Renal tubular acidosis is a type of tubulopathy, which is accompanied by an imbalance of electrolytes due to a failure of the excretion of hydrogen ions (I), a violation of the reverse absorption of bicarbonates (II), abnormal production of aldosterone or interaction with it (IV). Type III is casually rare. The course may be asymptomatic or with manifestations of electrolyte disorders: weakness, nausea, bone deformities. Diagnosis of renal acidemia is based on measurements of urine pH and electrolytes, genetic analysis data, ultrasound. Treatment involves restoring the acid-base balance: alkalizing agents, elimination of hypo-hyperkalemia, etc.
ICD 10
N25.8 Other disorders caused by dysfunction of the renal tubules. Renal tubular acidosis of BDU.
Meaning
Renal tubular acidosis (RTA, tubular, tubular, renal tubule acidosis) is defined by nephrologists as a syndrome in which the excretion of hydrogen ions or the reabsorption of filtered bicarbonate is disrupted, which leads to chronic metabolic homeostasis disorder with hypochloremia. The most common variant is the generalized type of the disease, the second place is occupied by the lesion of the distal tubules of the nephrons, the form with pathology of the proximal tubules is less common. The exact level of morbidity is difficult to track, since latent forms are often not recognized. Hereditary renal tubulopathies are less common than acquired ones.
Causes
The main cause of pathology is the loss of the ability of the kidneys to acidify urine. There are many conditions that cause acidosis of the renal tubules, in some diseases distal parts are affected, in others – proximal, sometimes the pathology is combined or caused by a number of disorders associated with aldosterone. The characteristic reasons for each type are:
- Classic (Type 1). In congenital conditions, the acid-base balance is altered by mutations of the genes ATP6V1B1, ATP6V0A4 S1C4A, which initiates distal renal tubular acidosis (Butler-Albright syndrome or disease). The secondary form is the result of taking medications, kidney transplantation and certain diseases (sickle cell anemia, systemic lupus erythematosus, Sjogren’s syndrome). Medullary spongiform kidney, cirrhosis and chronic obstructive uropathy are also considered as potential triggers.
- Proximal (Type 2). Proximal renal tubular acidosis accompanies Fanconi syndrome, nephropathy on the background of multiple myeloma, as a complication develops with prolonged administration of acetazolamide, sulfonamides, ifosfamide, tetracycline. Less often it has a different etiology: vitamin D deficiency, chronic hypocalcemia with secondary hyperparathyroidism, a number of hereditary pathologies: fructose intolerance, oculocerebrorenal syndrome, cystinosis.
- Generalized (Type 3). Renal tubular acidosis is caused by a deficiency of aldosterone or a violation of its interaction with receptors. Taking potassium-preserving diuretics, cyclosporine, heparin, and other drugs is considered as the root cause of the violation. Of nephrological diseases, tubulopathy is provoked by CKD, chronic interstitial nephritis, HIV infection with kidney damage, in urology – all situations associated with urinary tract obstruction. Tubular renal acidosis (IV) causes autoimmune dysfunction (SLE), sickle cell anemia, diabetes.
The aggravating factors include diarrhea, poisoning with heavy metal salts, surgical interventions on the gastrointestinal tract with the installation of drains that remove the bases together with liquid contents or secret (for example, pancreas). Prolonged diarrhea and increased stool volume lead to additional loss of bicarbonates. Taking certain medications – calcium chloride, magnesium sulfate, cholestyramine disrupt homeostasis, in combination with renal pathology aggravate the condition.
Pathogenesis
In the first type, there is a failure of secretion or absorption of hydrogen ions in the distal tubules, which causes high acidity of the blood with hyperchloremia. At the same time, the ability of the kidneys to maintain a normal gradient of hydrogen ion concentration between blood and tubular fluid is impaired. Hypothetically, this may be due to a decrease in the activity of cells secreting hydrogen ions, a defect in the energy mechanism, a deficiency in transportation systems, pathological changes in the A and P cells of the nephron responsible for the production of H+. Hypercalciuria, reduced excretion of citrates leads to nephrolithiasis.
In type II, there is dysfunction of the proximal tubules with impaired bicarbonate reabsorption, HCO3-, but the acidogenetic function of the distal structures of the nephron remains intact. The pathogenesis of proximal tubular acidosis is explained by a deficiency or complete absence of carbonic anhydrase I-(C), a decrease in the activity of carbonic anhydrase 1-(B) in blood and/or mitochondrial HCO3-ATPASE in the epithelial membranes of the proximal tubules. Mechanisms of osteomalacia and osteopenia (including rickets in children) include hypercalciuria, hyperphosphaturia, vitamin D dysmetabolism.
Type IV initiates aldosterone deficiency or immunity of distal tubules to it. An imbalance of electrolytes is characteristic: sodium, potassium, chlorine and bicarbonate. Hypokalemia contributes to a decrease in ammonia secretion, leading to metabolic acidemia. This disorder – the most common variant of renal distal tubulopathy – has a secondary or sporadic character in relation to the violation of the axis of the renin-aldosterone-renal system.
