Predicting Kidney Transplantation Outcomes from Donor and Recipient Characteristics at Time Zero: Development of a Mobile Application for Nephrologists.

(1) Background: We report on the development of a predictive tool that can estimate kidney transplant survival at time zero. (2) Methods: This was an observational, retrospective study including 5078 transplants. Death-censored graft and patient survivals were calculated. (3) Results: Graft loss was associated with donor age (hazard ratio [HR], 1.021, 95% confidence interval [CI] 1.018-1.024, p < 0.001), uncontrolled donation after circulatory death (DCD) (HR 1.576, 95% CI 1.241-2.047, p < 0.001) and controlled DCD (HR 1.567, 95% CI 1.372-1.812, p < 0.001), panel reactive antibody percentage (HR 1.009, 95% CI 1.007-1.011, p < 0.001), and previous transplants (HR 1.494, 95% CI 1.367-1.634, p < 0.001). Patient survival was associated with recipient age (> 60 years, HR 5.507, 95% CI 4.524-6.704, p < 0.001 vs. < 40 years), donor age (HR 1.019, 95% CI 1.016-1.023, p < 0.001), dialysis vintage (HR 1.0000263, 95% CI 1.000225-1.000301, p < 0.01), and male sex (HR 1.229, 95% CI 1.135-1.332, p < 0.001). The C-statistics for graft and patient survival were 0.666 (95% CI: 0.646, 0.686) and 0.726 (95% CI: 0.710-0.742), respectively. (4) Conclusions: We developed a mobile app to estimate survival at time zero, which can guide decisions for organ allocation.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination of Death Simultaneous Pancreas - Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation is the optimal treatment for patients with type 1 diabetes and renal failure. The use of pancreas grafts from donation after circulatory death (DCD), using normothermic regional perfusion (NRP), is still marginal worldwide, mainly due to possible additional risks of graft dysfunction and complications compared with grafts from donors after brain death. METHODS: Case series of patients who underwent simultaneous pancreas-kidney transplantation after DCD-NRP between January 2018 and September 2022. This study evaluated early postoperative grafts and survival outcomes. RESULTS: Four patients were included. One patient lost the pancreatic graft due to arterial thrombosis requiring transplantectomy. Another patient required a laparotomy due to hemoperitoneum. Overall, 1-year pancreas and kidney graft survival was 75% and 100%, respectively. One patient developed a lymphoma during the follow-up. CONCLUSION: The use of pancreas grafts from DCD after NRP preservation is safe and feasible. Comparative studies with donors after brain death grafts and larger series are required to confirm the feasibility of DCD-NRP pancreas transplantation.

Update of the recommendations on the management of the SARS-CoV-2 coronavirus pandemic (COVID-19) in kidney transplant patients.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country. This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

Enfermedad linfoproliferativa difusa postrasplante renal: estudio longitudinal de 21.546 receptores durante 2 décadas en España / Lymphoproliferative disorders after renal transplantation along 2 decades: A large longitudinal study of 21.546 recipients

Introducción: La enfermedad linfoproliferativa difusa postrasplante (ELPD) es un grupo heterogéneo de enfermedades que se caracteriza por una proliferación de linfocitos después de un trasplante de órgano sólido y que presenta un espectro que comprende desde hiperplasias a agresivos linfomas. Material y métodos: Hemos evaluado, en un estudio observacional multicéntrico retrospectivo que incluye 21.546 receptores adultos de trasplante renal simple trasplantados en España de 1990 al 2009, la incidencia de ELPD durante un periodo de 22 años, su relación con el virus de Epstein-Barr, los factores de riesgo clásico y su pronóstico. Resultados: Un total de 275 receptores desarrollaron ELPD durante el seguimiento (1,2%), siendo 195 varones (70,9%) y 80 mujeres (29,1%), con una mediana de edad al diagnóstico de 59,2 (p25 44,7; p75 68) años. Doscientos cuarenta y cinco (89,0%) eran primeros trasplantes y 269 (97,8%) fueron de donante cadáver. Se objetivó virus de Epstein-Barr en el tejido proliferativo de 94 de los 155 casos estudiados (60,6%) y el 86,0% de las proliferaciones eran linfocitos B. La mediana del tiempo de desarrollo después del trasplante fue de 42 (p25 12; p75 77,5) meses. Un total de 188 receptores de 275 (68,3%) tenían algún factor de riesgo clásico. La incidencia anual fue de 0,14% el primer año y de 0,98% la acumulada en 10 años postrasplante. El periodo de seguimiento postrasplante de los receptores fue de 3 a 22 años. Durante el seguimiento 172 pacientes murieron (62,5%) y 103 (37,5%) tuvieron remisión completa. La causa de muerte más frecuente fue la progresión (n=91, 52,9%), seguida de la sepsis (n=24, 13,9%). La supervivencia del paciente después del diagnóstico fue del 51% al año, del 44% al segundo año y del 39% al quinto año. La supervivencia del injerto fue de 48, 39 y 33%, respectivamente. (AU)

