Cystinuria

Cystinuria is an inherited condition in which there is an excess of cystine in the urine. This excess predisposes to the formation of cysteine stones.

Terminology

"Cysteine" refers to the amino acid. "Cystine" is the oxidized dimer of the amino acid.

Epidemiology

It is thought to occur in 1:7000 persons overall (although there is marked variability among different genetic groups).

Although it is an uncommon source of stones in those with renal stone disease (1-2%), it is more common in pediatric patients (up to 10%).

Clinical presentation

Cystine stones present similarly to other renal stones: flank pain, nausea and vomiting, hematuria.

Pathology

The formation of urine cystine crystals arises from an inability to reabsorb cysteine at the proximal tubule (defect in the amino acid transporter for cysteine).

Mutations in two genes are associated with the defect in the transporter: SLC3A1 (solute carrier family 3A1) and SLC7A9. Incomplete penetrance of the gene often results in a lower concentration of cystine in the urine and not all patients with the mutation will form stones.

Cystine crystals have a flat hexagonal appearance in urine specimens .

Radiographic features

Cystine stones tend to be larger relative to other etiologies for stone disease and frequently coalesce to form large branching staghorn calculi.

Cystine stones appear similar to other renal stones. They are thought to have lower attenuation than calcium stones and a slightly lower attenuation than struvite stones, but there is overlap in values . They are thought to have a higher attenuation than uric acid stones.

Dual-energy CT may allow for more specific characterization of cystine stones .

Treatment and prognosis

The stones also tend to recur more often than stones from other etiologies. Treatments include

• increase fluid intake
• increase cystine solubility through urinary alkalinization: e.g potassium citrate, sodium citrate, and sodium bicarbonate
• decrease cysteine intake (e.g. decrease animal protein intake)
• thiol-containing agents (d-penicillamine and α-mercaptopropionylglycine)
  • side effects limit the use of these agents