Idiopathic Hypercalciuria

　　How is idiopathic hypercalciuria caused? Briefly described as follows:

　　First, Etiology

　　The etiology of this disease is not well understood. Due to the significant familial genetic predisposition, it may be related to autosomal dominant genetic defects. The gene mutation leads to various abnormalities in the transport of substances, especially related to the disorder of vitamin D metabolism. Vitamin D metabolism disorder can cause increased intestinal calcium absorption, dysfunction of renal tubular calcium reabsorption, or dysfunction of both the intestines and renal tubules, leading to increased urinary calcium. In addition, dietary and environmental factors are also related to the disease.

　　Second, Pathogenesis

　　This disease has a significant familial genetic predisposition, and the pathogenesis is related to autosomal dominant inheritance and gene mutation. The causes of high urinary calcium in this disease include:

　　1. Deficiency in the function of renal tubular reabsorption of calcium ions, also known as excessive calcium leakage in the kidney (leakage type). When the renal tubules have a reduced reabsorption of certain regulatory proteins or the recycling disorder of protein channels involved in calcium ion transport on the luminal membrane, the reabsorption of calcium ions in the urine decreases, leading to increased urinary calcium and decreased blood calcium levels. Due to the decrease in blood calcium levels, the parathyroid gland secretes more parathyroid hormone (PTH), and at the same time, the synthesis of active vitamin D metabolites increases, maintaining normal blood calcium levels. The reduced reabsorption of phosphorus by the renal tubules leads to renal phosphorus loss and secondary hypophosphatemia. The feedback effect increases the synthesis of 1,25(OH)2D3, which in turn increases intestinal calcium absorption and maintains normal blood calcium levels. The increased absorption of calcium ions by the jejunum also increases the filtrable calcium ions, further increasing urinary calcium excretion.

　　2. Increased calcium absorption in the jejunum, also known as intestinal hypercalciuria (absorption type). This is mainly due to excessive selective absorption of calcium by the jejunum, leading to increased blood calcium levels, which in turn causes an increase in glomerular filtration of calcium and excessive urinary calcium excretion. Another cause is the inhibition of parathyroid secretion function, which increases the ultrafiltration load of the glomerulus and reduces the reabsorption of calcium ions by the renal tubules, leading to increased urinary calcium and increased absorption of calcium ions excreted in the urine. Therefore, blood calcium levels do not increase and can maintain normal levels. The mechanism of this type is unclear, and some believe it is related to vitamin D regulation disorders.

　　Idiopathic hypercalciuria often complicates with urinary tract infection, urinary tract stones, secondary hyperparathyroidism, malnutrition, osteoporosis, fractures, bone deformities, short stature, failure to gain weight, muscle weakness, and other conditions.

　　The early stage of this disease is relatively concealed, and it can only be manifested as low molecular weight proteinuria, with the relative molecular weight of proteins generally less than 40,000 Da. The main components include β2-microglobulin, retinol-binding protein, α1-microglobulin, and lysozyme, etc., which are small tubular marker proteins. The 24-hour urine protein excretion in children is mostly below 1g, and in adults, it is 0.5 to 2.0g. Nephrolithiasis, renal calcification, and progressive renal insufficiency may occur in adulthood.

　　Patients with this disease often suffer from hematuria and renal colic, urinary tract infection, and bladder irritation symptoms (frequency, urgency, dysuria), difficulty in urination syndrome, abdominal pain, lumbar pain, enuresis, and other symptoms, and have polydipsia, thirst, polyuria, and urine sediment is often white, a few may develop into chronic renal failure.

　　1. Hematuria and proteinuria are visible in all age groups, gross hematuria or microscopic hematuria, generally believed to be caused by urinary tract injury due to calcium crystals, and this hematuria belongs to normal red blood cell morphology hematuria (i.e., non-glomerular hematuria), and hematuria is the most common manifestation of pediatric idiopathic hypercalciuria (IH), which can be transient or persistent, and proteinuria is generally mild to moderate, with a small molecular weight, mainly composed of β2-microglobulin, retinol-binding protein, and α1-microglobulin, etc.

　　2. Urinary tract stones in adult idiopathic hypercalciuria (IH) show a significantly higher incidence of stone formation than in children. There are reports that up to 40% to 60% of adult IH patients, while only 2% to 5% of children's urinary stones are caused by IH, and such stones are mostly formed by oxalate calcium or phosphate calcium, and occur at an earlier age than those caused by non-IH. If not treated in time, they can develop into obstructive nephropathy.

