Universität zu Köln

Babickova, Janka ORCID: 0000-0001-7859-9242, Klinkhammer, Barbara M., Buhl, Eva M., Djudjaj, Sonja, Hoss, Mareike, Heymann, Felix, Tacke, Frank, Floege, Juergen, Becker, Jan U. and Boor, Peter ORCID: 0000-0001-9921-4284 (2017). Regardless of etiology, progressive renal disease causes ultrastructural and functional alterations of peritubular capillaries. Kidney Int., 91 (1). S. 70 - 86. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Progressive renal diseases are associated with rarefaction of peritubular capillaries, but the ultrastructural and functional alterations of the microvasculature are not well described. To study this, we analyzed different time points during progressive kidney damage and fibrosis in 3 murine models of different disease etiologies. These models were unilateral ureteral obstruction, unilateral ischemia-reperfusion injury, and Col4a3-deficient mice, we analyzed ultrastructural alterations in patient biopsy specimens. Compared with kidneys of healthy mice, we found a significant and progressive reduction of peritubular capillaries in all models analyzed. Ultrastructurally, compared with the kidneys of control mice, focal widening of the subendothelial space and higher numbers of endothelial vacuoles and caveolae were found in fibrotic kidneys. Quantitative analysis showed that peritubular capillary endothelial cells in fibrotic kidneys had significantly and progressively reduced numbers of fenestrations and increased thickness of the cell soma and lamina densa of the capillary basement membrane. Similar ultrastructural changes were also observed in patient's kidney biopsy specimens. Compared with healthy murine kidneys, fibrotic kidneys had significantly increased extravasation of Evans blue dye in all 3 models. The extravasation could be visualized using 2-photon microscopy in real time in living animals and was mainly localized to capillary branching points. Finally, fibrotic kidneys in all models exhibited a significantly greater degree of interstitial deposition of fibrinogen'. Thus, peritubular capillaries undergo significant ultrastructural and functional alterations during experimental progressive renal diseases, independent of the underlying injury. Analyses of these alterations could provide read-outs for the evaluation of therapeutic approaches targeting the renal microvasculature.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Babickova, Janka UNSPECIFIED orcid.org/0000-0001-7859-9242 UNSPECIFIED Klinkhammer, Barbara M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buhl, Eva M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Djudjaj, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoss, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Heymann, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Tacke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Floege, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boor, Peter UNSPECIFIED orcid.org/0000-0001-9921-4284 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-248072
DOI:	10.1016/j.kint.2016.07.038
Journal or Publication Title:	Kidney Int.
Volume:	91
Number:	1
Page Range:	S. 70 - 86
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL-GROWTH-FACTOR; REMNANT KIDNEY MODEL; TUBULOINTERSTITIAL INJURY; IMPAIRED ANGIOGENESIS; ALTERED EXPRESSION; CHRONIC REJECTION; CROSS-TALK; FACTOR-A; PDGF-C; HYPOXIA Multiple languages Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24807