Distal renal tubular acidosis

　　The etiology of distal renal tubular acidosis (RTA) can be divided into primary and secondary types. The primary type is related to heredity, showing autosomal dominant inheritance with a family history, but most are sporadic. The secondary type can be caused by various diseases, with the most common underlying disease being chronic tubulointerstitial nephritis, among which chronic pyelonephritis is more common. In addition, other congenital hereditary kidney diseases such as cavernous kidney, Fabry disease, and idiopathic hypercalciuria can also cause it. In China, distal RTA secondary to Sjögren's syndrome, systemic lupus erythematosus, and other autoimmune diseases has a high incidence. There are also reports of distal renal tubular acidosis (DRTA) caused by cottonseed oil poisoning in cotton-producing areas.

　　The complications of distal renal tubular acidosis (DRTA) mainly include malnutrition, vitamin C deficiency disease or osteomalacia, some cases develop into renal calculi or renal calcification, and in the late stage, it may develop into uremia. A few cases may have neurosensory hearing loss. Primary cases are often sporadic, while secondary cases can be secondary to various diseases.

　　Distal renal tubular acidosis (DRTA) is the most common clinical type of renal tubular acidosis, which can occur at any age, more common in 20-40 years old, especially in women. The disease can be asymptomatic in mild cases, and the typical symptoms are as follows:

　　1. Hyperchloremic acidosis

　　Due to the decrease in urinary titratable acid and NH4 excretion caused by H+ blockage, the urine cannot be acidified, and the urinary pH is often greater than 6. In addition, since the function of the proximal renal tubules is still good, they can reabsorb HCO3-, and the excretion of urinary HCO3- is not very high. Due to the persistent loss of Na, the extracellular fluid volume contracts, aldosterone secretion increases, the reabsorption of chloride increases, and hyperchloremia is formed. Some people believe that hyperchloremia is caused by a certain unknown reason that increases the permeability of the renal unit to chloride, leading to 'renal chloride diuresis'.

　　2. Electrolyte disorder

　　Due to the decreased function of the H pump in the distal renal unit and the H-K pump in the cortical collecting duct, the kidney cannot maintain potassium and concentrate urine, leading to polyuria, hypokalemia, and acidosis. Hypokalemia also leads to polyuria, and polyuria further aggravates hypokalemia. If there is an additional burden from a comorbid disease, the aggravation of acidosis and hypokalemia can lead to death; acidosis inhibits the reabsorption of Ca2+ by the renal tubules and the activity of vitamin D, causing hypercalciuria and hypocalcemia, forming electrolyte disorder of 'three lows and one high' (hypokalemia, hyp钠emia, hypocalcemia, and hyperchlorideemia). In addition, hypokalemia can also cause muscle weakness and muscle paralysis. Due to the reduced H-Na exchange in the tubular fluid, it can also cause a large loss of sodium in the urine, and patients may occasionally experience neurosensory hearing loss.

　　3. Osteopathy

　　Parathyroid hyperfunction caused by low blood calcium leads to bone pain, fractures, and other phenomena of bone demineralization, which further develops into osteomalacia (in adults) or scurvy (in children).

　　4. Renal calcification and kidney stones

　　Due to the large excretion of calcium, the decrease in urinary citrate leads to alkaline urine, which is extremely prone to the precipitation of calcium salts, forming renal calcification and kidney stones, and further leading to renal colic, hematuria, and urinary tract infection.

　　5. Renal function damage

　　Early on, polyuria may occur due to the impaired tubular concentrating function, while in the late stage, glomerular involvement may lead to uremia. According to the interrelation of clinical symptoms, the disease is clinically divided into 4 types. The myopathic type is characterized by muscle weakness and paralysis, even respiratory muscle paralysis and dyspnea. Hypokalemia, increased urinary potassium, and electrocardiogram showing hypokalemia can be accompanied by atrioventricular block and arrhythmias, which may lead to emergency due to hypokalemia paralysis and should be vigilant. The osteopathic type is mainly characterized by bone pain and pathological fractures, and patients may reduce their activity due to bone pain, even becoming bedridden. X-ray examination shows osteoporosis, multiple, symmetrical, and pseudofractures, and there may be symptoms of loose teeth and easy falling out, and children may not grow teeth. The urinary tract stone type is characterized by urinary sand, urinary stones, hematuria, renal colic, urinary tract obstruction, and recurrent urinary tract infections. A few patients do not show systemic acidosis, only presenting renal tubular failure to produce acidic urine, known as incomplete distal renal tubular acidosis. The urine pH does not decrease in the ammonium chloride load test. Incomplete distal renal tubular acidosis can progress to complete type.

　　For primary hereditary causes of type I renal tubular acidosis (RTA), there are no effective preventive measures. The prevention of secondary diseases should start with the treatment of the underlying disease, controlling its development into renal tubular acidosis. Patients with the disease should be treated actively to prevent the progression of the disease and strive for a good prognosis.