Introduction: Posttransplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein-Barr virus. The use of antilymphocyte antibodies, Epstein-Barr virus seronegativity in the recipient, acute rejection and CMV infection have been identified as classical risk factors. Material and methods: We have studied, in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with Epstein-Barr virus, presence of classical risk factors and outcome in 21,546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. Results: A total of 275 recipients developed PTLD (1.2%), 195 males (70.9%), 80 females (29.1%), aged 59.2 (p25 44.7; p75 68) years. Two hundred forty-five (89.0%) were first transplant recipients and 269 (97.8%) from cadaveric donors. Epstein-Barr virus in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42 (p25 12; p75 77.5) months. One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62.5%) and 103 (37.5%) had a complete remission. The main cause of death was PTLD progression (n=91, 52,9%), followed by sepsis (n=24, 13.9%). The follow-up period post-transplant of the recipients was between 3 and 22 years. The incidence was 0.14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years. Patient survival after diagnosis was 51, 44 and 39% after one, 2 and 5 years, respectively. Finally, overall graft survival was 48, 39 and 33% at the same periods. (AU)

Changes over time in the causes of death with a functioning graft in kidney transplantation recipients.

INTRODUCTION: Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). OBJECTIVE: To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. METHODS: Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). RESULTS: A total of 9905 KT were performed, registering 1861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%). In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 1996-2007: 29%, 2008-2018: 26.8%) (P < .001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras. In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. CONCLUSIONS: Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.

Cambios en el tiempo de las causas de muerte con injerto funcionante en los receptores de trasplante renal / Changes over time in the causes of death with a functioning graft in kidney transplantation recipients

Introducción: La muerte con injerto funcionante (MCIF) es la causa más frecuente de pérdida del trasplante renal (TR). Objetivo: Analizar la evolución de las etiologías de MCIF y la frecuencia de los tipos de neoplasia causantes. Métodos: Estudio retrospectivo de los TR en Andalucía desde 1984 hasta 2018. Analizamos la evolución de las MCIF según etapas (1984-1995; 1996-2007; 2008-2018) y según período post-TR (muerte precoz: primer año post-TR; muerte tardía: tras el primer año post-TR). Resultados: Se realizaron 9.905 TR; se produjeron 1.861 MCIF. Las causas más frecuentes fueron enfermedad cardiovascular (25,1%), infecciones (21,5%) y neoplasias (19,9%). En las muertes precoces no observamos cambios en el tiempo; las infecciones siempre fueron la causa principal. En las tardías, desciende la muerte cardiovascular (1984-1995: 35,2%; 1996-2007: 22,6%; 2008-2018: 23,9%) y aumentan las muertes por infecciones (1984-1995: 12,5%; 1996-2007: 18,3%; 2008-2018: 19,9%) y, sobre todo, por cáncer (1984-1995: 21,8%; 1996-2007: 29%; 2008-2018: 26,8%) (p<0,001). En el análisis multivariante para muerte tardía cardiovascular, edad del receptor, retrasplante, diabetes y primera etapa fueron factores de riesgo, mientras que el riesgo de muerte tardía por cáncer e infecciones se asoció con las etapas recientes. La neoplasia más frecuente en el primer año post-TR fue la enfermedad linfoproliferativa post-TR y tras el primer año el cáncer de pulmón, sin diferencias entre etapas. Conclusiones: A pesar de la mayor comorbilidad del receptor, las muertes cardiovasculares han descendido. Las neoplasias son la principal causa de muerte tardía en los últimos años. El cáncer de pulmón es la neoplasia más frecuente causante de MCIF en TR. (AU)

