6th February 2024

Cystinuria

Cystinuria is characterised by impaired reabsorption of amino acid, cystine, by the kidneys. It is a rare inherited condition (affecting 1 in 2000 in the UK) caused by mutations in the SLC3A1 and SLC7A9 genes, responsible for encoding proteins involved in transporting cystine and other amino acids in the kidney. The kidneys usually filter the blood, removing waste products and reabsorbing necessary substances into the bloodstream. However, in cystinuria, the defect prevents reabsorption, resulting in excretion in the urine. 

The main consequence of cystinuria is the formation of cystine kidney stones. Cystine is poorly soluble in urine, and when concentration is high, it crystallises and aggregates, forming stones. The stones formed vary in shape and size but often cause pain and discomfort as they pass through the urinary tract. Recurrent stone formation can lead to complications, including urinary tract obstruction, infection and kidney dysfunction.

There are three types of cystinuria, classified according to underlying genetic mutation and impact on amino acid excretion.

• Type I
  • Caused by mutations in the SLC3A1 gene, this type is characterised by defective reabsorption of cystine, arginine, lysine and ornithine.
• Type II
  • Caused by mutations in the SLC7A9 gene, this type is characterised by cystine and, to a lesser extent, dibasic amino acids like ornithine and lysine.
• Mixed type
  • Patients with mixed type may have mutations in both genes, resulting in a mixed type of cystinuria.

Clinical features

Typical features of cystinuria reflect urinary stone symptoms; they depend on the size and location of the stones. Common symptoms include flank pain, haematuria, and frequent urinary tract infections. Age of onset and severity of symptoms can be variable amongst individuals, but the defining feature is that these patients are troubled by recurrent stone episodes.

Diagnosis

Cystinuria is typically diagnosed through stone analysis or analysis of 24-hour urine samples to assess amino acid composition. 

Management

The mainstay of treatment for cystinuria is first to prevent stone formation, then to manage symptoms and reduce the risk of complications when stones are present. This involves increasing urine volume and decreasing cystine concentration, mainly by increasing fluid intake, maintaining a low-sodium diet (as sodium encourages stone formation), and alkalinising the urine (with potassium citrate). 

Cystine is made in the body from methionine. Therefore, patients with cystinuria can find it helpful to follow a diet low in methionine (i.e. a low animal protein diet) to reduce cystine burden. Patients require regular monitoring, with urine analysis, renal function tests and imaging to detect stones.

Medications, including tiopronin or alpha-mercaptopropionylglycine (α-MPG), may be prescribed to decrease cystine levels in the urine, further preventing stone formation. In some instances, surgical intervention is required to manage large stones that have caused complications.

Genetic counselling may be recommended for individuals with cystinuria and their families to understand inheritance patterns and assess the risk of passing on the condition to future generations.