Sexual and gender minority relevant policies in Canadian and United States organ and tissue donation and transplantation systems: An opportunity to improve equity and safety.

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients.

Human rights in pandemics: criminal and punitive approaches to COVID-19.

In the early years of the HIV epidemic, many countries passed laws criminalising HIV non-disclosure, exposure and/or transmission. These responses, intended to limit transmission and punish those viewed as 'irresponsible', have since been found to undermine effective HIV responses by driving people away from diagnosis and increasing stigma towards those living with HIV. With the emergence of COVID-19, human rights and public health advocates raised concerns that countries might again respond with criminal and punitive approaches. To assess the degree to which countries adopted such strategies, 51 English-language emergency orders from 39 countries, representing seven world regions, were selected from the COVID-19 Law Lab, a database of COVID-19 related laws from over 190 countries. Emergency orders were reviewed to assess the type of restrictions identified, enforcement mechanisms and compliance with principles outlined in the Siracusa Principles on the Limitation and Derogation Provisions in the International Covenant on Civil and Political Rights, including legality, legitimate aim, proportionality, non-discrimination, limited duration and subject to review. Approximately half of all orders examined included criminal sanctions related to violations of lockdowns. Few orders fully complied with the legal requirements for the limitation of, or derogation from, human rights obligations in public health emergencies. In future pandemics, policymakers should carefully assess the need for criminal and punitive responses and ensure that emergency orders comply with countries' human rights obligations.

Global Estimates of Capacity for Kidney Transplantation in World Countries and Regions.

BACKGROUND: Kidney transplantation (KT) is the optimal treatment for kidney failure and is associated with better quality of life and survival relative to dialysis. However, knowledge of the current capacity of countries to deliver KT is limited. This study reports on findings from the 2018 International Society of Nephrology Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, and quality of KT across countries and regions. METHODS: Data were collected from published online sources, and a survey was administered online to key stakeholders. All country-level data were analyzed by International Society of Nephrology region and World Bank income classification. RESULTS: Data were collected via a survey in 182 countries, of which 155 answered questions pertaining to KT. Of these, 74% stated that KT was available, with a median incidence of 14 per million population (range: 0.04-70) and median prevalence of 255 per million population (range: 3-693). Accessibility of KT varied widely; even within high-income countries, it was disproportionately lower for ethnic minorities. Universal health coverage of all KT treatment costs was available in 31%, and 57% had a KT registry. CONCLUSIONS: There are substantial variations in KT incidence, prevalence, availability, accessibility, and quality worldwide, with the lowest rates evident in low- and lower-middle income countries. Understanding these disparities will inform efforts to increase awareness and the adoption of practices that will ensure high-quality KT care is provided around the world.

Decline and Pronounced Regional Disparities in Medical Cocaine Usage in the United States.

Background: Cocaine is a stimulant and Schedule II drug used as a local anesthetic and vasoconstrictor. Objective: This descriptive study characterized medical cocaine use in the United States. Methods: Retail drug distribution data from 2002 to 2017 were extracted for each state from the Drug Enforcement Administration, which reports on medical, research, and analytical chemistry use. The percentage of buyers (pharmacies, hospitals, and providers) was obtained. Use per state, corrected for population, was determined. Available cross-sectional data on cocaine use as reported by the Medicare and Medicaid programs for 2013-2017 and electronic medical records were examined. Results: Medical cocaine use decreased by -62.5% from 2002 to 2017. Hospitals accounted for 84.9% and practitioners for 9.9% of cocaine distribution in 2017. The number of pharmacies carrying cocaine dropped by -69.4%. The percentages of hospitals, practitioners, and pharmacies that carried cocaine in 2017 were 38.4%, 2.3%, and 0.3%, respectively. There was a 7-fold difference in 2002 (South Dakota, 76.1 mg/100 persons; Delaware, 10.1 mg/100 persons). Relative to the average state in 2017, those reporting the highest values (Montana, 20.1; North Dakota, 24.1 mg/100 persons) were significantly elevated. Cocaine use within the Medicare and Medicaid programs was negligible. Cocaine use within the Geisinger system was rare from 2002 to 2007 (<4 orders/100 000 patients per year) but increased to 48.7 in 2018. Conclusion and Relevance: If these pharmacoepidemiological patterns continue, licit cocaine may soon become a historical relic. The pharmacology and pharmacotherapeutics education of health care providers may need to be adjusted accordingly.

Providing Care for Transgender Persons With Kidney Disease: A Narrative Review.

