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.

In the US more than 700,000 people suffer from end stage renal disease (ESRD). Of those, 97.5% are reliant on dialysis. Among dialysis patients, cardiovascular (CV) related events are the leading cause of death; in fact, this population has a 20‐fold higher CV related mortality. Despite therapeutic advancements the continued, and often worsening, CVD following the onset of dialysis treatment poses an interesting clinical challenge that necessitates further studies focused on elucidating the effects of dialysis on CV function. Based on clinical reports, we hypothesized that peritoneal dialysis (PD) would not improve CV outcomes in the 5/6 nephrectomy model of cardiorenal syndrome. We performed 5/6Nx (n=12), or sham surgery (n=13), on 10 week old male Sprague‐Dawley rats. Peritoneal catheters were implanted in all animals 4 weeks post‐surgery. PD was initiated 3 days later in some of the 5/6Nx (n=7) and sham (n=7) animals (15ml [Baxter Dianeal PD‐2] 15‐minute dwells 3x per day). Echocardiography was performed at baseline, 4, and 7 weeks after the initial surgery to evaluate left ventricle (LV) remodeling and function. At week 7 pressure volume analysis was performed prior to plasma and tissue collection. Statistical significance of all data was determined via two‐way ANOVA. Plasma creatinine was increased by 5/6Nx (5/6Nx 1.35 ± 0.38 vs. sham 0.63 ± 0.09; p <0.05). Chronic PD had no effect on plasma creatinine in sham animals but attenuated the rise in 5/6Nx (5/6Nx 1.35 ± 0.38 vs. 5/6Nx + PD 1.00 ± 0.10; p <0.05). PD does not alter kidney weight in sham animals nor does it alter remnant kidney weight in 5/6Nx. PD trended to decrease heart weight in both sham and 5/6Nx animals (sham 0.41 ± 0.02 vs sham + PD 0.35 ± 0.02 and 5/6Nx 0.46 ± 0.05 vs 5/6Nx + PD 0.42 ± 0.03; N.S.). LV ventral wall thickness increases in 5/6Nx animals compared to sham (5/6Nx 3.49 ± 0.14 vs sham 2.99 ± 0.04; p <0.05). PD did not alter wall thickness in sham animals but tended to attenuate the increase observed in 5/6Nx (5/6Nx 3.49 ± 0.14 vs 5/6Nx + PD 3.18 ± 0.15; N.S.). 5/6Nx animals have an increased ejection fraction (EF) compared to sham (5/6Nx 84.65 ± 2.49 vs sham 75.97 ± 1.06 and 5/6Nx 47.08 ± 2.88 vs sham 37.89 ± 0.90, respectively; p <0.05). There was no change in EF induced by PD in sham animals, but PD prevents the increase in EF in 5/6Nx (5/6Nx 84.65 ± 2.49 vs 5/6Nx + PD 78.91 ± 1.25, respectively; p <0.05). Acute systolic blood pressure (BP) was unchanged by 5/6Nx. PD tended to increase BP in 5/6Nx animals (5/6Nx 122.04 ± 11.36 vs 5/6Nx + PD 135.44 ± 5.82; N.S.). These data combined suggest that PD may influence CV outcomes in CKD, however it is unclear if these changes would be beneficial or detrimental if the treatment were extended for a longer period of time. The differences in wall thickness suggests PD is possibly altering hypertrophic growth signaling and preventing cardiac remodeling in response to reduced renal mass. However, increased BP may hint to other confounding factors that may be responsible for the increased CV mortality in this population. These data indicate further studies are necessary to understand the effects of dialysis on CV function, as well as other physiological functions, in order to improve dialysis treatment and improve clinical outcomes for ESRD patients.Support or Funding InformationAHA ‐ 18PRE34000045This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.