2 English references Proximal renal tubular acidosis
To summarize proximal tubular acidosis (PRTA), also known as type II RTA. The disease is caused by perchloric acid poisoning due to the defect of proximal renal tubular reabsorption of HCO _ 3, the decrease of renal HCO _ 3 threshold, and the decrease of plasma HCO _ 3 concentration caused by excessive urine loss. Primary proximal tubule acidosis (PRTA) mostly occurs in boys and children, and mostly begins in childhood, which may be related to heredity. Secondary proximal tubular acidosis (PRTA) is mainly caused by systemic diseases, drug poisoning and Fanconi syndrome.
Symptoms of proximal tubular acidosis are usually mild, such as growth retardation, malnutrition, fatigue, weakness, anorexia, polyuria, polydipsia or hypokalemia. Typical cases have hyperchloremia, but the acidification function of distal renal tubules is normal, and the urine pH can be reduced below 5.5, or accompanied by bone damage (osteomalacia, osteoporosis), glycosuria, amino acid urine and so on.
There is no specific treatment for proximal renal tubular acidosis, and symptomatic treatment is generally used to supplement the lost HCO3 and endogenous acidic substances. Patients with mild proximal renal tubular acidosis can temporarily stop taking drugs and follow up. When the symptoms are obvious, alkaline drugs should be used for treatment, usually sodium bicarbonate. When severe proximal renal tubular acidosis or diuretics are used, potassium must be supplemented. When large doses of bicarbonate cannot be tolerated or the situation is serious, diuretics are needed. Calcium, vitamin D, protein synthetic agent, etc. Patients with bone injury (generally mild) should be supplemented. Note that large doses can cause vomiting, abdominal discomfort, diarrhea and so on. If the dose is gradually increased, most patients can tolerate it. If you take phosphate for a long time, hyperphosphatemia and secondary hyperparathyroidism may occur. Serum phosphorus level should be monitored and maintained at1~1.3 mmol/L.
Primary proximal tubular acidosis is usually a self-limiting disease, which usually relieves with age. If this type can be treated as early as possible and kept taking medicine for several years, the general prognosis is good, and some minor symptoms can heal themselves. Without early diagnosis, he may die of acidosis or hypokalemia. The prognosis of secondary patients depends on the primary disease.
4 disease name proximal renal tubular acidosis
5 English name proximal renal tubular acidosis
6 abbreviation PRTA
7. Proximal renal tubular acidosis type II RTA alias; ; Proximal renal tubular acidosis; Proximal renal tubular acidosis (type Ⅱ)
8 classification kidney disease > renal tubular disease > renal tubular acidosis.
9 ICDNo。 N 15.8
10 epidemiology Primary proximal tubular acidosis is common in male children. Childhood onset, some spontaneously relieved with age. Secondary cases are the most common. The incidence of primary renal tubular acidosis was 23.5%, and the incidence of secondary renal tubular acidosis was 76.5%. RTA related to immune diseases accounts for about 27.8%.
1 1 Etiology of proximal tubular acidosis 1 1. 1 The etiology of primary proximal tubular acidosis is unknown, which is generally considered to be related to heredity. It only shows bicarbonate absorption disorder, and there is no other renal tubular and glomerular dysfunction.
(1) Sporadic babies are temporary.
(2) Inheritance is persistent, autosomal dominant inheritance or autosomal recessive inheritance.
1 1.2 secondary is often secondary to systemic diseases, which may be accompanied by various renal tubular dysfunction, with Fanconi syndrome being the most common.
11.2.1(1) Other genetic diseases with other proximal tubule dysfunction, such as idiopathic Fanconi syndrome, cystitis, eye-brain-kidney syndrome (Lowe syndrome), hereditary fructose intolerance, tyrosinemia, galactosemia, glycogen storage disease, etc.
