The Reality of Inadequate Patient Care and the Need for a Global Action Framework in Organ Donation and Transplantation.

BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.

Associations between female birth sex and risk of chronic kidney disease development among people with HIV in the USA: A longitudinal, multicentre, cohort study.

Background: Women represent a meaningful proportion of new HIV diagnoses, with Black women comprising 58% of new diagnoses among women. As HIV infection also increases risk of chronic kidney disease (CKD), understanding CKD risk among women with HIV (WWH), particularly Black women, is critical. Methods: In this longitudinal cohort study of people with HIV (PWH) enrolled in CFAR Network of Integrated Clinical Systems (CNICS), a multicentre study comprised of eight academic medical centres across the United States from Jan 01, 1996 and Nov 01, 2019, adult PWH were excluded if they had ≤2 serum creatinine measurements, developed CKD prior to enrollment, or identified as intersex or transgendered, leaving a final cohort of 33,998 PWH. The outcome was CKD development, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1·73 m2 calculated using the CKD-EPI equation, for ≥90 days with no intervening higher values. Findings: Adjusting for demographic and clinical characteristics, WWH were 61% more likely to develop CKD than men (adjusted hazard ratio [aHR]: 1·61, 95% CI: 1·46-1·78, p<0·001). This difference persisted after further adjustment for APOL1 risk variants (aHR female sex: 1·92, 95% CI: 1·63-2·26, p<0·001) and substance abuse (aHR female sex: 1·70, 95% CI: 1·54-1·87, p<0·001). Interpretation: WWH experienced increased risk of CKD. Given disparities in care among patients with end-stage kidney disease, efforts to engage WWH in nephrology care to improve chronic disease management are critical. Funding: US National Institutes of Health.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients.

Introduction: The management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited. Methods: This retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression. Results: There were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03-7.48), P = 0.044). Conclusion: Despite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Health-related quality of life and associated factors in HIV-positive transplant candidates and recipients from a HIV-positive donor.

INTRODUCTION: HRQOL in transplant candidates and recipients who are also infected with HIV and are awaiting a kidney, or have received one from a HIV-positive donor, has not been previously investigated. METHODS: The HRQOL of 47 HIV-positive kidney transplant candidates and 21 recipients from HIV-positive donors was evaluated using the Short Form-36 (SF-36) and face to face interviews at baseline and at 6 months. The correlation between SF-36 scores and sociodemographic, clinical and nutritional factors was determined. RESULTS: 68 patients completed the SF-36 at baseline and 6 months. Transplant candidates: transplant candidates had lower HRQOL than recipients. The main mental stressors were income, employment and waiting for a donor. Physical health complaints were body pain (BP) and fatigue. Pre-albumin and BMI was positively correlated with general health at baseline (r = 0.401, p = 0.031 and r = 0.338, p = 0.025). Besides a positive association with role physical (RP) and BP, albumin was associated with overall physical composite score (PCS) (r = 0.329, p = 0.024) at 6 months. Transplant recipients: Transplant recipients had high HRQOL scores in all domains. PCS was 53.8 ± 10.0 and 56.6 ± 6.5 at baseline and 6 months respectively. MCS was 51.3 ± 11.5 and 54.2 ± 8.5 at baseline and 6 months respectively. Albumin correlated positively with PCS (r = 0.464, p = 0.034) at 6 months and role emotional (RE) (r = 0.492, p = 0.024). Higher pre-albumin was associated with better RE and RP abilities and MCS (r = 0.495, p = 0.034). MAMC was associated with four domains of physical health and strongly correlated with PCS (r = 0.821, p = 0.000). CONCLUSION: Strategies to improve HRQOL include ongoing social support, assistance with employment issues and optimising nutritional status.

Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.

Transplant centers seeking to increase coronavirus disease 2019 (COVID-19) vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.

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.

In Defense of Patient Autonomy in Kidney Failure Care When Treatment Choices Are Limited.

