Evaluation of the rat renal allograft model in comparison to man: a physiological perspective

Fabre has previously questioned the rat kidney allograft model from an immunologic perspective and raised some important considerations. The present study addresses further the fidelity of the rat renal allograft model from a physiologic rather than immunologic perspective. We reviewed several rat renal allograft studies from several laboratories, including our own, that followed BUN or urea levels during renal failure. Also examined were several studies from the literature concerning patient survival and uremia. The percentage of patient and rat survival was plotted against maximal BUNs attained. The frequency of survival was significantly (p less than 0.05) increased in the rats by comparison to the patient population over a range of median BUNmax values. Additional human data that were utilized for analysis included a group of 16 patients who experienced renal failure and subsequently chose not to undergo dialysis. Comparing the mean BUN at death in rats from our laboratory to this patient population, we found that there was a significant difference (p less than 0.001, 292 +/- 142 mg./dl. versus 127 +/- 51 mg./dl., respectively). When all of the rat data was combined, including results from the literature, and compared to the patients, a significant (p less than 0.001) increase in BUN at death was confirmed (204 +/- 95 versus 127 +/- 51, respectively). We also found that 82% of the rats that died with uremia possessed BUNs greater than 200 mg./dl. at some time during their course. In contrast, only one of the 16 patients (6%) that died with uremia demonstrated BUN levels as great as this. Although the rats frequently (13%) went on to indefinite survival after experiencing high levels of uremia, the vast majority did not. We conclude that the rats exhibit superior ability to tolerate high concentrations of urea in comparison to man. However, as a group, they demonstrated little ability to sustain their uremic condition for prolonged periods. This latter consideration is of utmost importance, since most renal transplant studies base their conclusions on length of animal survival following organ allograft failure due to rejection. We feel this is a salient feature of the rat renal allograft model.