Classification
Renal tubular acidosis (IV), according to some experts in the field of nephrology, does not have a clinical syndrome similar to other variants of renal tubulopathies. It was included in the classification because it is associated with a weak shift of equilibrium to the acidic side due to a physiological decrease in ammonium excretion in the proximal tubules. The third type is often not added to the systematization, since only a few dozen cases have been registered in the world. Types of renal tubular disorders with acidemia:
- The first (tubular classical, distal). The disease is caused by a decrease in the production of hydrogen molecules by distal tubules, increased excretion of HCO3- . Often accompanied by nephrocalcinosis, stone formation. There are congenital (autosomal dominant, autosomal recessive with hearing loss, autosomal recessive without hearing impairment) and acquired variants.
- The second (tubular proximal). Occurs due to pathology of the proximal renal tubes. Acidemia is less pronounced due to the preservation of distal intercalated acid-producing cells. The main feature of the syndrome is the demineralization of bone tissue (osteomalacia, rickets) due to depletion of phosphate metabolism. There are autosomal recessive, autosomal dominant, sporadic (transient childhood and persistent adult) renal acidosis.
- The third (tubular juvenile). It is a combination of the classical and the second type of renal acidemia. Autosomal recessive pathology associated with a genetic mutation. It is registered extremely rarely. Tubulopathy is supported by an inherited deficiency of carbonic anhydrase 2.
- The fourth (tubular hyperkalemic). Caused by deficiency or resistance to aldosterone. Concomitant hyperkalemia leads to pathological processes in the myocardium. Renal function is not impaired or suffers slightly. The condition occurs mainly in adults, in most cases it has a secondary character.
Symptoms
Symptoms are variable, associated with causal factors. With primary genetically determined distal renal tubular acidosis, pallor of the skin, muscle hypotension, polyuria and, as a consequence, polydipsia are detected in children before the appearance of detailed clinical manifestations. In some cases, hereditary pathology is accompanied by hearing loss, ocular abnormalities. Body temperature is slightly elevated, there is a tendency to constipation. Sometimes the only symptom is a lag in physical development from peers.
In severe cases, without treatment, approximately upon reaching the age of 2, deformation of the bones of the skeleton occurs. By the age of 3-4, if the pathology is not diagnosed and the child does not receive treatment, growth retardation and intellectual abilities progress. The bones of the lower extremities are X-shaped, the chest becomes barrel-shaped, the head looks disproportionately large. Pathological fractures, bone pain, decreased muscle tone indicate the progression of the pathological process.
Reactions from the nervous system with long-term metabolic disorders are irritability, aggressiveness. Typically, early onset of puberty. Against the background of developed nephrocalcinosis, recurrent urinary tract infections are joined, which manifest themselves with cuts with frequent urination, lumbar pain, fever. Nephrolithiasis and independent discharge of concretions are accompanied by renal colic, nausea, vomiting.
The proximal type of tubular renal acidosis has similar symptoms, but ricketlike changes develop earlier, and nephrocalcinosis is detected much less frequently. The second variant of tubulopathy is characterized by a more severe course, without treatment, the pathology can progress to an acidemic coma. Typical is exicosis (dehydration) with fainting, severe cyanosis, shortness of breath. The hairline undergoes a change: the hair is prickly, hard, with appropriate therapy it becomes softer. Sometimes the pathological condition passes on its own without any treatment by 3-10 years.
In adults, electrolyte disorders are asymptomatic or give rise to milder symptoms. Hypokalemia causes muscle weakness, decreased reflexes, paralysis. Manifestations from the musculoskeletal system include osteomalacia, pain. Such signs are more typical for proximal renal acidosis, but they can also be determined with dysfunction of the distal tubules. The fourth type is more often asymptomatic, diagnosed with the detection of minor acidemia. There is a risk of cardiac arrhythmias, especially if the condition is accompanied by severe hyperkalemia.
Complications
Without proper treatment, chronic blood acidity is complicated by growth retardation, nephrolithiasis, fractures. Patients have recurrent pyelonephritis, nephrocalcinosis, gradual loss of renal function up to the terminal stage of CRF. The main consequence of distal tubulopathy is hypokalemia, which is accompanied by arrhythmia, which often causes death. In children, the lack of therapy leads to severe bone deformities, mental retardation. Severe hyperkalemia (IV) is complicated by changes in blood pressure, bronchospasm, intestinal colic.
Diagnostics
The leading role in the diagnosis belongs to laboratory tests. Instrumental studies are prescribed to determine the underlying pathology in secondary renal tubular acidosis. If there are hereditary diseases in the genus, a geneticist’s consultation is necessary, with signs of obstructive nephropathy, a urologist’s examination is required. In children with hereditary forms accompanied by congenital deafness, a surdologist takes part in the examination. The diagnostic algorithm is individual, the results of analyses and instrumental methods are variable.
