Document Detail


Early glomerular alterations in genetically determined low nephron number.
MedLine Citation:
PMID:  20943767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An association between low nephron number and subsequent development of hypertension in later life has been demonstrated. The underlying pathomechanisms are unknown, but glomerular and postglomerular changes have been discussed. We investigated whether such changes are already present in prehypertensive "glial cell line-derived neurotrophic growth factor" heterozygous mice (GDNF+/-) with lower nephron number. Twenty-six-week-old mice [22 GDNF+/-, 29 C57B6 wild-type control (wt)] were used for in vivo experiments with intra-arterial and tail cuff blood pressure measurements. After perfusion fixation, kidneys were investigated with morphological, morphometric, stereological, and immunohistochemical techniques and TaqMan PCR analysis. As expected at this age, blood pressure was comparable between GDNF+/- and wt. Nephron number per kidney was significantly lower in GDNF+/- than in wt (-32.8%, P < 0.005), and mean glomerular volume was significantly higher (+49.5%, P < 0.001). Renal damage scores, glomerular and tubular proliferation, analysis of intrarenal arteries and peritubular capillaries, expression of relevant tubular transporter proteins, as well as gene expression of profibrotic, proinflammatory, or prohypertensive markers were not significantly different between GDNF+/- and wt. Compensatory glomerular hypertrophy in GDNF+/- was accompanied by higher numbers of endothelial and mesangial cells as well as PCNA-positive glomerular cells, whereas podocyte density was significantly reduced. Further electron microscopic analysis showed marked thickening of glomerular basement membrane. In conclusion, lower nephron number is associated with marked early glomerular structural changes, in particular lower capillary supply, reduced podocyte density, and thickened glomerular basement membrane, that may predispose to glomerular sclerosis.
Authors:
Kerstin Benz; Valentina Campean; Nada Cordasic; Britta Karpe; Winfried Neuhuber; Gerhard Mall; Andrea Hartner; Karl F Hilgers; Kerstin Amann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  300     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-04     Completed Date:  2011-03-30     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F521-30     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Erlangen-Nürnberg, Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / genetics
Female
Glial Cell Line-Derived Neurotrophic Factor / genetics*
Glomerular Basement Membrane / metabolism,  ultrastructure
Hypertension / genetics*,  pathology
Kidney Glomerulus / metabolism,  ultrastructure*
Male
Mice
Mice, Inbred C57BL
Nephrons / metabolism,  ultrastructure*
Chemical
Reg. No./Substance:
0/Glial Cell Line-Derived Neurotrophic Factor

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