Increased urinary calcium

Introduction Idiopathic hypercalciuria (IH) is a disease in which the cause of urinary calcium is not fully understood and accompanied by urinary calculi, 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. The cause of the disease is still unclear and may be related to autosomal dominant genetic defects. In addition, the symptoms are caused by vitamin D metabolic disorders, pay attention to good eating habits, and pay attention to nutritional balance is an effective measure to prevent the disease.

Cause

Cause:

(1) Causes of the disease

The cause of this disease is not clear. Due to the apparent familial genetic predisposition, it may be related to autosomal dominant genetic defects. The resulting gene mutation causes a variety of substance transport abnormalities, especially vitamin D metabolic disorders. Vitamin D metabolic disorders can cause intestinal absorption of calcium hyperactivity, 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 a distinct 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 disease gene was found on the human chromosome Xpll.22, which encodes the chloride channel protein CLC-5 of the renal tubular epithelial cell membrane. CLC-5 is involved in the formation of endocytic vesicles by cellular reabsorption of small molecular weight proteins. After the mutation, the channel structure is abnormal, the chloride ion is blocked across the vesicle membrane, the vesicle acidification is disordered, affecting protein reabsorption, small molecular proteinuria occurs, and the vesicle can not be acidified, affecting cell membrane surface receptor recycling. , and then caused a variety of substance transport abnormalities. The causes of high urinary calcium in this disease 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 reabsorption of a certain regulatory protein or the protein channel recirculation barrier involved in calcium transport on the luminal membrane, Reducing calcium ion reabsorption in the original urine, causing an increase in urinary calcium and a decrease in blood calcium. As the blood calcium is reduced, the secretion of PTH by the parathyroid glands is increased, and the synthesis of vitamin D active products is increased, so that the blood calcium is maintained at a normal level. Renal tubules reduce phosphorus reabsorption, renal hypophosphatemia causes secondary hypophosphatemia, and feedback increases the synthesis of 1,25(OH)2D3, which increases intestinal calcium absorption and maintains normal blood calcium. Increased absorption of calcium ions by the jejunum also increases the amount of filterable calcium ions, further increasing 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, causing an increase in blood calcium to increase glomerular filtration calcium, secondary urinary calcium excretion High; another inhibition of parathyroid secretion function, increase glomerular ultrafiltration load, and renal tubular reabsorption of calcium ions, causing increased urinary calcium, increased absorption of calcium ions from 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.

an examination

Related inspection

Urinary fibrin degradation product urine routine

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. The amount of 24h urine protein is mostly below 1g for children and 0.5 to 2.0g for adults. Kidney stone disease, renal calcinosis and progressive renal insufficiency can occur in adulthood.

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 due to urinary calculi, and have more drink, Polydipsia, polyuria, and urine sedimentation are mostly white, and a few can develop chronic renal failure.

1. Hematuria proteinuria: Gross hematuria or microscopic hematuria can be seen in all age groups. It is generally believed that calcium crystallization causes urinary tract injury. This hematuria belongs to normal red blood cell morphology hematuria (ie, non-glomerular hematuria). And hematuria is the most common manifestation of pediatric IH, hematuria can be transient, but also persistent. Proteinuria is generally light, moderate, and has a small molecular weight. The main components are -microglobulin, retinol-binding protein, -microglobulin, and the like.

2. Urinary tract stones: 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 children's urinary stones are caused by IH. Such 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: Renal diabetes, amino aciduria, uric acid and other proximal renal tubular dysfunction can also occur. Due to the large loss of calcium from the urine, the body has a long-term negative calcium balance, a small number of patients can be secondary to hyperparathyroidism, patients may develop joint pain, osteoporosis, fractures, deformities and vitamin D deficiency, a small number of patients showed short stature , weight does not increase, muscle weakness and so on.

According to the above clinical features, 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 examinations in the laboratory and the exclusion of other causes of increased urinary calcium.

1. Clinical features: For patients with simple hematuria of unknown cause, the family should be asked whether there is a history of urinary stones. For patients with clinical manifestations of urinary tract infection and urinary calculi, 24h urine should be collected and urine calcium (Uca) and urinary creatinine (Ucr) should be measured; 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. Characteristics of urine test: urinalysis can have microscopic hematuria, leukocytosis, no proteinuria or only mild proteinuria, no tubular urine. Calcium oxalate and/or phosphate crystals can be seen, and urine pH determination helps to identify the nature of urinary crystals. Pediatric expression can impair the function of urinary concentration.

3. Calcium load test: Those who have the condition can be used as a calcium load test to identify whether it is an absorption type or a renal leakage type. The low-calcium diet test has a daily intake of less than 300 mg of calcium for a total of 3 days. On the fourth day, the 2 h urinary calcium level is still higher than that of normal people. In recent years, some authors believe that the oral calcium load test does not contribute to the expected nephrolithiasis. This test is not recommended as a routine diagnostic assessment of hypercalciuria in children unless the serum parathyroid hormone concentration is elevated. Another author suggested using calcium-limited and venous calcium tolerance test analysis to confirm the disease. The method was as follows: low-calcium and low-phosphorus diet for 3 days, on the fourth day, calcium 15 mg/kg was administered intravenously. After 5 hours, the blood calcium was measured at the third hour, and urine calcium was measured for 24 hours. If the urinary calcium excretion minus the basic urinary calcium is still more than 50% of the amount of calcium instilled, the urinary phosphorus excretion will decrease by 20% from the 4th to 12th hour after the calcium drop, indicating that the test is positive.

Differential diagnosis

1. The main clinical manifestation of Fanconi syndrome is due to the proximal renal tubules caused by multiple substances reabsorption disorder, glucose urinary, full amino acid urine, different degrees of phosphate urine, bicarbonate urine and uric acid and other organic aciduria, also Can involve both proximal 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, and decreased blood phosphorus. Calcium ions are generally normal in idiopathic urinary calcium, and 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 large amount of light chain deposition in the kidney and hypercalcemia caused by the above symptoms. Renal biopsy and bone marrow aspiration can be used as a basis for diagnosis.

4. Renal tubular acidosis: increased urinary calcium excretion and decreased blood calcium. Clinical manifestations of bone pain and pathological fractures. With urinary calculi, easy secondary urinary tract infection, and even renal calcification. Renal tubular concentrating function is impaired, showing low specific gravity urine and alkaline urine.

5. Medullary sponge kidney: This 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. Involved in the distal renal tubules showed a decline in renal acidification, renal venography can be used as the main basis for diagnosis. 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. The amount of 24h urine protein is mostly below 1g for children and 0.5 to 2.0g for adults. Kidney stone disease, renal calcinosis and progressive renal insufficiency can occur in adulthood.

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