Distal renal tubular acidosis

PURPOSE OF REVIEW: Research in the past several years has led to the understanding of numerous genetic mutations that lead to inheritable forms of distal renal tubular acidosis (dRTA). Most of these mutations affect the physiology of the A-intercalated cells of the renal cortical collecting duct. These include mutations of genes encoding carbonic anhydrase II, kidney anion exchanger 1, and different subunits of the H+-ATPase proton pump. Genetic defects in any one of these components may impair renal acidification and thereby result in persistent acidosis, failure to thrive, and nephrocalcinosis. RECENT FINDINGS: The present review provides a summary of the most recently identified genetic mutations resulting in a dRTA phenotype and, when possible, describes a mechanism. Most causes of dRTA are due to loss of function or inappropriate targeting of transporters. SUMMARY: The collaboration of clinicians, geneticists, and renal physiologists has enabled us to better understand at the cellular level the different mechanisms leading to dRTA. Such information should lead to earlier diagnosis and treatment, thereby minimizing the irreversible complications affecting patients with this or similar diseases.     

Distal renal tubular acidosis with hereditary spherocytosis

Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with coexistence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.     

Proximal renal tubular acidosis associated with glycogen storage disease, type 9

A 2 1/2-year-old Japanese boy with glycogen storage disease, type 9, developed proximal renal tubular acidosis (RTA). The RTA significantly improved in response to cornstarch therapy, implying a direct causal relationship between subtle metabolic derangements in glycogen storage disease, type 9, and proximal RTA.     

Concomitant hypercalcemia and hyperammonemia associated with distal renal tubular acidosis

We describe an infant with concomitant hypercalcemia and hyperammonemia associated with nonanion gap metabolic acidosis secondary to distal renal tubular acidosis (dRTA). The levels of both serum calcium and ammonia rapidly normalized with the correction of dehydration and metabolic acidosis. To the best of our knowledge, there has been only one previous case report of concomitant hypercalcemia and hyperammonemia associated with dRTA that has been reported in the literature. We describe the causes and emergent management of hypercalcemia and review the possible mechanisms of this rare association with dRTA.     

Hypokalemic periodic paralysis and distal renal tubular acidosis associated with renal morphological changes

We report an unusual case of 5-yrs-old girl presenting with recurrent episodic weakness with documented hypokalemia, polyuria and failure to thrive. The child was finally diagnosed as having distal renal tubular acidosis. Imaging studies revealed associated hypoechoic spaces in renal medulla. Long term treatment with alkali and maintenance of normokalemia lead to regression of these morphological changes.     

Distal renal tubular acidosis in infancy: a bicarbonate wasting state.

Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.     

Hyperammonaemia with distal renal tubular acidosis

The case is reported of an infant with hyperammonaemia secondary to severe distal renal tubular acidosis. A clinical association between increased concentrations of ammonia in serum and renal tubular acidosis has not previously been described. In response to acidosis the infant''s kidneys presumably increased ammonia synthesis but did not excrete ammonia, resulting in hyperammonaemia. The patient showed poor feeding, frequent vomiting, and failure to thrive, but did not have an inborn error of metabolism. This case report should alert doctors to consider renal tubular acidosis in the differential diagnosis of severely ill infants with metabolic acidosis and hyperammonaemia.

     

Type I primary hyperoxaluria associated with type I renal tubular acidosis

An 8-year-old boy who had suffered from recurrent stone formation since the age of 4 years, was admitted as an emergency due to anuria for a half day on November 20, 1986. Kidney-ureter-bladder film showed that the urethra was obstructed by a stone, and emergent cystoscopy was performed to remove it. He is the product of consanguinous marriage, his parents being first cousins. There was no family history of renal stone. Laboratory investigations showed hypokalemic, hyperchloremic metabolic acidosis. The ammonium chloride loading test revealed inability to acidify the urine and a markedly decreased excretion of titrable hydrogen ion and ammonium ion in the urine. These results indicate that this is a case of Type I renal tubular acidosis. His 24-hour urinary excretion of oxalate and glyoxylate were also markedly increased. There were no underlying causes leading to the development of secondary hyperoxaluria. These results also establish the diagnosis of Type I primary hyperoxaluria. The patient then received regimens of Polycitra 1ml/kg/day and Vitamin B6 50mg/day for 4 months. However, urinary stone developed again in this patient 4 months later. To our knowledge, Type I primary hyperoxaluria in association with Type I renal tubular acidosis has not been previously reported.     

Evaluation of renal tubular acidosis

Renal tubular acidoses (RTA) comprises of a group of disorders characterized by a low capacity for net acid excretion and persistent hyperchloremic, metabolic acidosis. The RTAs are classified into chiefly three types (types 1,2 and 4) based on clinical and laboratory characteristics. Correct diagnosis involves careful evaluation, including exclusion of other entities causing acidosis. A variety of tests are required to be administered in a stepwise fashion for the diagnosis and characterization of RTA.     

Self-limited neonatal familial hyperparathyroidism associated with hypercalciuria and renal tubular acidosis in three siblings

Three siblings with neonatal familial hyperparathyroidism diagnosed at age 4 months, 2 months, and 5 days, respectively, were treated. Hypercalciuria, nephrocalcinosis, and renal tubular acidosis were present in each child. In all three, there were higher responses of serum parathyroid hormone to serum calcium and higher elevation of serum calcium with oral calcium loading. The metabolism of vitamin D and calcitonin seemed to be intact. Hypercalcemia associated with the abnormal response of parathyroid hormone secretion disappeared when the children passed the age of approximately 2 years, although renal tubular acidosis and nephrocalcinosis remained. An autosomal recessive inheritance seems likely.     

Increased renal threshold of bicarbonate due to carbon dioxide retention associated with proximal renal tubular acidosis

We report a neonate who manifested type II (proximal) renal tubular acidosis (RTA). Hypoventilation secondary to hypothalamic dysfunction led to carbon dioxide retention. The consequent changes in acid base regulation are detailed and discussed.     

Proximal renal tubular acidosis in a child with type 1 glycogen storage disease

A 6 1/2-year-old Japanese girl with type 1 glycogen storage disease developed a profound metabolic acidosis refractory to bicarbonate renal tubular acidosis and hyperphosphaturia. There was no evidence of distal tubular dysfunction.