Respect for patient autonomy is a primary ethical obligation of health care providers. In kidney health care, clinical practice recommendations commonly include strategies to promote shared decision making with patients and their families about treatment options to promote patient autonomy and improve patient outcomes. However, for many people with kidney failure, treatment options may be unavailable or inaccessible. In these circumstances some clinicians may act paternalistically and withhold information from patients because of a fear of causing harm or because clinicians believe that patient autonomy is not a relevant consideration. In this article, we reflect on the concept of autonomy in the context of clinical decision making in kidney failure care, with particular attention to resource-constrained settings and the disclosure of information to patients for whom treatment may be inaccessible. We examine and address key concerns that patient autonomy may be impossible, irrelevant, or harmful in the context of limited treatment choices, and discuss factors that may influence paternalistic practices in such settings. We conclude that respect for autonomy is intrinsically and instrumentally valuable, and argue that in neglecting patient autonomy in resource-constrained settings, clinicians may exacerbate and entrench the structural inequalities and health inequities they are committed to addressing.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. CONCLUSIONS: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies.

BACKGROUND: HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. METHODS: We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients. RESULTS: We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group. CONCLUSIONS: HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

Developing the ethical framework of end-stage kidney disease care: from practice to policy.

Ethical issues relating to end-stage kidney disease (ESKD) care are increasingly being discussed by clinicians and ethicists but are still infrequently considered at a policy level or in the education and training of health care professionals. In most lower-income countries, access to kidney replacement therapies such as dialysis is not universal, leading to overt or implicit rationing of resources and potential exclusion from care of those who are unable to sustain out-of-pocket payments. These circumstances create significant inequities in access to ESKD care within and between countries and impose emotional and moral burdens on patients, families, and health care workers involved in decision-making and provision of care. End-of-life decision-making in the context of ESKD care in all countries may also create ethical dilemmas for policy makers, professionals, patients, and their families. This review outlines several ethical implications of the complex challenges that arise in the management of ESKD care around the world. We argue that more work is required to develop the ethics of ESKD care, so as to provide ethical guidance in decision-making and education and training for professionals that will support ethical practice in delivery of ESKD care. We briefly review steps that may be required to accomplish this goal, discussing potential barriers and strategies for success.

The role of kidney transplantation as a component of integrated care for chronic kidney disease.

Kidney transplant provides superior outcomes to dialysis as a treatment for end-stage kidney disease. Therefore, it is essential that kidney transplantation be part of an integrated treatment and management plan for chronic kidney disease (CKD). Developing an effective national program of transplantation is challenging because of the requirement for kidney donors and the need for a multidisciplinary team to provide expert care for both donors and recipients. This article outlines the steps necessary to establish a national kidney transplant program, starting with the requirement for effective legislation that provides the legal framework for transplantation whilst protecting organ donors, their families, recipients, and staff and is an essential requirement to combat organ trafficking. The next steps involve capacity building with the development of a multiskilled workforce, the credentialing of transplant centers, and the reporting of outcomes through national or regional registries. Although it is accepted that most transplant programs will begin with living related kidney donation, it is essential to aspire to and develop a deceased donor program. This requires engagement with multiple stakeholders, especially the patients, the general community, intensivists, and health departments. Development of transplant centers should be undertaken in concert with the development of a dialysis program. Both are essential components of integrated care for CKD and both should be viewed as part of the World Health Organization's initiative for universal health coverage. Provisions to cover the costs of treatment for patients need to be developed taking into account the state of development of the overall health framework in each country.

Infectious Complications of Transplant Tourism.

PURPOSE OF REVIEW: To outline the impact of transplant tourism on the type and severity of post-transplant infections that may be seem in returning transplant tourists. This review outlines infections that might be expected and provides recommendations on screening tests that may assist in the diagnosis and management of such patients. RECENT FINDINGS: Transplant tourists may develop unusual or resistant infections that pose a public health risk in their home country. The practice of transplant tourism is associated with a significantly increased risk of surgical and infectious complications after transplant. Returning transplant tourists require a thorough evaluation for active and latent infections. Transplant centers must be vigilant for new and emerging pathogens in this population.