Urinary Concentrating Defect in Experimental Hemochromatosis
| Title: | Urinary Concentrating Defect in Experimental Hemochromatosis |
|---|---|
| Authors: | Zhou, X.J.; Vaziri, MD, N.D.; Pandian, D.; Wang, Z.Q.; Mazowiecki, M.; Liao, S.Y.; Oveisi, F. |
| Publisher: | Journal of the American Society of Nephrology |
| Date Published: | January 01, 1996 |
| Reference Number: | 40 |
We studied the urinary concentrating capacity in experimental hemochromatosis. Sprague-Dawley rats were randomized into iron (Fe)-loaded (injected sc with 1.2 g elemental iron/kg body weight as iron dextran) and pair-fed control groups. The urinary concentrating ability was studied after 10 months of iron loading. At basal condition, urine osmolality (Uosm) was significantly lower (P is less than 0.05) in the Fe-loaded rats compared with the control animals despite comparable urinary arginine-vasopressin (AVP) excretion in the two groups. Although 48-h water deprivation resulted in comparable rises in plasma concentration and urinary excretion of AVP in the two groups, maximal Uosm in the Fe-loaded animals was significantly lower than that seen in the control group (P is less than 0.01). Moreover, the observed urinary concentrating defect could not be corrected by pharmacological doses of exogenous AVP. There was no significant difference in renal chloride, sodium, calcium, or magnesium handling at either basal or sodium depleted states. Histologic studies showed marked iron deposition in the cortex and outer medulla accompanied by mild tubular atrophy particularly in the distal convoluted tubules. Thus, chronic experimental iron overload leads to nephrogenic diabetes insipidus marked by AVP-resistant urinary concentrating defect.
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)
Examination revealed that the iron-loaded rats developed nephrogenic diabetes insipidus (NDI). This disorder involves an inability of the kidneys to respond to the antidiuretic hormone, arginine vasopressin (AVP), resulting in the kidneys' inability to concentrate urine. NDI is characterized by excessive thirst and excessive, dilute urine. AVP initiates the physiological sequence that enables the kidneys to concentrate urine. The iron-loaded rats had the required amount of AVP naturally occurring in their body, but the kidneys weren't able to take advantage of it. Further, when the iron-loaded rats were given injections of synthetic AVP, their kidneys showed no response to it and continued to be unable to concentrate urine. This is a hallmark of NDI.
When the authors examined the kidney tissues of the iron-loaded rats, they showed significant amounts of iron deposited in both the outer and inner layers of the kidney. The kidney has many little tubes in it, which help filter bodily fluids, and many of the tubes of the iron-loaded rats were mildly atrophied.