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. 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
• 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

Clinical Features

• 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)

Differential Diagnosis

• 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

Renal tubular disorders

• 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

Evaluation

Workup

• 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)

Diagnosis

• 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

Management

• 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

Disposition

• 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

See Also

• Nephrolithiasis
• Cystinosis
• Fanconi syndrome
• Renal colic

External Links

• StatPearls — Cystinuria
• Urol Ann — Cystinuria: Overview of Diagnosis and Medical Management (2022)
• GeneReviews — Cystinuria