　　3. Other manifestations can also include renal glycosuria, aminoaciduria, uric aciduria, and other proximal renal tubular dysfunction, due to the large loss of calcium from urine, the body is in a negative calcium balance for a long time, a few patients may develop secondary hyperparathyroidism, patients may experience joint pain, osteoporosis, fractures, deformities, and vitamin D deficiency disease, a few patients may show short stature, no weight gain, muscle weakness, and other symptoms.

　　How to prevent idiopathic hypercalciuria? Briefly described as follows:

　　The onset of this disease may be caused by vitamin D metabolism disorder, related to dietary and environmental factors. Rational feeding, more sun exposure, and active prevention and treatment of nutritional diseases should be advocated for pediatric patients. For patients with multiple complications, early diagnosis and treatment should be carried out to try to reduce kidney damage and prevent renal failure.

　　What examinations should be done for idiopathic hypercalciuria? Briefly described as follows:

　　1. Urine examination. Increased urine calcium, female urine calcium > 6.25mmol/24h, male > 7.5mmol/24h; mild hematuria, proteinuria, and non-renal tubular casts may be present, oxalate calcium, phosphates crystals, and impaired urine concentration function can be seen, and an increase in urinary leukocytes may occur when complicated with infection.

　　2. Blood examination. Blood calcium is normal, blood phosphorus may decrease, alkaline phosphatase increases, and serum parathyroid hormone concentration increases.

　　3. Experimental method of calcium loading. Low calcium and low phosphorus diet for 3 days, intravenous infusion of calcium (15mg/kg) on the 4th day, completed within 5 hours, and blood calcium is measured for the next 3 hours, and 24-hour urine is collected for urine calcium measurement.

　　Judgment of results: If the amount of urinary calcium excretion minus the daily basic urinary calcium excretion exceeds 50% of the calcium intake; the urinary phosphorus excretion decreases by 20% in the 4-12 hours after calcium infusion compared to the 0-4 hours, it indicates a positive result.

　　4. Renal tissue pathological examination. The main manifestations are non-specific renal tubular atrophy and interstitial fibrosis. The deposition of calcium in the kidneys mainly occurs in the renal medulla, but it does not correspond to the time and degree of renal failure.

　　5. Routine examinations include ultrasound, X-ray film, intravenous urography, or CT scan.

　　The diet of patients with idiopathic hypercalciuria should be light, with more vegetables and fruits and easily digestible foods. Avoid salty, greasy, cold foods, and avoid smoking and drinking. Maintain a reasonable schedule, engage in moderate physical exercise and sports.

　　What are the treatment methods for idiopathic hypercalciuria? The following is a brief description:

　　I. Treatment

　　1. General Treatment

　　Increase water intake, limit high-calcium, high-sodium, and high-oxalate diets. For those with severe hematuria or stones, strict low-calcium diet should be provided, but for children, the need for growth and development should be considered, and the daily supply of calcium should not be less than the basic need.

　　2. Drug Treatment

　　(1) Thiazide diuretics: Hydrochlorothiazide (dihydrochlorothiazide) is commonly used at a dose of 1-2mg/kg per day. Its action is to promote the reabsorption of calcium in the distal renal tubules, restoring normal urinary calcium levels; and regulate parathyroid hormone and 1,25(OH)2D3 to normal levels, making intestinal calcium absorption normal. The course of treatment is 6 weeks, and adults should take it for a long time.

　　(2) Application of other drugs: Bendiadrene can reduce the excretion of urinary calcium and increase diuresis; sodium cellulose phosphate, when used in combination with the aforementioned diuretics, can reduce intestinal calcium absorption (10-30g/d, divided into 3-4 times); oral inorganic phosphate can reduce urinary calcium by combining with calcium in the intestines, preventing the formation of urinary stones; commonly used phosphate buffer solution.

　　(3) Treatment of urinary stones: It should be treated according to the conventional methods for urinary system stones, while preventing and treating infection.

　　II. Prognosis

　　If the disease is diagnosed and treated early, the prognosis is good. Severe illness and long-term illness can lead to various complications, such as recurrent urinary tract infections, stones, causing obstructive kidney damage of the urinary tract, and ultimately leading to renal failure.