Chapter 195

### Abstract

1. Renal tubular acidosis (RTA) is a clinical syndrome characterized by hyperchloremic metabolic acidosis secondary to an abnormality in renal acidification. The acidification defect may be manifested by an inappropriately high urine pH, bicarbonaturia, and, by definition, reduced net acid excretion. Classical distal renal tubular acidosis and proximal renal tubular acidosis are frequently associated with hypokalemia. Distal renal tubular acidosis can also result from a generalized dysfunction of the distal nephron, in which case it is usually accompanied by hyperkalemia and may be associated with either hypoaldosteronism or aldosterone resistance.

2. Proximal renal tubular acidosis may result from an isolated defect of acidification in the proximal nephron. The isolated defect in acidification could be the result of selective dysfunction of the Na+/H+ antiporter, the proximal tubule H+-ATPase or the Na+/HCO3 /CO3 = symporter.

3. More commonly, proximal renal tubular acidosis occurs as one manifestation of a generalized defect in proximal tubule function. Patients with this generalized abnormality, the Fanconi syndrome, usually have glycosuria, aminoaciduria, citraturia, and phosphaturia. The acidification defect associated with this generalized tubular dysfunction may be the result of (a) impairment of cellular ATP generation, (b) cellular phosphate depletion, or (c) a selective abnormality of the basolateral Na+, K+-ATPase.

4. Vitamin D deficiency is associated with the Fanconi lesion. The transport defect may be due to a combination of factors including reduction in 1,25-dihydroxy vitamin D3 levels, elevated parathyroid hormone levels, hypocalcemia, and intracellular phosphate depletion.

5. The diagnosis of proximal renal tubular acidosis is based on the demonstration of a chronic hyperchloremic metabolic acidosis and an acid urine pH. Correction of the metabolic acidosis with alkali raises the plasma bicarbonate level above the renal threshold and results in prominent bicarbonaturia and an alkaline urine pH. The fractional excretion of bicarbonate may exceed 15 percent of the filtered load in such conditions, and hypokalemia is common. Bone disease, which commonly accompanies this disorder, is expressed as rickets in children and osteopenia in adults.

6. The goal of therapy in proximal renal tubular acidosis is to maintain a near normal serum bicarbonate concentration while avoiding potassium deficiency. Concomitant administration of thiazide diuretics to reduce intravascular volume, and secondarily to reduce the filtered load of bicarbonate, is often beneficial.

7. The mechanisms underlying hypokalemic classical distal renal tubular acidosis have not been fully elucidated. Nevertheless, important advances in our understanding of the molecular bases of this disorder have been made recently. Distal RTA may be inherited or acquired. The hypokalemia that is particularly prevalent in the acquired forms, suggests a lesion in the medullary collecting duct or a selective lesion in the cortical collecting tubule. Possible mechanisms include an abnormal leak pathway or “gradient” lesion or a “secretory” defect. An example of a leak defect is that induced by amphotericin B in which the urine minus the arterial blood PCO2 (U−B PCO2) is normal. Only two patients, both young children, have been ...

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