idiopathic hypercalciuria
Introduction
Introduction to idiopathic urinary calcium Idiopathic hypercalciuria (IH) is a disease in which the cause of urinary calcium is not fully understood and accompanied by urinary chrome stones, and blood calcium is normal. In 1953, Albright first reported a group of unexplained kidney stones with normal blood calcium, and increased urinary calcium excretion, named idiopathic urinary calcium. basic knowledge The proportion of illness: the incidence rate is about 0.004%-0.008% Susceptible people: no specific population Mode of infection: non-infectious Complications: urinary tract infection secondary hyperparathyroidism osteoporosis
Cause
The cause of idiopathic urinary calcium
(1) Causes of the disease
The etiology of this disease is not clear, because of the obvious familial genetic predisposition, may be related to autosomal dominant genetic defects, resulting in genetic mutations caused by a variety of substance transport disorders, especially vitamin D metabolic disorders, vitamin D metabolic disorders Can cause intestinal absorption of calcium hyperthyroidism, renal tubular reabsorption of calcium dysfunction or intestinal and renal tubular dysfunction, and increased urinary calcium; in addition, diet and environmental factors are also related to the incidence.
(two) pathogenesis
The disease has obvious familial genetic predisposition, and the pathogenesis is related to autosomal dominant inheritance and gene mutation. Using family analysis, restriction fragment length polymorphism and microsatellite DNA polymorphism analysis, the diseased gene is located in human chromosome. Xpll.22, a chloride channel protein CLC-5 encoding a tubular epithelial cell membrane, is associated with the formation of endocytic vesicles by cell reabsorption of small molecular weight proteins. After mutation, the channel structure is abnormal, and chloride ions cross vesicles. Membrane flow is blocked, vesicle acidification disorder, affecting protein reabsorption, small molecular proteinuria, and vesicles can not be acidified, affecting cell membrane surface receptor recycling, which in turn causes abnormal transport of various substances, high urinary calcium production The reasons are:
1. Renal tubule reabsorption of calcium ion function defects, also known as renal leakage of calcium excess (renal leak type) when the renal tubules reduce the re-absorption of a certain regulatory protein or the protein channel recirculation barrier involved in calcium transport on the luminal membrane, Calcium reabsorption in the original urine is reduced, causing an increase in urinary calcium, a decrease in blood calcium, a decrease in blood calcium, an increase in the secretion of PTH in the parathyroid glands, and an increase in the synthesis of vitamin D active products, which maintains normal levels of blood calcium and renal tubules. Reduced reabsorption, renal hypophosphatemia caused by secondary hypophosphatemia, feedback increased 1,25 (OH) 2D3 synthesis, intestinal calcium absorption and maintenance of normal blood calcium, jejunal absorption of calcium ions increased, also The increase in calcium ions can be filtered to further increase the excretion of urinary calcium.
2. Increased absorption of calcium by jejunal transport, also known as intestinal calcium absorption (absorption type) Mainly due to excessive absorption of calcium by the jejunum, which leads to an increase in blood calcium, an increase in glomerular filtration calcium, and a secondary urinary calcium excretion. Another inhibition of parathyroid secretion, increased glomerular ultrafiltration load, and renal tubular reabsorption of calcium ions, causing increased urinary calcium, increased calcium absorption by the urine, so blood calcium does not rise and Can maintain normal, this type of mechanism is unknown, some people think that vitamin D regulation disorders.
Prevention
Idiopathic urinary calcium increase prevention
The onset of this disease can be caused by vitamin D metabolic disorders, and is related to diet and environmental factors. For children, it is recommended to promote reasonable feeding, more sun exposure, and actively prevent the occurrence of nutritional diseases. For patients with multiple comorbidities, early diagnosis and Treatment to minimize kidney damage and prevent kidney failure.