Introduction: Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). Objective: To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. Methods: Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). Results: A total of 9,905 KT were performed, registering 1,861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%). In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 11996-2007: 29%, 2008-2018: 26.8%) (P<0.001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras. In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. Conclusions: Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients. (AU)

Short- and Long-Term Intestinal Complications After Combined Pancreas-Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is the treatment of choice in patients with type 1 diabetes and end-stage renal disease, because it improves survival and quality of life. Currently, enteric exocrine drainage is the most commonly used method. Intestinal complications continue to be a major cause of posttransplant morbidity despite improvements in surgical technique. This study analyzed early and late intestinal complications related to SPK transplantation. MATERIALS AND METHODS: We performed a retrospective analysis of 100 adult patients undergoing SPK transplantation between January 2009 and December 2019. We performed systemic venous drainage and exocrine enteric drainage with duodenojejunostomy. Statistical analysis was performed using SPSS v2. This study was performed in accordance with the Declaration of Istanbul and the 1964 Declaration of Helsinki. Informed consent was obtained from all participants involved in the study. RESULTS: Intestinal complications were reported in 18 patients. Ten patients (10%) had the following early intestinal complications including: ileus (n = 4), intestinal obstruction (n = 2), graft volvulus (n = 1), duodenal graft fistula (n = 1), and jejunal fistula after pancreas transplantation (n = 1). Two cases required relaparotomy: graft repositioning with Roux-en-Y conversion (n = 1) and Y-roux conversion (n = 1). Eight patients had repeated episodes of intestinal obstruction (8%), of whom 2 required surgery for resolution with 100% postoperative mortality. CONCLUSIONS: SPK transplantation with enteric drainage via duodenojejunostomy has a low rate of short- and long-term postoperative intestinal complications. Surgery in patients with recurrent intestinal obstruction has a high mortality risk and should be performed in reference transplant centers.

Second and Third Chance to Stop Having Diabetes. Pancreas Retransplant With Functional Kidney Graft: A Single-Center Experience.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplant is the primary option in patients with type 1 diabetes mellitus who develop end-stage kidney disease. Pancreas retransplant (PRt) has become an alternative in patients who experience pancreas graft failure (PGF). There is a lack of evidence regarding PRt in international registers. There are small series of published research with indeed heterogeneous results. We aim to compare PRt outcomes with primary SPK transplant in our center. METHODS: The study was designed as a descriptive study of a cohort of 234 patients who received SPK transplant and received another PRt because of PGF at Reina Sofía University Hospital between 1988 and 2021. Kaplan-Meier analysis was performed to calculate patient and allograft survival. RESULTS: Of these 234 SPK transplants, 53 pancreas grafts (22.6%) were lost initially. In total, 15 PRts were performed. The major cause of first PGF was surgical, whereas the medical cause was the most frequent in the PRt group. There were 60 deaths in the SPK group compared with only 1 in the PRt group. In Kaplan-Meier analysis, the PRt group showed worse survival than the SPK group, with statistically significant difference between groups (P = .05). Patient survival was not different between both groups. CONCLUSIONS: PRt constitutes a viable option for recipients who experience PGF in the absence of formal contraindication. Although graft retransplant survival seems to be inferior to first graft in our series, these results are difficult to compare because of the scarce number of procedures performed.

Long-term Kidney Function Evolution in Living Kidney Donors: A Single Center Experience.

