Distal renal tubular acidosis in children
Introduction
Brief introduction of distal renal tubular acidosis in children Renal tubular acidosis (RTA) is a clinical syndrome caused by the reabsorption of HCO3- by hydrogen ions and/or proximal tubular epithelial cells in distal renal tubular epithelial cells. Normal high chloride metabolic acidosis, renal calcification, and kidney stones are characteristic. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: rickets, kidney stones, uremia, neurological deafness
Cause
Causes of distal renal tubular acidosis in children
(1) Causes of the disease
Primary dRTA is autosomal dominant or recessive, and secondary dRTA is often caused by other diseases affecting tubular function, which can be seen in hypergammaglobulinemia, primary hyperparathyroidism, Vitamin D poisoning, transplanted kidney rejection, medullary sponge kidney, obstructive nephropathy, idiopathic hypercalciuria renal calcification, Wilson disease, loss of salt congenital adrenal hyperplasia, drugs and toxins cause kidney damage (such as lithium , amphotericin B, toluene, digoxin, etc.).
(two) pathogenesis
1. Pathogenesis: The main defect of dRTA is the deficiency of H+ function in distal tubules. There is an intercalated cell in the epithelial cells of renal cortical collecting duct, and there is H+-ATPase (proton pump) on the membrane. It can secrete H+, H+ binds to NH3 and NaHP04 in the lumen, and is excreted in the form of NH+4 and H2PO-4. The medullary collecting tube has the function of absorbing sodium and excreting potassium. The dysfunction of the cell can lead to insufficient H+ secretion, and the following mechanisms are currently considered:
(1) Secretion defect: H+-ATPase dysfunction, tubular epithelium can not secrete H+.
(2) Gradient defect: Cell membrane defects increase H+ permeability, and H+ reverses into tubular epithelial cells.
(3) rate-dependent defect: the proton pump secretion H+ rate decreases.
(4) Voltage-dependent defect: the negative potential difference in the lumen is reduced, there are two kinds of gene mutations in the primary dRTA, and the autosomal dominant inheritance mainly involves the cell Cl-HCO3-anion exchange transporter ( AE1) gene mutation, euchromatin recessive inheritance involves the defect of the proton pump B subunit (ATP6B1).
2. Pathophysiology: Under normal circumstances, the distal renal tubules and collecting ducts are secreted by H+-Na+ to secrete H+ to regulate the acid-base balance. In this disease, the distal renal tubules are H+ disorders, H+ accumulates in the body, and urine NH Reduced excretion of +4 and titratable acid (TA), causing metabolic uric acidosis and acidosis, resulting in K+-Na+ exchange predominance due to reduced exchange of H+-Na+ in the distal tubule, resulting in loss of large amounts of K+, resulting in hypokalemia Symptoms, while Na+ absorption decreases, causing hyponatremia and secondary aldosterone increase to increase Na+ and Cl- absorption, Cl- retention causes hyperchloremia, long-term hypokalemia causes distal renal tubular concentration Loss, polydipsia, polyuria, persistent acidosis cause the body to use the bone buffer system, calcium in the bone, phosphorus free into the blood, increased urinary calcium excretion, lower blood calcium, thus stimulating parathyroid hormone secretion, promote Osteolytic destruction, reduce bone formation, increase urinary calcium, inhibit phosphorus reabsorption, increase urinary phosphorus, lower blood phosphorus, alkaline urine contributes to increased concentration of urinary calcium, urinary phosphorus forms kidney stones and kidney Substantial calcium salt deposition, which in turn causes kidney Interstitial damage, eventually leading to kidney failure, calcium citrate is an important factor dissolved, acidosis, citrate excretion decreased reabsorption increase, promote renal calcification.
Prevention
Prevention of distal renal tubular acidosis in children
Secondary RTA can be seen in tubulointerstitial nephritis, primary hyperthyroidism or hyperparathyroidism, vitamin D poisoning, cirrhosis, chronic active hepatitis, lithium poisoning, etc., therefore, active treatment and prevention of the above diseases A reliable method for preventing secondary RTA.
Complication
Pediatric distal renal tubular acidosis complications Complications, kidney disease, uremia, neurological deafness
Nutritional disorders, rickets or osteomalacia, partial renal calcification or renal calcification, late development into uremia, a small number of neurological deafness.
Symptom
Symptoms of distal renal tubular acidosis in children Common symptoms Metabolic acidosis slow growth polyuria diarrhea polydipsia kidney stones hematuria dehydration kidney calcification constipation
Clinically, it can be divided into infant type and infant type. The former has a disease within a few months after birth. It is more common in male infants and is autosomal recessive. The latter often develops symptoms after 2 years of age, and is more common in women. Sexual inheritance, the main clinical features of dRTA are:
1. Age of onset: Primary dRTA can have clinical manifestations after birth, but the typical symptoms are more than 2 years old.
