Overview.
Cystinuria, which refers to the presence of large amounts of cystine in the urine, is a relatively common genetic disorder caused by defective tubular cystine transport in the kidney. It can occur at any age and is more common in children. The disease is mostly prone to the formation of urinary stones, which usually form in the bladder. Clinical manifestations often include renal colic, hematuria, fever, urinary frequency, urgency and pain, and renal insufficiency. At present, there is no cure for this disease, and symptomatic treatment is mostly adopted to prevent stone formation and its complications.
Etiology
Autosomal recessive inheritance. Due to the decrease of cystine reabsorption in renal tubules and the increase of its content in urine, cystine stones are often formed in the urinary tract. Due to the low solubility of cystine, 300-400mg per liter is dissolved in urine at 37°C pH 4.5. The amount of cystine in the patient’s urine can reach 1-2g per day, and cystine crystals are easily precipitated to form stones. The amount of lysine, arginine and ornithine in the patient’s urine is also increased, but it is easily dissolved and generally not involved in stone formation.
The disease is associated with two genotypes, namely, complete recessive genotype and incomplete recessive genotype.
1. Complete recessive genotype
May be heterozygous for an abnormal gene, with no abnormal amino acid urine other than cystinuria.
2. Incomplete recessive genotype
There is also increased excretion of lysine, etc. According to the function of amino acid transport in the intestine, the incomplete recessive genotype can be further divided into three types.
(1) Type I is the most common, in which patients have defective active transport of cystine, lysine, and arginine by the small intestinal mucosa, and serum cystine concentrations do not increase during oral cystine loading tests.
(2) Patients with type II have reduced active transport of cystine and also have impaired lysine transport, and the results of an oral cystine loading test are the same as for type I.
(3) Type III patients have decreased active transport of all three amino acids, and the serum cystine concentration rises slowly during oral cystine loading tests.
Symptoms
The main manifestation is urinary tract stones. The most common renal colic usually occurs between the ages of 10 and 30 years. Urinary stones are prone to recurrence and can cause urinary tract obstruction, secondary infections, secondary hypertension, and progressive renal hypoplasia.
Examination
1. Urine examination
Urine sediment microscopy shows hexagonal flat cystine crystals, urinary cystine concentration >250m/L. Quantitative chromatographic analysis shows cystine excretion >300mg/L. Nitroprusside cyanide test is positive.
2. Typing test
Oral cystine loading test.
3.X-ray examination
Cystine stones contain sulfur impermeable to X-ray, but are not as dense as calcium or magnesium salt stones. Calcium salt stones may form after secondary infection and are easily detected by X-ray.
Diagnosis
Cystine stones can occur in the renal pelvis or bladder. Antler-shaped stones are common. Cystine forms yellow-brown, hexagonal crystals in the urine. Excess cystine in the urine can be detected by the nitroprusside cyanide test. Chromatography and electrophoresis can further clarify the diagnosis.
Treatment
1. Fluid intake must be adequate
The first step is to drink more water to ensure that the urine output reaches 4L/d. Patients should drink 600ml or more of water every 4h to maintain nocturia 1～2 times.
2. Alkalize the urine
Alkalize the urine with sodium bicarbonate as appropriate, so that the urine pH>7.5, which can significantly increase the solubility of cystine, but also due to the ease of formation of phosphate stones and subject to certain restrictions.
3.Drugs
Oral acetazolamide at bedtime can help increase the solubility of cystine in the urine, or oral penicillamine, penicillamine can interact with cystine to generate easily soluble cysteine and penicillamine and cysteine combined with disulfide. However, toxic reactions occur in about half of patients on long-term penicillamine therapy, including fever, rash, arthralgia, nephrotic syndrome, various types of hematopoiesis, and lupus erythematosus (SLE)-like reactions, which are relatively rare.