1 1.2.2 (2) Kidney damage caused by drugs and toxins, such as carbonic anhydrase inhibitors, expired tetracycline, methyl tribromide, maleic acid poisoning, heavy metal (calcium, lead, copper, mercury) poisoning, etc.
1 1.2.3 (3) Others such as subacute necrotizing encephalomyelitis (Leigh syndrome), tetralogy of Fallot, intestinal malabsorption, hyperparathyroidism, renal cyst disease, hereditary nephritis, chronic rejection of renal transplantation, multiple myeloma, Sj? Green's syndrome, amyloidosis, chronic active hepatitis, recurrent kidney calculi's disease, renal medullary cyst disease, Wilson's disease, etc.
12 Under normal conditions, 39.9% of HCO filtered by glomerulus is reabsorbed, of which 80% ~ 90% is reabsorbed by proximal tubule, the remaining 2% is in medullary loop and 8% is reabsorbed by distal tubule. The reabsorption of HCO3 _ 3 is closely related to the secretion of H+ by renal tubular cells. H+Na+ is exchanged in tubules, and Na+ is reabsorbed into cells, combined with HCO3 to form NaHCO3, and then enters the blood to store alkali for the body. According to the activity of Na+ K+ATPase pump, the proximal tubule passively reabsorbs most of sodium, chlorine and water in glomerular filtrate with Na+. In addition, the proximal tubule actively reabsorbs all K+, 2/3 calcium and some phosphate.
Proximal renal tubular acidosis (PRTA) is the lack of reabsorption of HCO _ 3 by proximal renal tubules, and the renal threshold of HCO is reduced, which is 25 ~ 26 mmol/L for normal people, 22mmol/L for infants and 65,438+08 ~ 20 mmol/L for PRTA. When the patient's plasma HCO _ 3 concentration is normal, more than 65438 05% HCO _ 3 is discharged into urine (only 65438 0% in normal people). Even in mild acidosis, if the patient's plasma HCO _ 3 concentration is still higher than the renal threshold, HCO _ 3 will still be discharged into urine. Only when there is severe acidosis can the patient excrete acidic urine.
Because the reabsorption of HCO3 _ 3 by proximal renal tubules is reduced, Na+H+ exchange is reduced, and Na+ is lost from urine, resulting in hyponatremia and dehydration. The loss of sodium ion leads to secondary aldosterone increase and retention of sodium ion and chloride ion. In addition, due to the increase of HCO3 loss, Cl is retained to maintain anion balance, thus hyperchloremia occurs. Under the action of aldosterone, Na+K+ exchanges and Na+ stays, which can cause hypokalemia. Long-term metabolic acidosis may cause growth and development disorders by hindering the secretion or reaction of growth hormone. The reason for the obstacle of bicarbonate reabsorption in proximal renal tubules is unclear, which may be due to the immature renal tubular function. In the secondary etiology, most of them are caused by endogenous metabolites or foreign substances damaging the proximal tubule epithelium.
Clinical manifestations of proximal renal tubular acidosis 13 The symptoms of proximal renal tubular acidosis are usually mild, such as growth retardation, malnutrition, fatigue, fatigue, anorexia, polyuria, polydipsia or hypokalemia. Typical cases have hyperchloremia, but the acidification function of distal renal tubules is normal, and the urine pH can be reduced below 5.5, or accompanied by bone damage (osteomalacia, osteoporosis), glycosuria, amino acid urine and so on. The main clinical features of type Ⅱ proximal tubular acidosis (PRTA) are:
Primary proximal tubule acidosis (PRTA) is mainly found in male infants, often accompanied by other proximal tubule reabsorption defects, such as glycosuria and phosphoruria, which can disappear by itself when 1 ~ 2 years old.
Due to metabolic acidosis and hyponatremia and hypokalemia, patients may have symptoms of acidosis such as growth retardation, nausea and vomiting, and may also have hyponatremia and hypokalemia such as weakness, fatigue, myasthenia and constipation. Because the renal threshold of HCO3 _ 3 _ 3 can be discharged after PRTA is reduced to 15 ~ 18 mmol/L and acidic urine is lower than 15mmol/L (pH < 5.5), severe acidosis is rare.