2. Chronic acidosis: growth and development and anorexia, nausea, vomiting, diarrhea, constipation and other chronic metabolic acidosis, sometimes growth is the only performance, incomplete dRTA can be acid-free and only low potassium, Muscle weakness or kidney calcification.
3. Urine concentrating function is reduced, polydipsia, polyuria, dehydration for unknown reasons, dehydration heat, shock, due to hypophosphatemia caused by decreased urine concentration.
4. Hypokalemia: low potassium performance such as muscle weakness, weakness and even periodic spasm is prominent. It is caused by hypokalemia caused by decreased H+ secretion. In severe cases, it affects the heart, and causes severe arrhythmia and circulatory failure such as premature contraction.
5. Caries manifestations: bone decalcification, bone softening, skeletal deformity, anterior sacral wide and closed delay and other rickets manifestations, vitamin D treatment is ineffective.
6. Renal calcification and kidney stones: Kidney stones are common in older children and adults. They can occur simultaneously or separately with renal calcification, and may be accompanied by hematuria, hydronephrosis and urinary tract infections. Calcium is mostly calcium phosphate, and a few are oxalic acid. Calcium and struvite, pyuria often persist, may be related to renal calcification.
7. Several special dRTA
(1) Both proximal renal tubular acidosis and distal renal tubular acidosis (type III): found in infants, can occur as early as 1 month after birth, with the increase of age, HCO3- loss can be alleviated.
(2) Incomplete dRTA: may be associated with renal calcification but no metabolic acidosis. Although the urine acidification disorder, but more NH + 4, less TA, most of the screening of the complete dRTA family found, There are also many cases of sporadic cases or secondary to other diseases.
(3) dRTA with deafness: autosomal recessive inheritance, both men and women can be sick, the time of deafness varies from neonatal to older.
(4) Transient renal tubular acidosis: first reported by Lightwood in 1935, acidosis is transient, may be caused by some unrecognized environmental factors, such as vitamin D poisoning, sulfa drug kidney damage or mercury poisoning, etc. More self-healing at around 2 years old.
(5) secondary dRTA: seen in a variety of systemic diseases or kidney disease, the patient also has the clinical manifestations of the primary disease, the typical diagnosis of this disease is not difficult, according to growth and development, polydipsia, polydipsia, polyuria, Refractory rickets and kidney calcification, kidney stones and other manifestations, blood biochemical examination has five low and two high characteristics, namely hypophosphatemia, hypokalemia, hypocalcemia, low blood sodium and low carbon dioxide binding (or low serum pH) As well as high blood chlorine, high serum alkaline phosphatase, and in the case of acidosis, urine pH>6.0 can determine the diagnosis, the following diagnostic tests are mainly used for the diagnosis of incomplete dRTA with insignificant acidosis, and for understanding dRTA is a secreted H+ defect, a voltage-dependent defect (high K+ dRTA), or a gradient defect (reverse leak type).
Examine
Examination of distal renal tubular acidosis in children
1. Urine pH: Urine pH reflects the amount of H+ in urine. DRTA, although blood pH is <7.35, urine pH is still 6.0, and can be as high as 6.5,7.0 or higher. pH measurement, pH test paper and urine must be used to determine urine pH. The results measured by the liquid analyzer are not accurate enough. Only the urine pH has certain limitations. The urine pH <5.5 does not indicate that the uric acid function must be intact. If the child has a NH3 disorder, the small amount of H+ cannot be combined with NH3 to form NH+. 4, urine pH can still be <5.5, so urine pH and urine NH + 4 should be measured simultaneously, to comprehensive analysis and judgment.
2. Determination of urine titratable acid and urine NH+4: Most of the H+ secreted by the distal renal tubules is combined with NH3 to form NH+4, and the other part is discharged as titratable acid. Therefore, urine can titrate acid and NH. The sum of +4 represents the net acid excretion of the kidney. When the acidity in the body increases, the normal human urine pH can be <5.5, and the urine titratable acid and NH+4 excretion rate can reach 25mol/min and 39mol/min, respectively. When renal tubular acidosis occurs, both are significantly reduced.
3. Urine electrolytes and urinary anion gap: most of dRTA have increased urinary sodium excretion and increased urinary calcium, urine Ca/Cr>0.21, 24h urinary calcium>4mg/(kg·d), urinary anion gap=Na++K+-Cl - It can reflect the urine NH+4 level. When it is positive, it indicates that the urine NH+4 excretion is reduced.
4. Blood gas analysis and electrolytes: The typical change of dRTA is normal metabolic acidosis with hyperchloritemia anion gap. Incomplete dRTA may be characterized by compensatory metabolic acidosis or normal, anion gap (anion gap, AG)=Na++K+-(C1-+HCO3-), normal 8~16mmol/L, the increase indicates the accumulation of acidic products such as inorganic acid radicals (such as nitrate, sulfate) or (and) organic acid ions in the body. When RTA is used, C1-compensates for the decrease of HCO3-, so AG is normal, and the decrease of blood potassium is also an important manifestation of dRTA. Even the only manifestation of incomplete dRTA, blood sodium and blood calcium can be normal or decreased.
