansion, and pH manipulation in the right direction

Crystal	Cause	Urine pH effect	Prevention
Aciclovir	High-dose IV, rapid bolus	Insoluble in alkaline/concentrated urine	Slow infusion over 1 h + hydration, dose for eGFR
Methotrexate	High-dose IV	Insoluble in acid urine	Alkalinise to pH >7, hydrate, folinic acid rescue, glucarpidase; avoid NSAIDs, PPIs, penicillins
Sulfonamides (sulfadiazine, cotrimoxazole)	High dose	Insoluble in acid urine	Alkalinise, hydrate
Indinavir, atazanavir	Protease inhibitors	Insoluble at high pH	Hydration
Ciprofloxacin	High dose	Insoluble in alkaline urine	Hydration
Ampicillin, amoxicillin	High dose IV		Hydration
Foscarnet, ganciclovir, triamterene, orlistat
Uric acid	Tumour lysis syndrome	Insoluble in acid urine	Hydration + rasburicase (or allopurinol)
Calcium phosphate	Tumour lysis, oral sodium phosphate bowel prep	Insoluble in alkaline urine	Do not alkalinise if phosphate is high
Calcium oxalate	Ethylene glycol, high-dose vitamin C, enteric hyperoxaluria (short bowel, bariatric surgery, orlistat), primary hyperoxaluria		Fomepizole/ethanol + dialysis

Urine microscopy is the diagnostic test
- Ethylene glycol -> envelope-shaped (dihydrate) and needle/dumbbell (monohydrate) calcium oxalate crystals, plus a raised osmolar gap then a high anion gap acidosis
- Aciclovir -> needle-shaped birefringent crystals
- Uric acid -> pleomorphic, rhomboid, "bipyramidal"
- Sulfadiazine -> "shocks of wheat" / fan-shaped sheaves
Tumour lysis - inc K, inc phosphate, inc urate, dec Ca; both urate and calcium-phosphate deposition
- Rasburicase is contraindicated in G6PD deficiency (haemolysis and methaemoglobinaemia)
- Do not routinely alkalinise urine in tumour lysis - it lowers urate solubility risk but precipitates calcium phosphate

Any AKI in a patient on high-dose IV aciclovir, methotrexate or a sulfonamide -> send urine microscopy before anything else
High-dose methotrexate protocols mandate urinary alkalinisation, hydration, level monitoring and folinic acid rescue; drugs that reduce methotrexate clearance (NSAIDs, penicillins, PPIs, probenecid, cotrimoxazole) must be withheld
Ethylene glycol - treat on suspicion: fomepizole (or ethanol) blocks alcohol dehydrogenase, plus haemodialysis for acidosis, high level or renal failure
- Oxalate crystalluria plus hypocalcaemia plus a high osmolar gap is the triad
Enteric hyperoxaluria after bariatric surgery or in short bowel - fat malabsorption binds calcium, leaving oxalate free to absorb; treat with calcium with meals, low oxalate diet, hydration
Contrast this with acute interstitial nephritis (eosinophiluria, WCC casts, drug rash) and with ATN - crystals point to a different mechanism and a different fix

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