Urinary Content of Aquaporin 1 and 2 in Nephrogenic Diabetes Insipidus
|Title:||Urinary Content of Aquaporin 1 and 2 in Nephrogenic Diabetes Insipidus|
|Authors:||Deen, Peter M.T.; van Aubel, Remon A.M.H.; van Lieburg, Angenita; van Os, Carel|
|Publisher:||Journal of the American Society of Nephrology|
|Date Published:||June 01, 1996|
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
In patients suffering from nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to AVP. In the inherited form of NDI, the majority of cases are due to a mutation in the V2R gene, the gene that produces the vasopressin 2 receptor (V2R). V2R normally will bind with AVP, allowing it to begin the chain of events that results in urine concentration. The other cause of inherited NDI are mutations in the AQP2 gene, the gene that produces AQP2.
Laboratory research studying activity of AQP2 in cell cultures showed the AQP2s from mutant AQP2 genes were nonfunctional and were equally or less stable than normal AQP2s. Deen, et al., studied the relative stability of mutant and normal AQP2s, not in cell cultures, but in living human beings, by measuring the level of AQP2 excretion in the urine of NDI patients and healthy individuals.
They tested their subjects after both a diuretic state (i.e. after a three hour period where they drank at least .75 liters of water per hour) and an antidiuretic state (i.e. after an 11 hour period where they took no liquids). The urine samples from the healthy subjects showed clear levels of AQP1 and AQP2 in their antidiuretic state but not in their diuretic state. No AQP2 was located in the urine of any of the four patients with mutations in their AQP2 gene nor in the urine of a patient with a T204N mutation in his V2R gene. (Every gene is composed of many parts, any of which could be faulty. Researchers have mapped out the constituent parts of many genes, including the V2R gene, and thus can locate and code the mutated area on the gene.) The finding that none of the patients with AQP2 mutations had AQP2s in their urine suggests that AQP2 mutations reduce the stability of their AQP2s.
The differences in stability between normal and mutant AQP2s, as revealed in this study using human subjects, seem more pronounced than previously concluded from experiments conducted with laboratory cell cultures. The authors attribute this difference to the smaller amounts of AQP2 found in the kidney's collecting tube cells in the kidney (where they naturally live) compared with the amount of AQP2s injected into the laboratory cell cultures. In addition, mutant AQP2s in the kidneys' collecting tube cells may keep their numbers down, a phenomenon that does not happen in cell cultures.