Children with complete distal renal tubular acidosis

　　1. Causes of the disease

　　Almost all types IV RTA are secondary to other diseases, and primary cases are rare. Common secondary causes include:

　　1. Simple aldosterone deficiency, such as salt-losing congenital adrenal hyperplasia, aldosterone deficiency syndrome, Addison's disease, and so on.

　　2. Chronic kidney disease with insufficient secretion of renin and aldosterone, such as diabetic nephropathy, purpura nephritis, sickle cell nephropathy, renal sclerosis, interstitial nephritis, and so on.

　　3. Acute glomerulonephritis with insufficient secretion of renin and aldosterone.

　　4. Reduced responsiveness of the renal tubules to aldosterone, such as primary pseudoaldosteronism in infants, secondary pseudoaldosteronism (including infant urinary tract obstruction, infant renal vein thrombosis, chloride shunt syndrome, i.e., Gordon syndrome).

　　5. Excessive supplementation of potassium chloride, excessive use of potassium-sparing diuretics, heparin, prostaglandin inhibitors, and so on.

　　Second, pathogenesis

　　Aldosterone is the main endocrine hormone that regulates Na+-K+ and Na+-H+ exchange. When aldosterone is insufficient or the tubular responsiveness to aldosterone is reduced, Na+-K+ and Na+-H+ exchange decreases, the reabsorption of Na+ by the tubules decreases, HCO3- loss increases,泌H+ and excretion of K+ are impaired, thus leading to hyperkalemic acidosis.

　　It can complicate respiratory muscle paralysis leading to dyspnea, severe cases may develop ventricular fibrillation, renal insufficiency, hypotension or hypertension, etc. RTA patients are prone to develop rickets, osteomalacia, hypokalemic nephropathy, renal calcification or nephrolithiasis, which should be noted. Some reports suggest that certain sudden deaths of unknown cause may be related to hypokalemia caused by incomplete RTA.

　　Many pathogenic factors and primary diseases can cause RTA, and when these factors exist or act, hyperchloremic metabolic acidosis may occur, leading to delayed growth and development in children, anorexia, nausea, fatigue, polyuria with thirst, low urine specific gravity or dehydration, mild renal function impairment, and severe osteopathy. Children may have refractory rickets, and older children may also develop rickets, pathological fractures, renal calcification or nephrolithiasis. There is often a certain degree of glomerular function impairment, but this disease often has hyperchloremic metabolic acidosis and hyperkalemia before chronic renal insufficiency occurs. Glomerular filtration rate decreases [but usually GFR > 20ml/(min·1.73m2)], and the decrease in GFR is difficult to explain the degree of acidosis. Clinically, there are often unexplained hypokalemia or hyperkalemia. Hyperkalemia can lead to arrhythmias or myocardial paralysis. If hypokalemia occurs, it can cause muscle weakness, decreased tendon reflexes, and paralysis. Blood biochemical and urine pH tests confirm acidosis and alkaline urine. Due to tubular acidification dysfunction, there is abnormal alkaline urine or frequent alkaline urine, with a general urine pH ≥ 6.0. The total trend of human metabolism is that acid production is more than base production. Adults with ordinary diet produce about 1mmol/kg (BW) of non-volatile acid (mainly from protein) every day. Therefore, urine generally shows a certain degree of acidity (pH 5.0～6.0), and only after eating a large amount of vegetables and fruits or taking alkaline drugs, transient alkaline urine may occur. However, under the basic metabolism, the urine pH of children still ≥ 6.0.

　　Actively treat the primary disease, such as hormone replacement therapy for adrenal cortical disease, avoid excessive potassium chloride supplementation, excessive use of potassium-sparing diuretics, heparin, prostaglandin inhibitors, and avoid taking drugs and foods that damage kidney function. Exercise should be strengthened to enhance physical fitness, and traditional Chinese medicine such as Liuwei Dihuang Wan can be taken.

