Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Jul 2005
Vasopressin-V2 receptor stimulation reduces sodium excretion in healthy humans.
In addition to its effect on water permeability, vasopressin, through its V2 receptors (AVPR2), stimulates Na reabsorption in the collecting duct by increasing the activity of the amiloride-sensitive sodium channel ENaC. This study evaluated whether dDAVP (a potent AVPR2 agonist) reduces sodium excretion in healthy humans (n = 6) and in patients with central (C; n = 2) or nephrogenic (N) diabetes insipidus (DI) as a result of mutations of either the aquaporin 2 gene (AQP2; n = 3) or AVPR2 (n = 10). dDAVP was infused intravenously (0.3 microg/kg body wt in 20 min), and urine was collected for 60 min before (basal) and 150 min after the infusion. dDAVP markedly reduced both urine flow rate and sodium excretion in healthy individuals. A reduction in sodium excretion was also observed in CDI and NDI-AQP2 patients but not in NDI-AVPR2 patients. ⋯ These results suggest that the dDAVP-induced antinatriuresis is due to a direct V2 receptor-dependent stimulation of sodium reabsorption in the collecting duct and is not secondary to a hemodynamic effect. In conclusion, this study reveals a potent V2-dependent antinatriuretic effect of vasopressin in humans. The possibility that an inappropriate stimulation of ENaC by vasopressin might lead to significant sodium retention in chronic situations remains to be determined.
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J. Am. Soc. Nephrol. · Jul 2005
Involvement of renal progenitor tubular cells in epithelial-to-mesenchymal transition in fibrotic rat kidneys.
Renal progenitor tubular cells (label-retaining cells [LRC]) were recently identified in normal kidneys by in vivo bromodeoxyuridine (BrdU) labeling. This study was conducted to examine the behavior of LRC in renal fibrosis. BrdU was injected intraperitoneally into normal rats daily for 7 d. ⋯ Most of these cells were BrdU+. Neither the total content of BrdU in the kidneys nor the number of LRC in bone marrow significantly changed after UUO. Collectively, these results suggest that LRC is a cell population that proliferates, migrates, and transdifferentiates into fibroblast-like cells during renal fibrosis.
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J. Am. Soc. Nephrol. · Jun 2005
Chloride transport in the kidney: lessons from human disease and knockout mice.
Knockout mouse models and human inherited diseases have provided important new insights into the physiologic role of chloride transport by CLC Cl(-) channels and KCC K-Cl co-transporters. ClC-K/barrtin Cl(-) channels are important for renal salt reabsorption and possibly for acid secretion by intercalated cells. ⋯ KCC4 is important for recycling Cl(-) for the basolateral anion exchanger in intercalated cells, as is evident from the renal tubular acidosis resulting from its knockout. Finally, both KCC3 and KCC4 are crucial for proximal tubular cell volume regulation.
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J. Am. Soc. Nephrol. · Apr 2005
Intrarenal injection of bone marrow-derived angiogenic cells reduces endothelial injury and mesangial cell activation in experimental glomerulonephritis.
Loss of glomerular endothelial cells has been suggested to contribute to the progression of glomerular injury. Although therapeutic angiogenesis induced by administration of bone marrow-derived endothelial progenitor cells has been observed in disease models of endothelial injury, the effects on renal disease have not been clarified. Whether administration of culture-modified bone marrow mononuclear cells would mitigate the glomerular endothelial injury in anti-Thy1.1 nephritis was investigated. ⋯ Culture-modified mononuclear cells secreted 281.2 +/- 85.0 pg of vascular endothelial growth factor per 10(5) cells per day. In conclusion, intra-arterial administration of culture-modified bone marrow mononuclear cells reduced endothelial injury and mesangial activation in anti-Thy1.1 glomerulonephritis. Incorporation into the glomerular endothelial lining and production of angiogenic factor(s) are likely to contribute to the protective effects of culture-modified mononuclear cells against glomerular injury.
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J. Am. Soc. Nephrol. · Mar 2005
Review Comparative StudyAre 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors renoprotective?
Statins reduce serum cholesterol and cardiovascular morbidity and mortality. The mechanisms for these beneficial effects are reviewed. ⋯ This review critically considers the available data whereby dyslipidemia mediates renal dysfunction by modulating the inflammatory response to diverse cytokines. Also reviewed is the emerging database indicating that statins may modulate renal function by altering the response of the kidney to dyslipidemia.