PURPOSE OF REVIEW: Nephrologists are increasingly providing care to transgender individuals with chronic kidney disease (CKD). However, they may lack familiarity with this patient population that faces unique challenges. The purpose of this review is to discuss the care of transgender persons and what nephrologists should be aware of when providing care to their transgender patients. SOURCES OF INFORMATION: Original research articles were identified from MEDLINE and Google Scholar using the search terms "transgender," "gender," "sex," "chronic kidney disease," "end stage kidney disease," "dialysis," "transplant," and "nephrology." METHODS: A focused review and critical appraisal of existing literature regarding the provision of care to transgender men and women with CKD including dialysis and transplant to identify specific issues related to gender-affirming therapy and chronic disease management in transgender persons. KEY FINDINGS: Transgender persons are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Individuals with CKD have a degree of hypogonadotropic hypogonadism and decreased levels of endogenous sex hormones; therefore, transgender persons with CKD may require reduced exogenous sex hormone dosing. Exogenous estradiol therapy increases the risk of venous thromboembolism and cardiovascular disease which may be further increased in CKD. Exogenous testosterone therapy increases the risk of polycythemia which should be closely monitored. The impact of gender-affirming hormone therapy on glomerular filtration rate (GFR) trajectory in CKD is unclear. Gender-affirming hormone therapy with testosterone, estradiol, and anti-androgen therapies changes body composition and lean body mass which influences creatinine generation and the performance for estimated glomerular filtration rate (eGFR) equations in transgender persons. Confirmation of eGFR with measured GFR is reasonable if an accurate knowledge of GFR is needed for clinical decision-making. LIMITATIONS: There are limited studies regarding the intersection of transgender persons and kidney disease and those that exist are mostly case reports. Randomized controlled trials and observational studies in nephrology do not routinely differentiate between cisgender and transgender participants. IMPLICATIONS: This review highlights important considerations for providing care to transgender persons with kidney disease. Additional research is needed to evaluate the performance of eGFR equations in transgender persons, the effects of gender-affirming hormone therapy, and the impact of being transgender on outcomes in persons with kidney disease.

MOTIF DE LA REVUE: Dans leur pratique, les néphrologues sont de plus en plus appelés à traiter des personnes transgenres atteintes d'insuffisance rénale chronique (IRC). Une population de patients qui fait face à des défis particuliers et avec laquelle les spécialistes ne sont pas toujours familiers. L'objectif de cette revue est de discuter des soins prodigués aux personnes transgenres et des enjeux auxquels les néphrologues qui soignent ces patients devraient être sensibilisés. SOURCES: Les articles de recherche originaux ont été répertoriés sur MEDLINE et Google Scholar à l'aide des termes transgender (transgenre), gender (genre), sex (sexe), chronic kidney disease (insuffisance rénale chronique), end stage kidney disease (insuffisance rénale terminale), dialysis (dialyse), transplant (transplantation) et nephrology (néphrologie). MÉTHODOLOGIE: On a procédé à un examen ciblé et une évaluation critique de la documentation portant sur les soins aux personnes transgenres atteintes d'IRC, notamment la dialyse et la transplantation, afin de cerner les enjeux liés spécifiquement aux thérapies d'affirmation du genre et à la prise en charge de la néphropathie chronique chez les personnes transgenres. PRINCIPAUX RÉSULTATS: Les personnes transgenres courent un risque accru d'événements défavorables comparativement à la population cisgenre, notamment en matière de santé mentale, de maladies cardiovasculaires, de tumeurs malignes, d'infections transmissibles sexuellement et de mortalité. Les individus atteints d'IRC présentent un certain degré d'hypogonadisme hypogonadotrope et des taux réduits d'hormones sexuelles endogènes; les personnes transgenres atteintes d'IRC pourraient ainsi nécessiter un dosage réduit d'hormones sexuelles exogènes. L'estradiol exogène augmente le risque de thrombo-embolie veineuse et de maladies cardiovasculaires, un risque pouvant être augmenté davantage en contexte d'IRC. La testostérone exogène augmente le risque de polycythémie et doit être surveillée étroitement. L'impact de l'hormonothérapie d'affirmation du genre sur la trajectoire du débit de filtration glomérulaire (DFG) en IRC est encore mal connu. L'hormonothérapie d'affirmation du genre avec testostérone, estradiol et anti-androgène altère la composition corporelle et la masse maigre, ce qui influe sur la production de créatinine et la performance des équations calculant le DFG estimé (DFGe) chez les personnes transgenres. La confirmation du DFGe à l'aide du DFG mesuré est raisonnable si connaître la valeur précise du DFG est nécessaire pour la prise de décision clinique. LIMITES: Peu d'études se sont penchées sur l'intersection des personnes transgenres et de la néphropathie, et les études existantes consistent principalement en des rapports de cas. Les essais contrôlés randomisés et les études observationnelles en néphrologie ne font pas systématiquement de distinction entre les participants cisgenres et transgenres. CONCLUSION: Cette revue met en lumière des considérations importantes pour la prise en charge des personnes transgenres atteintes de néphropathies. D'autres recherches sont nécessaires pour évaluer la performance des équations calculant le DFGe, les effets de l'hormonothérapie d'affirmation du genre et l'incidence d'être transgenre sur les résultats des personnes atteintes de néphropathies.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

