Renal tubular disease

　　1. Type 1 (distal) tubular acidosis

　　1. Primary:Tubular function often has congenital defects, which can be sporadic, but most are autosomal recessive inheritance.

　　2. Secondary:Pyelonephritis is the most common.

　　(1) Autoimmune diseases: Sjögren's syndrome, systemic lupus erythematosus, thyroiditis, chronic active hepatitis, idiopathic hypergammaglobulinemia, cryoglobulinemia, rheumatoid arthritis, pulmonary fibrosis, primary biliary cirrhosis, vasculitis, etc.

　　(2) Diseases related to renal calcification: hyperparathyroidism, hyperthyroidism, vitamin D intoxication, Milk-Alkali syndrome, idiopathic hypercalciuria, hereditary fructose intolerance, Fabry disease, Wilson's disease, etc.

　　(3) Drug or toxic nephropathy: amphotericin B (amfortericin B), analgesics, lithium (lithium), gossypol, crude cottonseed oil, toluene cyclohexanecarboxylate (toluene

　　(cyclamate) and others.

　　(4) Genetic systemic diseases: Ehlers-Danlos syndrome (cutis laxa), sickle cell anemia, hereditary elliptocytosis, Marfan syndrome, osteosclerosis with deficiency of carbonic anhydrase II, medullary sponge kidney, medullary cyst disease, etc.

　　(5) Others: Chronic pyelonephritis, obstructive nephropathy, renal transplantation, hyperoxaluria, leprosy, etc.

　　2. Type 2 (proximal) tubular acidosis:A simple HCO3--reabsorption defect (such as the lack of carbonic anhydrase) is rare, while a compound reabsorption defect of multiple substances is more common.

　　1. Primary:It is mostly autosomal dominant inheritance or sporadic, such as Na+ in the kidney.

　　Mutations in the coding gene SLC4A4 for HCO3- cotransporter can cause permanent simple proximal RTA with ocular disease.

　　2, Transient (temporary):Mostly occurs in infants.

　　3, Changes or deficiency in carbonic anhydrase activity:Such as CAⅡgene mutation leading to osteosclerosis, RTA, brain calcification, and sodium retention.

　　Third, type 4 renal tubular acidosis

　　1, Decreased aldosterone secretion

　　(1) Primary aldosterone deficiency: Addison's disease, bilateral adrenalectomy, various enzymes for synthesizing adrenal salt corticosteroids, such as 21-hydroxylase deficiency, carbon chain cleavage enzyme deficiency, etc.; defects in the enzyme catalyzing the 18-methylation of corticosterone, etc.

　　(2) Long-term and large-scale use of heparin can inhibit aldosterone synthesis.

　　(3) Insufficient stimulation of aldosterone secretion due to low renin levels: diabetic nephropathy, interstitial renal tubular disease, drugs (beta-blockers, ACEIs or AT1 receptor blockers, etc.) blocking or inhibiting the action of the renin-angiotensin system, non-steroidal anti-inflammatory drugs, etc.

　　2, Altered response of distal renal tubules to aldosterone (aldosterone resistance).

　　If not treated in time, renal rickets or osteomalacia may occur; bone calcification and (or) renal calculi, etc., a few patients may have deafness, sudden fractures, renal colic with hematuria, and loose teeth.

　　1, Impaired renal concentration function:Manifested as polyuria, diabetes insipidus, thirst, dehydration, and hyponatremia, etc.;

　　2, Renal acidification dysfunction:Manifested as hyperchloremic metabolic acidosis, dizziness, fatigue, anorexia, nausea, alkaline urine;

　　3, Defects in renal tubular reabsorption function:Manifested as hypokalemia, hyponatremia, hypocalcemia, and hypomagnesemia. The principle of treatment is to treat the primary disease and maintain water and electrolyte balance.

　　It varies depending on the location and severity of renal tubular damage, but common manifestations include varying degrees of metabolic acidosis.

