Incomplete distal renal tubular acidosis in children

Abstract

Renal tubular acidosis (RTA) includes a group of diseases that manifest as normal anion gap hyperchloremic metabolic acidosis caused by disordered renal tubule function in the regulation of acid-base equilibrium, in the presence of normal or moderately impaired glomerular filtration rate. 1 Distal RTA (DRTA) is characterised by the inability of collecting duct to maximally acidify urine and by reduced urinary ammonium (NH4+) excretion despite coexisting metabolic acidosis. 2 In infants and children, most cases of DRTA result from loss-of-function mutations in either the ATP6VOA4 or the ATPV6V1B1 genes coding protein subunits of the H+-ATPase responsible for secreting hydrogen ions (H+) to the urine in the luminal side of type A intercalated cells of collecting duct. However, in adults, DRTA is usually acquired, secondary to systemic diseases, that is Sjögren syndrome, systemic lupus erythematosus. The term incomplete DRTA (iDRTA) is often used in the literature to describe adult patients having inability to acidify the urine but do not develop spontaneous metabolic acidosis. 3 The defect in urine acidification in iDRTA is less severe than in complete DRTA, and the glomerular filtration rate and the NH4+ excretion are greater in iDRTA than in complete DRTA patients. 4 These findings may explain

Evaluation of urinary acidification in children: Clinical utility

“…However, dRTA in children is mostly primary, caused by genetic alterations ( 41 , 42 , 46 , 47 ) and the increasing availability of genetic testing has partly relegated functional tests in this context.…”

“…Incomplete dRTA is a disorder defined by an inability to maximally acidify urine in the absence of spontaneous metabolic acidosis ( 47 ). It is a condition that has been reported mostly in adults, since its first description in 1959 ( 48 ).…”

“…In these patients, the acidification defect is milder and NH 4 + excretion is greater than in those with complete dRTA ( 49 ), a fact that may account for the absence of overt metabolic acidosis. The underlying mechanism that causes the impairment in urinary acidification is not well understood and may be dependent on the associated disorders ( 47 ).…”

“…The diagnosis of incomplete dRTA can be difficult to perform, since, by definition, serum acid-base balance parameters (including HCO 3 − ) are normal. Incomplete dRTA can be suspected in case of a persistently high UpH, but its confirmation requires the measurement of UpH and UNH 4 + in the same functional tests used to identify complete dRTA ( 42 , 46 , 47 , 50 ). However, a low spontaneous UpH is usually considered to rule out an acidification defect without the need for functional tests ( 41 , 47 ).…”

Results of a Gene Panel Approach in a Cohort of Patients with Incomplete Distal Renal Tubular Acidosis and Nephrolithiasis

“…Incomplete dRTA has been reported to be frequent in “primary” osteoporosis, particularly in men [22, 23], and in calcium nephrolithiasis. In addition, up to 13% of recurrent “idiopathic” calcium stone formers have idRTA [16, 18, 24, 25].…”