bubble_chart Overview

Renal tubular acidosis (RTA) is a clinical syndrome caused by defects in the proximal renal tubule's reabsorption of bicarbonate or the distal renal tubule's secretion of hydrogen ions. Based on the site of renal tubule damage and its pathophysiological basis, it is classified into four types: Type I is distal renal tubular acidosis (DRTA), also known as classic renal tubular acidosis. Type II is proximal renal tubular acidosis (PRTA). Type III is a mix of Type I and Type II, also known as mixed type. Type IV renal tubular acidosis is caused by congenital or acquired aldosterone deficiency or the renal tubule's insensitivity to aldosterone, leading to metabolic acidosis and hyperkalemia. Each type can be further divided into primary or secondary renal tubular acidosis based on the disease cause.

bubble_chart Diagnosis

To diagnose renal tubular acidosis, it is essential to first conduct a thorough medical history inquiry and a meticulous physical examination. In cases where children exhibit delayed growth and development, anorexia, nausea, weakness, polyuria, polydipsia, low urine specific gravity, or unexplained dehydration and acidosis, this condition should be considered. Clinical manifestations such as persistent rickets in children, or the occurrence of rickets, pathological fractures, renal calcification, or nephrolithiasis in older children, warrant further testing of blood generation and transformation and urine pH. The diagnosis is essentially confirmed when acidosis and alkaline urine are verified. To determine the clinical subtype and identify the disease cause, the following diagnostic steps can be taken: ① Measure urinary ammonium; this is aimed at excluding proximal renal tubular acidosis and non-renal hyperchloremic acidosis. If urinary ammonium is <50mmol/d, distal renal tubular acidosis should be considered. ② Measure blood potassium: if hyperkalemia is present, type IV RTA can be diagnosed. If blood potassium is low or normal, urine pH should be measured, and further tests such as the sodium bicarbonate test, neutral phosphate test, and sodium sulfate test should be conducted for differentiation.

bubble_chart Treatment Measures

1. Alkaline drugs: Due to reduced excretion of H⁺ in the distal renal tubules, metabolic acidosis occurs as a result of retention in the body. In proximal renal tubular acidosis, the reabsorption function of HCO₃^- is impaired, and the renal threshold for bicarbonate in children decreases to below 17-20 mmol/L (normal is 25-26 mmol/L, and 22 mmol/L in infants). Even when plasma HCO₃^- is normal, due to the lowered renal threshold, a large amount of HCO₃

^- in the filtrate is excreted in the urine, causing acidosis. The use of alkaline drugs aims to correct acidosis, and early use can improve or completely alleviate clinical symptoms. There are two commonly used preparations: ① Sodium bicarbonate and citrate mixture. Sodium bicarbonate can act directly and is suitable for both acute and chronic acidosis. Type I patients lose very little bicarbonate and only need to neutralize acidic products in the body, generally given 1-5 mmol/(kg·d); Type II renal tubular acidosis requires alkaline drug treatment not only to neutralize the retained acidic products but also to compensate for the bicarbonate lost in the urine, hence a larger dose is needed, starting with 5-10 mmol/(kg·d), administered intravenously or orally. During treatment, the dose should be adjusted based on blood bicarbonate or carbon dioxide combining power and 24-hour urinary calcium excretion, with urinary calcium excretion being a sensitive indicator to guide treatment. The dose should be adjusted to keep 24-hour urinary calcium excretion below 2 mg/kg. Excessive doses of sodium bicarbonate can cause side effects such as abdominal distension and fullness, and belching. ② Citrate mixture: There are two preparations, one containing 100g each of sodium citrate and potassium citrate, diluted to 1000 ml, with each ml containing 2 mmol of base. The other contains 100g of sodium citrate and 140g of citric acid, diluted to 1000 ml, with each ml containing 1 mmol of sodium. The dose is 1 mmol/(kg·d), divided into 4-5 oral doses.

2. Potassium salt supplementation: In addition to hyperchloremic acidosis, renal tubular acidosis also involves impaired H⁺ secretion in the distal renal tubules, reduced H⁺-Na⁺ exchange, and increased competitive K⁺-Na⁺ exchange, leading to excessive potassium excretion and hypokalemia; in the proximal renal tubules, due to the massive loss of NaHCO₃, plasma volume decreases, causing secondary aldosteronism, resulting in increased NaCl reabsorption, replacing the lost NaHCO₃ and producing hyperchloremic acidosis; sodium absorption and potassium excretion cause significant hypokalemia, making potassium supplementation crucial. When significant hypokalemia is present, potassium salts should be supplemented before correcting acidosis to avoid inducing a critical phase of low potassium. Commonly used potassium-containing citrate mixtures start at 2-4 mmol/(kg·d), divided into 3-4 oral doses, with a maximum dose of 4-10 mmol/(kg·d) for patients with proximal renal tubular acidosis to maintain normal blood potassium levels. The dosage should be adjusted based on the condition and blood potassium levels during treatment. Potassium chloride, containing chloride ions, should be used with caution.