　　The clinical examination methods for distal renal tubular acidosis mainly include the following aspects:

　　1. Urine pH measurement

　　Urine pH reflects the amount of H in the urine, and in DRTA, although blood pH

　　2. Determination of urine titratable acid and urine NH4

　　Most of the H secreted by the distal renal tubules combines with NH3 to form NH4 and excreted, and the other part is excreted in the form of titratable acid. Therefore, the sum of urine titratable acid and NH4 represents the net acid excretion of the kidney. When there is an increase in acidic substances in the body, the urine pH of normal people can

　　3. Urine electrolyte and urine anion gap measurement

　　DRTA mostly has increased urine sodium excretion and increased urine calcium, urine Ca/Cr>0.21, 24h urine calcium>4mg/(kg·d). Urine anion gap = Na+K-Cl- can reflect urine NH4 levels, and a positive value indicates reduced urine NH4 excretion. Urine pH>6.0, and HCO3- excretion fraction is high.

　　4. Blood gas analysis and electrolyte measurement

　　The typical change of DRTA is hyperchloremic normoglycemic metabolic acidosis. Incomplete DRTA can manifest as compensatory metabolic acidosis or normal. The blood anion gap (anion gap, AG) = Na+K-(Cl-+HCO3-), which is normally 8-16mmol/L, and an increase indicates the retention of inorganic acid radicals (such as nitrate and sulfate) and/or organic acid radical ions and other acidic products in the body. In RTA, Cl- compensates for the decrease in HCO3-, so the AG is normal. Blood potassium levels may decrease, which is also an important manifestation of DRTA, and even the only manifestation of incomplete DRTA. Blood sodium and calcium levels may be normal or decreased.

　　5. Urine CO2 partial pressure detection

     In normal people, after giving 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-, which then combines with HCO3- to form H2CO3, and further generates CO2, increasing the urine CO2 partial pressure. In DRTA, due to the obstacle of hydrogen secretion, urine CO2 does not increase, and the difference between urine CO2 partial pressure and blood CO2 partial pressure is 30mmHg.

　　6. 24h urine citrate

　　It often decreases in DRTA.

　　7. Blood tests

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

　　8. Ultrasonic imaging examination

　　It can be understood whether there is calcification and calculus in the kidneys.

　　Patients with distal renal tubular acidosis (DRTA) should develop good living and dietary habits, and rationally match their diet. They should eat fresh vegetables and fruits, and foods with high water content, rich in minerals and vitamins, and avoid eating animal meats, high-fat meats, and foods that promote dampness and heat.

　　Active treatment of the primary and concurrent diseases is essential. For secondary distal renal tubular acidosis (RTA), the underlying disease should be treated, and the cause should be controlled and removed, such as treating pyelonephritis and relieving urinary tract obstruction. For patients with RTA who cannot be cured by the root 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.

　　1. Correction of Metabolic Acidosis

　　This is the key to treatment, and alkali supplementation therapy is very effective. Commonly used drugs include sodium bicarbonate, sodium citrate, and potassium citrate. Depending on the severity of the condition, sodium bicarbonate can be taken, and for severe acidosis, sodium bicarbonate can be administered intravenously. Alternatively, a compound sodium citrate mixture can be taken orally. With the correction of acidosis, the consumption of sodium, as well as the excretion of calcium and potassium in urine, decreases. Citrate is metabolized and converted into HCO3- in the liver, which can correct acidosis and promote the absorption of calcium in the intestines. The excretion of citrate calcium in urine reduces the risk of kidney stones and renal calcification, making citrate superior to sodium bicarbonate. The dosage of alkaline drugs needs to be individualized, adjusted according to blood pH, CO2CP, and urinary calcium excretion, among which the 24-hour urinary calcium excretion (

　　2. Potassium Supplementation

　　Potassium supplementation should begin as soon as acidosis correction starts, especially for severe hypokalemia patients, potassium supplementation should start before correcting acidosis to avoid triggering a hypokalemia crisis. In principle, potassium supplementation should be given regardless of blood potassium levels, and sodium supplementation should also be provided. Potassium citrate mixture or citrate mixture can be used. Generally, 10% potassium citrate is taken orally for hypokalemia. Chloride potassium should be avoided, otherwise it will worsen hyperchloremia; only severe hypokalemia (

　　3. Prevention and Treatment of Osteoporosis with Calcium Supplements and Vitamin D

　　When RTA is complicated with osteomalacia, rickets, or other bone diseases or severe hypocalcemia, calcium supplements and vitamin D should be administered, and vitamin 1,25(OH)2D3 should be used when necessary. With the improvement of clinical biochemical indicators, when blood phosphorus levels rise and alkaline phosphatase (AKP) returns to normal, the dosage can be reduced or discontinued (blood calcium I≥2.5mmol/L). To avoid hypercalcemia and vitamin D intoxication, as vitamin D2 can easily increase urinary calcium, it should be used with caution to prevent vitamin D intoxication and renal calcification. At the same time, high-phosphorus diet, protein synthesis agents, and other supplements should be taken, especially for children in the growth and development period. However, calcium supplements and vitamin D should not be used for those with concurrent renal calcification and kidney stones. In addition, nandrolone phenylpropionate can be given to treat osteoporosis and promote bone growth.

　　4. Partially Incomplete Renal Tubular Acidosis (RTA)

　　Can be treated with hydrochlorothiazide (dihydrochlorothiazide), similar to the treatment of idiopathic hypercalciuria.