Complex management and descriptive cost analysis of kidney transplant candidates: a descriptive cross-sectional study.

BACKGROUND: The organisational care needs involved in accessing kidney transplant have not been described in the literature and therefore a detailed analysis thereof could help to establish a framework (including appropriate timing, investment, and costs) for the management of this population. The main objective of this study is to analyse the profile and care needs of kidney transplant candidates in a tertiary hospital and the direct costs of studying them. METHODS: A descriptive, cross-sectional study was conducted using data on a range of variables (sociodemographic and clinical characteristics, study duration, and investment in visits and supplementary tests) from 489 kidney transplant candidates evaluated in 2020. RESULTS: The comorbidity index was high (> 4 in 64.3%), with a mean of 5.6 ± 2.4. Part of the study population had certain characteristics that could hinder their access a kidney transplant: physical dependence (9.4%), emotional distress (33.5%), non-adherent behaviours (25.2%), or language barriers (9.4%). The median study duration was 6.6[3.4;14] months. The ratio of required visits to patients was 5.97:1, meaning an investment of €237.10 per patient, and the ratio of supplementary tests to patients was 3.5:1, meaning an investment of €402.96 per patient. CONCLUSIONS: The study population can be characterised as complex due to their profile and their investment in terms of time, visits, supplementary tests, and direct costs. Management based on our results involves designing work-adaptation strategies to the needs of the study population, which can lead to increased patient satisfaction, shorter waiting times, and reduced costs.

Alloimmune risk assessment for antibody-mediated rejection in kidney transplantation: A practical proposal.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Although an improvement in graft survival has been observed in the last decades with the use of different immunosuppressive drugs, this is still limited in time with antibody-mediated rejection being a main cause of graft-loss. Immune monitoring and risk assessment of antibody-mediated rejection before and after kidney transplantation with useful biomarkers is key to tailoring treatments to achieve the best outcomes. Here, we provide a review of the rationale and several accessible tools for immune monitoring, from the most classic to the modern ones. Finally, we end up discussing a practical proposal for alloimmune risk assessment in kidney transplantation, including histocompatibility leukocyte antigen (HLA) and non-HLA antibodies, HLA molecular mismatch analysis and characterization of peripheral blood immune cells.

A comprehensive assessment of long-term SARS-CoV-2-specific adaptive immune memory in convalescent COVID-19 Solid Organ Transplant recipients.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.

Assessment of pre-donation glomerular filtration rate: going back to basics.

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors.

Considerations for an integrated population health databank in Africa: lessons from global best practices.

Background: The rising digitisation and proliferation of data sources and repositories cannot be ignored. This trend expands opportunities to integrate and share population health data. Such platforms have many benefits, including the potential to efficiently translate information arising from such data to evidence needed to address complex global health challenges. There are pockets of quality data on the continent that may benefit from greater integration. Integration of data sources is however under-explored in Africa. The aim of this article is to identify the requirements and provide practical recommendations for developing a multi-consortia public and population health data-sharing framework for Africa. Methods: We conducted a narrative review of global best practices and policies on data sharing and its optimisation. We searched eight databases for publications and undertook an iterative snowballing search of articles cited in the identified publications. The Leximancer software © enabled content analysis and selection of a sample of the most relevant articles for detailed review. Themes were developed through immersion in the extracts of selected articles using inductive thematic analysis. We also performed interviews with public and population health stakeholders in Africa to gather their experiences, perceptions, and expectations of data sharing. Results: Our findings described global stakeholder experiences on research data sharing. We identified some challenges and measures to harness available resources and incentivise data sharing.  We further highlight progress made by the different groups in Africa and identified the infrastructural requirements and considerations when implementing data sharing platforms. Furthermore, the review suggests key reforms required, particularly in the areas of consenting, privacy protection, data ownership, governance, and data access. Conclusions: The findings underscore the critical role of inclusion, social justice, public good, data security, accountability, legislation, reciprocity, and mutual respect in developing a responsive, ethical, durable, and integrated research data sharing ecosystem.

Luminex screening first vs. direct single antigen bead assays: Different strategies for HLA antibody monitoring after kidney transplantation.

