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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2014 ; 25
(9
): 1924-31
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Fluorescence microangiography for quantitative assessment of peritubular
capillary changes after AKI in mice
#MMPMID24652794
Kramann R
; Tanaka M
; Humphreys BD
J Am Soc Nephrol
2014[Sep]; 25
(9
): 1924-31
PMID24652794
show ga
AKI predicts the future development of CKD, and one proposed mechanism for this
epidemiologic link is loss of peritubular capillaries triggering chronic hypoxia.
A precise definition of changes in peritubular perfusion would help test this
hypothesis by more accurately correlating these changes with future loss of
kidney function. Here, we have adapted and validated a fluorescence
microangiography approach for use with mice to visualize, analyze, and quantitate
peritubular capillary dynamics after AKI. A novel software-based approach enabled
rapid and automated quantitation of capillary number, individual area, and
perimeter. After validating perfusion in mice with genetically labeled
endothelia, we compared peritubular capillary number and size after moderate AKI,
characterized by complete renal recovery, and after severe AKI, characterized by
development of interstitial fibrosis and CKD. Eight weeks after severe AKI, we
measured a 40%±7.4% reduction in peritubular capillary number (P<0.05) and a
36%±4% decrease in individual capillary cross-sectional area (P<0.001) for a
62%±2.2% reduction in total peritubular perfusion (P<0.01). Whereas total
peritubular perfusion and number of capillaries did not change, we detected a
significant change of single capillary size following moderate AKI. The loss of
peritubular capillary density and caliber at week 8 closely correlated with
severity of kidney injury at day 1, suggesting irreparable microvascular damage.
These findings emphasize a direct link between severity of acute injury and
future loss of peritubular perfusion, demonstrate that reduced capillary caliber
is an unappreciated long-term consequence of AKI, and offer a new quantitative
imaging tool for understanding how AKI leads to future CKD in mouse models.