In addition, if there is no phosphorus absorption disorder in the proximal tubule, there will be no hyperphosphatemia, and metabolic osteopathy, renal calcification and kidney calculi will rarely occur. Non-selective patients may have increased urine phosphorus, urine sugar and amino acid urine.
Secondary proximal tubular acidosis (PRTA) not only has the above manifestations, but also has primary symptoms. And it is easy to be covered up by the symptoms of the primary disease, so we should be alert to the occurrence of secondary PRTA.
Complications of proximal renal tubular acidosis 14 Proximal renal tubular acidosis can cause nutritional disorders, metabolic acidosis, hypokalemia, rickets and growth retardation.
15 Laboratory examination 15. 1 Blood biochemical examination showed that plasma HCO3, pH decreased, hyperchloremia, sodium and potassium were normal or decreased.
15.2 urine pH value can be alkaline or acidic according to the blood HCO3 level. 24-hour urine HCO4 _ 4 can only titrate acid normally, and urine calcium can be increased or normal (when urine PCO _ 2 is measured, nah co _ 3 can be injected to alkalize urine, and when urine pH > blood pH, urine PCO _ 2 > blood PCO _ 2 is more than 2.66kPa, which has diagnostic significance).
15.3 urinary cystine examination is common in proximal convoluted tubule diseases, and positive urine is helpful for diagnosis (cyanide nitrohydrocyanate test: take 5ml urine, add 1 drop concentrated ammonia water, 3 drops of 5% sodium cyanide, purple reaction is positive).
15.4 For the acid load test method, see type I renal tubular acidosis. In the acid load test, if the urine pH value is less than 5.5 or lower, it is diagnosed as type II renal tubular acidosis.
15.5 alkali load test (1) oral sodium bicarbonate method: from1mmol/(kg d), increase the dose to10mmol/(kg d) day by day. After correcting acidosis, HCO concentration in blood and urine and glomerular filtration rate were measured, and urine HCO was calculated. Normal human urine HCO3 is zero; Type ⅱ and mixed renal tubular acidosis is more than 65438 05%, and type ⅰ renal tubular acidosis is less than 3% ~ 5%.
(2) Intravenous drip of sodium bicarbonate: drip 5% NaHCO 3 at a speed of 4ml/min for 2 hours. Blood pH, PCO 2 and HCO 3 concentrations, and urine pH and HCO 3 concentrations were measured before injection. After 30 and 90 minutes of injection, the blood pH, PCO 2 and HCO 3 concentrations were measured respectively. Urine pH and HCO _ 3 concentration were measured at 60,654 38 0.20 minutes. When the patient's blood HCO _ 3 concentration returned to normal, the urine HCO _ 3 excretion was greater than the glomerular filtration rate of 65438 0.5%, suggesting that the proximal convoluted tubule was impaired in absorbing HCO _ 3. Urine HCO 3 excretion fraction = (urine HCO 3/ plasma HCO 3 )/ (urine creatinine/blood creatinine). When the plasma concentration of HCO _ 3 is normal, the excretion fraction of HCO _ 3 in type II renal tubular acidosis is > 65438 05%, and that in type I renal tubular acidosis is < 5%. This method can distinguish type ⅰ and type ⅱ renal tubular acidosis. 16 auxiliary examination of routine electrocardiogram, imaging examination and B-ultrasound examination.
