Chapter 523 Renal Tubular Acidosis
Normal Urinary Acidification
Kidneys contribute to acid-base balance by reabsorption of filtered bicarbonate (HCO3−) and excretion of hydrogen ion (H+) produced every day. Hydrogen ion secretion from tubule cells into the lumen is key in the reabsorption of HCO3−, formation of titratable acidity (H+ bound to buffers such as HPO42−), and formation of ammonium ions (NH4+). Because loss of filtered HCO3− is equivalent to addition of H+ to the body, all filtered bicarbonate should be absorbed before dietary H+ can be excreted. About 90% of filtered bicarbonate is absorbed in the proximal tubule and the remaining 10% in the distal segments, mostly thick ascending limb and outer medullary collecting tubule (CT) (Fig. 523-1). In the proximal tubule and thick ascending limb of the loop of Henle (TAL) H+ from water is secreted by the Na+-H+ exchanger on the luminal membrane. H+ combines with filtered bicarbonate resulting in the formation of H2CO3, which splits into water and CO2 in the presence of carbonic anhydrase (CA) IV. CO2 diffuses freely back into the cell, combines with OH− (from H2O) to form HCO3− in the presence of CA II, and returns to systemic circulation via the Na+-3HCO3− cotransporter situated at the basolateral membrane of the cell. In the CT, H+ is secreted into lumen by H+ATPase (adenosine triphosphatase) and H-CO3− is returned to systemic circulation by HCO3–-Cl− exchanger located on the basolateral membrane. The H+ secreted proximally and distally in excess of the filtered HCO3− is excreted in the urine either as titratable acid or as NH4+.
523.1 Proximal (Type II) Renal Tubular Acidosis
Rajasree Sreedharan and Ellis D. Avner
Pathogenesis
Proximal RTA can be inherited and persistent from birth or occur as a transient phenomenon during infancy. Although rare, it may be primary and isolated. Proximal RTA usually occurs as a component of global proximal tubular dysfunction or Fanconi syndrome, which is characterized by low molecular weight proteinuria, glycosuria, phosphaturia, aminoaciduria, and proximal RTA. The causes of proximal RTA and Fanconi syndrome are outlined in Table 523-1. Many of these causes are inherited disorders. In addition to cystinosis and Lowe syndrome, autosomal recessive and dominant pRTA are addressed further in this section. Other inherited forms of Fanconi syndrome include galactosemia (Chapter 81.2), hereditary fructose intolerance (Chapter 81.3), tyrosinemia (Chapter 79.2), and Wilson disease (Chapter 349.2). Dent disease, or X-linked nephrolithiasis, is discussed in Chapter 525.3. In children, an important form of secondary Fanconi syndrome is exposure to ifosfamide, a component of many treatment regimens for Wilms tumor and other solid tumors.
Table 523-1 COMMON CAUSES OF RENAL TUBULAR ACIDOSIS
PROXIMAL RENAL TUBULAR ACIDOSIS
Primary
Secondary
DISTAL RENAL TUBULAR ACIDOSIS
Primary
Secondary
HYPERKALEMIC RENAL TUBULAR ACIDOSIS
Primary
Secondary
