A mouse model of renal failure, which is induced by the sequential electrocoagulation of the right renal cortex and left nephrectomy, was examined for the capacity to reproduce the characteristics of chronic uremia. Assessment was conducted six weeks after the second surgical procedure in 13 week old female C57BL/6 inbred mice with renal failure and in normal and sham-operated controls. The surgery, which was well tolerated, was free of local and systemic signs of inflammation or infection. Growth was significantly delayed in all animals post surgery however renal failure mice presented the most severe growth retardation. Biochemical analysis of plasma revealed multiple abnormalities with commensurate elevations of urea and creatinine. In addition to the expected hyperphosphatemia, hyperkalemia and acidosis, a significant increase in cholesterol was present. Furthermore, in contrast to controls, renal failure mice produced large volumes of urine which contained significant levels of protein. Renal failure mice presented profound hematological changes in the red cell series in which anemia was evident. Changes in plasma biochemistry and in bone histology revealed the presence of severe secondary hyperparathyroidism. It was therefore concluded that the described mouse model of chronic renal failure presented characteristics consistent with those observed clinically in end-stage renal disease.

The development and characterization of a mouse model of chronic Staphylococcus epidermidis foreign body infection was done with two clinical isolates that differed in degree of extracellular slime production. Segments of Silastic catheters bearing preformed S. epidermidis biofilms were implanted intraperitoneally, and mice were assessed after 3 and 6 months. Both test strains of S. epidermidis persisted at the implant site through the 6-month follow-up in 80% of the mice, regardless of the degree of slime production. There was no evidence of overt animal morbidity, and microbiologic assessment of other peritoneal sites did not reveal dissemination of bacteria from the infected focus. In comparison with control mice, animals harboring chronic foreign body infection presented marked peripheral neutrophilia and mild anemia.

A gradual loss of cell viability was observed during in vitro incubation of peritoneal cells from chronically uremic mice in commercial peritoneal dialysis solutions. The magnitude of this cytotoxicity toward peritoneal cells harvested from uremic mice and controls was comparable. Resident peritoneal cells were always found to be more susceptible than thioglycolate-elicited peritoneal populations of either macrophages or polymorphonuclear cells. In order to elucidate the factors contributing to this phenomenon, resident peritoneal cells recovered from normal mice were incubated in vitro for 1 h in various solutions of known pH and osmolarity consisting of buffered and unbuffered commercial peritoneal dialysis solutions. The results clearly show that the major part of the cytotoxicity is attributable to the low pH of the solutions. Once pH was corrected, the hyperosmolarity of these solutions had no effect on cell viability; however, a small but significant cytotoxicity remained. Factors other than those addressed in this study probably account for the observed residual cytotoxicity.

The role of renal failure in the pathogenesis of the Staphylococcus epidermidis (S. epidermidis) peritonitis presented by end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis was investigated in a mouse model of surgically-induced renal failure. Six weeks after the surgery, an i.p. inoculum of 10(6) colony forming units S. epidermidis was administered to renal failure mice and their sham-operated and normal controls, and assessment of bacterial clearance and inflammatory response was conducted over the next 72 hours. Peritoneal clearance of S. epidermidis was complete in most animals; however, the process was significantly delayed in renal failure mice compared to sham-operated controls. Viable bacteria invariably remained associated with the peritoneum after peritoneal washings had become culture negative. Peritoneal inflammatory response was markedly diminished in renal failure mice, the early polymorphonuclear cell response being particularly affected. Peripheral response consisted of a prompt and short-lived polymorph increase which was similar in renal failure and sham-operated mice. The factors responsible for the observed impairment of local inflammatory response in association with delayed bacterial clearance in renal failure mice following i.p. challenge with S. epidermidis remain to be defined.