　　1, Uric acid test:There is usually a certain degree of glomerular dysfunction, but this disease often presents with hyperchloremic metabolic acidosis and hyperkalemia before chronic renal insufficiency. Jiang Yongdi et al. believe that uric acid test is the preferred screening test for the diagnosis of RTA. Some cases remain positive for several years after treatment, and 40/115 cases were found to have RTA through this test.

　　2, Decreased glomerular filtration rate:GFR is usually > 20 ml/(min·1.73m2), and the decrease in GFR is difficult to explain the degree of acidosis.

　　3, Urinalysis:Trace protein, Tamm-Horsfall glycoprotein, and other indicators can reflect tubular interstitial damage. There is no diabetes, aminoaciduria, hyperphosphaturia, and other functional disorders of the proximal renal tubules. Acidosis can cause the urine to become acidic, but the excretion of ammonia still decreases, and the excretion of HCO3- is very little or none. When the blood HCO3- concentration is normal, the excretion of HCO3- in urine often increases, the excretion of NH4+ is significantly reduced, the excretion of potassium decreases, and the excretion of HCO3- increases, and the production of ammonia decreases.

　　4, Blood biochemistry:Blood biochemistry changes are similar to pRTA, with blood Cl- > 105 mmol/L, pH < 7.35, and HCO3- < 22 mmol/L.

　　5, Other:Antigenic renal tubular acidosis (+), indicating an immune disease. This disease usually does not cause renal calcification and kidney stones, and bone damage is only seen in uremic patients. Imaging studies, electrocardiogram, and ultrasound examination can reveal corresponding findings, which can help in diagnosis and differential diagnosis.

　　Pay attention to eating vegetables rich in potassium, calcium, and vitamins in the diet. The main foods high in potassium are underground tubers such as potatoes, sweet potatoes, and yams, and fruits such as oranges and bananas. If kidney function is still normal, calcium supplementation is also very important. In terms of acid-base regulation, it includes sodium bicarbonate, calcium carbonate, and kidney disease dietary guidelines.
　　1. General dietary principles: eat light and avoid drinking alcohol and spicy foods. Eat less greasy and rich in animal protein foods (such as fatty meat, shrimp, crab, etc.). Different kidney diseases require different diets.
　　2. Normal adults usually consume about 5-6 grams of salt per day, which is sodium chloride, soda ash is sodium bicarbonate, and baking soda is sodium bicarbonate. Excessive intake of sodium-rich salt and alkali can easily cause water retention in the human body, leading to edema. Therefore, patients with nephrotic edema should control the intake of salt and alkali, and low-salt diet means consuming 2-3 grams of salt per person. A salt-free diet is also not scientific, as it can easily lead to fatigue, dizziness, and other symptoms over time.
　　3. The normal urine volume of a healthy person is generally 1500-2000 ml per day. For patients with acute nephritis, acute renal failure oliguria phase, as well as nephrotic syndrome, chronic renal failure with oliguria and edema, it is necessary to control the intake of water (including drinking water, water content in food, and the volume of intravenous medication). Because the water taken in cannot be excreted, water retention in the human body aggravates edema and is also easy to aggravate hypertension. At this time, the intake of water should be 500 ml more than the urine output. After the urine output increases, the intake of water can be relaxed. While patients with normal urine output can drink normally. In addition, for patients with urinary system infections such as acute pyelonephritis, urethritis, cystitis, etc., in addition to timely seeking medical treatment and taking medication, drinking more water and urinating more are very beneficial to the recovery of the disease.
　　4. For kidney patients, the diet of high-quality protein is 0.7-1.0 gram per kilogram of body weight per day, which needs to be guided by urine protein quantity and kidney function for individualization.
　　5. Some kidney patients have a long course of disease and a slow recovery, and they often discuss and exchange information and experiences. It should be noted that everyone has their own characteristics, and do not imitate each other.
　　6. During the treatment, if there are symptoms such as colds, fever, infection, etc., it is necessary to contact a specialist doctor in an emergency so as to receive timely treatment and avoid the aggravation of complications.
　　7. Do not overeat or eat unclean food. 8. Keep the bowels open, which is conducive to the excretion of waste and reducing the absorption of toxins. Develop the habit of regular defecation, eat more vegetables and fruits, and use softeners if necessary.

