Pediatric proximal renal tubular acidosis

　　First, the cause of the disease

　　1, The primary cause is unknown, and it is generally believed to be related to heredity, manifesting only as an HCO3- reabsorption disorder without other renal tubular or glomerular dysfunction.

　　(1) The sporadic infantile form is transient.

　　(2) The hereditary form is persistent, showing either autosomal dominant inheritance or autosomal recessive inheritance.

　　2, Secondary forms often occur in systemic diseases, accompanied by various renal tubular dysfunction, with Fanconi syndrome being the most common.

　　（1）伴其他遗传病：伴有其他近端肾小管功能障碍的遗传性疾病：如特发性范可尼综合征，胱氨酸病，眼-脑-肾综合征（Lowe综合征），遗传性果糖不耐受症，酪氨酸血症，半乳糖血症，糖原累积病，线粒体肌病，异染性脑白质营养不良等。

　　（2）药物和毒素肾损害：如碳酸酐酶抑制物，过期四环素，甲基3-色酮，马来酸中毒，重金属（钙，铅，铜，汞）中毒等。

　　（3）其他：如亚急性坏死性脑脊髓病（Leigh综合征），法洛四联征，肠吸收不良，甲状旁腺功能亢进，肾囊肿病，遗传性肾炎，肾移植慢性排斥反应，多发性骨髓瘤，Sjgren综合征，淀粉样变性，慢性活动性肝炎，复发性肾结石，肾髓质囊性病，Wilson病等。

　　二、发病机制

　　在正常情况下，肾小球滤过的HCO3-99％被重吸收，其中近端小管重吸收80％～90％，其余2％在髓襻，8％在远端小管重吸收，而HCO3-重吸收和小管细胞分泌H+的功能密切相关，在小管中H+-Na+交换，Na+被重吸收入细胞内与HCO3-结合成NaHCO3，再进入血液中，为身体保留了碱储备，依赖Na+-K+-ATP酶，近端小管重吸收肾小球滤液中大部分的钠，Cl-和水随Na+被动重吸收，另外，近端小管主动重吸收全部K+，2/3钙和部分磷酸盐，pRTA为近端肾小管重吸收HCO3-不足，HCO-肾阈降低，正常人为25～26mmol/L，婴儿为22mmol/L，而pRTA时为18～20mmol/L，当患者血浆HCO3-浓度正常时，即有15％以上的HCO3-排至尿中（正常人仅为1％），即使在轻度酸中毒时，若患者血浆中HCO3-浓度仍高于肾阈，则HCO3-仍排至尿中，只有严重酸中毒时，患者可排出酸性尿，由于近端肾小管对HCO3-重吸收减少，使Na+-H+交换减少，Na+从尿中大量丢失，引起低钠，脱水，失Na+导致继发性醛固酮增多，使Na+，Cl-潴留，加之由于HCO3-丢失增多，为维持阴离子平衡，而保留C1-，因而出现高氯血症，在醛固酮作用下，以Na+-K+交换而保留Na+，可引起低钾血症，长期代谢性酸中毒可能通过阻碍生长激素的分泌或应答而引起生长发育障碍，导致近端肾小管重吸收HCO3-障碍的原因尚不清楚，可能是由于肾小管功能发育不成熟，在继发性病因中，大都是由于内生代谢产物或外来物质损坏近端小管上皮引起。

　　Children with pediatric proximal renal tubular acidosis may have complications such as malnutrition, metabolic acidosis, hypokalemia, osteomalacia, delayed growth and development, etc., which affect the health and growth and development of the children. It is necessary to treat them in a timely manner.

　　1. Primary pRTA:It is mainly seen in male infants, often accompanied by other proximal renal tubular reabsorption defects such as diabetes and phosphaturia, which can spontaneously disappear at 1-2 years of age.

　　2. Metabolic acidosis and hyponatremia, hypokalemia:There may be symptoms of acidosis such as delayed growth and development, nausea, vomiting, as well as symptoms of hyponatremia and hypokalemia such as weakness, fatigue, muscle weakness, and constipation. Due to the HCO3- renal threshold dropping to 15-18 mmol/L in pRTA, acidic urine (pH < 5.5) can be excreted after it falls below 15 mmol/L, and severe acidosis is rare.

　　3. Others:Since there is usually no severe acidosis, and without proximal tubular phosphorus absorption disorder, there is no hyperphosphatemia, and metabolic bone disease, renal calcification, and kidney stones rarely occur.

　　4. Secondary pRTA:In addition to the above symptoms, there are also symptoms of the primary disease, which are easily masked by the symptoms of the primary disease. Some patients may spontaneously improve with age, so secondary pRTA should be vigilant.

　　Primary pRTA has no reliable preventive method due to the unknown etiology; the prevention of pRTA secondary to systemic diseases mainly involves active prevention and treatment for those with secondary renal damage due to drugs and toxins, as well as other diseases such as malabsorption of the intestines and hyperthyroidism.

　　Blood biochemical examination of pRTA shows decreased plasma HCO3- and pH, hyperchloremia, normal or decreased sodium and potassium levels, urine pH can be alkaline or acidic according to the blood HCO3- level, 24h urine HCO3- can only be titrated acid normal, urine calcium can be increased or normal. Routine imaging examinations such as electrocardiogram and B-ultrasound should be performed.

　　Patients with proximal renal tubular acidosis in children should pay attention to dietary issues in their daily life, pay attention to supplementing the nutrients lacking in the body, eat more fresh fruits and vegetables, pay attention to nutritional balance, and eat less salty and sugary foods.

　　Firstly, Treatment

　　Firstly, oral sodium bicarbonate, starting dose of 5-10 mmol/(kg·d), increase the dose according to the condition, some patients may need 10-15 mmol/(kg·d), to maintain a constant concentration of HCO3- in the blood, the above dose is taken orally in divided doses. Due to the resistance of pRTA to alkali supplementation, the dose of alkaline drugs is usually 2-3 times higher than that of dRTA. Citrate buffer solution: sodium citrate 50g, potassium citrate 50g, citric acid 100g, add water to 1000ml, take orally 3 times a day, 50ml each time.

　　Secondly, potassium salts are generally not needed for potassium supplementation, but for patients with secondary Fanconi syndrome, more than half of the alkali preparations require potassium salts, and potassium supplementation should also be given when using diuretics.

　　Thirdly, for patients with severe disease, it is often difficult to achieve the desired effect with alkali preparations alone. It is necessary to use diuretics in combination, usually chlorothiazide, whose effects include.

　　(1) Reduce the extracellular fluid volume, thereby increasing the reabsorption of HCO3- in the renal tubules.

　　(2) Reduce calcium excretion in urine, increase blood calcium concentration, reduce the secretion of parathyroid hormone, thereby increasing the reabsorption of HCO3- in the renal tubules (parathyroid hormone can inhibit the reabsorption of HCO3- in the renal tubules), furosemide can also reduce HCO3- excretion, but unlike hydrochlorothiazide, it can increase calcium excretion in urine, so it is less commonly used.

　　Secondly, Prognosis

　　Primary pRTA, if treated early and medication continued, generally has a good prognosis, some mild cases can be self-healing; if not diagnosed early, can die due to acidosis or hypokalemia, the prognosis of secondary cases depends on the primary disease.