Cystinuria

According to recent genetic studies, mutations in the SLC3A1 and SLC7A9 genes are thought to be the main cause of an increased risk of stones. Both genes code for subunits of important transport proteins in the renal tubules and the small intestine. If a gene defect is present, there is a disturbance of the transport in the sense of resorption disorders and, as a consequence, an increased excretion of the amino acids cysteine, ornithine, lysine and arginine.

What role does cystine play?

Although all of the amino acids mentioned reach a high concentration in the urine, cysteine is considered the stone-forming substance. This is because cystine (cysteine-cysteine) is insoluble in acidic to normal urine pH range. This leads to cystine precipitation, the formation of cystine crystals and consequently to stone formation.

Who is affected by the disease?

In the course of life, more than 50% of patients suffer from cystine-related stone condition, whereby the manifestation of the disease can basically occur at any age. In more than 80% of cases, the disease becomes apparent in the first two decades of life. Early onset of stones seems to be more likely in male patients than in female patients. In addition, male patients are more frequently affected than female individuals.

Symptoms and course of the disease

The increased excretion of cystine alone does not usually cause any symptoms. These first appear through the formation of cystine crystals and later through cystine stones, which in turn can lead to serious complications.

These include:

• Renal colic, characterized by acute stone-related pain in the flanks, back and groin.
• Infections of the kidneys and urinary tract
• Hydronephrosis: This refers to urinary retention due to a disturbance of the urine outflow, e.g. due to a urinary stone. The result can be, for example, a rupture of the ureter, damage to the kidney tissue or blood poisoning.
• a decrease in kidney performance, which can lead to kidney failure and make kidney replacement therapy (dialysis) or transplantation necessary.

However, especially in younger children, the symptoms are more unspecific, which is why it is often difficult to find the right diagnosis.

Symptoms that occur in children

• Irritability
• Non-specific abdominal pain in the umbilical region, also with vomiting
• Microhaematuria
• Urinary tract infections

How is the diagnosis made?

If Cystinuria is suspected, the following examinations can be carried out to clarify the findings:

• Taking a history of the disease (anamnesis): this should clarify whether you or one of your family members has already suffered from a stone disease. In addition, your nutritional status, current medication status and any previous illnesses will be clarified.
• Metabolic diagnostics: in addition to a blood test, this also includes the evaluation of the 24-hour urine collection and can provide information on electrolytes, cystine levels, uric acid, urea, creatinine and thus, for example, on kidney performance or the probability of stone formation.
• Imaging procedures: to prove or exclude a stone, it is recommended to check the kidneys and efferent urinary passages by means of sonography, among other methods. Microscopic examination of the urinary sediment and urinary stones, on the other hand, can provide information about the existing stone composition.
• Genetic diagnostics: a molecular genetic examination via a blood test can provide absolute clarity as to whether a genetic defect is present. If this is confirmed, first- and second-degree relatives can be examined in a so-called cascade screening and, once the diagnosis has been made, can be given early treatment.

Patients who have already been treated with medication should visit their doctor at regular intervals for follow-up examinations to measure the success of the therapy.

Current treatment and therapy

Since Cystinuria is a genetically determined stone formation, a cure for the causal cause - the genetic defect - is not possible at this time. The aim of treatment is to prevent further complications, whereby the general prospect of therapeutic success depends on the following factors:

• the severity and progress of the Cystinuria condition
• the response to the therapeutic measures
• adherence to therapy
• the presence of other risk factors

Conservative therapy

The pillars of conservative therapy serve the goal of reducing the increased cystine concentration 24 hours a day - day and night - to a normal range. This reduces the likelihood of developing a kidney stone and can prevent rare but serious complications.

• Increasing fluid intake helps dilute the cystine in the urine.
• A low-protein diet to ensure a lower intake of the amino acid cystine from protein-containing foods such as meat.
• Pharmacological therapy: if nutritional therapy fails, pharmacological therapy may be useful.

Interventional therapy

If the above treatment options are not effective and a stone forms or an emergency situation occurs, e.g. a complete blockage of the urinary tract and thus a life-threatening urine backflow into the kidney, various invasive and surgical treatment options can be used, depending on the size and location of the stones. Since Cystinuria predominantly takes a recurrent-chronic course, adequate adjustment of the cystine concentration is essential for the prevention of further events.

General notice:

The information on this website is for general educational purposes only and is not intended to make a diagnosis or to recommend a treatment. Please consult a doctor for any medical questions regarding this condition.