Abstracts from the Mid-Atlantic Section of the AUA 2020

MA AUA 2020 Abstracts Effects of Myristoylated Protein Kinase C Beta II Peptide Inhibitor on Severe Bilateral Warm Renal Ischemia-Reperfusion Injury in Mice R. Decker 1 ; T. Dean 2 ; Q. Chen 2 ; R. Barsotti 2 ; J. George 3 ; A. Agarwal 3 ; L. Young 2 1 Rowan University School of Osteopathic Medicine, Stratford, NJ, USA; 2 Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 3 University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA Introduction: Delayed graft function (DGF), premature renal failure within one week of transplantation, occurs in approximately 30% of renal allografts. DGF is associated with reactive oxygen species (ROS)-induced ischemia-reperfusion (I/R) injury, for which there are currently no effective therapeutics. We propose to prophylactically mitigate ROS-induced renal I/R injury with cell-permeable myristoylated protein kinase C beta II peptide inhibitor (N-myr-SLNPEWNET; myr-PKCβII-). Myr-PKCβII- inhibits isolated rat leukocyte superoxide release and restores cardiac function with reduced infarct size when administered upon reperfusion in rat myocardial I/R models. We hypothesized that myr-PKCβII- would attenuate injury in a murine model of severe bilateral warm renal I/R (20 min/96h) quantified by serum creatinine (Cr) reduction compared to a scrambled peptide control for myristoylation (N-myr-WNPESLNTE; myr-PKCβII-scram). Materials &Methods: Renal pedicles of anesthetized male C57BL/6J mice (25-30 g) were clamped bilaterally for 20 min. One minute before unclamping, 2.0 mg/kg (20 μM serum concentration) myr-PKCβII- (n=9) or myr-PKCβII-scram (n = 9) was infused by tail vein. SerumCr (mg/dL) was measured at baseline and 24h, 72h, and 96h post-injury. Data were evaluated by unpaired Student’s t-test. Results: Myr-PKCβII- significantly reduced serum Cr vs. myr-PKCβII-scram controls at 24h (1.36 ± 0.11; n = 9 vs. 1.59 ± 0.06; n = 8; *p = .041) and 72h (0.73 ± 0.15; n = 9 vs. 1.28 ± 0.25; n = 8; *p = .040) post-injury. Serum Cr reduction continued 96h post-injury (0.51 ± 0.09; n = 8 vs. 0.72 ± 0.15; n = 6; p = .107) but was not statistically significant. Conclusions: Mice treatedwithmyr-PKCβII- exhibitedmarked reduction of serum Cr in the first 72h compared to myr-PKCβII-scram controls. Results suggest that a single dose of myr-PKCβII- accelerates renal recovery following severe I/R injury. Future studies will investigate optimal dosing to achieve more rapid return to baseline compared to non-treated and scrambled peptide controls as a strategy for mitigating ROS-induced DGF. MP6-09 Active Surveillance for Small Renal Masses is Safe and Non-Inferior: 10-Year Update from the Delayed Intervention and Surveillance for Small Renal Masses Registry J. Cheaib 1 ; R. Alam 1 ; H. Patel 1 ; M. Metcalf 1 ; M. Biles 1 ; T. Wlajnitz 1 ; A. Wagner 2 ; P. Chang 2 ; M. Johnson 1 ; J. McKiernan 3 ; M. Allaf 1 ; P. Pierorazio 1 1 Johns Hopkins Medicine, Baltimore, MD, USA; 2 Beth Israel Deconess Medical Center, Boston, MA, USA; 3 Columbia University Irving Medical Center, New York, NY, USA Introduction: Active surveillance (AS) is an alternative to primary intervention (PI) aimed at reducing over-treatment of small renal masses (SRM), defined as solid renal masses ≤ 4.0 cm (cT1a), suspicious for renal cell carcinoma (RCC). We sought to describe the 10-year outcomes for patients with SRM enrolled in a multi- institutional, prospective study. Materials & Methods: Since 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled patients with SRM who chose to undergo PI or AS. Primary outcomes were cancer-specific survival (CSS) and overall survival (OS); secondary outcomes included progression-free survival (PFS). Progression was strictly defined as growth rate > 0.5 cm/year, greatest tumor diameter > 4.0 cm, metastatic disease, or elective crossover. The Kaplan-Meier method and log-rank test were used to evaluate outcomes. Results: Of 785 enrolled patients, 351 (44.7%) chose PI and 434 (55.3%) chose AS. From theAS cohort, 71 (16.4%) underwent delayed intervention. Median follow-up was 3.3 years, with 292 (37.2%) patients followed for 5 years or more. At baseline, patients who choseAS were older (P< 0.001) and had higher comorbidity status (P< 0.001) than those who chose PI. There was no difference in CSS at 10 years between PI andAS [Figure 1A]; however, OS was higher in PI patients when compared toAS [Figure 1B]. In the AS cohort, 113 (26%) developed progression: 81 due to growth rate > 0.5 cm/year, 27 due to elective crossover, 4 due to tumor diameter > 4.0 cm, and 1 due to metastatic disease. 10-year PFS was 62%. Conclusions: In a large multi-institutional registry with 10 years of experience, AS appears to be safe and non-inferior to PI for carefully selected patients with SRM suspicious for RCC. MP6-08 Poster Session 6: Urologic Oncologic Disease 43