Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress.

BACKGROUND: Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT. METHODS: The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973-October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias. RESULTS: Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine , Transplantation , and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%). CONCLUSIONS: This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.

Trasplante renal en la próxima década: estrategias, retos y visión de futuro / Kidney transplant in the next decade: Strategies, challenges and vision of the future

Aunque los resultados del trasplante renal (TR) han mejorado sustancialmente en los últimos años, continúa observándose una pérdida crónica e inexorable de los injertos debido principalmente a la muerte del paciente y a la disfunción crónica del TR. Por tanto, los objetivos para optimizar esta situación en la próxima década se centran fundamentalmente en minimizar la tasa de pérdida de injertos renales, mejorar la supervivencia de los pacientes, incrementar la tasa de obtención de órganos y su distribución, fomentar la investigación y la formación de los profesionales sanitarios y la elaboración de registros científicos que proporcionen una información clínica y fiable que nos permita optimizar nuestra práctica clínica en el campo del TR. Con esta perspectiva, esta revisión profundizará en: 1) estrategias para evitar la disfunción crónica y la pérdida del injerto a medio y largo plazo; 2) prolongar la supervivencia del paciente; 3) estrategias para incrementar la donación, mantenimiento y distribución de órganos; 4) promocionar la investigación clínica y básica y la actividad formativa en TR; y 5) el análisis de los resultados en TR mediante la optimización y fusión de los registros. (AU)

Although the results of kidney transplantation (KT) have improved substantially in recent years, a chronic and inexorable loss of grafts mainly due to the death of the patient and chronic dysfunction of the KT, continues to be observed. The objectives, thus, to optimize this situation in the next decade are fundamentally focused on minimizing the rate of kidney graft loss, improving patient survival, increasing the rate of organ procurement and its distribution, promoting research and training in health professionals and the development of scientific registries providing clinical and reliable information that allow us to optimize our clinical practice in the field of KT. With this perspective, this review will deep into: (1) strategies to avoid chronic dysfunction and graft loss in the medium and long term; (2) to prolong patient survival; (3) strategies to increase the donation, maintenance and allocation of organs; (4) promote clinical and basic research and training activity in KT; and (5) the analysis of the results in KT by optimizing and merging scientific registries. (AU)

Alteraciones neoplásicas en el paciente trasplantado renal. Una revisión sistemática / Neoplastic alterations in the renal transplant patient. A systematic review

Introducción: El trasplante renal se ha destacado como la mejor terapia renal sustitutiva para la enfermedad renal crónica terminal, aunque conlleva una serie de riesgos entre los que el cáncer se destaca cada vez más, por lo que parece importante determinar el impacto que tiene en esta población.Objetivo:Conocer y sintetizar la evidencia científica acerca de la incidencia de neoplasias en pacientes trasplantados renales, así como las variables relacionadas con las mismas.Metodología:Se realizó una revisión sistemática en la que se incluyeron 14 artículos procedentes de las bases de Pubmed, Scopus, Scielo, WOS y Google Académico. Como términos MeSH se utilizaron: neoplasias (neoplasms), trasplante de riñón (kidney transplantation), incidencia (incidence), riesgo (risk), factores de riesgo (risk factors). Se incluyeron artículos originales en inglés y español, en población trasplantada adulta.Resultados:Se incluyeron 14 artículos de diseño observacional. De la revisión emergieron como principales variables: incidencia general, datos demográficos y tratamientos previos, otras características asociadas, tumores más frecuentes y medidas preventivas.Conclusiones:La incidencia de neoplasias en el paciente trasplantado es alta, sobre todo en la edad avanzada y pacientes con tratamiento inmunosupresor con ciclosporina y azatioprina siendo este último, junto al trasplante procedente de cadáver, los principales factores de riesgo encontrados. Los cánceres de piel no melanoma son los más prevalentes y como medidas de prevención se destaca llevar a cabo un cribado rutinario, fomento de una vida saludable, y promoción y potenciación de la vacunación de la hepatitis B. (AU)