5. Detection of urinary carbon dioxide partial pressure: After administration of sodium bicarbonate or neutral phosphate in normal people, HCO3- or HPO42- reaches the distal tubule, and the former combines with H+ to form H2CO3; the latter combines with H+ to form H2PO4-, and then And HCO3- generate H2CO3, and then produce CO2, so that the partial pressure of urinary CO2 is increased. Due to hydrogen secretion disorder, urinary CO2 does not rise during dRTA, the difference between urinary CO2 partial pressure and blood CO2 partial pressure is <20mmHg, normal person>30mmHg, 6.24 h uric acid dRTA is often reduced, imaging examination can understand the bone disease and found kidney stones, ultrasound to understand whether the kidney is calcified and stones, ECG examination can find electrolyte disorders, such as hypokalemia and heart damage.
Diagnosis
Diagnosis and diagnosis of distal renal tubular acidosis in children
diagnosis
1. NH4Cl load test: NH4Cl load test to test the tubular hydrogen secretion function by taking acidic drugs to cause metabolic acidosis in the body, mainly for the diagnosis of light or incomplete dRTA.
(1) Three-day method: oral ammonium chloride [0.1g / (kg · d), divided into 3 times] or calcium chloride [0.5g / (kg · d), divided into 3 times] 3 days, when blood gas Analysis showed pH <7.35, HCO3-<20mmol/L, urine pH still >5.5 indicates the presence of renal tubular acidification dysfunction, suggesting that dRTA, severe acidosis should be avoided in the test, blood HCO3- should not be lowered too low (< 15mmol/L).
(2) A simple method of single agent: oral ammonium chloride (0.1g / kg) within 30min, followed by 6h urine test urine pH, because this dose of ammonium chloride can reduce HCO 3-4 ~ 6mmol / L, so such as urine pH >5.5 is positive.
2. Sodium sulfate test: The principle is that in the case of sodium storage factor, the instillation of sodium sulfate increases the Na+ reaching the distal nephron and is effectively absorbed, while the SO is absorbed in the negative ion, which increases the intraluminal The negative potential increases the potential difference between renal tubular epithelial cells and the lumen, and the negative potential promotes the excretion of H+ (mainly increases the excretion of urine NH+4). If there is no response to sodium sulfate instillation, the urine cannot be acidified, indicating H+ secretion defect, test method: oral storage of salt hormone 9-fluorocortisone 1mg 12h before the test, or intramuscular injection of deoxycorticosterone 5mg before the test 12h and 2~4h before the test, if using a low-salt diet before the test The results were more correct. 4% Na2SO4 1000ml was intravenously infused within 40~60min, and 30mEq of NaHCO3 was added per liter to avoid poisoning due to rapid perfusion of Na2SO4. The urine specimen should be collected for 3 hours after perfusion. The normal human urine pH should be Drop to below 5.5 (usually <5.0), H+ barrier and voltage-dependent type >5.5, but back-leakage (gradient defect) can also be <5.5.
3. Furosemide test: intramuscular furosemide 2mg/kg (<40mg/kg), decreased myocardial cl-absorption, increased distal Cl tube and collecting tube Cl-, increased negative charge, and the same effect as infusion of Na2SO4 The method is simple, sensitive and reliable.
4.NaHCO3 load test: reflect the ability of the collection tube to secrete hydrogen and maintain the H+ gradient. When there is dysfunction of H+ pump or hydrogen secretion due to voltage-dependent defects, the lack of HCO3- in the urine makes the pressure of urine CO2 not rise, urine The difference of blood CO2 partial pressure <20mmHg, back leakage type can be >30mmHg, method: intravenous injection of 1mmol / L NaHCO3, 3ml / min, every 15 ~ 30min upright position urination once, urine pH and CO2 partial pressure, when When the urine pH was > 7.8 for 3 consecutive times, the blood was taken from the second urination to check the CO2 partial pressure, and the difference between the urinary CO2 partial pressure and the blood CO2 partial pressure was calculated.
5. Neutral phosphate load test: The principle is the same as the NaHCO3 load test, and is also used to distinguish the back leak type dRTA.
Differential diagnosis
dRTA should be clinically differentiated from glomerular acidosis, various rickets, and familial periodic paralysis.
1. Glomerular acidosis: previous history of kidney disease, obvious urinary abnormalities, often accompanied by anemia and hypertension, blood Cr-normal and increased serum creatinine, blood and urine pH consistency.
2. Familial periodic paralysis: family history, more common in men, normal urine test, no acidosis, often full of meals before the attack, high sugar diet, strenuous exercise, trauma, infection and other incentives, 3. familial hypophosphatemia Sexual anti-vitamin D rickets are characterized by signs and symptoms of rickets, but no acidosis and other dRTA manifestations.
