title: Positive renal response to intravenous acetazolamide in patients with carbonic anhydrase II deficiency.
abstract: Carbonic anhydrase II (CA II) is the only soluble isozyme of CA which is known to be expressed in kidney. We recently identified a deficiency of this enzyme as the basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. In order to explore the physiological importance of CA II in the kidney, we studied the renal response to intravenously infused acetazolamide in two CA II-deficient patients and two control subjects. Following acetazolamide infusion, the CA II-deficient patients exhibited a prompt rise in urinary pH and HCO3- excretion similar to the response seen in control subjects. These findings indicate that CA II-deficient patients, who lack detectable CA II in their erythrocytes, still expressed an acetazolamide-inhibitable CA activity in their kidneys. These results can be explained in three ways: 1) the CA II deficiency which is profound in the erythrocytes of these patients may not be expressed in their kidney. 2) An acetazolamide-sensitive CA other than CA II, such as CA I and CA III, which is not normally expressed in kidney, is expressed in kidneys of CA II-deficient patients. 3) The CA II deficiency is expressed in kidney in these patients but the acetazolamide response is due to inhibition of the luminal, membrane-bound CA which is the product of a different gene and unaffected by the CA II deficiency mutation. We favor the third possibility.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000141:Acidosis, Renal Tubular / Q000188:drug therapy* / Q000235:genetics / Q000652:urine; D000328:Adult; D002256:Carbonic Anhydrases / Q000172:deficiency*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000172:deficiency*; D008297:Male; D010022:Osteopetrosis / Q000235:genetics
chemical_list: D007527:Isoenzymes; D002256:Carbonic Anhydrases; D000086:Acetazolamide