An in vitro model for analyzing the nephrotoxicity of XXXX and preservation injury.

@entity1 @entity8 @entity870 @entity235 @entity63 @entity7222 @entity205 @entity519 @entity130
@entity8 caused by @entity205 ( @entity870 ) has been documented. Clinical experiences have shown preservation injury further potentiates @entity870 nephrotoxicity. This study examined the mechanism of nephrotoxicity defined by changes in protein synthesis, DNA synthesis, and @entity7222 decarboxylase activity in an in vitro model. Initial results showed that @entity870 inhibited @entity235 kidney epithelium cell (MDCK) replication at a dose of 200 ng after 24 hr (P less than .01) and 100 ng after 48 hr (P less than .01). Protein synthesis was inhibited with 100 ng after 24 and 48 hr (P less than .01). There was a reduction in ODC activity with 200 ng @entity870 (P less than .05). Methods for simulating transplant-related @entity130 were then developed. Under ischemic conditions, 18 hr were required before a synergistic effect with @entity870 produced a reduction in replication (P less than .05). Incubation of MDCK cells in preservative solution at 4 degrees C under @entity519 conditions resulted in a time-dependent reduction in synthetic and replicative capacity that plateaued at 24 hr (P less than .01). The next step was to simulate the clinical situation by combining treatments. MDCK cells were incubated for 24 hr in preservative solution under @entity519 conditions at 4 degrees C, and then @entity870 was added at defined intervals. The addition of @entity870 before 24 hr resulted in a significant decrease in cell replication (P less than .05) compared with @entity870 addition after 48 hr. Similar results were obtained with cells incubated for 48 hr in preservative solution with @entity519 . These data suggest that @entity8 from @entity63 and cold storage requires a period of cellular repair and replication. Administration of @entity870 before this period results in further @entity8 . Our analysis offers an explanation of @entity870 nephrotoxicity seen in the @entity1 situation and, therefore, may provide a model for studying @entity1 nephrotoxicity.
