Clinical and laboratory approaches in the diagnosis of renal tubular acidosis

Abstract

In the absence of a gastrointestinal origin, a maintained hyperchloremic metabolic acidosis must raise the diagnostic suspicion of renal tubular acidosis (RTA). Unlike adults, in whom RTA is usually secondary to acquired causes, children most often have primary forms of RTA resulting from an inherited genetic defect in the tubular proteins involved in the renal regulation of acid-base homeostasis. According to their pathophysiological basis, four types of RTA are distinguished. Distal type 1 RTA, proximal type 2 RTA, mixed-type 3 RTA, and type 4 RTA can be differentiated based on the family history, the presenting manifestations, the biochemical profile, and the radiological findings. Functional tests to explore the proximal wasting of bicarbonate and the urinary acidification capacity are also useful diagnostic tools. Although currently the molecular basis of the disease can frequently be discovered by gene analysis, patients with RTA must undergo a detailed clinical study and laboratory work-up in order to understand the pathophysiology of the disease and to warrant a correct and accurate diagnosis.

Treatment and long-term outcome in primary distal renal tubular acidosis

“…The excess acid in the blood is mainly buffered by the bone, leading to release of calcium from the skeleton, which, together with impaired tubular calcium reabsorption in acidosis, results in hypercalciuria that can be associated with nephrocalcinosis and/or nephrolithiasis (9). Faltering growth is a common presenting symptom in children with dRTA (10).…”

Incomplete distal renal tubular acidosis in children

“…In the absence of clinically appreciable spontaneous metabolic acidosis, the following tests have been used to assess whether the kidneys retain a normal ability to secrete H+ and to acidify the urine. 1 Exogenous acid load. Several acidifying agents, such as ammonium chloride (NH4Cl), calcium chloride (0.2 g/kg) or hydrochloride arginine (150 mEq/m 2 of H+, iv).…”

Review of the Diagnostic Evaluation of Normal Anion Gap Metabolic Acidosis

“…The combination of both increased distal Na + delivery, and the mineralocorticoid effect will stimulate distal H + secretion by both an increase in the luminal electronegativity and a direct stimulation of H + secretion. Normal subjects will lower urine pH to values below 5.5 with either maneuver [39,42] .…”

“…Nowadays, its clinical application is quite restricted because the NH 4 Cl test is poorly tolerated since it induces nausea and vomiting. Also, the ability to acidify the urine may be assessed with less aggressive explorations [42] .…”

“…Hyperkalemic RTAs include hypoaldosteronism (type 4) and a voltage-dependent RTA, which is caused by defects in distal sodium reabsorption and is perhaps a subtype of distal RTA. RTA type 3 is a mixed RTA form of type 1 and type 2 [15] . Tubular defects are inherited or acquired.…”