Type I renal tubular acidosis

　　The etiology of type I renal tubular acidosis is as follows:
　　Primary diseases:Familial and sporadic, and may be accompanied by certain genetic diseases such as osteosclerosis, hepatolenticular degeneration, and carbonic anhydrase deficiency.
　　Caused by drugs:Amphotericin B, lithium, toluene, and aminoglutethimide.
　　Disorders of calcium metabolism:Idiopathic hypercalciuria, hyperparathyroidism, vitamin D excess, etc.
　　Autoimmune diseases:Primary hypergammaglobulinemia, systemic lupus erythematosus, Sjögren's syndrome, Hashimoto's thyroiditis, liver cirrhosis.
　　Renal interstitial disease:Obstructive nephropathy, renal transplant rejection,海绵肾, analgesic nephropathy, sickle cell disease, etc.

　　Complications of type I renal tubular acidosis include nutritional disorders, scurvy, or osteomalacia, some may develop kidney stones or renal calcification, and in the late stage, it may develop into uremia, and a few may have neurological hearing loss, etc.

　　The symptoms of type I renal tubular acidosis include metabolic acidosis and electrolyte disorders:

　　Metabolic acidosis
　　Symptoms may include anorexia, nausea, vomiting, palpitations, shortness of breath, fatigue, and growth and development delays in infants.

　　Electrolyte imbalance
　　1. Impaired secretion of H+ in the distal renal tubules, reduced excretion of urinary NH4+ and titratable acid, inability to lower urinary pH below 6.0, increased excretion of urinary potassium, sodium, and calcium. Patients often have symptoms such as thirst, polyuria, and dehydration.
　　2. Increased urinary sodium excretion leads to decreased blood sodium, which increases the secretion of aldosterone to enhance sodium reabsorption, exacerbating the excretion of potassium in the urine, and is prone to develop hyponatremia and hypokalemia. Patients often have symptoms such as muscle weakness and flaccidity, and in severe cases, it can affect respiration and lead to arrhythmia.
　　3. Increased urinary calcium often leads to decreased blood calcium, which can cause hyperparathyroidism and promote the dissolution rate of bone. Moreover, the presence of acidosis causes the absorption of alkaline minerals in the bone, aggravating the demineralization of bone, often manifesting as fibrous osteitis, osteoporosis, and even pathological fractures. Increased urinary calcium excretion, low renal tubular secretion of H+, and a tendency for calcium stones to form in the kidney can worsen the degree of renal tubular acidosis if obstruction occurs.

　　For type I RTA (renal tubular acidosis) caused by primary hereditary factors, there is no effective preventive measure. The prevention of secondary diseases should start with the treatment of the underlying disease, controlling its development into renal tubular acidosis. For patients who have the disease, active treatment should be carried out to prevent the progression of the disease and strive for a good prognosis.

　　Laboratory examination for type I renal tubular acidosis (DRTA):

　　Laboratory examination:
　　1. Determination of urinary pH Urinary pH reflects the amount of H+ in urine. During DRTA, although blood pH < 7.35, the urinary pH is still ≥ 6.0, and can even reach above 6.5 and 7.0. The determination of urinary pH must be done using a pH meter. The measurement of urinary pH alone has certain limitations. Urinary pH < 5.5 does not necessarily indicate that the acidification function is intact. If the patient has an obstacle in ammonia secretion, due to a small amount of H+ that cannot combine with NH3 to form NH+4, the urinary pH can still be < 5.5. Therefore, it is necessary to simultaneously measure urinary pH and urinary NH+4 to make a comprehensive analysis and judgment.

　　2. Determination of urinary titratable acid and urinary NH+4 Most of the H+ secreted by the distal renal tubules combines with NH3 to form NH+4 and is excreted. The other part is excreted in the form of titratable acid. Therefore, the sum of titratable acid and NH+4 in urine represents the net acid excretion of the kidney. When there is an increase in acidic substances in the body, the urinary pH of a normal person can be < 5.5, with the excretion rates of titratable acid and NH+4 reaching 25μmol/min and 39μmol/min, respectively. In distal renal tubular acidosis, both rates are significantly reduced.

　　3. Determination of urinary electrolytes and urinary anion gap DRTA often shows increased urinary sodium excretion and elevated urinary calcium levels, with urinary Ca/Cr > 0.21 and 24-hour urinary calcium > 4mg/(kg?d). The urinary anion gap, which is Na+ + K+ - Cl-, can reflect urinary NH+4 levels. A positive value indicates reduced excretion of urinary NH+4. Urinary pH > 6.0, with a high percentage of HCO- excretion fraction < 5%, and urinary NH4+ < 500mmol/d, along with increased excretion of urinary Na+, K+, Ca2+, and PO43-.

