Extent of glomerular tubularization is an indicator of the severity of experimental acute kidney injury in mice.
BACKGROUND
Acute kidney injury (AKI) secondary to ischemia continues to be a major clinical problem due to its high morbidity and mortality, and limited treatment options. Animal models are critical to both the study of the pathophysiology of AKI and the development of new interventions. Although histological changes at the glomerulotubular junction have been described in AKI, we examined here whether the extent of glomerular tubularization correlates with the degree of renal insufficiency in this condition.


METHODS
Groups of mice with ischemia/reperfusion AKI were utilized in which the severity of renal insufficiency was defined. The resulting level of glomerular tubularization was analyzed, and the involved cell type was identified by immunohistochemistry and electron microscopy.


RESULTS
The extent of glomerular tubularization increased significantly with the degree of renal insufficiency. Low level glomerular tubularization was present in normal mouse kidneys, while it was more common and increasingly circumferential in mice with more severe loss of kidney function. The parietal monolayer of cuboidal cells in glomeruli was contiguous with proximal tubular cells, showing a well-developed luminal brush border and positive staining for proliferating cell nuclear antigen and Lotus tetragonolobus, a proximal tubular cell-specific lectin.


CONCLUSIONS
Increased levels of glomerular tubularization represent a poorly understood response to ischemic AKI in mice. As such, this glomerular 'tubularization score' may be useful to complement standard injury scores in experimental and, if detected, in clinical AKI.
Isaac
Jorge
J
Division of Anatomic/Renal Pathology, Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Tögel
Florian E
FE
Westenfelder
Christof
C
D000208:Acute Disease; D000818:Animals; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
D018809:Proliferating Cell Nuclear Antigen