Introduction: Renal transplantation has been considered the best renal replacement therapy for end-stage chronic kidney disease, even though it carries a number of risks among which cancer is increasingly prominent. Therefore, it is necessary to determine the impact on this population.Objective:To understand and synthesise the scientific evidence on the incidence of neoplasms in renal transplant patients, as well as the related variables.Methodology:A systematic review was carried out including 14 articles from Pubmed, Scopus, Scielo, Web of Science and Google Scholar databases. The MeSH terms used were: neoplasms, kidney transplantation, incidence, risk, risk factors. Original articles written in English and Spanish, studying adult transplanted population were included.Results:Fourteen articles with observational design were included. The main variables that emerged from the review were: overall incidence, demographic data and previous treatments, other associated characteristics, most frequent tumours and preventive measures.Conclusions:TThe incidence of neoplasms in transplant patients is high, especially in the older age group and in patients with immunosuppressive treatment with cyclosporine and azathioprine; the latter, together with transplantation from cadaver, being the main risk factors found. Non-melanoma skin cancers are the most prevalent and prevention measures include routine screening, promotion of a healthy lifestyle, and promotion and enhancement of hepatitis B vaccination. (AU)

Resultados del trasplante renal con donante en asistolia controlada expandido / Kidney transplant outcome of expanded criteria donors after circulatory death

El incremento en el número de pacientes en lista de espera de trasplante renal ha llevado a intentar aumentar el número de posibles donantes incorporando candidatos que anteriormente no se habrían considerado óptimos, incluyendo entre estos a los donantes de pacientes de asistolia (DA) y aquellos con criterios «expandidos» (DCE). Los receptores de injertos de DA controlada (DAc) sufren más función retrasada del injerto, pero presentan una evolución a largo plazo equiparable a los de donantes de muerte encefálica, lo que ha permitido un aumento en el número de trasplantes de DAc en distintos países en los últimos años. De forma paralela, el uso de DAc con criterios expandidos (DAc/DCE) se ha incrementado en los últimos años en diferentes países, permitiendo acortar la lista de espera del trasplante renal. El uso de estos injertos, aunque se relaciona con una mayor frecuencia de función retrasada del injerto, ofrece supervivencias del injerto a largo plazo similares o solo ligeramente inferiores a las de los donantes de muerte encefálica con criterios expandidos. Distintos estudios han observado que los receptores de injertos DAc/DCE tienen peor función renal que los DAc/estándar y que los donantes de muerte encefálica/DCE. La mortalidad asociada al trasplante de injertos de DAc/DCE se relaciona principalmente con la elevada edad del receptor. Los pacientes que reciben un trasplante renal de DAc/≥ 60 años presentan mejor supervivencia que los que continúan en la lista de espera, aunque este hecho no se ha demostrado en los receptores de DAc/> 65 años. La utilización de este tipo de órganos debe llevar pareja la optimización de los tiempos quirúrgicos y el menor tiempo de isquemia fría posible. (AU)

The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with “expanded” criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and brain death/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia. (AU)

Trends in Survival for Pediatric Transplantation.

OBJECTIVES: Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. METHODS: Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. RESULTS: Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. CONCLUSIONS: Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.

Evaluation of Racial, Ethnic, and Socioeconomic Disparities in Initiation of Kidney Failure Treatment During the First 4 Months of the COVID-19 Pandemic.

