Renal Counterbalance and the Reversibility of Renal Atrophy with Reduced Renal Mass

Abstract

The mechanisms that regulate renal survival and atrophy under pathological stress remain incompletely understood. This knowledge is essential for developing new strategies to preserve renal function in patients with various forms of renal disease. We have utilized the 5/6 nephrectomy (5/6Nx) model to study the effects of renal insufficiency in 10 week old male Sprague Dawley rats. In this model excision of 2/3 of the left kidney and the entire right kidney induced substantial hypertrophy of the remnant kidney within 7 weeks of surgery. Conversely, excision of 2/3 of the left kidney, while leaving the right kidney intact (1/3 nephrectomy; 1/3Nx), resulted in atrophy of the remnant kidney within the same period. This lead us to hypothesize that removal of the right kidney 7 weeks after 1/3 surgery could induce hypertrophic remodeling of the left remnant kidney even after atrophic remodeling has occurred. To test this, we performed sham surgeries consisting of laparotomy and renal vessel isolation, right uninephrectomy (1Nx), 1/3Nx, or 5/6Nx surgery, as described above (n= 4–11/group). After 7 weeks we performed ultrasound analysis to evaluate the transverse renal cross‐sectional area (CSA) of the left kidney in each model. Sham surgery was then performed on all animals except for a subset of the 1/3Nx group which had their right kidneys excised. The animals were allowed to recover for another 3 weeks before the left kidney remodeling was again evaluated by ultrasound, acute anesthetized blood pressure was measured, and blood and tissues were collected for analysis. Statistical analysis of ultrasound data was completed using two‐way RM ANOVA, and all other by one‐way ANOVA. Ultrasound analysis of left kidney CSA revealed significant hypertrophy in the 1Nx and 5/6Nx models by week 7, when compared to sham‐operated controls, with no further increase in size evident by week 10. We observed the anticipated reduction in CSA in the 1/3Nx group by week 7 (1.06 ± 0.02, sham vs. 0.58 ± 0.01 cm2, 1/3Nx; p <0.05). The 1/3Nx rats subjected to removal of the right kidney experienced a significant hypertrophy of the remnant kidney (1.31 ± 0.04 cm2) between weeks 7 and 10, however this hypertrophy failed to reach the level observed in the 5/6Nx model (2.06 ± 0.05 cm2). Those 1/3Nx rats that retained their right kidney had no apparent change in remnant kidney size by week 10 (0.56 ± 0.03 cm2). These changes in renal dimensions were consistent with wet weights of the remnant kidney weights. Systolic and diastolic blood pressures measured at the end of the study were not statistically different from that of sham operated controls in any surgical group, however pressures tended to be higher in the 1/3Nx rats that had their right kidneys removed at week 7. We determined that removal of the right kidney could stimulate an atrophied left kidney to hypertrophy. In conclusion, the changes observed in this study suggest that these surgical models will allow us to study the mechanisms that regulate hypertrophy and atrophy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.