Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.

Background: Non-ideal donors provide acceptable allografts and may expand the donor pool. This study evaluates donor utilization across solid organs over 15-years in the United States. Methods: We analyzed the OPTN STAR database to identify potential donors across three donor eras: 2005–2009, 2010–2014, and 2015–2019. Donors were analyzed by a composite Donor Utilization Score (DUS), comprised of donor age and comorbidities. Outcomes of interest were overall and organ-specific donor utilization. Descriptive analyses and multivariable logistic regression modeling were performed. p-values < 0.01 considered significant. Results: Of 132,465 donors, 32,710 (24.7%) were identified as non-ideal donors (NID), based on a DUS ≥ 3. Compared to ideal donors (ID), NID were older (median 56 years, IQR 51–64 years vs. 35 years, 22–48 years, p < 0.001) and more frequently female (44.3% vs. 39.1%, p < 0.001), Black (22.1% vs. 14.6%, p < 0.001) and obese (60.7% vs. 19.6%, p < 0.001). The likelihood of overall DBD utilization from NID increased from Era 1 to Era 2 (OR 1.227, 95% CI 1.123–1.341, p < 0.001) and Era 3 (OR 1.504, 1.376–1.643, p < 0.001), while DCD donor utilization in NID was not statistically different across Eras. Compared to Era 1, the likelihood of DBD utilization from NID for kidney transplantation was lower in Era 2 (OR 0.882, 0.822–0.946) and Era 3 (OR 0.938, 0.876–1.004, p = 0.002). The likelihood of NID utilization increased in Era 3 compared to Era 1 for livers (OR 1.511, 1.411–1.618, p < 0.001), hearts (OR 1.623, 1.415–1.862, p < 0.001), and lungs (OR 2.251, 2.011–2.520, p < 0.001). Conclusions: Using a universal definition of NID across organs, NID donor utilization is increasing; however, use of DUS may improve resource utilization in identifying donors at highest likelihood for multi-organ donation.

The present study evaluated expanded cause of death (COD) definitions and its implications on donor utilization for solid organ transplantation. The OPTN Standard Transplant and Research file was queried for potential donors between 2005 and 2019. Donor- and organ-specific utilization were evaluated. Expanded donor COD were identified: trauma, cardiovascular (CV), cerebrovascular accident (CVA) or stroke, drug intoxication (DI), anoxia not otherwise specified (NOS), and other. Descriptive analyses and multivariable logistic regression analyses for donor utilization were performed. Among 132 783 potential donors identified, the most common COD was CVA/Stroke (n=44 707, 33.7%), followed by trauma (n=43 356, 32.7%), CV (n=20 053, 15.1%), anoxia-NOS (n=12 261, 9.2%), DI (n=10 205, 7.7%), and other causes (n=2201, 1.7%). Significant differences between CV, DI, and anoxia-NOS groups existed for donor age, sex, ethnicity, body mass index, and comorbidities. Donors from trauma had the highest unadjusted utilization rate (97.2%) while CV donors had the lowest (90.1%). Multivariable analysis of brain-dead donors (DBD) showed that compared to trauma, donors from DI had higher likelihood of utilization (odds ratio 1.217, 95% 1.025–1.446) while CV donors were lower (OR 0.717, 95% CI 0.642–0.800, P<0.001). Among donation after circulatory death (DCD) donors, there was decreased utilization compared to trauma for both CV (OR 0.607, 95% CI 0.523–0.705) and DI (OR 0.754, 95% CI 0.603–0.914, P<0.001). Current COD definitions should be expanded to capture significant differences in the donor population. DI donors are the fastest growing cohort and the most likely utilized DBD donors, while trauma donors remain the most likely utilized DCD donors.

Background.: Interleukin-6 (IL-6) is an important driver of humoral immunity and a target for treatment of antibody-mediated rejection (AMR) in kidney transplantation. Data on IL-6 inhibition for treatment of AMR are mixed and their efficacy remains inconclusive. In this retrospective observational study, we investigated the association of monthly tocilizumab infusions with the trajectory of estimated glomerular filtration rate (eGFR) among kidney transplant patients with histologic features of chronic active AMR. Methods.: Through institutional database review, 85 adult kidney transplant patients with histologic features of chronic active AMR treated with monthly tocilizumab 8 mg/kg intravenous infusions were identified. Piecewise linear mixed effects models were fitted to compare eGFR trajectories 12 mo before and after tocilizumab initiation. Results.: The eGFR declined at a rate of –0.70 mL/min/1.73 m²/mo (95% confidence interval, –1.03 to –0.36) preceding tocilizumab initiation and stabilized after treatment onset to a slope of –0.07 (–0.35 to 0.21) mL/min/1.73 m²/mo (slope difference: 0.59 [0.22-0.97] mL/min/1.73 m²/mo, P = 0.002).The distribution of the sum mean fluorescence intensity of donor specific antibodies (DSA) among 65 DSA⁺ patients remained unchanged from baseline to 1 y after treatment; however, 14 of 65 DSA⁺ patients (22%) no longer had DSA at 1 y. There was 1 graft loss and 2 deaths, both COVID-19-related, by 12 mo after treatment onset. Conclusions.: This study suggests that monthly treatment with the anti-IL-6 receptor monoclonal antibody, tocilizumab, may stabilize allograft function among kidney transplant patients with chronic active AMR and that further studies to confirm its efficacy should be conducted.