BACKGROUND: Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. METHODS: We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. RESULTS: Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). CONCLUSIONS: ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.

Sexual Health and Wellbeing through the Life Course: Ensuring Sexual Health, Rights and Pleasure for All.

This commentary summarizes the context and positioning of sexual health, sexual rights and sexual pleasure, as three interlinked and indivisible aspects of sexual health and wellbeing (SH&W). In turn, sexual health is a major domain within broader sexual and reproductive health and rights (SRHR), both in its own right as a human right, and owing to the importance of good sexual health for ensuring good reproductive outcomes. Furthermore, SRHR is a necessary, core part of overall health, thus sexual health and wellbeing is a fundamental aspect of general health that is often overlooked or even denied for some. In this commentary, we utilize a life course approach to illustrate how the tripartite of sexual health, rights and pleasure manifest themselves with different interlocking linkages, and actively contribute to overall health throughout life. As other papers in this series attest, the linkages of pleasure with the right to and attainment of health has received inadequate attention to date, both within the scientific literature and in policy narratives.

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

RATIONALE: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. OBJECTIVES: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. METHODS: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). CONCLUSIONS: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).

Dialysis and acute kidney injury: current evidence.

Optimization of renal replacement therapy (RRT) for severe acute kidney injury (AKI) has been intensively studied over the last decade. Several large recently published randomized trials have clarified uncertainties regarding dialysis modality selection as well as dialysis dosage. This information will help inform decision makers regarding resource allocation and establishment of treatment targets. The decision to initiate dialysis remains a clinical one, based on individual patient needs. Despite technological advances in renal replacement therapy, AKI continues to be associated with poor outcomes.

The tripeptide feG inhibits leukocyte adhesion.

BACKGROUND: The tripeptide feG (D-Phe-D-Glu-Gly) is a potent anti-inflammatory peptide that reduces the severity of type I immediate hypersensitivity reactions, and inhibits neutrophil chemotaxis and adhesion to tissues. feG also reduces the expression of beta1-integrin on circulating neutrophils, but the counter ligands involved in the anti-adhesive actions of the peptide are not known. In this study the effects of feG on the adhesion of rat peritoneal leukocytes and extravasated neutrophils to several different integrin selective substrates were evaluated. RESULTS: The adhesion of peritoneal leukocytes and extravasated neutrophils from rats to adhesive proteins coated to 96-well plates was dependent upon magnesium (Mg2+) ion, suggestive of integrin-mediated adhesion. feG inhibited leukocyte adhesion, but only if the cells were stimulated with PAF (10-9M), indicating that feG's actions in vitro require cell activation. In the dose range of 10-10M to 10-12M feG inhibited the adhesion of peritoneal leukocytes to fibrinogen and fibronectin, but not IgG, vitronectin or ICAM-1. feG inhibited the binding of extravasated neutrophils to heparin, IgG, fibronectin and CD16 antibody. Antigen-challenge of sensitized rats reduced the adhesion of peritoneal leukocytes to most substrates and abolished the inhibitory effects of feG. However, pretreating the animals with intraperitoneal feG (100 mug/kg) 18 h before collecting the cells from the antigen-challenged animal restored the inhibition of adhesion by in vitro feG of peritoneal leukocytes and extravasated neutrophils to fibronectin. CONCLUSION: The modulation of leukocyte adhesion by feG appears to involve actions on alphaMbeta2 integrin, with a possible interaction with the low affinity FcgammaRIII receptor (CD16). The modulation of cell adhesion by feG is dual in nature. When administered in vivo, feG prevents inflammation-induced reductions in cell adhesion, as well as restoring its inhibitory effect in vitro. The mechanism by which in vivo treatment with feG exerts these effects remains to be elucidated.