- Distal variant. In the classical variant of renal tubular acidosis, the urine reaction is alkaline, exceeds 5.5-6. HCO3 plasma before treatment is less than 15 mmol / l, typically a decrease in the excretion of ammonium and citrate, hypokalemia. The excretion of bicarbonates is not higher than 3%, the plasma content is more than 20 mmol / l. In controversial cases, ammonium chloride is administered, in the absence of pathology, the pH is less than 5.2. Screening of the ABB is carried out, the biochemistry of urine is examined: acids, ammonium, Ca, phosphates, sugar, protein, the ratio of calcium / creatinine and phosphates / creatinine is determined. Blood biochemistry is evaluated – chlorides, K, Ca, Na, P, creatinine.
- The proximal variant. The pH of urine is less than 5.5, normal parameters of citrate and ammonium excretion, bicarbonate excretion is more than 15-20% (in plasma its content exceeds 20 mmol / liter), hypokalemia. For testing, the introduction of sodium bicarbonate is used, the confirming criteria are pH above 7.5, the excretion of bicarbonate above 15%. KSHS is evaluated, the biochemical composition of daily urine is examined: calcium, phosphates, sugar, protein fractions, the ratio of creatinine to calcium and phosphate. Determine the content of K, Na, chlorides, Ca, P, glucose and creatinine in the blood.
- Generalized version. In addition to identifying the underlying condition that led to renal tubular acidosis (IV), the diagnosis is confirmed by a study of the K level (hyperkalemia is more common), the determination of HCO3- (mild metabolic acidosis, concentration of 18-22 mmol/ l, urine pH below 5.5). Depending on the pathogenetic factor, the levels of aldosterone, cortisol, and renin may change. In all cases, the plasma anion gap index is calculated, this allows us to estimate the concentration of residual plasma anions: Na+ – (Cl- + HCO3).
Instrumental diagnostics includes ultrasound of the kidneys and bladder, CT and MRI to exclude obstructive uropathies, nephrolithiasis. With tubular acidosis (I), the pathology of the kidneys is always determined on sonograms, it is uncharacteristic for the proximal type. On radiographs in children, rickety changes in the skeleton, damage to the tubular bones of the shins, hands are visualized. Bone mineral density is determined by densitometry. Demineralization of bones without obvious rickets or osteomalacia accompanies types 1 and 4, vitamin D-associated rickets, osteomalacia are characteristic of 2 variants.
Differential diagnosis is carried out between possible types of acid-base balance disorders, renal pathologies of a different genesis. Fanconi syndrome has similar manifestations with proximal and distal tubular acidosis. Genetically determined forms of distal renal acidosis are distinguished with pseudohypoaldosteronism, primary hyperoxalaturia, nephrocalcinosis of a different genesis. Sometimes differentiation with renal insufficiency, diabetes mellitus, salicylate nephropathy is required.
Treatment
Treatment is aimed at correcting the imbalance of electrolytes (potassium, calcium, phosphates), preventing complications, correlates with the type of pathology. Operations are performed only to correct severe deformities of the bones. The main measure remains the appointment of alkalizing therapy, without treatment for tubular renal acidosis in children, growth slows down, mental development suffers. Alkaline agents help to achieve a relatively normal concentration of plasma bicarbonates, correct violations.
Drug therapy
Treatment of classical renal tubular acidosis is necessary to support growth in children, eliminate bone changes, and prevent the accumulation of calcium by interstitial tissue. Sodium bicarbonate is prescribed, potassium-sodium hydrogen citrate. In osteopathy, active metabolites of vitamin D3 are used, which requires caution due to the risk of hypercalciuria. Therapy of the proximal variant includes oral administration of potassium citrate. In case of resistance, hydrochlorothiazide is added to the scheme. In the juvenile version, sodium citrate or potassium citrate is used. Doses are selected individually.
The main treatment of the fourth option is aimed at replenishing or replacing aldosterone. Patients are advised to exclude foods rich in potassium from their diet. Additionally, NaCl is administered against the background of monitoring for blood, aldosterone, plasma renin. It is necessary to stop taking medications that support hyperkalemia, to treat the underlying pathology (HRT with mineralocorticoids). Diuretics (furosemide, hydrochlorothiazide) are prescribed. In the absence of a response to treatment, fludrocortisone, sodium bicarbonate are used to compensate for acidemia and increase excretion of K.
Prognosis and prevention
Timely treatment improves the outcome for all cases. In distal tubulopathy, taking medications before the addition of nephrocalcinosis favorably affects the prognosis. The proximal transient form can be stopped independently with age, but alkalizing therapy ensures normal growth and prevents demineralization, rickets, in adults treatment prevents the development of osteomalacia. The prognosis of renal acidosis (IV) is determined by the severity of the underlying disease. Patients are monitored, blood electrolytes are monitored every 12 weeks, kidney ultrasound is performed once every 6 months.
There are no preventive measures for congenital pathology, with a burdened family history, a geneticist’s consultation is indicated. Timely treatment of urological and nephrological diseases, which can lead to severe forms of tubulopathy, is important. Patients with renal tubular acidosis on the background of uremia (renal insufficiency with impaired glomerular filtration rate, high creatinine, urea levels) require special supervision. Patients receiving adequate treatment usually do not have pronounced symptoms, many of them can lead a normal life.
