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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
2016 ; 27
(4
): 1102-12
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Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model
of Cisplatin-Induced CKD
#MMPMID26303068
Torres R
; Velazquez H
; Chang JJ
; Levene MJ
; Moeckel G
; Desir GV
; Safirstein R
J Am Soc Nephrol
2016[Apr]; 27
(4
): 1102-12
PMID26303068
show ga
Traditional histologic methods are limited in their ability to detect pathologic
changes of CKD, of which cisplatin therapy is an important cause. In addition,
poor reproducibility of available methods has limited analysis of the role of
fibrosis in CKD. Highly labor-intensive serial sectioning studies have
demonstrated that three-dimensional perspective can reveal useful morphologic
information on cisplatin-induced CKD. By applying the new technique of
multiphoton microscopy (MPM) with clearing to a new mouse model of
cisplatin-induced CKD, we obtained detailed morphologic and collagen
reconstructions of millimeter-thick renal sections that provided new insights
into pathophysiology. Quantitative analysis revealed that a major long-term
cisplatin effect is reduction in the number of cuboidal cells of the glomerular
capsule, a change we term the "uncapped glomerulus lesion." Glomerulotubular
disconnection was confirmed, but connection remnants between damaged tubules and
atubular glomeruli were observed. Reductions in normal glomerular capsules
corresponded to reductions in GFR. Mild increases in collagen were noted, but the
fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume
and number remained unaltered with cisplatin exposure, but cortical
tubulointerstitial mass decreased. In conclusion, new observations were made
possible by using clearing MPM, demonstrating the utility of this technique for
studies of renal disease. This technique should prove valuable for further
characterizing the evolution of CKD with cisplatin therapy and of other
conditions.