　　4. Blood gas analysis and electrolyte measurement The typical change of DRTA is hyperchloremic metabolic acidosis with a normal anion gap. Incomplete DRTA can manifest as compensatory metabolic acidosis or normal. The blood anion gap (anion gap, AG) = Na+ + K+ - (Cl- + HCO3-), which is normal for 8-16mmol/L, and an increase indicates the retention of inorganic acid radicals (such as nitrate, sulfate) and/or organic acid radicals in the body, etc. In RTA, Cl- compensates for the decrease in HCO3-, so the AG is normal. Blood potassium can be normal or decreased. Blood sodium and calcium can be normal or decreased.

　　5. Urine carbon dioxide partial pressure detection After normal people are given sodium bicarbonate or neutral phosphate, the amount of HCO3- or HPO42- reaching the distal tubules increases, the former combines with H+ to form H2CO3; the latter combines with H+ to form H2PO4-, and then combines with HCO3- to form H2CO3, and then generates CO2, increasing the urine CO2 partial pressure. In DRTA, due to the obstacle of hydrogen secretion, the urine CO2 does not increase, and the difference between the urine CO2 partial pressure and the blood CO2 partial pressure is less than 20mmHg, which is greater than 30mmHg in normal people.

　　6. 24h urine citrate It is often reduced in DRTA.

　　7. Blood examination The main manifestations are low blood K+, Ca2+, Na+, and PO43-, increased blood Cl-, decreased plasma HCO3-, and reduced CO2 binding power.

　　Other auxiliary examinations:
　　1. Imaging examination It can understand the condition of bone disease and find kidney stones.
　　2. Ultrasound examination It can be understood whether there is calcification and calculus in the kidneys.

　　The patient's diet should be light, avoid alcohol and spicy,刺激性 food, and eat less greasy and rich in animal protein food (such as fatty meat, shrimp, crab, etc.). Specific questions can be asked to the relevant doctor or nutritionist, and a corresponding dietary plan can be formulated according to different conditions.

　　The treatment for type I renal tubular acidosis (DRTA) is as follows:

　　1. Correct metabolic acidosis This is the key to treatment, alkali therapy is very effective. Commonly used include sodium bicarbonate, sodium citrate, and potassium citrate. According to the severity of the condition, sodium bicarbonate can be taken at a dose of 4-10g/d, divided into 4 doses, (1g NaHCO3 is approximately equal to 12mmol HCO3-). It can also be taken at a dose of 1.0-1.5mmol/kg (84-126mg/kg) per day, children need a larger amount of alkali [2.5-7.0mmol/(kg?d)], and sodium bicarbonate can be administered intravenously for severe acidosis. Pay attention to reducing the intake of fixed acids (SO42-, Cl-, etc.) in food during the treatment of acidosis, low sulfur protein diet, and low salt diet to reduce chloride ions.

　　2. Potassium Supplementation and Acid Correction Potassium supplementation should begin immediately, especially for severe hypokalemia patients, potassium supplementation should start before correcting acidosis to avoid triggering a hypokalemia crisis. In principle, potassium supplementation should be performed regardless of the level of blood potassium, and sodium supplementation should also be performed. Potassium citrate mixture (Albright's solution, consisting of 98g of potassium citrate, 140g of citric acid dissolved in water to 1,000ml, 10-15ml per time, 3 times a day) can be selected.

　　3. Supplementation of Calcium and Vitamin D Prevention and treatment of osteoporosis in RTA with osteomalacia, rickets, and other bone diseases or severe hypocalcemia can be supplemented with calcium and vitamin D, with a common dose of 50,000 to 100,000 U/d, and vitamin 1,25(OH)2D3 can be selected when necessary. At the same time, high-phosphorus diet, protein synthesis agents, etc., should be supplemented, especially for children in the growth and development period, more attention should be paid. However, calcium and vitamin D cannot be used in patients with concurrent renal calcification and kidney stones. In addition, nandrolone phenylpropionate can be given to treat osteoporosis and promote bone growth.

　　4. Incomplete RTA Hydrochlorothiazide (dihydrochlorothiazide) can be used for treatment, similar to the treatment of idiopathic hypercalciuria.

　　5. Treatment of the Cause Active treatment of the primary disease and its complications, for secondary RTA, treat the underlying disease, control and remove the cause. For example, for the treatment of pyelonephritis, to relieve urinary tract obstruction, etc. For patients who currently cannot be cured of the cause, lifelong medication treatment is required, not only to correct acidosis, but also to delay bone disease and other complications, so that renal function can be maintained stable for a long time.

　　6. Regular Follow-up During the treatment process, it is necessary to frequently reexamine various biochemical indicators to avoid overcompensation. After hyperchloremic acidosis, hypercalciuria urine pH and other normal values, patients should be followed up and re-examined at least twice a year for the above items.