Diagnosis of proximal renal tubular acidosis 17 Proximal renal tubular acidosis is more common in male children, which mostly occurs in childhood, and some of them spontaneously relieve with age. Symptoms are usually mild, such as growth retardation, malnutrition, weakness, anorexia, polyuria, polydipsia or hypokalemia. Typical cases have hyperchloremia, but the acidification function of distal renal tubules is normal, and the urine pH can be reduced below 5.5. Or bone injury (osteomalacia, osteoporosis), diabetes, amino acid urine, etc. According to the above performance and laboratory examination, the diagnosis can be established. When necessary, bicarbonate reabsorption test and renal HCO 3 threshold determination can be carried out. If the urinary HCO 3 excretion rate is greater than the filtered volume of 65438 05%, a diagnosis can be made.
Diagnostic points of type Ⅱ renal tubular acidosis;
1. Perchloric acid poisoning? Except for non-nephrogenic diseases. If metabolic acidosis is serious [HCO3 in plasma is less than 15 ~ 18mmol/L, while the pH value in morning urine is less than 5.5, and the output of NH+4 is more than 40μ mol/(min 1.73m2), and the loss of HCO3 in gastrointestinal tract is excluded, proximal renal tubular acidosis can be diagnosed.
2. Unexplained hypokalemia, hypophosphatemia, positive urine sugar, increased urine potassium, increased urine phosphorus and hyperuricemia.
3. Urine pH > 6.0.
4. The acid-base load test was positive.
18 differential diagnosis 1. It is distinguished from other diseases of acidosis caused by nitrogen retention, such as diarrhea and ketoacidosis.
2. Differentiate from other types of renal tubular acidosis. In particular, it should be differentiated from type I.
The main clinical manifestation of proximal renal tubular acidosis is hyperchlorinated metabolic acidosis. The growth retardation of young children is often the most important or even the only manifestation of this disease. Therefore, attention should be paid to whether there is proximal tubular acidosis (PRTA) in children with growth retardation. Anyone suffering from correctable dehydration and acidosis should be alert to the possibility of this disease and make corresponding examinations. The dosage of bicarbonate or citric acid buffer should be 6 mmol/(kg d) to maintain the plasma CO2 binding force at 22mmol/L, which can be distinguished from distal renal tubular acidosis. Urine concentration dysfunction is lighter than distal renal tubular acidosis.
Treatment of proximal renal tubular acidosis 19 There is no specific treatment for proximal renal tubular acidosis, and symptomatic treatment is generally used to supplement the lost HCO3 _ 3 and endogenous acidic substances.
19. 1 drug or metal poisoning, multiple myeloma, nephrotic syndrome, tubulointerstitial diseases and other etiological treatments.
19.2 correction of mild acidosis If the symptoms of proximal renal tubular acidosis are mild, the drug can be temporarily stopped and followed up. When the symptoms are obvious, alkaline drugs should be used for treatment. Commonly used sodium bicarbonate generally starts with a daily dose of 5 ~ 10 mmol/kg. Because the concentration of HCO _ 3 in blood increases after taking medicine, the excretion of HCO _ 3 in urine also increases, so it is often necessary to take it in large doses for many times, and sometimes it can be increased to 10 ~ 25 mmol/kg per day to maintain the concentration of HCO _ 3 in blood constant. The above doses can be taken orally several times. Because proximal renal tubular acidosis (PRTA) is resistant to alkali supplementation, the dosage of alkaline drugs is 2 ~ 3 times higher than that of DRTA. However, when high-dose sodium salt is used, the NaK exchange in renal tubules will increase, which will aggravate potassium loss and even seriously lose potassium. Therefore, low-salt (sodium chloride) diet should be adopted while supplementing potassium, so as to reduce perchloric acid poisoning and potassium loss, limit sodium intake and reduce urine HC03 excretion. Therefore, the symptoms are more common in infants, and the amount of HCO _ 3 supplementation in children is about10 mmol/(kg d), and then the dosage is adjusted to keep the blood concentration of HCO _ 3 within the normal range. Citrate buffer: 50g sodium citrate, 50g potassium citrate and 100g citric acid can also be used. Add water to 1000ml and take orally, 50ml each time, three times a day.