Importance: Persons with kidney failure require treatment (ie, dialysis or transplantation) for survival. The burden of the COVID-19 pandemic and pandemic-related disruptions in care have disproportionately affected racial and ethnic minority and socially disadvantaged populations, raising the importance of understanding disparities in treatment initiation for kidney failure during the pandemic. Objective: To examine changes in the number and demographic characteristics of patients initiating treatment for incident kidney failure following the COVID-19 pandemic by race and ethnicity, county-level COVID-19 mortality rate, and neighborhood-level social disadvantage. Design, Setting, and Participants: This cross-sectional time-trend study used data from US patients who developed kidney failure between January 1, 2018, and June 30, 2020. Data were analyzed between January and July 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Number of patients initiating treatment for incident kidney failure and mean estimated glomerular filtration rate (eGFR) at treatment initiation. Results: The study population included 127 149 patients with incident kidney failure between January 1, 2018, and June 30, 2020 (mean [SD] age, 62.8 [15.3] years; 53 021 [41.7%] female, 32 932 [25.9%] non-Hispanic Black, and 19 835 [15.6%] Hispanic/Latino patients). Compared with the pre-COVID-19 period, in the first 4 months of the pandemic (ie, March 1 through June 30, 2020), there were significant decreases in the proportion of patients with incident kidney failure receiving preemptive transplantation (1805 [2.1%] pre-COVID-19 vs 551 [1.4%] during COVID-19; P < .001) and initiating hemodialysis treatment with an arteriovenous fistula (2430 [15.8%] pre-COVID-19 vs 914 [13.4%] during COVID-19; P < .001). The mean (SD) eGFR at initiation declined from 9.6 (5.0) mL/min/1.73 m2 to 9.5 (4.9) mL/min/1.73 m2 during the pandemic (P < .001). In stratified analyses by race/ethnicity, these declines were exclusively observed among non-Hispanic Black patients (mean [SD] eGFR: 8.4 [4.6] mL/min/1.73 m2 pre-COVID-19 vs 8.1 [4.5] mL/min/1.73 m2 during COVID-19; P < .001). There were significant declines in eGFR at initiation for patients residing in counties in the highest quintile of COVID-19 mortality rates (9.5 [5.0] mL/min/1.73 m2 pre-COVID-19 vs 9.2 [5.0] mL/min/1.73 m2 during COVID-19; P < .001), but not for patients residing in other counties. The number of patients initiating treatment for incident kidney failure was approximately 30% lower than projected in April 2020. Conclusions and Relevance: In this cross-sectional study of US adults, the COVID-19 pandemic was associated with a substantially lower number of patients initiating treatment for incident kidney failure and treatment initiation at lower levels of kidney function during the first 4 months, particularly for Black patients and people living in counties with high COVID-19 mortality rates.

Polymorphisms in the CYP3A5 gene significantly affect the pharmacokinetics of sirolimus after kidney transplantation.

Aim: Sirolimus (SIR) is an immunosuppressant with limitations, including a narrow treatment window, multiple adverse reactions and large differences within and among individuals. Objective: The correlation between numerous SNPs and SIR in terms of trough concentration in the early stage after kidney transplantation was analyzed. Materials & methods: A retrospective cohort study involving 69 kidney transplantation recipients was designed. Blood samples were collected to extract total DNAs, and trough SIR concentrations were measured. Logistic regression was used to analyze the association between SNPs and SIR trough concentrations. Results: At 7 days, 1 month and 3 months, the mean SIR trough concentration of patients in the CYP3A5 rs4646453-CC group was significantly higher than that in the CYP3A5 rs4646453-AA and CYP3A5 rs4646453-CA groups (p < 0.001) and CYP3A5 rs15524-AA group was significantly higher than that in the CYP3A5 rs15524-AG and CYP3A5 rs15524-GG groups (p < 0.001). Conclusion: Our study indicated that both CYP3A5 rs4646453 and CYP3A5 rs15524 had a certain influence on SIR trough concentration at 7 days, 1 month and 3 months.

The Role of Immune-Related miRNAs in the Pathology of Kidney Transplantation.

MicroRNAs (miRNAs) are members of the non-coding regulatory RNA family that play pivotal roles in physiological and pathological conditions, including immune response. They are particularly interesting as promising therapeutic targets, prognostic and diagnostic markers due to their easy detection in body fluids and stability. There is accumulating evidence that different miRNAs provide disease-specific signatures in liquid samples of distinct kidney injuries. Using experimental models and human samples, there have been numerous suggestions that immune-related miRNAs are also important contributors to the development of different kidney diseases as well as important markers for monitoring response after kidney transplantation. However, there are limited data for understanding their function in the molecular pathways of allograft pathologies. In our review, we focused on microRNAs that are related to different aspects of immune response after kidney transplantation.

Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study.

BACKGROUND: Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function. METHODS: The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex. RESULTS: The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively. CONCLUSIONS: High percent normal saline administration is associated with delayed graft function in kidney transplant recipients.