Living donor kidney transplant is the best treatment for end-stage kidney disease, posing minimal perioperative morbimortality for the donor, although long-term consequences are subject of debate if donor acceptance widens. We present a retrospective observational study analyzing clinical, demographic, and analytical variables throughout the follow-up period of 60 kidney donors whose procedures were performed between 1985 and 2021 at our hospital. Donors were divided according to their previous high blood pressure status, analyzing kidney function and other clinical parameters throughout follow-up. There were no statistically significant differences, although there was a trend toward a higher uric acid levels and lower high-density lipoprotein cholesterol in predonation patients with hypertension, not yielding an excess of end-stage kidney disease between groups at the end of the follow-up. We also analyzed the evolution of estimated glomerular filtration rate (eGFR), dividing patients into tertiles, which resulted in none of the parameters associating a higher rate of progression. All donors had an eGFR >71 mL/min/1.73 m2 at the time of donation. Over time, a decline in eGFR <60 mL/min/m/1.73 m2 was observed in 26 patients (53.6%), measured by Chronic Kidney Disease Epidemiology Collaboration estimation and in 55.4% of the total (31 patients) by Modification of Diet in Renal Disease. At our center, kidney donors with adequate predonation eGFR, although presenting a reduction in postnephrectomy eGFR, remain stable afterward, with none of them reaching an eGFR <30 mL/min/1.73 m2. We found no differences in the impact of high blood pressure on long-term eGFR, nor predictive factors influencing the rate of eGFR decline. Studies with larger number of patients are needed to confirm these results.

Incidence of Lymphoproliferative Disorders After Renal Transplantation is Down, but the Poor Prognosis Remains. Multicenter 32-Year Cohort Study.

BACKGROUND: Post-transplant lymphoproliferative disorders represent rare but serious complications of kidney transplantation. METHODS: We assessed incidence, risk factors, and outcomes in 21,546 patients receiving grafts between 1990 and 2009. Data were compared by decade of transplant (1990-1999 vs 2000-2009). Patients were followed for at least 12 years over a 32-year study period. RESULTS: In total, 331 patients (1.5%) developed PTLD: 189 of 9740 transplanted in the first decade, and 142 of 11,806 in the second. Incidence decreased significantly (19.40 vs12.02 cases/1000 patients; P < .001). Mean age at diagnosis was 50.2 years (standard deviation 14.7), and the median time from transplant to PTLD diagnosis was 48 months (interquartile range, 14.7-77.5), with no difference between cohorts. The origin of PTLD was mostly (86%) B-cell proliferation. No classical risk factors were reported in 31.7% of affected patients. Compared with 2000 to 2009, in 1990 to 1999 there was a higher frequency of induction therapy (P = .023) and detection of the Epstein-Barr virus in lymphoproliferative tissue (71.3% vs 52.7% P = .019). After diagnosis, 1- and 5-year patient survival was 51% and 38%. Graft survival was 48% and 33%. Survival was stable throughout the study period. CONCLUSION: Post-transplant lymphoproliferative disorders have a low and decreasing incidence, but the poor prognosis has not changed.

[Update of the recommendations on the management of the SARS-CoV-2 coronavirus pandemic (COVID-19) in kidney transplant patients.] / Actualización de las recomendaciones en el manejo de la pandemia por coronavirus SARS-CoV-2 (COVID-19) en pacientes con trasplante renal.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country.This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial.

BACKGROUND: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS: In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION: NCT03123627.

Influence of Donor and Recipient Sex Matching in Simultaneous Pancreas-Kidney Transplantation Outcomes.

