Development of an in vitro model for renal ischemia and elevated hydrostatic pressure associated with obstructive uropathy
Abstract
Kidney damage and/or failure caused by urinary obstruction affects thousands of patients each year. It has been hypothesized that reduced blood flow (ischemia) and/or elevated levels of hydrostatic pressure within the kidney during obstructive uropathy contribute to renal failure. Moreover, renal ischemia results in decreased oxygen supply (hypoxia), increased carbon dioxide content (hypercapnia), glucose depletion, and waste accumulation within the affected tissues. Although investigators have examined some of these insults individually, their synergistic effects may lead to renal failure. To begin to investigate this, an in vitro model of renal ischemia was first created. Porcine renal proximal tubule epithelial LLC-PK1 cells (cell line CL-101; ATCC) were used for this purpose and subjected to hypoxia, hypercapnia, and/or glucose deprivation. Later, an in vitro model for obstructive uropathy was developed. Cells were exposed to hydrostatic pressure (80 cmH2O) and/or ischemic insults. For both of these in vitro models, cellular responses including proliferation, morphology and/or cell death were quantified immediately after exposure to insult(s) and following a recovery period. Data collected from these studies was statistically analyzed to identify factor main effects and interactions. Results indicated that multiple factors interact and alter cellular behavior during renal ischemia and obstructive uropathy; their pathophysiologies cannot be attributed to a single insult. Furthermore, insults' effects were rarely superimposable. Rather, insults interacted in a complex manner to alter cellular behavior. Ultimately, results from this investigation may lead to the development of mitigating therapies for renal failure due to ischemia and/or obstructive uropathy and related pathologies.
Degree
Ph.D.
Advisors
Haberstroh, Purdue University.
Subject Area
Biomedical research|Pathology
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