Citations

Renal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered. Additionally, NBCe1-A deletion almost completely blocked the ability to increase ammonia excretion after exogenous acid loading. Under basal conditions and during acid loading, urine pH was more acidic in mice with NBCe1-A deletion than in wild-type controls, indicating that the abnormal ammonia excretion was not caused by a primary failure of urine acidification. Instead, NBCe1-A deletion altered the expression levels of multiple enzymes involved in proximal tubule ammonia generation, including phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and glutamine synthetase, under basal conditions and after exogenous acid loading. Deletion of NBCe1-A did not impair expression of key proteins involved in collecting duct ammonia secretion. These studies demonstrate that the integral membrane protein NBCe1-A has a critical role in basal and acidosis-stimulated ammonia metabolism through the regulation of proximal tubule ammonia-metabolizing enzymes.

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments.

Objective: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. Background: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. Methods: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. Results: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. Conclusions: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Summary Hepatitis B virus ( HBV ) infection in the United States is the most common among Asians followed by non‐Hispanic blacks. However, there have been few studies that describe HBV infection and immunity by racial group. Our study aimed to assess racial/ethnic disparities in the prevalence and awareness of HBV infection and immunity using nationally representative data. In the National Health and Nutrition Examination Survey 2011‐2014, 14 722 persons had HBV serology testing. We estimated the prevalence of HBV infection, past exposure, and immunity by selected characteristics and calculated adjusted odds ratios using survey‐weighted generalized logistic regression. Awareness of infection and vaccination history was also investigated. The overall prevalence of chronic HBV infection, past exposure and vaccine‐induced immunity was 0.34% [95% CI 0.24‐0.43], 4.30% [95% CI 3.80‐4.81], and 24.4% [95% CI 23.4‐25.4], respectively. The prevalence of chronic infection was 2.74% [95% CI 1.72‐3.76] in Asians, 0.64% [95% CI 0.35‐0.92] in non‐Hispanic blacks, and 0.15% [95% CI 0.06‐0.24] in non‐Asian, non‐blacks. Only 26.2% of those with chronic infection were aware of their infection. The prevalence of the past exposure was 21.5% [95% CI 19.3‐23.7] in Asians, 8.92% [95% CI 7.84‐9.99] in non‐Hispanic blacks, 2.05% [95% CI 1.49‐2.63] in non‐Hispanic whites and 4.47% [95% CI 3.25‐5.70] in Hispanics. Prevalence of vaccine‐induced immunity by each race was 34.1% [95% CI : 32.0‐36.2] in Asians, 25.5% [95% CI : 24.0‐27.0] in non‐Hispanic blacks, 24.0% [95% CI : 22.6‐25.4] in non‐Hispanic whites and 22.2% [95% CI : 21.3‐23.3] in Hispanics. There are considerable racial/ethnic disparities in HBV infection, exposure and immunity. More active and sophisticated healthcare policies on HBV management may be warranted.