Total distal renal tubular acidosis in children

Introduction to pediatric full-end renal tubular acidosis Renal tubular acidosis (RTA) is a clinical syndrome caused by defects in the proximal tubule reabsorption of bicarbonate or distal renal tubular excretion of hydrogen ions. According to the damaged part of the renal tubule and its pathophysiological basis Divided into 4 types: Type I is distal renal tubular acidosis (dRTA), also known as classical renal tubular acidosis. Type II is proximal renal tubular acidosis (pRTA). Type III is a mixture of Type I and Type II, also known as a hybrid type. Type IV renal tubular acidosis is caused by insufficiency of congenital or acquired aldosterone or insensitive to aldosterone response by renal tubules. The type of each type can be divided into primary or secondary. Primary renal tubular acidosis. Totally distant renal tubular acidosis (hyperkalemicrenal tubular acidosis) is caused by insufficient aldosterone secretion or low renal tubular response to high blood chloride metabolic acidosis and sustained high Potassiumemia, although metabolic acidosis, is different from dRTA in that urine can be acidic. Unlike pRTA, urine excretion HCO3- is lower. basic knowledge The proportion of illness: 0.0025% Susceptible people: children Mode of infection: non-infectious Complications: hypotension, hypertension, rickets, kidney stones, sudden death

The cause of total distal renal tubular acidosis in children

(1) Causes of the disease

Almost all type IV RTAs are secondary to other diseases, rare with primary disease, and common secondary causes are:

1. Simple aldosterone deficiency: such as loss of salt congenital adrenal hyperplasia, aldosterone deficiency, Addison disease.

2. Chronic kidney disease with insufficient secretion of renin and aldosterone: such as diabetic nephropathy, purpuric nephritis, sickle cell nephropathy, renal cirrhosis, interstitial nephritis.

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

4. Renal tubules have reduced reactivity to aldosterone: such as primary pseudo-aldosterone deficiency in infants, secondary pseudo-aldosterone deficiency (including infant urinary tract obstruction, infant renal vein thrombosis, chloride shunt syndrome or Gordon syndrome).

5. Drugs and toxins: Supplement potassium chloride too much, use excessive potassium-sparing diuretics, heparin, prostaglandin inhibitors, etc.

(two) pathogenesis

Aldosterone is the main endocrine hormone that regulates the exchange of Na+-K+ and Na+-H+. When aldosterone is insufficient or the renal tubular response to aldosterone is reduced, the exchange of Na+-K+ and Na+-H+ is reduced, the reabsorption of renal tubules by Na+ is reduced, and HCO3- is lost. Increased, secreted H +, K + disorder, resulting in hyperkalemia acidosis.

Pediatric total distal renal tubular acidosis prevention

Active treatment of primary diseases, such as hormone replacement therapy for patients with adrenal cortical diseases, avoid excessive potassium chloride supplementation, use excessive potassium-sparing diuretics, heparin, prostaglandin inhibitors, etc., and banned kidney damage The medicines and foods should be strengthened and exercised. You can take Liuwei Dihuang Pills.

Pediatric total distal renal tubular acidosis complications Complications, hypotension, hypertension, rickets, kidney stones, death

Can be complicated by respiratory muscle paralysis to dyspnea, severe cases of ventricular fibrillation, renal insufficiency, hypotension or hypertension, RTA patients are prone to rickets, rickets, hypokalemia, renal calcification or kidney stones, should be noted There are reports in the literature that some unexplained sudden death may be related to hypokalemia caused by incomplete RTA.

Pediatric total distal renal tubular acidosis symptoms common symptoms nausea and fatigue, polyuria, specific gravity, anorexia, metabolic acidosis, hyperkalemia, hypokalemia, urinary phosphorus arrhythmia