3. Application of Calcium Preparations Chronic acidosis can lead to increased urinary calcium excretion, hindering the conversion of 25(OH)D to 1,25(OH)₂D. Additionally, some patients with gastric acid deficiency may experience impaired intestinal calcium absorption, resulting in low blood calcium levels. Hypocalcemia can cause secondary hyperparathyroidism, increasing phosphorus clearance. The reduction of phosphate and calcium ions in the blood prevents bone mineralization, leading to rickets. Hypocalcemia may also occur during the correction of acidosis, potentially causing convulsions. Calcium supplementation is necessary in these cases. Severe hypocalcemia can be treated with intravenous infusion of 10% calcium gluconate, at a dose of 0.5–1.0 mg/kg or 5–10 mg per dose, diluted and administered slowly. Cardiac monitoring is required during administration, and the infusion should be stopped if the heart rate drops below 60 beats per minute to prevent cardiac arrest. If necessary, the treatment can be repeated every 6–8 hours. For mild hypocalcemia, oral calcium supplements can be administered at a dose of 15 mg/kg of calcium ions.

4. Vitamin D Therapy Chronic acidosis can affect vitamin D and calcium metabolism, especially in cases of distal renal tubular acidosis with significant rickets, where vitamin D supplementation is necessary. It promotes the absorption of calcium in the gastrointestinal mucosa and renal tubules, increases blood calcium levels, and benefits bone mineralization. The following vitamin D preparations can be used: ① Regular vitamin D₂ or D₃, starting at a dose of 5000 to 10000U, gradually increasing, with some cases requiring up to 100,000U/d. ② 25(OH)D, 50μg/d, or dihydrotachysterol 0.1～0.2mg/d. ③ 1,25(OH)₂D, at a dose of 0.5～1.0μg/d, can achieve good therapeutic effects. During treatment, blood calcium must be closely monitored, initially weekly, then monthly. When blood calcium returns to normal and rickets symptoms alleviate, the dose should be reduced to prevent hypercalcemia and vitamin D toxicity.

5. Diuretics can reduce renal calcium salt deposition in type I and III cases; for severe type II cases requiring large amounts of bicarbonate, they not only increase the renal threshold for bicarbonate, reducing urinary loss, but also decrease the dosage of alkaline drugs; for type IV renal tubular acidosis, concurrent use of diuretics helps correct acidosis and lower blood potassium levels.

6. Treatment of Type IV Renal Tubular Acidosis In addition to correcting acidosis according to principles, due to pathological changes such as aldosterone deficiency or reduced response of the distal tubule and collecting duct to aldosterone, the renal tubule's reabsorption of NaHCO₃ is reduced, leading to increased excretion of NaHCO₃, decreased urinary excretion of acid, potassium, and ammonium, resulting in the retention of H⁺ and K⁺ in the body, causing metabolic acidosis and hyperkalemia. Therefore, potassium supplementation is contraindicated in type IV patients. Type IV renal tubular acidosis is commonly seen in Addison's disease, congenital adrenal hyperplasia (also known as adrenogenital syndrome), and renal dysplasia, requiring supplementation with glucocorticoids or mineralocorticoids. Currently, the commonly used glucocorticoid is hydrocortisone, at a dose of 10～20mg/m², and the mineralocorticoid often used is fludrocortisone, at a dose of 0.15mg/m².

If renal tubular acidosis is accompanied by impaired renal concentrating function, sufficient water must be provided, approximately 2～5l/m² per day.

bubble_chart Prognosis

Most cases of this condition require long-term treatment, and some may even need lifelong therapy. Regular outpatient follow-ups are necessary to monitor blood pH levels, bicarbonate concentrations, and urinary calcium excretion, with careful adjustment of medication doses. The prognosis depends on early diagnosis, timely and appropriate treatment, and long-term adherence to regular therapy. If treated early and appropriately, severe renal calcification and renal insufficiency can be prevented, leading to a better prognosis. However, if treatment is interrupted, clinical symptoms caused by metabolic acidosis may recur, potentially resulting in renal insufficiency or failure, leading to a poor prognosis.