Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient.

We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Impact of infections and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae on graft and patient survival in a kidney transplantation program in Mexico.

INTRODUCTION: Immunosuppressive treatments have improved graft and patient survival rates, but can increase the incidence of post-transplant infections. OBJECTIVES: To analyze data from kidney transplant patients and describe the pathogens responsible for the infections they experience. METHODS: Longitudinal, analytical, observational study of 103 patients who underwent kidney transplantation. The follow-up period was 5.07 ± 1.28 years. RESULTS: Overall mortality rate was 10.68% and graft loss rate was 14.56%. Regarding recipient risk of death, the Cox regression model showed a hazard ratio (HR) of 5.66 for positive bacterial cultures and 2.22 for positive extended-spectrum beta-lactamase (ESBL)-producing strains; as for graft loss, HR was 4.59 in those with positive bacterial cultures and 4.25 in those who were positive for ESBL-producing strains. CONCLUSIONS: Significant death risk was found in kidney transplant recipients with positive bacterial cultures and an increased risk of graft loss in those with positive bacterial cultures and in those who were positive for ESBL-producing Enterobacteriaceae isolates. The rate of ESBL-producing Enterobacteriaceae is high, and stricter strategies are therefore necessary to control the use of antibiotics.

INTRODUCCIÓN: Los tratamientos inmunosupresores han mejorado las tasas de supervivencia del injerto y del paciente, pero pueden incrementar las infecciones postrasplante. OBJETIVOS: Analizar los datos de pacientes con trasplante renal y describir las bacterias responsables de las infecciones que presentan. MÉTODOS: Estudio observacional, longitudinal y analítico de 103 pacientes sometidos a trasplante renal. El periodo de seguimiento fue de 5.07 ± 1.28 años. RESULTADOS: La tasa de mortalidad fue de 10.68 % y la de pérdida del injerto de 14.56 %. Respecto al riesgo de muerte del receptor, el modelo de regresión de Cox mostró un cociente de riesgo (HR, hazard ratio) de 5.66 en los pacientes con cultivo bacteriano positivo y de 2.22 en aquellos con cepas productoras de betalactamasas de espectro extendido (BLEE); en cuanto a la pérdida del injerto, el HR fue de 4.59 en quienes tuvieron cultivo bacteriano positivo y de 4.25 en aquellos con cepas productoras de BLEE. CONCLUSIONES: Se encontró riesgo significativo de muerte en receptores de trasplante renal con cultivo bacteriano positivo y mayor riesgo de pérdida del injerto en aquellos con cultivo bacteriano positivo y aislamiento de cepas productoras de BLEE. La tasa de enterobacterias productoras de BLEE es alta, por ello son necesarias estrategias más estrictas para controlar del uso de antibióticos.

Kidney transplant. Pan-American and Iberian productivity analysis in 2019 with a Mexican and chronic kidney disease perspective.

BACKGROUND: Kidney transplant (KT) is the most common solid organ transplantation in the world. OBJECTIVE: To analyze the information from Mexico on KT, waiting lists (WL) and patients on dialysis between 2012 and 2019 and compare that of 2019 with those of the countries of the American Continent, Spain and Portugal. MATERIAL AND METHODS: The required information was obtained from the Global Observatory on Organ Donation and Transplantation (GODT). RESULTS: Between 2012 and 2019, the annual number of kidney transplants (KTs) in Mexico increased by 12.5%, while the WL by December 31 of each year did it by 86.1%. In 2019, Spain and the US reported the highest KT rates, while Mexico ranked 8th in the Pan-American and Iberian comparison, 6th in the American Continent and 4th in Latin America. Mexico did not report to GODT the number of patients on dialysis in 2019 and 2018. CONCLUSIONS: KTs should be considered an integral part of renal replacement therapies. The GODT reports include the numbers of patients on dialysis for each country. Mexico does not always report this data, probably due to the lack of a national registry of chronic kidney disease, the creation of which should be supported.

ANTECEDENTES: El trasplante renal (TR) es el trasplante de órgano sólido más frecuente en el mundo. OBJETIVO: Analizar la información de México sobre TR, listas de espera (LE) y pacientes en diálisis entre 2012-2019 y comparar la del año 2019 con la de los países del continente americano, España y Portugal. MATERIAL Y MÉTODOS: La información requerida se obtuvo del Global Observatory on Organ Donation and Transplantation (GODT). RESULTADOS: Entre 2012-2019 en México el número anual de trasplantes renales (TR) se incrementó en un 12.5%, mientras que la LE al 31 de diciembre de cada año lo hizo en un 86.1%. En 2019, España y EE.UU. reportaron las tasas más altas de TR, mientras que México ocupó el 8.° lugar en la comparativa panamericana e ibérica, 6.° en el Continente Americano y 4.° en América Latina. México no reportó al GODT el número de pacientes en diálisis en 2019 y 2018. CONCLUSIONES: Los TR deben considerarse parte integral de las terapias de reemplazo renal. Los reportes del GODT incluyen las cifras de pacientes en diálisis de cada país. México no siempre reporta este dato, probablemente por carecer de un registro nacional de enfermedad renal crónica, cuya creación debe apoyarse.

