Cystinuria

Background

Cystinuria is an autosomal recessive disorder of renal tubular amino acid transport causing excessive urinary excretion of cystine, which precipitates into recurrent kidney stones.^[1] It accounts for ~1-2% of adult and 6-8% of pediatric kidney stones.
Patients present with renal colic indistinguishable from other stone types but tend to form larger stones, more frequently, starting at a younger age.
The key EM considerations are recognizing the diagnosis (young/recurrent stone former), knowing that cystine stones are resistant to ESWL, and ensuring aggressive IV hydration and appropriate urologic follow-up.
80% form their first stone before age 20^[1]
Cystine stones are faintly radiopaque on plain film (often missed on KUB) but visible on CT
Pathognomonic finding: hexagonal crystals on urine microscopy
Up to 40% form mixed stones (cystine + calcium oxalate/phosphate)
Cystinosis — cystinuria causes stones only; cystinosis is a lysosomal storage disease causing systemic cystine accumulation, Fanconi syndrome, and multiorgan disease

Presents identically to other renal colic: acute flank pain radiating to groin, hematuria, nausea/vomiting
Suspect cystinuria when:
- Young patient (child, adolescent, young adult) with kidney stones
- Recurrent stone former with multiple procedures
- Bilateral or staghorn calculi in a young person
- Family history of early-onset stones
Complications: ureteral obstruction, infected stone, chronic kidney disease (higher CKD rate than typical stone formers)

Other causes of renal colic (stone type cannot be determined clinically):
- Calcium oxalate/phosphate (most common), uric acid (radiolucent; dissolves with alkalinization), struvite (infection stones)
Other causes of recurrent pediatric stones: primary hyperoxaluria, distal RTA, hyperparathyroidism
Cystinosis — completely different disease despite similar name

Salt-wasting tubulopathies
- Gitelman syndrome — distal convoluted tubule (NCC defect); hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis
- Bartter syndrome — thick ascending limb (NKCC2/ROMK/ClC-Kb defect); hypokalemia, hypercalciuria, metabolic alkalosis
- Liddle syndrome — collecting duct (ENaC gain-of-function); hypokalemia, hypertension, metabolic alkalosis
Renal tubular acidosis
- Renal tubular acidosis type I (distal) — hypokalemia, metabolic acidosis, nephrocalcinosis
- Renal tubular acidosis type II (proximal) — hypokalemia, metabolic acidosis, Fanconi syndrome
- Renal tubular acidosis type IV — hyperkalemia, metabolic acidosis, hypoaldosteronism
Inherited disorders of tubular transport
- Cystinuria — proximal tubule amino acid transport defect; recurrent cystine stones
- Fanconi syndrome — proximal tubule generalized dysfunction; glucosuria, aminoaciduria, phosphaturia
- Nephrogenic diabetes insipidus — collecting duct (aquaporin/V2R defect); polyuria, hypernatremia
- Dent disease — proximal tubule (ClC-5 defect); low molecular weight proteinuria, nephrocalcinosis
Acquired tubulopathies
- Diuretic use/abuse (thiazide mimics Gitelman; loop mimics Bartter)
- Aminoglycosides nephrotoxicity
- Cisplatin nephrotoxicity
- Amphotericin B nephrotoxicity
- Lithium-induced nephrogenic DI

CT abdomen/pelvis without contrast: identifies stone; cystine density typically 600-1200 HU (lower than calcium stones)
Urinalysis: hematuria; look for hexagonal crystals (pathognomonic but not always present)
BMP: creatinine, electrolytes
Urine culture if fever or pyuria
KUB is unreliable (cystine stones are faintly radiopaque and easily missed)

Stone analysis after passage or retrieval is the most reliable confirmation
Hexagonal crystals on urine microscopy — pathognomonic
Cyanide-nitroprusside test: positive (turns purple) when urine cystine >75 mg/L
24-hour urine cystine (>300 mg/day confirms; normal <30 mg/day) — not an ED test

Acute episode: manage per standard renal colic protocols
- Aggressive IV hydration (both therapeutic and helps dilute cystine)
- Analgesia: ketorolac, opioids as needed
- Antiemetics: ondansetron
- Tamsulosin for medical expulsive therapy if stone <10 mm
Obstructing stone + infection: urology emergency — urgent decompression (stent or nephrostomy) + IV antibiotics
Continue home medications: potassium citrate, tiopronin if already prescribed
Cystine stones are resistant to ESWL — ureteroscopy with laser lithotripsy or percutaneous nephrolithotomy is preferred for stones requiring surgical intervention^[1]

Admit: obstructing stone with infection/sepsis, intractable pain/vomiting, AKI, solitary kidney with obstruction
Discharge: small (<10 mm) non-obstructing stone, controlled pain, tolerating PO, normal renal function, no infection
- Urology follow-up within 1-2 weeks
- Strain urine and send any passed stone for analysis
- If cystinuria newly suspected (young/recurrent), arrange nephrology or urology referral for 24-hour urine and long-term prevention planning
Key patient instruction: drink enough to produce >3 L urine daily, including a large glass at bedtime and overnight — the single most important preventive measure

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