When should cystinuria be suspected in a patient?

When to Suspect Cystinuria

Cystinuria should be suspected in patients with recurrent kidney stones, particularly those with stones that begin at a young age, have a family history of stones, or have hexagonal crystals in their urine. 1

Clinical Presentations That Should Raise Suspicion

• Recurrent stone formation, especially with high stone burden and frequent need for surgical interventions 2, 3
• Early onset of kidney stones (mean age at stone onset is 21.8 years, though stones can present from infancy through the ninth decade) 4, 3
• Family history of kidney stones, consistent with the autosomal recessive inheritance pattern of cystinuria 4, 5
• Presence of hexagonal crystals in urinalysis, which are pathognomonic for cystine stones (though these are only visible in 19-26% of homozygous patients) 4
• Poor response to conventional stone prevention measures 6
• High recurrence rate (83% at 5 years after first stone) 3

Laboratory Findings

• Positive cyanide-nitroprusside test (Brand's test), which is a suitable screening test for homozygous cystinuric patients 4, 3
• Urinary cystine excretion ≥250 mg/g creatinine in a 24-hour urine collection defines homozygous cystinuria 4, 6
• Elevated urinary excretion of dibasic amino acids (arginine, lysine, and ornithine) in addition to cystine 4

Stone Analysis

• Stone analysis revealing cystine composition is diagnostic and should be obtained at least once when a stone is available 1
• Stone composition of cystine implicates specific metabolic or genetic abnormalities that require targeted preventive measures 1

Risk Factors and Demographics

• Cystinuria accounts for approximately 1-2% of kidney stones in adults and 6-8% in pediatric populations 4, 5
• Male to female ratio is approximately 1:0.62 3
• Patients with cystinuria have more stone events and surgical interventions compared to other stone formers 2
• Higher risk of progression to chronic kidney disease and end-stage kidney disease 2

Diagnostic Approach

1. Initial screening: Perform cyanide-nitroprusside test in all patients at the onset of renal stone disease 3
2. Confirmation: Quantitative measurement of urinary amino acids by ion-exchange chromatography in patients with positive screening test 3
3. Stone analysis: When available, stone analysis should be performed at least once 1
4. 24-hour urine collection: Should include measurement of cystine in addition to standard parameters (volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine) 1
5. Family screening: Consider screening family members, as 21% of asymptomatic family members with excessive cystine excretion may have cystine calculi 3

Common Pitfalls in Diagnosis

• Mixed stone composition can disguise the presence of cystinuria, leading to delayed diagnosis many years after initial symptoms 3
• Relying solely on visible crystals in urine is insufficient, as they are present in only a minority of patients 4
• Failure to perform stone analysis when available can miss this important diagnosis 1
• Not considering cystinuria in young patients with recurrent stones 4, 3

By maintaining a high index of suspicion in the appropriate clinical context and following a systematic diagnostic approach, clinicians can identify cystinuria early and implement appropriate preventive measures to reduce the significant morbidity associated with this condition.