Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (547 page)

   All forms of RTA (1–4) are characterized by normal anion gap and hyperchloremic metabolic acidosis.

   Distal RTA (Type 1)

   Characterized by impaired secretion of H
⁺
and therefore ammonium by the collecting ducts.

   It should be suspected in any patient with metabolic acidosis with normal anion gap (AG) and inappropriately high urine pH.

   Major causes in adults include autoimmune disease (e.g., Sjögren syndrome, SLE, rheumatoid arthritis) and hypercalciuria (e.g., vitamin D intoxication, hyperparathyroidism). In addition, drugs (e.g., ifosfamide, amphotericin B) or other diseases (pyelonephritis, Hodgkin disease, cryoglobulinemia, amyloidosis, sarcoidosis, medullary sponge kidney) can also cause distal RTA. In children, hereditary distal RTA is the most common cause.

   Laboratory Findings

   High urine pH (>5.3; usually in the 6.5–7 range) regardless of serum bicarbonate concentration. Urinary pH below 5.3 generally excludes distal (but not proximal) RTA. Urine sodium concentration is typically >25 mEq/L. Urine ammonium excretion is reduced and can be estimated indirectly by measurement of the urine anion gap or osmolal gap. This parameter can distinguish patients with distal RTA from those who have normal anion gap metabolic acidosis and hypokalemia due to other causes.

   Blood potassium level is usually low.

   Hyperchloremic acidosis and low serum bicarbonate concentration (may be <10 mEq/L).

   Ammonium loading test shows inability to acidify urine below pH 5.3.

   Proximal RTA (Type 2)

   This condition results from defective bicarbonate reabsorption in the proximal tubule, causing bicarbonate wasting in the urine. This wasting continues until serum bicarbonate concentration reaches a level that is low enough to allow all of the filtered bicarbonate to be reabsorbed.

   It can be present as an isolated disorder or in association with a generalized proximal tubular dysfunction called Fanconi syndrome, in which reabsorption of other solutes such as phosphate, glucose, uric acid, and amino acids is impaired resulting in bone demineralization (osteomalacia or rickets) due to phosphate wasting.