　　1, Type 1

　　It is the most common type in clinical practice. Like type 2, hereditary cases usually occur in infants and children, and can also be seen in early adulthood. Secondary cases are more common, and children with the disease are often discovered due to unstable gait, a symptom related to osteomalacia. The most common clinical manifestation in adult patients is recurrent hypokalemic paralysis. Generally, it is more likely to occur at night or after fatigue. During an attack, mild cases may only feel weakness in the limbs, and standing up from a sitting position requires support from the hands. Severe cases may completely lose the ability to move the limbs autonomously, except for the head and neck, and may even cause respiratory muscle paralysis and difficulty breathing. Attacks may last for several hours or 1 to 2 days. Mild cases can recover spontaneously; severe cases require intravenous infusion of potassium chloride before recovery. The pathogenesis of hypokalemic paralysis is directly related to the potassium ion gradient inside and outside the cell, and is unrelated to the absolute level of potassium in plasma. Due to increased calcium excretion in urine and secondary hyperparathyroidism, it is easy to develop renal calcification and urinary tract stones, the latter of which can cause renal colic and is prone to recurrent pyelonephritis. Due to skeletal mineralization disorders, children are prone to rickets and incomplete fractures, while adults may develop osteomalacia. Children with the disease also have delayed growth and development, which may be caused by acidosis leading to a lack of IGF-1 receptors in cartilage.

　　2, Type 2

　　Hereditary cases often occur in children, with a family history, and are autosomal dominant inheritance. Secondary cases can also occur in adults. Spontaneous and secondary cases are more common than familial and hereditary cases. The main clinical manifestations are metabolic acidosis, hypokalemia, and myopathy. Children may have growth and development delay, malnutrition, and rickets due to the loss of nutrients such as sugar, amino acids, and phosphates in urine. Hypokalemia can cause muscle weakness, fatigue, and the appearance of hypokalemia on an electrocardiogram, but it is rare to develop hypokalemic paralysis, which may be related to this type of 'limited' renal tubular acidosis.

　　3, Type 3 (mixed type):The main clinical manifestation of this type of patient is metabolic acidosis. The blood potassium level is normal, so there is no muscle weakness or hypokalemic paralysis. Some clinical manifestations of patients with types 1 and 2 can occur.

　　4, Type 4:In addition to hyperchloremic metabolic acidosis, the main clinical characteristics of patients are hyperkalemia and decreased blood sodium. Some patients may develop orthostatic hypotension due to reduced blood volume.

　　In addition to the above clinical manifestations, in secondary patients with various types of renal tubular acidosis, there are also clinical manifestations of primary diseases.

　　Nursing measures for renal tubular acidosis:Severe cases of renal tubular acidosis require bed rest. They should be provided with a diet that is high in calories, high in protein, and rich in various vitamins. The ward should maintain appropriate temperature and humidity, ventilate regularly, and during various nursing procedures, both strict aseptic operation should be followed, and the patient's warmth should be maintained to avoid catching a cold or flu.

　　It is also necessary to accurately record the intake and output of fluids, and perform various laboratory tests. The intake and output of fluids are important indicators reflecting the balance of water, electrolytes, and acid-base in the body, which can directly reflect the changes in the patient's condition. Various laboratory tests also provide a good basis for the diagnosis of the disease. Therefore, it is necessary to correctly collect blood, urine, and other specimens and deliver them for timely testing.

　　The acid-base imbalance, electrolyte disorder, and low immunity in patients with renal tubular acidosis can cause urea to be excreted from the salivary glands and deposited on the skin, leading to halitosis, oral ulcers, and skin itching. Therefore, while strengthening oral and skin care, health education should be provided, and personal hygiene should be maintained. Close observation of the patient's consciousness, body temperature, pulse, respiration, blood pressure, urine output, and reactions to medication should be conducted. These can not only indicate the progression of the disease but also help to identify abnormal conditions. For example, renal tubular acidosis can be caused by many kidney diseases, and kidney diseases can lead to hypertension. Hypertension can further worsen renal vascular lesions, leading to further deterioration of renal function. Therefore, by observing the changes in the patient's blood pressure, the changes in the patient's condition can be understood.

　　Renal tubular acidosis is prone to recurrence and exacerbation, so health education and discharge guidance should be provided. Patients should arrange their diet and lifestyle reasonably, avoid upper respiratory tract infections and infections in other parts, and strengthen exercise to enhance their body's resistance.

　　1. Urine test

　　The urine pH value of type 1 patients is often above 5.5 and often increases to 7 (even though there is obvious blood acidosis), and incomplete cases only appear in this situation after ammonium chloride loading test. In type 2 patients, the urine pH value only increases when severe acidosis occurs, and the urine pH value can be normal when the acidosis is not severe.

