Idiopathic hypercalciuria in children

　　Provide a detailed introduction to the etiology and pathogenesis of idiopathic hypercalciuria in children:

　　First, etiology

　　1, Causes There are three possible causes: it may be due to enhanced intestinal absorption leading to increased urinary calcium; dysfunction of renal tubular calcium reabsorption leading to increased urinary calcium; dysfunction in both the intestine and renal tubules.

　　2, Classification Primary hypercalciuria, the cause is unknown, 2.2% to 6.2% of children in the population are asymptomatic IH. According to the pathogenesis, it can be divided into absorption type and renal leakage type. In summary, the pathogenesis of this disease may be due to vitamin D metabolism disorder, and there is a significant familial genetic predisposition, which is an autosomal dominant inheritance. In addition, diet and environmental factors are also related to the onset of the disease.

　　Second, pathogenesis

　　1, Enhanced intestinal calcium absorption: Mainly due to excessive selective absorption of calcium by the jejunum, which temporarily increases blood calcium levels, resulting in increased glomerular filtration of calcium; the inhibition of parathyroid secretion reduces calcium reabsorption in renal tubules; increased urinary calcium excretion while blood calcium levels can be maintained, the mechanism of this type is unclear, and some believe it is due to vitamin D regulation disorder.

　　2, Excessive renal calcium excretion: Due to the defect of calcium reabsorption in renal tubules, excessive calcium excretion occurs in urine, stimulating parathyroid secretion, increasing the synthesis of 1,25-(OH)2D3, and enhancing intestinal calcium absorption while maintaining normal blood calcium levels.

　　Idiopathic hypercalciuria in children often complicates with urinary tract infection, which can develop into obstructive nephropathy, and may secondary parathyroid hyperfunction, malnutrition, and other conditions. It affects patient health, and it is necessary to treat it in a timely manner.

　　Children with idiopathic hypercalciuria often have hematuria and urinary tract stones, polydipsia, thirst, polyuria, and urinary sediment is often white. A few may develop into chronic renal failure.

　　1, Hematuria is the most common manifestation of idiopathic hypercalciuria in children, which can be gross hematuria or microscopic hematuria, occurring in all age groups. Stapleton reported that 58 cases of IH were accompanied by hematuria, of which 64% were gross hematuria. Hematuria can be transient or persistent, and it is generally believed that it is caused by urinary tract injury due to calcium crystals. This type of hematuria belongs to normal red blood cell morphology hematuria (i.e., non-glomerular hematuria).

　　2. Urinary tract stones The incidence of urinary stone in adult IH is significantly higher than that in children. There are reports that up to 40% to 60% of adult urinary stone patients are accompanied by IH, while only 2% to 5% of pediatric urinary stones are caused by IH. According to Stapleton's report of 58 cases, only 9 cases (16%) were accompanied by stones. Such stones are mostly formed by calcium oxalate or calcium phosphate. The onset age is earlier than that caused by non-IH. If not treated, it can develop into obstructive nephropathy, which should attract the attention of doctors.

　　3. Other manifestations, in addition to hematuria, can also include bladder irritation symptoms (frequency, urgency, dysuria), difficulty in urination syndrome, proteinuria, abdominal pain, lumbar pain, and enuresis, etc. It is easy to develop urinary tract infection, which is a common clinical manifestation of IH. Due to the large loss of calcium from urine, the body is in a negative calcium balance. A few patients may develop hyperparathyroidism, resulting in osteoporosis. A few patients may also show symptoms such as short stature, no weight gain, muscle weakness, etc.

　　Pediatric idiopathic hypercalciuria has a significant familial genetic predisposition, which is an autosomal dominant inheritance. Preventive measures should span from pre-pregnancy to prenatal care. Pre-marital physical examination plays a positive role in preventing birth defects, and the extent of its role depends on the examination items and content, mainly including serological tests (such as hepatitis B virus, syphilis spirochete, HIV), reproductive system examination (such as screening for cervical inflammation), general physical examination (such as blood pressure, electrocardiogram), and inquiries about family medical history, personal medical history, and family medical history, etc. Good genetic counseling work should be done, and pregnant women should try to avoid harmful factors, including staying away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, and toxic and harmful heavy metals, etc. During the process of prenatal care during pregnancy, systematic screening for birth defects should be carried out, including regular ultrasound examination, serological screening, etc. Chromosome examination may also be required if necessary. Once abnormal results are found, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there are sequelae after birth, whether they can be treated, and what the prognosis is, etc. Practical and feasible diagnostic and treatment measures should be taken. The onset of this disease can also be caused by vitamin D metabolism disorder, which is related to diet and environmental factors. Therefore, it is recommended to promote reasonable feeding methods, get more sun exposure, and actively prevent and treat nutritional diseases.

　　The clinical diagnosis of pediatric idiopathic hypercalciuria can be made through blood tests and urinalysis.

　　1. Urinalysis:Increased urinary calcium, 24h urinary calcium > 0.1 mmol/kg (> 4 mg/kg), Uca/Ucr > 0.21; hematuria, when complicated with infection, the number of leukocytes in urine increases, there may be mild proteinuria, no casts in urine, and calcium oxalate and phosphate crystals can be seen; the function of urine concentration is impaired.

　　2. Blood test:Serum calcium is normal, serum phosphorus can be reduced, alkaline phosphatase is increased, serum parathyroid hormone concentration is elevated, and routine examinations such as B-ultrasound, X-ray film, intravenous urography, or CT can detect urinary tract stones and other lesions.

　　Pediatric idiopathic hypercalciuria should pay attention to daily living habits, eat more light and nutritious foods. It is recommended to drink more water, limit high-calcium and high-oxalate diets, and for those with absorption type accompanied by severe hematuria or stones, a low-calcium diet should be provided, but the nutritional needs of children's growth and development should be considered, and the daily supply of calcium should not be less than the basic need.

　　Pediatric idiopathic hypercalciuria can be treated in the following ways:

　　I. Treatment

　　1. General Treatment

　　It is recommended to drink more water, limit high-calcium and high-oxalate diets, and for those with absorption type accompanied by severe hematuria or stones, a low-calcium diet should be provided, but the nutritional needs of children's 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, so that urinary calcium returns to normal; Adjust parathyroid hormone and 1,25-(OH)2D3 to normal levels, so that intestinal calcium absorption is normal, the course of treatment is 6 weeks, adults often take long-term, there is a lack of long-term application experience in pediatrics, recent research has found that after 2 weeks of treatment with hydrochlorothiazide (dihydrochlorothiazide), urinary calcium excretion reaches the lowest value, but attention should be paid to the side effects of the drug, such as dehydration, potassium loss, uric acid retention, increased blood sugar, and changes in serum lipoprotein composition, including a significant increase in total serum cholesterol, a slight decrease in HDL (high-density lipoprotein), and a significant increase in the LDL/HDL ratio. Therefore, hydrochlorothiazide (dihydrochlorothiazide) should be used with caution for long-term treatment.

　　(2) Application of other drugs: Bendroflumethiazide can reduce urinary calcium excretion and increase diuresis (5～10mg/d); Sodium cellulose phosphate, when used in combination with the above diuretics, can reduce intestinal calcium absorption (10～30g/d, taken 3～4 times a day), and oral phosphates can reduce urinary calcium and prevent the formation of urinary stones. Phosphate buffer solutions are commonly used, and there is a lack of experience in the pediatric application of the above drugs.

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

　　II. Prognosis

　　Severe illness, protracted, can lead to various complications, such as recurrent urinary tract infections, causing urinary tract obstruction, leading to kidney damage, and ultimately leading to renal failure.