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Etiology and diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis

Michael Emmett, MD
Biff F Palmer, MD
Section Editor
Richard H Sterns, MD
Deputy Editor
John P Forman, MD, MSc


Distal (type 1) and proximal (type 2) renal tubular acidosis (RTA) are uncommon disorders, particularly in adults. Proximal RTA is characterized by a reduction in proximal bicarbonate reabsorptive capacity that leads to bicarbonate wasting in the urine until the serum bicarbonate concentration has fallen to a level low enough to allow all of the filtered bicarbonate to be reabsorbed. By comparison, the primary defect in distal RTA is impaired distal acidification. These different pathogenetic mechanisms result in different clinical manifestations, but some degree of hypokalemia is commonly present with most forms of distal and proximal RTA (table 1).

The etiology and diagnosis of distal and proximal RTA will be reviewed here. The pathogenesis of the different forms of RTA, the treatment of these disorders, the impact they have on potassium balance, and an overview of RTA are discussed separately. (See "Overview and pathophysiology of renal tubular acidosis and the effect on potassium balance" and "Treatment of distal (type 1) and proximal (type 2) renal tubular acidosis".)

Type 4 RTA is another form of RTA in which the primary problem is either decreased aldosterone secretion or aldosterone resistance. These patients typically have a mild metabolic acidosis (serum bicarbonate concentration above 17 meq/L) with the major manifestation being hyperkalemia. (See "Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)".)

Although initially used to describe a transiently severe form of distal RTA in infants, the term "mixed (type 3) RTA" is most often applied to a rare autosomal recessive syndrome (resulting from carbonic anhydrase II deficiency) with features of both proximal and distal RTA [1,2]. In addition to RTA, affected patients suffer from osteopetrosis, cerebral calcification, and mental retardation. (See "Etiology and clinical manifestations of renal tubular acidosis in infants and children", section on 'Mixed (type 3) RTA'.)


The different forms of renal tubular acidosis (RTA), which lead to a hyperchloremic (normal anion gap) metabolic acidosis, can be caused by a wide variety of disorders, most of which are rare [3]. The most frequent causes vary with the type of RTA.

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Literature review current through: Nov 2017. | This topic last updated: May 18, 2016.
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