Development of a Model of Tubulointerstitial Fibrosis Using Transient Unilateral Renal Ischemia and Delayed Contralateral Nephrectomy in Domesticated Cats.

ABSTRACT

Tubulointerstitial fibrosis is a classic histologic feature of chronic kidney disease (CKD) in cats and a final common pathway toward end-stage renal disease. Domesticated cats have been used in models of ischemia-induced renal fibrosis. The objective of this study was to evaluate the performance of 2 variations of a transient unilateral renal ischemia and delayed contralateral nephrectomy model of tubulointerstitial fibrosis in cats. Purpose-bred, young adult, domesticated cats underwent 90 min of surgically induced ischemia to the right kidney followed by delayed contralateral nephrectomy performed 21 d (RI-CN21d group; n = 10) or 90 d postischemia (RI-CN90d group; n = 12). Control cats underwent sham surgery followed by left nephrectomy 21 d after (sham-CN group; n = 3). Renal functional parameters, including glomerular filtration rate and serum creatinine concentration, were evaluated before and after surgeries. The right kidneys were harvested 120 d postischemia/ sham. Renal histology with lesion scoring and histomorphometry for quantification of smooth muscle actin immunolabeling and collagen staining were performed on harvested kidneys. Severe acute kidney injury prompted euthanasia after left nephrectomy in 5/10 (50.0%), 2/12 (16.7%), and 0/3 (0%) of cats in the RI-CN21d, RI-CN90d, and sham-CN groups, respectively. A significant decrease in glomerular filtration rate by day 120, relative to baseline, occurred in cats in the RI-CN21d group (P < 0.001) and RI-CN90d group (P < 0.001) but not the sham-CN group (P = 0.76). All but one cat in the ischemia groups were azotemic at the study end. Kidneys subjected to ischemia had higher interstitial inflammation, tubular atrophy, and fibrosis scores compared with sham-operated kidneys. There were significant increases in smooth muscle actin immunolabeling and collagen staining in these kidneys, relative to the contralateral kidneys. In summary, 90 min of unilateral renal ischemia and delayed contralateral nephrectomy induced histologic and biochemical changes consistent with CKD in cats. A 90-d period between ischemia and nephrectomy resulted in improved survivability of the model.