MAIN PROBLEM: Luminex panel and single antigen beads (SAB) are used for screening and DSA specificity determination respectively. The cost of SAB may limit its general use, so some labs perform SAB tests only after positive screening. METHODS: We compared both strategies: 1) SAB only if positive screening with kits from manufacturer A, and 2) direct SAB from manufacturer B, and correlate their sensitivity with histological findings. RESULTS: We selected 118 kidney transplant recipients with a normal biopsy (n = 19), histological antibody-mediated damage (ABMR, n = 52) or interstitial fibrosis/tubular atrophy (IFTA, n = 47) following Banff 2015 and 2017 classification. Direct SAB detected DSA in 13 patients missed by screening. Strategy 1 detected DSA in 0% normal, 61.5% ABMR and 8.5% IFTA patients; percentages with strategy 2 were 5.2%, 78.8% and 14.8% (p=0.004). Strategy 2 identified DSA allowing full ABMR diagnosis in 17% cases missed by strategy 1. Thereafter, direct SAB from manufacturer A confirmed DSA in 46% DSA-positive cases with strategy 2 (55.5% ABMR cases). CONCLUSIONS: Luminex screening failed to identify clinically relevant HLA antibodies, hampering DSA detection in patients with possible ABMR. Direct SAB testing should be the chosen strategy for post-transplantation monitoring, albeit direct SAB from the two existing manufacturers may diverge in as much as 50% of cases.

Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value - a multi-centre cohort study.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) is a serious complication after kidney transplantation. FSGS relapse is suspected by a sudden increase in proteinuria but there is not an accurate noninvasive diagnostic tool to confirm this entity or to detect patients at risk. We aimed to validate the diagnostic performance of ApoA-Ib to detect FSGS relapses by measuring urinary ApoA-Ib in a retrospective cohort of 61 kidney transplanted patients (37 FSGS and 24 non-FSGS). In addition, to assess the ApoA-Ib predictive ability, ApoA-Ib was measured periodically in a prospective cohort of 13 idiopathic FSGS patients who were followed during 1 year after transplantation. ApoA-Ib had a sensitivity of 93.3% and a specificity of 90.9% to diagnose FSGS relapses, with a high negative predictive value (95.2%), confirming our previous results. In the prospective cohort, ApoA-Ib predated the recurrence in four of five episodes observed. In the nonrelapsing group (n = 9), ApoA-Ib was negative in 37 of 38 samples. ApoA-Ib has the potential to be a good diagnostic biomarker of FSGS relapses, providing a confident criterion to exclude false positives even in the presence of high proteinuria. It has also the potential to detect patients at risk of relapse, even before transplantation.

Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board.

Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation. Here, we have summarized the main knowledge and the main challenges of these seven topics with the aim to provide transplant professionals at large with key bullet points to successfully understand these new concepts.

Strategies for an Expanded Use of Kidneys From Elderly Donors.

The old-for-old allocation policy used for kidney transplantation (KT) has confirmed the survival benefit compared to remaining listed on dialysis. Shortage of standard donors has stimulated the development of strategies aimed to expand acceptance criteria, particularly of kidneys from elderly donors. We have systematically reviewed the literature on those different strategies. In addition to the review of outcomes of expanded criteria donor or advanced age kidneys, we assessed the value of the Kidney Donor Profile Index policy, preimplantation biopsy, dual KT, machine perfusion and special immunosuppressive protocols. Survival and functional outcomes achieved with expanded criteria donor, high Kidney Donor Profile Index or advanced age kidneys are poorer than those with standard ones. Outcomes using advanced age brain-dead or cardiac-dead donor kidneys are similar. Preimplantation biopsies and related scores have been useful to predict function, but their applicability to transplant or refuse a kidney graft has probably been overestimated. Machine perfusion techniques have decreased delayed graft function and could improve graft survival. Investing 2 kidneys in 1 recipient does not make sense when a single KT would be enough, particularly in elderly recipients. Tailored immunosuppression when transplanting an old kidney may be useful, but no formal trials are available.Old donors constitute an enormous source of useful kidneys, but their retrieval in many countries is infrequent. The assumption of limited but precious functional expectancy for an old kidney and substantial reduction of discard rates should be generalized to mitigate these limitations.