Pancreas transplantation.

PURPOSE OF REVIEW: To define recent changes and future directions in the practice of pancreas transplantation (PT). Two major events have occurred in the past 18 months: COVID-19 pandemic, and the first world consensus conference on PT. Several innovative studies were published after the consensus conference. RECENT FINDINGS: During COVID-19 pandemic PT activity decreased. COVID-19 in transplant recipients increases mortality rates, but data from kidney transplantation show that mortality might be higher in waitlisted patients.The world consensus conference provided 49 jury deliberations on the impact of PT on management of diabetic patients and 110 practice recommendations.Recent evidence demonstrates that PT alone is safe and effective, that results of simultaneous pancreas and kidney (SPK) remain excellent despite older recipient age and higher prevalence of type 2 diabetes, that use of hepatitis C virus (HCV)-positive donors into HCV-negative recipients is associated with good outcomes, and that use of sirolimus as primary immunosuppressant and costimulation blockade does not improve results of SPK. SUMMARY: COVID-19 pandemic and the first world consensus conference on PT were major events. Although COVID-19 pandemic should not reduce PT activity in the future, a major positive impact on both volume and outcomes of PT is awaited from the proceedings of the world consensus conference.

Paediatric deceased donor kidney transplant in Australia: A 30-year review-What have paediatric bonuses achieved and where to from here?

BACKGROUND: In this 30-year national review, we describe trends in DD transplantation for paediatric recipients, assess the impact of paediatric allocation bonuses and identify outstanding areas of need for this population. METHODS: A retrospective review of all DD kidney only transplants to paediatric recipients (<18 years old) in Australia between 1989 and 2018 was conducted using deidentified extracts from the ANZDATA. RESULTS: Of the 1011 kidney only transplants performed in paediatric recipients during the study period, 426 (42%) were from deceased donors. Paediatric candidates on the DD waiting list had consistently higher rates of transplantation and shorter time from dialysis initiation to transplantation compared with adult candidates (median 372 vs 832 days in 2018, for example). Donor characteristics remained more favourable for paediatric recipients, despite a decline in the overall quality of the donor pool. The mean number of HLA antigen mismatches for paediatric recipients of DD transplants increased each decade (2.86 [1989-1998], 3.85 [1999-2008], 4.01 [2009-2018]). Both patient and graft survival have improved for paediatric DD transplant recipients in the most recent era (5-year graft and patient survival 85% vs 65% and 99% vs 94%, respectively, for 2009-2018 vs 1999-2008). CONCLUSIONS: The current DD kidney allocation system in Australia provides rapid access to high-quality organs for paediatric recipients, and early graft loss has decreased significantly in recent years; however, additional targeted interventions to address HLA matching may improve long-term outcomes in this population.

Recipient Obesity and Kidney Transplant Outcomes: A Mate-Kidney Analysis.

RATIONALE & OBJECTIVE: The impact of extreme recipient obesity on long-term kidney transplant outcomes has been controversial. This study sought to evaluate the association of various levels of recipient obesity on kidney transplantation outcomes by comparing mate-kidney recipient pairs to address possible confounding effects of donor characteristics on posttransplant outcomes. STUDY DESIGN: Nationwide observational cohort study using mate-kidney models. SETTING & PARTICIPANTS: In analysis based on the Organ Procurement and Transplant Network/United Network of Organ Sharing database, 44,560 adult recipients of first-time deceased-donor kidney transplants from 2001 through 2016 were paired by donor. PREDICTORS: Recipient body mass index (BMI) categorized as 18-25 (n = 12,446), >25-30 (n = 15,477), >30-35 (n = 11,144; obese), and >35 (n = 5,493; extreme obesity) kg/m2. OUTCOMES: Outcomes included patient survival, graft survival, death-censored graft survival, delayed graft function (DGF), and hospital length of stay. ANALYTICAL APPROACH: Conditional logistic regression and stratified proportional hazards models were used to compare outcomes as odds ratios and hazard ratios (HRs), adjusted for recipient and transplant factors, using recipients with a BMI >35 kg/m2 as a reference. RESULTS: At a median follow-up of 3.9 years, adjusted odds ratios for DGF were 0.42 (95% CI, 0.36-0.48), 0.55 (95% CI, 0.48-0.62), and 0.73 (95% CI, 0.64-0.83) for BMI 18-25, >25-30, and >30-35 kg/m2, respectively (P < 0.001 for all). Death-censored graft failure was less frequent for BMI ≤25 and >25-30 kg/m2 (HRs of 0.66 [95% CI, 0.59-0.74] and 0.79 [95% CI, 0.70-0.88], respectively; P < 0.001 for both), but not for BMI >30-35 kg/m2 (HR, 0.91 [95% CI, 0.81-1.02]; P = 0.09). Length of stay and patient survival did not differ by recipient BMI. LIMITATIONS: Observational study with limited detail regarding potential confounders. CONCLUSIONS: Despite an increased risk of DGF likely unrelated to donor organ quality, long-term transplant outcomes among recipients with a BMI >35 kg/m2 are similar to those among recipients with a BMI >30-35 kg/m2, supporting a flexible approach to kidney transplantation candidacy in candidates with extreme obesity.