　　First, treatment

　　1. Reduce blood potassium level:

　　(1) Limit potassium intake: <30 mmol/d, avoid taking potassium-containing drugs.

　　(2) Potassium-wasting diuretics: DHCT 2 mg/(kg·d) or furosemide 2 mg/kg each time, 1-2 times/d.

　　2. Alkaline drugs:

　　Due to the reduction in the excretion of H+ in the distal renal tubules, acidosis accumulates in the body, causing metabolic acidosis. When there is acidosis in the proximal renal tubules, there is a dysfunction in the reabsorption of HCO3-, and the renal threshold of bicarbonate in children decreases to below 17-20 mmol/L (normal is 25-26 mmol/L, and in small infants it is 22 mmol/L). Even when plasma HCO3- is normal, due to the decreased renal threshold, a large amount of HCO3- in the filtrate is excreted into the urine, causing acidosis. The application of alkaline drugs is to correct acidosis, and early use can improve or completely disappear clinical symptoms. Common preparations include two types:

　　(1) Sodium Bicarbonate: Sodium bicarbonate can act directly, and it can be used in both acute and chronic acidosis, with a dose of 1.5 to 2 mmol/(kg·d). It can correct acidosis and reduce blood potassium concentration. During the treatment, the dose needs to be adjusted according to blood bicarbonate or carbon dioxide binding capacity and 24-hour urine calcium excretion. The urine calcium excretion is a sensitive indicator for guiding treatment, and the dose should be adjusted to keep the 24-hour urine calcium excretion below 2 mg/kg. Excessive dose of sodium bicarbonate can produce side effects such as abdominal distension and belching.

　　(2) Citrate Mixture: There are two formulations, one containing sodium citrate and potassium citrate, each 100g, dissolved in water to 1000ml, with 2mmol of base per milliliter. The other contains sodium citrate 100g and citric acid 140g, dissolved in water to 1000ml, with 1mmol of sodium per milliliter. The dose is 1mmol/(kg·d), taken orally in 4-5 divided doses.

　　3. Salt皮质激素治疗:Fludrocortisone (fludro-cortisone) 0.01mg/(kg·d), which can correct acidosis and lower blood potassium levels.

　　4. Treatment of the Primary Disease:The most important is to treat the primary disease and symptomatic treatment.

　　5. Calcium Preparations:Chronic acidosis can lead to increased urinary calcium excretion, hinder the conversion of 25-(OH)D3 to 1,25-(OH)2D3. In addition, some patients have a lack of gastric acid, which affects calcium absorption in the intestines, causing low blood calcium levels. Low blood calcium can cause secondary hyperparathyroidism, increase phosphorus clearance, and a decrease in phosphate and calcium ions in the blood, which prevents bone mineralization, leading to rickets; hypocalcemia may also occur during the correction of acidosis, even seizures, which all require calcium supplementation. Severe hypocalcemia can be treated with intravenous infusion of 10% calcium gluconate, 0.5-1.0 mg/kg or 5-10 mg per dose, diluted and infused slowly, with heart rate monitoring. If the heart rate is below 60 beats/min, stop the injection to prevent cardiac arrest. If necessary, repeat the use every 6-8 hours. Generally, hypocalcemia can be treated with oral calcium supplements, with a calcium ion supplementation of 15 mg/kg.

　　II. Prognosis

　　Most cases of this condition require long-term treatment, even lifelong treatment. Regular follow-up visits should be scheduled to measure blood pH, bicarbonate concentration, and urinary calcium excretion, and medication dosages should be adjusted cautiously. The prognosis depends on early diagnosis, early and rational treatment, and long-term adherence to regular treatment. If early and rational treatment is provided, severe renal calcification and renal insufficiency can be prevented, resulting in a better prognosis. If treatment is interrupted, symptoms of metabolic acidosis can recur, leading to renal insufficiency or failure, with a poor prognosis.