Complication
Idiopathic urinary calcium syndrome complications Complications Urinary tract infection Secondary hyperparathyroidism Osteoporosis
Often complicated by urinary tract infections, urinary tract stones, secondary hyperparathyroidism, nutritional disorders, osteoporosis, fractures, deformities, short stature, weight loss, muscle weakness and so on.
Symptom
Symptoms of idiopathic urinary hypercalcemia common symptoms proteinuria polydipsia polyuria leukocytosis urinary frequency urinary pain urgency urinary abdominal pain urinary calculi
The early stage of the disease is relatively hidden, which can only be expressed as small molecular proteinuria. The relative molecular weight of the protein is generally less than 40,000 Da. The main components are 2-microglobulin, retinol binding protein, 1-microglobulin and lysozyme. Marker protein, 24h urine protein amount in most children under 1g, adult 0.5 ~ 2.0g, to adult stage can occur nephrolithiasis, renal calcinosis and progressive renal insufficiency.
Patients with this disease often cause hematuria and renal colic, urinary tract infection and bladder irritation (urinary frequency, urgency, dysuria), dysuria syndrome, abdominal pain, back pain and enuresis, etc. due to urinary calculi, and more drink, Polydipsia, polyuria, urine sedimentation is mostly white, and a few can develop chronic renal failure.
1. Hematuria proteinuria can be seen in all age groups with gross hematuria or microscopic hematuria. It is generally believed that calcium crystallization causes urinary tract injury. This hematuria is normal red blood cell morphology hematuria (ie non-glomerular hematuria), and hematuria It is the most common manifestation of IH in children. Hematuria can be transient or persistent. Proteinuria is generally mild, moderate, and has a small molecular weight. The main component is -microglobulin, retinol-binding protein, . - Microglobulin and the like.
2. Urinary calculi adult IH showed urinary stones significantly higher than children, there are reports of adult urolithiasis with IH up to 40% to 60%, and only 2% to 5% of pediatric urinary stones caused by IH, this Calcium-like stones are mostly formed by calcium oxalate or calcium phosphate. Those with early age and non-IH may develop obstructive nephropathy if not treated in time.
3. Other manifestations may also show renal tubular dysfunction such as renal diabetes, amino aciduria, uric aciduria, etc. Due to the large loss of calcium from the urine, the body has a long-term negative calcium balance, and a small number of patients may have secondary parathyroid function. Hyperthyroidism, patients may have joint pain, osteoporosis, fractures, deformities and vitamin D deficiency, a small number of patients showed short stature, weight loss, muscle weakness and so on.
Examine
Examination of idiopathic urinary calcium
1. Urine examination increased urinary calcium, female urinary calcium>6.25mmol/24h, male>7.5mmol/24h (24h urinary calcium>0.1mmol/kg (>4mg/kg), Uca/Ucr>0.21; may be mild Hematuria, proteinuria, tubeless urine, calcium oxalate, phosphate crystals; impaired urine concentration, increased leukocytosis when infected.
2. Blood tests for normal blood calcium, blood phosphorus can be reduced, alkaline phosphatase is increased, and serum parathyroid hormone concentration is increased.
3. The calcium load test method is a low-calcium and low-phosphorus diet for 3 days. On the fourth day, calcium (15 mg/kg) is intravenously instilled, and the blood is dripped within 5 hours, and blood calcium is measured 3 hours later; and urine calcium is measured for 24 hours.
Judgment: If the urinary calcium excretion minus the daily urinary calcium excretion, the value exceeds 50% of the instilled calcium; the urinary phosphorus excretion decreased from the 4th to 12th hour after the infusion of calcium compared with the 0th to 4th hour. 20%, it is positive.
4. Renal histopathological examination mainly showed non-specific tubular atrophy and interstitial fibrosis. Calcium deposition in the kidney mainly occurred in the renal medulla, but it was inconsistent with the time and extent of renal failure.