It can cause a lot of pathogenic factors and primary diseases of RTA. When these factors exist or occur, there are high chloride metabolic acidosis, poor growth and development of children, anorexia, nausea, fatigue, polyuria, polydipsia and urine specific gravity. Low or dehydration, mild renal dysfunction, severe bone disease, refractory rickets in children, rickets in elderly children, pathological fractures, renal calcification or kidney calculi, often a certain degree of kidney The function of the small ball is impaired, but the disease often has high blood chlorine metabolic acidosis and hyperkalemia before the occurrence of chronic renal insufficiency, and the glomerular filtration rate is reduced [but usually GFR>20ml/(min· 1.73m2)], and the decline of GFR is difficult to explain the degree of acidosis, clinically, there are often unexplained hypokalemia or hyperkalemia, hyperkalemia can cause arrhythmia or myocardial paralysis, if hypokalemia can cause muscle Inability, sputum reflex and sputum, blood biochemistry and urine pH measurement confirmed acidosis and alkaline urine, due to renal tubular acidification dysfunction, abnormal alkaline urine or regular alkaline urine, urine generally pH6.0, human body General trend of metabolism The potential is to produce more acid than alkali, the average diet of adults, the daily production of non-volatile acids (mainly from protein) about 1mmol / kg (BW), so the urine generally shows a certain degree of acidity (pH 5.0 ~ 6.0), only after eating a lot of vegetables and fruits or after taking basic drugs, the transient alkaline urine is present, and the urinary pH is still 6.0 under basal metabolism.

Pediatric total distal renal tubular acidosis test

1. Uric acid test: There is often a certain degree of glomerular dysfunction, but this disease often has high blood chlorine metabolic acidosis and hyperkalemia before the occurrence of chronic renal insufficiency. Jiang Yongzheng thinks uric acidification. The trial is the preferred screening test for the diagnosis of RTA, and remains positive for several years after treatment, and 40/115 patients were found to have RTA by examining the test.

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

3. Urine test: such as trace protein, Tamm-Horsfall glycoprotein can reflect tubulointerstitial damage, no glucosuria, amino aciduria, hyperphosphatemia and other proximal tubular dysfunction, acidosis, urine can be acidic, but Urinary ammonia is still reduced, urinary HCO3-discharge is rare or absent. When blood HCO3-concentration is normal, urinary HCO3-displacement is often increased, urine NH4+ is significantly reduced, urinary potassium is decreased, urinary HCO3-discharge is increased, and urinary ammonia is formed. cut back.

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

5. Others: anti-renal collecting tube antibody (+), suggesting immune disease, the disease usually does not appear renal calcification and kidney stones, bone damage is only seen in uremic patients, imaging examination ECG and B-ultrasound, etc. Found to help diagnose and differential diagnosis.

Diagnosis and diagnosis of total distal renal tubular acidosis in children

Diagnosis of pediatric total distal renal tubular acidosis can be confirmed by the following four items:

1 hyperchlorous acidosis;

2 hyperkalemia;

3 urine pH can be reduced to above 5.5;

4 serum creatinine and urea nitrogen increased slightly.

1. Diagnostic clues:

(1) Familiar with the etiology of RTA: When there are pathogenic factors and diseases that can cause RTA, always pay attention to the acidification function of the kidney, and dynamically observe relevant clinical and experimental indicators to prevent missed diagnosis, incomplete renal tubular acidosis. In terms of diagnosis, this is especially important. Incomplete TRA has no significant high-chlorine metabolic acidosis in clinical practice, but its potential harm cannot be ignored. The hypokalemia caused by it can cause sudden death in children.

(2) Grasping the clue of RTA: When there are the following abnormalities in the clinic, the relevant inspection should be done in time to determine whether there is RTA:

1 Unexplained hypokalemia or hyperkalemia;

2 urine pH is often 6.0;

3 Chronic renal insufficiency glomerular filtration rate > 20ml / min, there is significant metabolic acidosis;

4 mild renal dysfunction, there is a serious bone disease.

2. Qualitative diagnosis: In the case of a diagnosis lead with RTA, the RTA can be diagnosed if the following abnormalities are present in the auxiliary examination.

(1) abnormal alkaline urine or regular alkaline urine: the general human urine pH is 5.0 ~ 6.0, can eat a lot of vegetables, fruits, or take alkaline drugs can present transient alkaline urine, to eliminate interference factors patients in the early morning fasting state for the second time to check urine, such as basal metabolism, urine pH is still 6.0, it suggests renal tubular acidification dysfunction, acidosis, especially with hypokalemia, normal kidney It can highly acidify urine and lower the pH of the urine to below 5.5. For example, when the acidosis is urinary, the pH of the urine is still >5.5, which indicates renal tubular acid dysfunction (RTA). However, when judging the clinical significance of urine pH, pay attention to the following Happening:

1 type II RTA patients: plasma HCO3- concentration decreased below the renal HCO3-reabsorption threshold, HCO3- in urine will not increase, and there is no abnormal alkaline urine;

2 patients with incomplete RTA: the urine pH is mostly normal when the acid load test is not performed;

3 gastrointestinal tract HCO3-loss: high chloride metabolic acidosis caused by loss of gastrointestinal HCO3-, often accompanied by sodium deficiency, which can be due to N+ deficiency in the distal nephron lumen, Na+ dependence in cortical collecting duct The sexual H+, K+ excretion is blocked, and the urine can not be acidified normally. After using furosemide or sodium sulfate, the urine pH can be lowered to below 5.5.

