COVID-19 in transplant recipients: The Spanish experience.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.

Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients.

Background: Sotrovimab is a neutralizing monoclonal antibody (mAb) that seems to remain active against recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. The evidence on its use in kidney transplant (KT) recipients, however, is limited. Methods: We performed a multicenter, retrospective cohort study of 82 KT patients with SARS-CoV-2 infection {coronavirus disease 2019 [COVID-19]} treated with sotrovimab. Results: Median age was 63 years. Diabetes was present in 43.9% of patients, and obesity in 32.9% of patients; 48.8% of patients had an estimated glomerular filtration rate under 30 mL/minute/1.73 m2. Additional anti-COVID-19 therapies were administered to 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs 36.1%; P < .001) or intensive care admission (2.2% vs 25%; P = .002) and COVID-19-related mortality (2.2% vs 16.7%; P = .020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome, including need for ventilator support, intensive care, and COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired kidney function events, or non-kidney side effects related to sotrovimab were observed. Conclusions: Sotrovimab had an excellent safety profile, even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease, while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of monoclonal antibody therapies.

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.

Live donor kidney transplantation. Situation analysis and roadmap.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spainhave adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

Live donor kidney transplantation. Situation analysis and roadmap. / Trasplante renal de donante vivo. Análisis de situación y hoja de ruta.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

[Variations in echocardiography after bariatric surgery. Biliopancreatic diversion vs vertical gastrectomy]. / Variaciones de la ecocardiografía tras la cirugía bariátrica. Derivación biliopancreática vs. gastrectomía vertical.

INTRODUCTION: Introduction: obesity has become a worldwide health problem due to its relationship with cardiovascular morbimortality, thus bariatric surgery is considered as one of the main solutions for the correction of excess weight and, consequently, the improvement of its associated heart diseases. Objective: to compare vertical gastrectomy (VG) and biliopancreatic diversion (BPD) by observing echocardiographic characteristics both before and after surgery, as well as to evaluate surgical outcome in terms of the BAROS scale. Methods: results were collected from the echocardiographic testing requested for the preoperative study of patients who underwent surgery over the course of 24 months (from January 2014 to December 2015), as well as their anthropometric data. These were compared with postoperative parameters measured at 3 years after surgery. Results: finally, 26 patients were selected (13 VG and 13 BPD) with a mean age of 42 yrs. VG: initial BMI: 44.6 ± 7.1; final BMI: 31.8 ± 11.3 (p < 0.01); BPD: initial BMI: 48.1 ± 14.2; final BMI: 32.7 ± 10.4 (p < 0.01). Echocardiography: normal systolic function: 100% vs 92%; normal diastolic function: 88.5% vs 69.2%; no valvulopathy: 80% vs 69%; normal left atrium: 76.9% vs 73.1% (p > 0.05); HTA: 38.5% vs 19.2% (p < 0.05), preoperatively and postoperatively, respectively. Conclusions: no significant differences were found between the two groups studied with different techniques, although a slight deterioration in diastolic function was found in both groups. The comorbidities associated with obesity improved in both groups, and the surgery was scored as positive. The scant variation revealed by echocardiography prompts to reconsider its systematic preoperative use in these patients given the low cost-benefit ratio.

INTRODUCCIÓN: Introducción: la obesidad se ha convertido en un problema de salud a nivel mundial por su relación con la morbimortalidad cardiovascular. La cirugía bariátrica se plantea como una de las soluciones para la corrección del exceso de peso y mejoría de las cardiopatías asociadas. Objetivo: comparar la gastrectomía vertical con la derivación biliopancreática de tipo Scopinaro para observar la repercusión de los cambios que se producen en la estructura cardiaca tras la cirugía. Además, evaluar el resultado quirúrgico en función de la escala BAROS. Material y métodos: se recogieron los resultados de la ecocardiografía incluida en el estudio preoperatorio de los pacientes candidatos a cirugía bariátrica de nuestro hospital, intervenidos en un periodo de 2 años, junto a los datos antropométricos y de comorbilidad. Estos se compararon con los resultados postoperatorios medidos a los 3 años de la cirugía. Resultados: finalmente se seleccionaron 26 pacientes (13 GV y 13 DBP), con una edad media de 42 años. GV: IMC inicial de 44,6 ± 7,1; IMC final de 31,8 ± 11,3 (p < 0,01). DBP: IMC inicial de 48,1 ± 14,2; IMC final de 32,7 ± 10,4 (p < 0,01). Ecocardiografía: función sistólica normal: 100% vs. 92%; función diastólica normal: 88,5% vs. 69,2%; sin valvulopatía: 80% vs. 69%; aurícula izquierda normal: 76,9% vs. 73,1% (p > 0,05); HTA: 38% vs. 19% (p < 0,05), en el preoperatorio y postoperatorio, respectivamente. Conclusiones: no se encontraron diferencias significativas entre los dos grupos estudiados con técnicas diferentes, si bien pudo encontrarse un ligero deterioro de la función diastólica en ambos grupos. Las comorbilidades asociadas a la obesidad mejoraron en ambos grupos y el grado de evaluación de la cirugía fue positivo. La escasa variación de la ecocardiografía hace replantearse su uso sistemático en el preoperatorio de estos pacientes por el bajo índice coste-beneficio.

Effect of isolation measures on the incidence and prevalence of hepatitis C virus infection in hemodialysis.

BACKGROUND: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. METHODS: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993-1995 period chronic HD patients were treated either in a room exclusively for HCV- patients or in a room shared by HCV+ and HCV- patients. Complete separation of HCV+ and HCV- patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. RESULTS: There has not been a single seroconversion in the rooms where only HCV- patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV- patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. CONCLUSIONS: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.

Treatment of tuberculosis with rifabutin in a renal transplant recipient.

Development of tuberculosis infection in a renal transplant patient is infrequent in Spain, although the prevalence is higher than in the general population. These patients usually receive calcineurin inhibitors as the main component of their immunosuppressive treatment. The metabolism of these drugs, whether cyclosporine or tacrolimus, involves cytochrome P-450 3A. Rifampin, a widely used agent in the treatment of tuberculosis, is also an important inducer of cytochrome P-450 3A metabolism and has the capacity to decrease serum levels of the calcineurin inhibitors. This metabolic interaction makes pharmacologic management of tuberculosis-infected transplant patients more complex and can result in a higher risk of acute rejection caused by decreased levels of the immunosuppressant in the blood. The authors present a case of a renal transplant patient with a soft tissue infection caused by Mycobacterium tuberculosis who was treated with rifabutin instead of rifampin, with excellent results in terms of graft survival and overall survival. The use of rifabutin allowed the authors to achieve better control of circulating immunosuppressant levels and a lower probability of acute graft rejection.