5. Regular B-ultrasound, X-ray film, intravenous urography or CT examination.
Diagnosis
Diagnosis and differentiation of idiopathic urinary calcium
diagnosis
According to the clinical characteristics, the increase of urinary calcium and normal blood calcium is an important basis for the diagnosis of this disease. The diagnosis should be based on the relevant examination of the laboratory and the exclusion of other causes of increased urinary calcium.
1. Clinical features For patients with unexplained simple hematuria, the family should be asked whether there is a history of urinary stones. For patients with clinical manifestations of urinary tract infections and urinary calculi, 24-hour urine should be collected and urine calcium (Uca) and urine should be measured. Creatinine (Ucr); if urinary calcium > 0.1mmol/kg per day (> 4mg/kg per day), the ratio of Uca/Ucr should be determined. If the ratio is >0.21, the disease can be initially diagnosed.
2. Urine test features urinalysis can have microscopic hematuria, leukocytosis, no proteinuria or only mild proteinuria, no tubular urine, calcium oxalate and/or phosphate crystals can be seen, urine pH determination helps differential analysis The nature of urinary crystallization, children can show impaired urine concentration.
3. Calcium load test can be used as a calcium load test to identify whether it is an absorption type or a renal leak type. The low calcium diet test is to consume less than 300 mg of calcium per day for 3 days, and the urinary calcium level is still high on the 4th day. It has diagnostic significance in normal people. In recent years, some authors believe that the oral calcium load test does not help to predict nephrolithiasis. It is not recommended to use this test as a routine diagnostic evaluation of hypercalciuria in children unless the serum parathyroid hormone concentration is elevated. Another author suggested using the calcium-restricted and intravenous calcium tolerance test to confirm the diagnosis of the disease, the method is low calcium and low phosphorus diet 3 days, on the 4th day, calcium 15mg / kg, intravenous input, after the end of 5h, the third hour Blood calcium measurement, and 24h urine to measure urinary calcium, if the urinary calcium output minus the basic urinary calcium, still exceed the 50% of the amount of calcium, the urinary phosphorus discharge in the 4th to 12th hour after the calcium is lower than the 0th A decrease of 20% in ~4 hours means that the test is positive.
Differential diagnosis
1.Fanconi syndrome
The main clinical manifestations are due to the proximal renal tubules of glucose respiration caused by multiple substances reabsorption, full amino acid urine, different degrees of phosphate urine, bicarbonate urine and uric acid and other organic aciduria, can also involve the proximal end And distal renal tubules, accompanied by renal tubular proteinuria and excessive electrolyte loss, and various metabolic secondary causes, such as hyperchloric acidosis, hypokalemia, high urinary calcium and abnormal bone metabolism However, due to the presence of polyuria at the same time, kidney stones and renal calcification rarely occur.
2. Hyperparathyroidism
In addition to the unique clinical manifestations, the main manifestations are elevated PTH, elevated blood calcium, decreased blood phosphorus, and calcium in normal idiopathic urinary hypercalcemia, blood phosphorus and PTH are often close to the normal low limit.
3. Myeloma
Clinical manifestations of proteinuria, nephrotic syndrome, chronic tubular insufficiency and acute and chronic renal failure, mainly due to the above-mentioned symptoms caused by massive deposition of light chain in the kidney and hypercalcemia, renal biopsy and bone marrow puncture can be used as a basis for diagnosis.
4. Renal tubular acidosis
Increased urinary calcium excretion, decreased blood calcium, clinical manifestations of bone pain and pathological fractures, accompanied by urinary calculi, easy secondary urinary tract infection, and even renal calcification, impaired renal tubular concentrating function, showing low specific gravity urine, alkaline urine .
5. Medullary sponge kidney
The disease is a congenital benign renal cystic disease, the main clinical manifestations of hematuria, mostly microscopic hematuria, easy to have kidney stones, causing low back pain, renal colic, urinary tract infection, etc., involving the distal renal tubules as kidney Concentrated acidification is reduced, and renal venography can be used as the main basis for diagnosis.