4 Selective aldosterone deficiency: Type IV RTA caused by selective aldosterone deficiency, the acidity of the nephron is mild, and the pH of the urine can be reduced to 5.0-5.5 during acidosis.

(2) High chloride metabolic acidosis: blood HCO3-concentration decreased, blood gas analysis indicated metabolic acidosis, blood Cl-concentration increased, serum anion gap (Na+ K+-Cl--HCO3-) normal, with or without Abnormal potassium metabolism, exclude the pathogenic factors of non-renal acidosis (especially HCO3-induced loss of gastrointestinal tract) RTA can be diagnosed, incomplete RTA blood HCO3-, Cl- and AG are basically normal, but can appear low potassium or high Potassiumemia.

(3) The urine anion gap is positive: the electrolyte in the urine remains electrically neutral (anion and anion equivalent), the conventionally determined urine electrolytes include Cl-, K+ and Na+, and the undetermined anions (UA) include HCO3-, SO42-, HPO42-, and organic anions, etc., unmeasured cations (UC) include NH4+ (mainly NH4+), Ca2, Mg2, and the relationship between various electrolytes in urine is Cl-+UA-=Na+ +K++UC+, UA-UC=Na++K+-Cl= anion gap, urine anion gap reflects the difference of unmeasured ions, the gap is positive, indicating that urine [HCO3-+SO42- +HPO42-+organic anion]>[NH4+Ca2+Mg2], suggesting an increase in HCO3-excretion in urine or (and) a decrease in NH4+ excretion, consistent with RTA changes in urine, if the gap is negative, indicating little in urine There is HCO3-excretion, and the increase of urinary NH4+ excretion is in line with the change of urine electrolyte concentration caused by the compensatory reaction of normal kidney to renal exogenous acidosis. Therefore, after normal human NH4Cl load or renal exogenous metabolic acidosis The urinary anion gap is negative (Na++K+-C1-<0), while RTA is positive, it is worth noting that some are usually not in the urine. If the child (such as a drug) excreted from the urine can interfere with the judgment of the result, even if the urinary acidosis of the normal kidney is increased, the urinary anion gap is caused by the excretion of a large amount of ketone anion from the urine. Positive value.

3. Localization diagnosis: Firstly, according to the clinical characteristics and etiology of RTA patients, the initial positioning diagnosis impression is established, and then the following tests are used to confirm that the qualitative and localized diagnosis of incomplete RTA depends on the following tests.

(1) Test for diagnosis of pRTA: NaHCO3 filtration and excretion test: Threshold of HCO3- reabsorption of renal tubules in normal adults (HCO3-minimum plasma HCO3- concentration in urine) is about 24-26 mmol/L, infusion of NaHCO3 to plasma When the concentration increased to 28mmol/L (about 21.522.5mmol/L for children), the renal tubular reabsorption reached the highest value (TmHCO3-). When the plasma HCO3- was below the renal threshold, the filtered HCO3- was all reabsorbed by the renal tubule. There is no HCO3-exhaustion in the urine, the patient is under NaHCO3 load, the blood concentration is at different levels, then the blood and urine HCO3-concentration, glomerular filtration rate, and HCO3-renal threshold, TmHCO3- and HCO3 can be calculated respectively. - Filtered excretion fraction (FEHCO3-).

