Renal Tubular Acidosis



The term renal tubular acidosis (RTA) describes a group of disorders whose individual features re­flect the site and mechanism of failure in tubular hydrogen ion transport (Fig. 34-3). Type I, or clas­sic distal RTA, represents an inability of the col­lecting duct to maintain a gradient of free hydro­gen ion between the blood and the urine. This failure to maintain a hydrogen ion gradient may be due to increased backleak of hydrogen ion from the tubular lumen to blood or to a failure in the hydrogen secretory mechanism. Type I RTA is ex­pressed as an inability to lower urine pH (the free hydrogen ion concentration) in the face of an acid challenge. Type II, or proximal RTA, involves an impairment in the rate of hydrogen ion secretion and therefore bicarbonate reabsorption in the proximal tubule. Proximal RTA is expressed as bicarbonaturia that persists until the serum bi­carbonate concentration and the filtered load of bicarbonate fall to levels that match the reduced proximal tubular absorptive capacity. Finally, Type IV RTA designates a defect in mineralocor-ticoid-dependent hydrogen ion secretion in the distal nephron. Type IV RTA usually accompan­ies some form of renal interstitial disease (as in lead or diabetic nephropathies) and results either from diminished aldosterone secretion or from a failure of collecting duct response to aldosterone.

Distal RTA may occur sporadically as an iso­lated disorder or may be secondary to a systemic disease or toxin. Prominent causes of distal RTA include primary and secondary hypergammaglob­ulinemias, nephrocalcinosis, amyloidosis, sickle cell disease, and amphotericin B administration.

Children often present with lethargy, anorexia, stunted growth, and bone disease. Adults have similar symptoms, often with bone pain or path­ological fractures, and a high incidence of renal stones. The origin of these symptoms appears to be bone buffering of hydrogen ion over an ex­tended period. This leads to bone calcium loss and hypercalciuria in the presence of an alkaline urine. Disordered calcium metabolism is ex­pressed as rickets in children and osteomalacia’, nephrocalcinosis, and nephrolithasis in adults. The distinguishing laboratory features include hyperchloremic metabolic acidosis with hypo­kalemia and a urinary pH that is consistently above pH 6.0 to 6.5.

An inability to lower urine pH below 5.3 in the face of spontaneous acidosis or an acid load (given as oral NH4C1] is diagnostic. Administration of a single dose of the loop diuretic furosemide also aids in the diagnosis of distal RTA. Normal in­dividuals and those with Type I, gradient-limited RTA increase urinary acid secretion concomitant to the increased delivery of Na+ to the distal nephron.

Treatment of distal RTA is accomplished by oral alkali replacement, either as sodium bicar­bonate or as Shohl’s solution, at the rate of 1 to 3 mEq/kg/day. The 60 to 70 mEq of bicarbonate re­quired to treat Type I RTA correspond to the nor­mal contribution of the distal nephron to H+ ex­cretion. Correction of acidosis by this means leads to cessation of hypercalciuria and renal stone formation and correction of hypokalemia, but normal growth and bone development in chil­dren require administration of several hundred milhequivalents of bicarbonate daily.

Proximal RTA occurs rarely as an isolated le­sion and is most often seen as a part of the Fanconi syndrome. Proximal RTA is a self-limiting process m that normal acidification of urine, measured both as a maximum reduction in urine pH and as a normal excretion of ammonia and titratable acid, is seen when the serum bicarbonate level reaches a reduced, steady-state value. This value is usually 14 to 18 mEq/L and represents the max­imal resorptive capacity of the proximal tubule in the disorder. At this moderate level of extracel­lular buffer reduction, daily H+ excretion is com­plete and long-term buffer deficits do not develop as in distal RTA.

Clinical signs and symptoms are few in proxi­mal RTA and relate to growth retardation. Hy­perchloremic metabolic acidosis is evident in all: cases. Hypokalemia, the result of increased deliv-” ery of sodium bicarbonate to the distal nephron,*, is prominent. Hypercalciuria, nephrocalcinosis4 and nephrolithiasis are absent. The urine pH can’ reach values of 4.5 to 5.0 as long as the serurrr bicarbonate level is below the proximal tubular! resorptive threshold. The diagnosis is confirmed” by the infusion of bicarbonate and observation of an increase in urine pH and bicarbonaturia at sub­normal levels of serum bicarbonate. The treatment of proximal RTA with alkali replacement is virtually impossible because any el­evation of the serum bicarbonate above the ab­sorptive capacity of the proximal tubule results in quantitative urinary excretion of the added bicar­bonate. Modest salt depletion, thereby increasing general proximal tubular absorption, will aid in raising the serum bicarbonate concentration.

Type IV RTA results from a diminished mineralocorticoid effect in the distal nephron and is ex­pressed as a decrease in the secretory rates of po­tassium and hydrogen. There are two forms of the disorder. Aldosterone levels may be reduced, either from primary adrenal disease, in which case renin levels are elevated, or from renal in­terstitial disease, in which case renin levels are grossly reduced. Alternatively, adequate levels of aldosterone may be present but the distal nephron is unresponsive to its effect. This type of the dis­order may be caused either by disease of the distal nephron; by the aldosterone-blocking diuretic, spironolactone; or by the potassium-sparing di­uretics, triamterene and amiloride.

Since both potassium and hydrogen secretion are blunted, hyperkalemia accompanies the hy-perchloremic metabolic acidosis of Type IV RTA. This is in contrast to the hypokalemia seen in Types I and II. A mild degree of renal insuffi­ciency is present in many of these patients. They often demonstrate relative salt wasting, that is, an inability to reduce urinary sodium excretion dur­ing salt restriction. Hyperkalemia decreases the renal generation and excretion of the major uri­nary buffer, ammonium. Therefore, patients with Type IV RTA have a decrease in total acid excre­tion, although the urine pH may be appropriately acidic. Basal and stimulated renin plus aldoster­one levels should be measured in these patients.

Mineralocorticoid replacement, as fludrocorti­sone, is effective therapy in patients with an ab­solute reduction in aldosterone. Because in­creased sodium delivery to the distal nephron augments potassium and hydrogen secretion even in the absence of aldosterone, a high-salt diet plus a loop diuretic (furosemide) will increase both po­tassium and hydrogen excretion in all these pa­tients. Reduction of the serum potassium alone increases urinary ammonium excretion and net urinary acid excretion and restores the hydrogen balance in some of these patients.





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