19.3 potassium supplementation is generally not needed for proximal renal tubular acidosis, but it must be supplemented in severe cases or when diuretics are used. Diuretics can improve symptoms and reduce urine volume, but it can't make the plasma HC03 concentration return to normal, but it will increase potassium loss. Potassium citrate mixture is often used to supplement potassium.
19.4 Application of diuretics When large doses of bicarbonate or serious cases cannot be tolerated, it is difficult to use alkali salts alone, and the supplied alkali salts are quickly excreted through urine, and the acidosis is difficult to correct, so it is necessary to use diuretics in combination. Hydrochlorothiazide (dihydrochlorothiazide) is the most effective diuretic, and its mechanism is that it causes mild dehydration after diuresis, reduces the volume of extracellular fluid, promotes the reabsorption of HCO3 _ 3 by proximal renal tubules, and corrects acidosis. In addition, it can promote renal tubular reabsorption of calcium, increase blood calcium, reduce urinary calcium excretion, reduce parathyroid hormone secretion, relieve the inhibition of HCO3 reabsorption, further increase plasma HCO 3, and correct acidosis. Pituitary diuretics, such as furosemide, glycolic acid (uric acid) and bumetanide (butamide), can increase urinary calcium excretion, but cannot increase plasma HCO3 concentration, so type II renal tubular acidosis is contraindicated. The dosage of hydrochlorothiazide (hydrochlorothiazide) is 1.5 ~ 2 mg/kg per day, taken orally twice. Attention should be paid to the occurrence of hypokalemia in treatment. After the acidosis is corrected, it is reduced to maintenance.
19.5 patients with bone injury (generally mild), such as osteoporosis and osteomalacia, should be supplemented with calcium and vitamin D. Treatment and precautions are the same as type I renal tubular acidosis. Type ⅱ proximal tubule phosphorus reabsorption defect, urinary phosphorus loss. If blood phosphorus is low, phosphorus 1 ~ 3g should be supplemented every day. The formula of phosphate mixture: sodium dihydrogen phosphate (NaH2PO4) 18g, disodium hydrogen phosphate (Na2H2PO4) 145g, dissolved in water to 1000ml (containing 20mg of phosphorus per ml), 20ml each time, 4-5 times /d, and it should be noted that high dosage can cause vomiting. And most patients can tolerate slowly increasing doses. If you take phosphate for a long time, hyperphosphatemia and secondary hyperparathyroidism may occur. Serum phosphorus level should be monitored and maintained at1~1.3 mmol/L.
Prognosis Primary proximal renal tubular acidosis is often a self-limiting disease, which often relieves with age. If this type can be treated as soon as possible, the general prognosis will be good, and some minor symptoms can heal themselves. Without early diagnosis, he may die of acidosis or hypokalemia. The prognosis of secondary patients depends on the primary disease.
2 1 prevention of proximal renal tubular acidosis patients with primary proximal renal tubular acidosis have no reliable prevention method because of unknown etiology. Clinically, active prevention and treatment are mainly given to renal damage caused by drugs and toxins, intestinal malabsorption, hyperthyroidism and other secondary diseases to prevent systemic metabolic disorder and renal function damage caused by long-term metabolic acidosis.
Related drugs include cystine, tetracycline, glucose, sodium bicarbonate, sodium chloride, sodium citrate, potassium citrate, hydrochlorothiazide, chlorothiazide, furosemide, itaconic acid, bumetanide and sodium dihydrogen phosphate.
Cystine, growth hormone, urinary phosphorus, urinary calcium, urinary cystine, urinary creatinine, urinary sugar, urinary potassium and vitamin D.
Amphotericin B for injection is related to proximal renal tubular acidosis. Urea nitrogen and creatinine increase, and creatinine clearance rate decreases, which can also cause renal tubular acidosis. 3. Hypokalemia is caused by a large amount of potassium ions discharged from urine. ...
Amphotericin b for injection