A re-evaluation of the renal ablation model of progressive renal disease in rats

Abstract

BACKGROUND: The remnant kidney model, usually involving sudden removal or ablation of 1- 1 / (2) to 1-5 / (6) of renal mass, results in compensatory hypertrophy followed by hypertension, proteinuria and declining glomerular filtration rate (GFR) associated with focal (FSG) and then global glomerulosclerosis (GS) and tubulointerstitial injury (TI). Since most renal diseases involve much more gradual injury, we asked whether slow ablation (SA) produced a different natural history than fast ablation (FA). METHODS: Male Münich-Wistar rats underwent heminephrectomy, 3 weeks later a second, and 3 weeks later a third heminephrectomy (SA). They were compared to littermates undergoing simultaneous removal of 1- 1 / (2) kidneys (FA) and sham operated controls (C). RESULTS: Three weeks after the second heminephrectomy, the SA rats had no FSG and glomerular volume (GV) was similar to that of FA rat renal tissue removed at that time. Eight weeks following the final surgical procedure (FSP), the SA and FA groups had similar blood pressures (BP) but higher than C. Albumin excretion rates (AER) were higher in SA and FA vs. C at 1 month after the FSP and, throughout most of the subsequent 5 months, greater in the SA vs. FA groups. At 24 weeks, cortical interstitial fractional volume was double C values in both the SA and FA groups. Percentage of glomeruli with FSG and size (score) of FSG lesions was much higher in SA and FA than C. Moreover, the percentage of FSG in SA (61.2+/-16%) and FSG score (1.7+/-0.7) was greater than in FA animals (35.6+/-11.9% and 0.9+/-0.4, p<0.01 for each comparison). Mean GV, increased at 24 weeks in both groups over C (1.4+/-0.2 X 10(6) micro m(3)) was greater in SA (3.4+/-0.7 X 10(6) micro m(3)) than FA rats (2.1+/-0.4 X 10(6) micro m(3); p<0.005). CONCLUSIONS: The gradual uninephrectomy in the SA group, insufficient per se to produce significant renal damage, preconditioned the residual kidney, upon further removal of another 1 / (2) kidney, to more albuminuria and FSG lesions than occurred following sudden 1- 1 / (2) nephrectomy, despite similarly elevated BP. Perhaps more time for glomerular enlargement in the SA group preconditioned the remnant kidney to accelerated injury.