Dysregulated Oxygen Metabolism of the Kidney by Uremic Toxins: Review
Journal
Journal of Renal Nutrition
Journal Volume
22
Journal Issue
1
Pages
77-80
Date Issued
2012
Author(s)
Abstract
Because kidneys consume a large amount of oxygen and are relatively inefficient in oxygen uptake, they are susceptible to hypoxia, especially in patients with advanced chronic kidney disease accompanied by loss of peritubular capillaries. Accumulating evidence suggests that chronic tubulointerstitial hypoxia acts as a final common pathway leading to end-stage renal disease. Some biologically active uremic retention molecules, considered as uremic toxins, accumulate as the renal function declines, and at this moment, more than 90 bioactive uremic toxins have been identified. Uremic toxins per se have been proven to accelerate the progression of renal failure. However, the causal relationship between uremic toxin and tubulointerstitial hypoxia remains unclear. Our studies provided direct evidence that uremic toxin dysregulates oxygen metabolism in the kidney. Indoxyl sulfate (IS), a representative protein-bound uremic toxin, increased oxygen consumption in proximal renal tubules, decreased renal oxygenation, and consequently aggravated hypoxia in the remnant rat kidneys. The increase in tubular oxygen consumption by IS was dependent on sodium-potassium adenosine triphosphatase and oxidative stress. Our work also indicated a possible connection between IS and the desensitization of the oxygen-sensing mechanism in erythropoietin-producing cells, which may partly explain inadequate erythropoietin production in hypoxic kidneys of end-stage renal disease patients. Studies of uremic toxins will open a new avenue in development of novel therapeutic approaches of kidney disease. ? 2012 National Kidney Foundation, Inc.
SDGs
Other Subjects
erythropoietin; indican; animal; anoxia; article; biosynthesis; cell proliferation; chronic kidney failure; cytology; drug antagonism; drug effect; homeostasis; human; kidney; kidney tubule; metabolism; oxidative stress; oxygen consumption; pathology; physiology; rat; uremia; vascularization; Animals; Anoxia; Cell Proliferation; Erythropoietin; Homeostasis; Humans; Indican; Kidney; Kidney Failure, Chronic; Kidney Tubules; Oxidative Stress; Oxygen Consumption; Rats; Uremia; Rattus
Type
journal article