　　2. Blood biochemistry

　　All types of patients have a decrease in blood pH value. Only incomplete type 1 patients can have blood pH values within the normal range. The blood CO2 binding capacity is the same as the blood pH value. Type 1 and 2 blood potassium levels are low, type 3 is normal, and type 4 is high. In severe distal renal tubular acidosis, there may be secondary increased blood ammonia. Miller et al. reported a case of an infant with severe distal renal tubular acidosis, where it is possible that the kidneys synthesize more ammonia but do not excrete it in the urine, leading to ammonia retrograde expansion into the blood circulation and causing increased blood ammonia levels.

　　3. Loading test

　　For incomplete type 1 renal tubular acidosis, ammonium chloride loading test can be performed to help with diagnosis. The method is to take 2g of ammonium chloride orally, 3 times a day, for 5 consecutive days after fasting from acidic or alkaline drugs. If the urine pH value cannot drop below 5.5 when the blood pH value decreases, it can be diagnosed as incomplete type 1 renal tubular acidosis. If the urine pH value cannot drop below 5.5 after taking 0.2g/kg of oral calcium chloride, it indicates that there is a barrier to acidification, and it can be diagnosed as incomplete type 1 renal tubular acidosis. If the concentration of HCO3- in the blood after intravenous infusion of 400ml of sodium bicarbonate within 2 hours is high, it supports the diagnosis of type 2 renal tubular acidosis.

　　4. Electrocardiogram examination:Patients with hypokalemia have ST segment depression, T wave inversion, and the appearance of U waves.

　　5. X-ray bone examination:Osteoporosis and softening are significant, especially in the lower limbs and pelvis. Some may present with fractures. Radionuclide bone scanning shows sparse and uneven radionuclide absorption.

　　6. Other:The urine citrate/creatinine ratio in patients with complete or incomplete type 1 renal tubular acidosis is all below 2.5. The determination of the CO2 gradient between urine and blood (the CO2 gradient between urine and blood)

　　1. Low-protein

　　The amount of supply is determined according to the condition, for those with mild symptoms, it should be controlled at 20~40g/d to reduce the burden on the kidneys; the duration of low-protein diet should not be too long to prevent anemia. Once the blood urea nitrogen and creatinine clearance rate approach normal, regardless of whether there is proteinuria, the protein supply should be gradually increased to 0.8g/kg per day to facilitate renal function repair. Opt for high-quality proteins containing a large number of essential amino acids and a small number of non-essential amino acids, such as eggs, milk, lean meat, and fish; it is not advisable to consume legumes and their products.

　　2. Limit sodium and water intake

　　At the onset of the disease, edema is the main symptom, and the kidneys cannot normally excrete water and sodium. Restricting fluid intake and avoiding salt is a good method to eliminate edema. Low-salt, salt-free, or low-sodium diets should be provided according to the condition, urine output, and edema situation. A low-sodium diet, in addition to not adding salt or soy sauce, should also avoid foods high in sodium. For specific reference, see the dietary and nutritional treatment principles for heart failure and renal failure in Chapter 27.

　　3, Control potassium intake

　　During oliguria or anuria, the potassium intake should be strictly controlled, and water intake should be limited to less than 500ml/d, avoiding the consumption of foods high in potassium, such as fresh mushrooms, shiitake mushrooms, jujube, shellfish, beans, vegetables, and fruits, etc.

　　4, Energy

　　Treatment combines rest, medication, and nutritional diet therapy. Severe cases may require bed rest, so energy consumption is reduced, and less activity reduces appetite. The daily supply of energy does not need to be too high, and it is advisable to provide 0.10~0.13MJ (25~30kcal)/kg, with a total of 6.69~8.37MJ (1600~2000kcal) per day.

　　5, Carbohydrates and fats

　　Most of the dietary energy is provided by carbohydrates. Supplementing sufficient carbohydrates can prevent insufficient energy, and also ensure that the small amount of protein provided by food is completely used for tissue repair and growth and development; it is advisable to add sweet pastries, noodles, and jelly. There is no need to strictly limit the total amount of fat, but foods rich in animal fats and fried foods should be given less. Acute nephritis often accompanied by hypertension is not advisable to eat too much animal fat to prevent the rise of blood lipids; it is advisable to increase sweet pastries, vegetables high in carbohydrates, and keep the diet light.

