Renal tubular acidosis

The renal tubular acidosis (RTA) syndrome encompass a disparate group of tubular transport defects which have in common an inability to secrete hydrogen ions (i.e., to reabsorb bicarbonate) that is out of proportion to any reduction in glomerular filtration rate (GFR). Unlike the metabolic acidosis resulting from severe reduction in renal function (GFR less than 20 ml per min), RTA is usually associated with a normal anion gap because the fall in plasma bicarbonate is matched by an increase in plasma chloride concentration. The RTA syndromes can be separated into two major categories: proximal and distal. Since the proximal tubule is the major site of reclamation of the filtered bicarbonate, a defect in this site of the nephron results in the delivery of large amounts of bicarbonate out of the proximal nephron. The capacity of the distal nephron for bicarbonate reabsorption is soon overwhelmed, causing urinary bicarbonate wastage. In contrast, a defect in the distal nephron, probably at the level of the collecting duct, results in minor bicarbonate loss because this segment of the nephron has a relatively low capacity for bicarbonate reabsorption. At this site of the nephron, however, the urinary pH reaches its lowest value. Hence, a defect in tubular transport at this nephron segment usually results in failure to lower urinary pH maximally, a characteristic (but not essential) feature of distal RTA. In patients with proximal RTA, the urinary pH can reach normally low values (i.e., below 5.5) when the plasma bicarbonate concentration falls to a level at which bicarbonate reabsorption is complete, causing bicarbonaturia to cease. In recent years, it has become clear that distal RTA, by far the most common form of RTA, can result from various mechanisms. The characterization of the mechanism responsible for distal RTA is best accomplished by the evaluation of urinary acidification in response not only to acidemic stimuli but also in response to agents that assess distal acidification independently of acidemia. Such evaluation involves the measurement of the urinary PCO₂ in response to bicarbonate and phosphate loading and the measurement of urinary pH in response to sodium sulfate infusion. The occurrence of a 'secretory' type of distal RTA has been reasonably well characterized in patients studied with these agents. Recent studies have also shown that inability to generate a normally negative potential difference in the lumen of the distal nephron may also result in a defect in hydrogen ion excretion. Such a 'voltage-dependent' defect might result, at least in part, from a primary impairment for sodium reabsorption at the level of the cortical collecting duct and is associated with decreased potassium secretion.