1HCO3-threshold concentration in the kidney: Normally, there is almost no HCO3-excretion in the urine under normal circumstances. Only when HCO3- is infused to increase the plasma concentration, HCO3- appears in the urine, indicating that the natural plasma HCO3- concentration is slightly lower in normal people. At the renal threshold, although the plasma HCO3- has been significantly decreased in patients with pRTA, the HCO3-excretion rate in the urine was significantly increased after supplementing or slightly supplementing HCO3-, indicating that the renal HCO3-reabsorption threshold was significantly lower in patients with pRTA;

2HCO3-filtered excretion fraction (FEHCO3-): the percentage of urinary HCO3-excretion per unit time as a percentage of glomerular filtration excess. When plasma HCO3- is below the renal threshold, FEHCO3- is zero, and after reaching the renal threshold Within a certain range, FEHCO3- increases with the increase of plasma HCO3- concentration, and the extent of renal tubular HCO3-reabsorption impairment is the plasma HCO3-FEHCO3- at normal level. The formula is: FEHCO3- =[Brain creatinine × urine HCO3-] / [urinary creatinine × blood HCO3-] × 100% pRTA patients with plasma HCO3- concentration at normal levels, FEHCO3-> 15%, severe cases can be as high as 25%, some slight Only 10% of patients, type IV RTA is below 10%, and patients with dRTA have FEHCO3- at around 3% to 5%. 3 highest HCO3-reabsorption rate (TmHCO3-): HCO3-resorption rate is calculated according to the following formula: HCO3-heavy Absorption rate = plasma HCO3-concentration × glomerular filtration rate - urinary HCO3-excretion rate, with the plasma HCO3-concentration gradually increasing, if the HCO3-reabsorption rate is unchanged for 2 consecutive times, the previous plasma HCO3-concentration For TmHCO3-blood concentration, this value is reduced in patients with pRTA, and mildly or normal in dRTA, it is worth noting that Renal tubule HCO3-maximal resorption rate = maximum reabsorption rate of single nephron tubule × total number of nephrons, therefore, in chronic renal insufficiency (reduced renal total number), TmHCO3- will also decrease, test method: 4ml/min The rate of intravenous infusion of 5% NaHCO3, the plasma concentration gradually increased, urine and blood collection every 30 to 60 minutes, plasma and urine creatinine, HCO3-concentration.

(2) Test for diagnosis of dRTA:

1 Determination of urinary ammonium excretion rate: more than half of the H+ excreted by the distal nephron excreted with NH3 to form NH4+ excreted from the urine. The urine NH4+ is a method that reflects the net acid excretion of the kidney (titration acid + NH4+-HCO3-) First, the normal urinary ammonium excretion rate of normal adults is about 40mmol/24h, and it will increase after high protein diet. When extrarenal factors cause chronic metabolic acidosis, renal tubular H+ excretion will increase, and urinary ammonium can increase. To 200-300mmol/24h, however, the urinary ammonium excretion rate at dRTA is always <40mmol/24h. It is worth noting that, like TmHCO3-, the urinary ammonium excretion rate is also affected by the total number of nephrons, and it will also decrease in chronic renal failure. ,

2 ammonium chloride (calcium) load test: This test is used for the diagnosis of incomplete dRTA. The typical dRTA has significant metabolic acidosis and there is no need to do acid load. The specific method is as follows:

A. Single-dose ammonium chloride load test: one oral administration of NH4Cl 0.1g/kg (BW), and the urine pH is measured once every hour within 3-8 hours after taking the drug;

B. Three-day ammonium chloride load test: daily oral administration of NH4Cl 0.1/kg (BW) for 3 days, repeated measurement of urine pH on day 3, C. calcium chloride load test (single day or 3 days): dose and NH4Cl load The test is the same, but the gastrointestinal irritation is small. The following reaction occurs in the small intestine after oral administration of calcium chloride, which consumes NaHCO3 in the intestine and aggravates metabolic acidosis: CaCl2+2NaHCO3CaCO3+CO2+H2O+2NaCl Normal in this experiment When significant acidosis occurs, the urine pH can be reduced to below 5.5, and the urinary ammonium excretion rate is also increased to 70mmol/24h. The urine pH of dRTA patients is >5.5, and the urine ammonium is <40mmol/24h.