　　6, Supply sufficient vitamins

　　Use more fresh green vegetables and fruits. Fresh vegetables can enhance the appetite of patients, unless potassium is restricted during the oliguria period, in which case vegetables should be limited; otherwise, fresh vegetables should be given more. During the recovery period, foods with nourishing effects such as yam, jujube, longan, lotus seeds, and silver ear can be provided more. Vitamin A, B vitamins, vitamin C, folic acid, vitamin B1, iron, and other nutrients are beneficial for the recovery of renal function and the prevention of anemia, and should be supplemented in sufficient amounts in food; foods such as sautéed cabbage with vinegar, scrambled eggs with tomatoes, and sautéed carrot shreds can be selected.

　　7, Supply more alkaline foods

　　During acute glomerulonephritis, the urine is acidic, and the acidity and alkalinity of food can adjust the urine pH value. Supply alkaline foods to make the urine nearly neutral, which is beneficial for treatment. During the oliguria period, fruits and vegetables rich in potassium should be limited to prevent the occurrence of hyperkalemia. Acidic foods are those that produce acidic substances after metabolism in the body, mainly including grain, beans, and meat rich in protein, while alkaline foods include vegetables, fruits, and dairy products, etc.

　　8, Limit刺激性 food

　　Limit the metabolism of spices and刺激性 food, such as anise, pepper, and other food metabolites contain purines, excreted by the kidneys, which can increase the burden on the kidneys, so it is not advisable to eat too much; animal organs such as liver and kidney contain a lot of nucleoprotein, and their metabolites also contain a lot of purines and uric acid, so they should also be eaten less.

　　There is currently no definitive cure for hereditary renal tubular acidosis, and gene therapy is under research.

　　For secondary renal tubular acidosis caused by other diseases, the primary disease should be treated first. If the primary disease can be cured, the renal tubular acidosis can also be cured accordingly. For those with primary diseases that cannot be cured,对症治疗 can only be adopted as with hereditary renal tubular acidosis.

　　Treatment of type 1 renal tubular acidosis

　　Firstly, alkali supplements should be taken to correct acidosis. The appropriate alkali is a mixture of citric acid, with 140g of citric acid, 100g of sodium citrate, and water added to 1000ml (also known as Shohl mixture). The dosage is 20-30ml/time, 3 times/d. This mixture, in addition to correcting acidosis, also has the effect of preventing urinary tract stone formation. Potassium salt is supplemented to correct hypokalemia. Such as potassium chloride tablets, potassium chloride sustained-release capsules, potassium citrate, etc.

　　Treatment of type 2 renal tubular acidosis

　　Because the patient loses a lot of bicarbonate sodium, it is advisable to supplement bicarbonate sodium, select different dosages according to the severity of the disease, generally 8-12g/d, taken in divided doses. The supplementation of bicarbonate can correct metabolic acidosis, but the excretion of bicarbonate in urine also increases, increasing the loss of urinary potassium, so potassium should be supplemented at the same time. In severe acidosis, the intake of sodium should be restricted, and hydrochlorothiazide should be taken orally to increase the excretion of Cl- (reduce the reabsorption of Cl-), alleviate the loss of HCO3- from urine, with a dosage of 25-50mg, 3 times/d. Generally, 10% potassium citrate should be taken orally to correct hypokalemia, with a dosage of 20-30ml, 3 times/d. The supplementation of bicarbonate sodium (bicarbonate sodium) can increase the loss of urinary potassium. Those with increased excretion of calcium and phosphates should supplement phosphates, which can be taken as 20ml of phosphate buffer solution, 1 time every 6 hours. At the same time, vitamin D preparations should be taken to increase intestinal calcium absorption, avoid the occurrence of secondary hyperparathyroidism and exacerbate the loss of urinary phosphates. Patients with severe osteopathy can try active vitamin D preparations.

　　Treatment of 3,4 types of renal tubular acidosis

　　Primarily, it is supplemented with salt皮质激素，which not only can correct hyperchloric metabolic acidosis, but also can correct hyperkalemia. The commonly used drug is fludrocortisone. The dosage is 0.2-0.5mg/time, 1 time/d. Furosemide can increase the excretion of Na+, Cl-, K+ and H+, so it can also be used to treat patients with type 4 renal tubular acidosis. The combination with fludrocortisone can enhance the efficacy.