BACKGROUND: Several studies in solid organ transplantation have shown a correlation between donor and recipient sex mismatch and risk of graft loss; however, it is possible influence is not well established. The aim of our study was to review the outcomes of pancreatic and kidney grafts in our series depending on sex matching. METHODS: We retrospectively analyzed a cohort of 199 patients who underwent simultaneous pancreas-kidney transplantation from February 1989 to June 2019 at the Reina Sofia University Hospital. RESULTS: Survival of patients in the series was 93.5% at 5 years, 84.3% at 10 years, and 71.5% at 15 years. In the sex-discordant group, survival of patients in the series at 5, 10, and 15 years was 94%, 82.3%, and 71.7% compared with 92.3%, 85.1%, and 72.2% in the concordant group, with no statistically significant differences (P = .86). Pancreatic graft survival censored for death at 5, 10, and 15 years was 79.5%, 60.8%, and 57.5% in the group with discordant sex vs 77.5%, 67.8%, and 65.5% in the concordant group, finding no statistically significant differences (P = .54). Kidney graft survival censored for death at 5, 10, and 15 years was 89.3%, 85%, and 78.1% in the sex-discordant group vs 87.3%, 83.5%. and 78.8% in the concordant group, with no differences (P = .69). No differences were observed between the 2 groups in the rate of serious postoperative complications or acute rejection. CONCLUSION: Our study shows that donor-recipient sex mismatch in simultaneous pancreas-kidney transplantation does not negatively influence perioperative outcomes and survival of the patient and both grafts.

First Report in the Literature of Biopsy-Proven Noncollapsing Focal Segmental Glomerulosclerosis Relapse in a Second Renal Transplant Presenting With Thrombotic Microangiopathy: A Case Report.

Primary focal segmental glomerulosclerosis (FSGS) is a podocytopathy with an irregular response to immunosuppressive therapies. FSGS relapse occurs in 30% to 80% of kidney grafts, and poor survival outcomes include large proteinuria and the nephrotic syndrome's cardinal clinical features. Thrombotic microangiopathy (TMA) is caused by endothelial injury due to complement dysregulation including acute kidney injury, proteinuria, and severe hypertension common renal presentations. Both pathologies have well-described genetic forms, but their relationship remains uncertain. FSGS lesions can be found in kidney biopsy specimens in patients with TMA, and TMA has been reported in patients with collapsing glomerulopathy. However, this combination has not been clearly described in renal transplant recipients. We present the case of a 22-year-old man who received his second kidney allograft and developed an early graft disfunction with nephrotic syndrome and clinical TMA. His background was remarkable for primary, biopsy-confirmed FSGS in childhood, and he started hemodialysis in 2006 and received a living donor kidney graft the same year. He presented with a FSGS relapse with malignant hypertension and seizures in the first posttransplant month and had an irregular response to plasma exchange and rituximab, and dialysis was reinitiated 10 years later. A total of 3 biopsies were performed after his second kidney transplant showing the evolution of a FSGS relapse with histologic and clinical TMA in the absence of identified genetic mutations. Partial responses to treatments with plasma exchange, eculizumab, and rituximab were obtained, but the allograft was lost after 26 months. This case is the first report of concomitant FSGS and TMA in a renal transplant recipient.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Case Report: Successful Response to Intravenous Immunoglobulin and Steroid Pulses in a Renal Transplant Recipient With Severe Covid-19 Disease and Associated Acute Allograft Failure.

The impact of Covid-19 pneumonia caused by SARS-CoV-2 on transplanted populations under chronic immunosuppression seems to be greater than in normal population. Clinical management of the disease, particularly in those patients worsening after a cytokine storm, with or without allograft impairment and using available therapeutic approaches in the absence of specific drugs to fight against the virus, involves a major challenge for physicians. We herein provide evidence of the usefulness of high-dose intravenous immunoglobulin (IVIG) combined with steroid pulses to successfully treat a case of Covid-19 pneumonia in a single-kidney transplanted patient with mechanical ventilation and hemodialysis requirements in the setting of a cytokine storm. A rapid decrease in the serum level of inflammatory cytokines, particularly IL-6, IL-8, TNF-α, MCP-1 and IL-10, as well as of acute-phase reactants such as ferritin, D-dimer and C-reactive protein was observed after the IVIG infusion and methylprednisolone bolus administration with a parallel clinical improvement and progressive allograft function recovery, allowing the patient's final discharge 40 days after the treatment onset. The immunomodulatory effect of IVIG together with the anti-inflammatory and immunosuppressive potential of steroids could be an alternative strategy to treat severe cases of Covid-19 pneumonia associated with an uncontrolled inflammatory response in transplanted populations.