The impact of COVID-19 on kidney transplantation and the kidney transplant recipient - One year into the pandemic.

The COVID-19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses on the impact of COVID-19 on kidney transplantation rates, mortality, policy decisions, and the clinical management of transplanted patients infected with COVID-19.

Scoping review: hotspots for COVID-19 urological research: what is being published and from where?

PURPOSE: Contemporary, original research should be utilised to inform guidelines in urology relating to the COVID-19 pandemic. This comprehensive review aimed to: identify all up-to-date original publications relating to urology and COVID-19, characterise where publications were from, and outline what topics were investigated. METHODS: This review utilised a search strategy that assessed five electronic databases, additional grey literature, and global trial registries. All current published, in-press, and pre-print manuscripts were included. Eligible studies were required to be original research articles of any study design, reporting on COVID-19 or urology, in any of study population, intervention, comparison, or outcomes. Included studies were reported in a narrative synthesis format. Data were summarised according to primary reported outcome topic. A world heatmap was generated to represent where included studies originated from. RESULTS: Of the 6617 search results, 48 studies met final inclusion criteria, including 8 pre-prints and 7 ongoing studies from online registries. These studies originated from ten countries according to first author affiliation. Most studies originated from China (n = 13), followed by Italy (n = 12) and USA (n = 11). Topics of the study included pathophysiological, administrative, and clinical fields: translational (n = 14), COVID-19-related outcomes (n = 5), urology training (n = 4), telemedicine (n = 7), equipment and safety (n = 2), urology in general (n = 4), uro-oncology (n = 3), urolithiasis (n = 1), and kidney transplantation (n = 8). CONCLUSION: This review has outlined available original research relevant to COVID-19 and urology from the international community. This summary may serve as a guide for future research priorities in this area.

Acute Versus Chronic Administration of Calcineurin-Inhibitors Differentially Affect T-Cell Function.

BACKGROUND: Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function. OBJECTIVE: We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC). METHODS: Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression. RESULTS: Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients. CONCLUSION: Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

Review of Newer Antidiabetic Agents for Diabetes Management in Kidney Transplant Recipients.

OBJECTIVE: This systematic review describes the efficacy, safety, and drug interactions of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose transport protein 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs). DATA SOURCES: Articles were identified by English-language MEDLINE search, published prior to May 2020, using the terms kidney transplant, OR PTDM, OR NODAT, AND metformin, OR DPP4, OR GLP1, OR SGLT2. STUDY SELECTION AND DATA EXTRACTION: All selected studies were included if the study population was composed of adult KTRs who were diagnosed with either impaired glucose tolerance, diabetes mellitus (DM), new-onset diabetes after transplant (NODAT), or posttransplantation diabetes mellitus (PTDM). DATA SYNTHESIS: In KTRs, there is evidence for safety with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors. However, urinary tract infections and a slight initial decrease in renal function may limit use of SGLT2 inhibitors. As compared with the nontransplant type 2 DM population, SGLT2 inhibitors are not as efficacious in KTRs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides an overview of the current literature on newer antidiabetic agents, addressing efficacy, safety, and drug interactions to help guide clinical decision-making for their use in KTRs. CONCLUSION: Newer antidiabetic agents have been recommended by the American Diabetes Association for potential cardiovascular, renal, and hypoglycemic benefits. Particular agents, such as DPP-4 inhibitors and GLP-1 RAs may play a role in correcting PTDM-related defects. Clinicians need to take into account both patient-specific and drug-specific characteristics when initiating these agents in KTRs.