3 sodium bicarbonate load test: high dose of NaHCO3 is given to increase the plasma concentration above the renal threshold, allowing a large amount of HCO3- to enter the distal nephron, where the H+ excretion function and H+ gradient maintenance ability are normal, then there is A large amount of H2CO3 is formed. The surface of the normal distal nephron epithelial cells lacks CA. H2CO3 can be excreted outside the kidney, slowly decomposes into H2O and CO2 in the urinary tract, and the urinary CO2 partial pressure (UPCO2) is significantly increased, such as distal renal tubules. When the H+ pump is dysfunctional or the back leak increases, the UPCO2 does not increase. The specific test method is:

A. Intravenous injection method: 7.5% NaHCO3 is continuously instilled at a rate of 1-2 ml/min, and the urine is urinated once every 5 to 30 minutes in the upright position after the rise of blood HCO3-, and the urine pH is measured. UPCO2, until the urine pH reaches 7.8 or more for 3 consecutive times, and PCO2 is measured by taking blood in the middle of the last two urine retention;

B. Oral method: On the test day, the water is forbidden, and NaHCO3 200mmol (1g NaHCO3=12mmol HCO3-) is taken orally. The next morning, urine and blood are taken to measure PCO2. Normal human urine HCO3- is increased to 150mmoL/L or urine pH>7.8. When UPCO2>9.31 kPa, or blood-urinary PCO2 difference>2.66 kPa, blood-urine PCO2 difference <2.0 kPa at dRTA.

4 distal nephron H+, K+ excretion stimulation test: after giving certain drug load, increase the Na+ concentration in the distal nephron, promote the formation of transmembrane potential difference in the cortical collecting duct, reduce the intracavitary potential, stimulate the place The voltage-dependent H+, K+ ion excretion, commonly used methods are:

A. Neutral sodium phosphate load test: Dissolve neutral sodium phosphate in physiological saline, inject 30mmol neutral sodium phosphate intravenously at a rate of 150mol/min, and take blood and urine for examination. Na+ in Na2HPO4 is reabsorbed. After that, HPO42- accepts one H+ to generate H2PO4-, which is not easy to return. Therefore, gradient defects will not affect the test results. When urinary phosphate reaches 20-30 mmol/L, UPCO2 is 3.99 kPa higher than BPCO2, and dRTA should be Less than 3.33 kPa;

B. Sodium sulfate load test: low-sodium diet for several days, oral administration of 9-fluorohydrocorticosterone 1mg 12h before the test, or intramuscular injection of deoxycorticosterone 5mg at 12h and 4h before the test, after 40-60min Drop 4% sodium sulfate 500ml, collect 2~3h urine after the drop, the test results are not affected by gradient defects (sulfate is not easy to return), such as urine pH>5.5, suggesting dRTA;

C. furosemide load test: furosemide inhibits the thick-segment Cl-reabsorption of the medullary ascending branch, Na+ reabsorption is thus reduced, Na+ increases into the distal nephron, and furosemide is administered intravenously at 1 to 1.5 mg/kg. After 30 minutes, the urine was repeatedly administered for examination. Furosemide increased the urinary K+ excretion in normal people, which was not only related to the negative potential generated in the cortical collecting lumen, but also related to increasing the urinary flow velocity in the collecting tube. The faster the urinary flow rate, the K+ row The more the secretion, the distal nephron H+, K+ excretion stimulation test results should be based on their own control, because this is conducive to the exclusion of renal insufficiency (reduced renal number) on certain indicators, so, in the trial Pre-existing blood and urine specimens should be routinely performed. The judgment indicators of this type of test include H+ excretion function and K+ excretion function of the distal nephron. The former includes urine pH before and after observation, urinary ammonium excretion, UPCO2 or U. -BPCO2, etc.; the latter includes urinary K+ excretion rate and K+ filtered excretion fraction, and the distal nephron acidification function is normal. After such load test, urine pH<5.5, urinary ammonium excretion rate, UPCO2, urinary acid excretion rate, Urinary potassium excretion rate and K+ filtered excretion score were compared Significantly increased; dRTA patient and H + excretion disorder performance occurs, or may not be associated with K + excretion barriers, with K + excretion disorders can be diagnosed as type RTA.

Differential diagnosis

Diagnosis of this disease should be distinguished from hyperkalemia distal renal tubular acidosis, both manifested as hyperkalemia and acidosis, but the disease in acidemia, urine pH <5.5, and if the glomerulus There was no significant decrease in filtration rate (>40ml/min). After alkalizing urine, the difference between urine and blood CO2 partial pressure was >2.66kPa (20mmHg). When urine HCO3- loss increased and blood HCO3- concentration was normal, it was easy. Confused with pRTA, the main point of identification is that the NH4+ emission is reduced in the case of acidosis, which can be identified by sodium sulfate instillation test.

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