Liver and Kidney Transplant During a 6-Month Period in the COVID-19 Pandemic: A Single-Center Experience.

OBJECTIVES: With the declaration of COVID-19 as a pandemic, many studies have indicated that elective surgeries should be postponed. However, postponement of transplants may cause diseases to get worse and increase the number in wait lists. We believe that, with precautions, transplant does not pose a risk during pandemic. Here, we aimed to evaluate our transplant results, which we safely performed during a 6-month pandemic period. MATERIALS AND METHODS: Until September 2020, 3140 kidney and 667 liver transplants have been performed in our centers. We evaluated 38 kidney transplants and 9 liver transplants procedures performed during the pandemic (March 1 to September 2, 2020). Recipient and donor candidates were screened for COVID-19 with polymerase chain reaction and thoracic computed tomography. All recipients had routine immunosuppressive protocol. During hospitalization at our COVID-19-free transplant facility, we restricted the interactions during multidisciplinary rounds. RESULTS: During the pandemic, 38 kidney transplants with an average length of hospital stay of 8.1 days were performed. Mean serum creatinine values of recipients were 0.91, 0.86, and 0.74 mg/dL on postoperative days 7, 30, and 90, respectively. During the pandemic, 9 living donor liver transplants (1 adult, 8 pediatric) were performed with an average length of hospital stay of 17.1 days. Mean serum total bilirubin levels were 0.9, 0.5, and 0.4 mg/dL on postoperative days 7, 30, and 90, respectively. Mean serum aspartate aminotransferase levels were 38.1, 28.3, and 22.3 U/L on postoperative days 7, 30, and 90, respectively. All recipients and donors were successfully discharged. Only 1 liver recipient died (on day 55 after discharge as a result of oxalosis-induced heart failure). CONCLUSIONS: According to our results, when precautions are taken, transplant does not pose a risk to patients during the pandemic period. We attribute the safety and success shown to our newly developed protocol in response to the COVID-19 pandemic.

Using Geographic Catchment Areas to Measure Population-based Access to Kidney Transplant in the United States.

BACKGROUND: Monitoring efforts to improve access to transplantation requires a definition of the population attributable to a transplant center. Previously, assessment of variation in transplant care has focused on differences between administrative units-such as states-rather than units derived from observed care patterns. We defined catchment areas (transplant referral regions [TRRs]) from transplant center care patterns for population-based assessment of transplant access. METHODS: We used US adult transplant listings (2006-2016) and Dartmouth Atlas catchment areas to assess the optimal method of defining TRRs. We used US Renal Data System and Scientific Registry of Transplant Recipient data to compare waitlist- and population-based kidney transplant rates. RESULTS: We identified 110 kidney, 67 liver, 85 pancreas, 68 heart, and 43 lung TRRs. Most patients were listed in their assigned TRR (kidney: 76%; liver: 75%; pancreas: 75%; heart: 74%; lung: 72%), although the proportion varied by organ (interquartile range for kidney, 65.7%-82.5%; liver, 58.2%-78.8%; pancreas, 58.4%-81.1%; heart, 63.1%-80.9%; lung, 61.6%-76.3%). Patterns of population- and waitlist-based kidney transplant rates differed, most notably in the Northeast and Midwest. CONCLUSIONS: Patterns of TRR-based kidney transplant rates differ from waitlist-based rates, indicating that current metrics may not reflect transplant access in the broader population. TRRs define populations served by transplant centers and could enable future studies of how transplant centers can improve access for patients in their communities.