Renal transplantation recipient patients survival.

INTRODUCTION: The Bajío High Specialty Regional Hospital started operating in 2007 to tackle the health demands of 5.8 million inhabitants. It has 184 beds and a transplant unit with 26 beds. In 2008, the renal transplant program launched activities. OBJECTIVE: To describe the survival of kidney transplant receptor patients and of the grafted kidney at the Bajío High Specialty Regional Hospital. METHODS: Retrospective cohort study, where consecutive transplants carried out between 2008 and 2016 were included. Statistical analysis was performed using the Kaplan-Meier method. RESULTS: A total of 837 transplants were analyzed. Graft survival censored for death, with a functional graft at 1 and 5 years, was 94.6% and 78.9%. Patient survival at 1 and 5 years was 95.4% and 88.1%. CONCLUSIONS: The renal transplant program is one of the the best programs established in Mexico, both for the number of deceased-donor kidney transplants performed and for the patient and graft survival achieved. These data indicate that the renal transplant program has had a sustained development.

INTRODUCCIÓN: El Hospital Regional de Alta Especialidad del Bajío inició sus funciones en 2007 para atender la demanda de salud de 5.8 millones de habitantes, cuenta con 184 camas y una unidad de trasplantes con 26 camas. En 2008 inició actividades el programa de trasplante renal. OBJETIVO: Presentar la supervivencia de los pacientes receptores de trasplante renal y del riñón injertado en el Hospital Regional de Alta Especialidad del Bajío, Guanajuato, México. MÉTODO: Estudio de cohorte retrospectivo en el que se incluyeron los trasplantes consecutivos realizados entre 2008 y 2016. El análisis estadístico se efectuó con el método de Kaplan-Meier. RESULTADOS: Se analizaron 837 trasplantes. La supervivencia del injerto censurada para muerte con injerto funcional a uno y cinco años fue de 94.6 y 78.9 %. La supervivencia del paciente a uno y cinco años fue de 95.4 y 88.1 %. CONCLUSIONES: El programa de trasplante renal constituye uno de los mejor establecidos en México, tanto por el número de trasplantes renales de donante fallecido realizados como por la supervivencia obtenida de paciente e injerto. Los datos indican que el programa de trasplante renal ha tenido un desarrollo sostenido.

Desempeño de las ecuaciones para estimar la tasa de filtración glomerular en pacientes mexicanos receptores de trasplante renal.

INTRODUCTION: The management of kidney transplant recipients requires glomerular filtration rate (GFR) monitoring, which is an indicator of graft primary function and patient survival. OBJECTIVE: To evaluate the performance of different creatinine or cystatin-based formulas in the estimation of glomerular filtration rate in Mexican patients receiving kidney transplantation. METHOD: 30 transplant recipients were included, in whom the glomerular filtration rate was measured by means of iothalamate, and was also calculated using seven equations based on cystatin or creatinine. RESULTS: The formula with the best performance was the one proposed by the chronic kidney disease epidemiology collaboration (CKD-EPI), with a bias of -2.4 mL/min/1.73 m2 and an accuracy of 9.6; 96.7 % of patients were within 30 % of the measured GFR. The second best formula was the modification of diet in renal disease (MDRD) equation. Cystatin-based equations showed a poor performance. CONCLUSIONS: Our study suggests that, in Mexican patients receiving kidney transplantations, the best equations to estimate GFR are the CKD-EPI and MDRD equations.

INTRODUCCIÓN: El manejo de los pacientes receptores de trasplante renal requiere vigilancia de la tasa de filtrado glomerular (TFG), la cual es un indicador de la función primaria del injerto y de la supervivencia del paciente. OBJETIVO: Evaluar el rendimiento en la estimación de la función renal de diferentes fórmulas basadas en creatinina o cistatina en pacientes mexicanos receptores de trasplante renal. MÉTODO: Se incluyeron 30 pacientes receptores de trasplante renal en quienes se midió tasa de filtrado glomerular por iodotalamato, la cual también se calculó por siete ecuaciones basadas en cistatina o creatinina. RESULTADOS: La fórmula con mejor desempeño fue la propuesta por CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), con un sesgo de −2.4 mL/minuto/1.73 m2 y precisión de 9.6; 96.7 % estaba dentro de 30 % de la tasa de filtrado glomerular medida. La segunda mejor ecuación fue la MDRD (Modification of Diet in Renal Disease). Las ecuaciones basadas en cistatina mostraron pobre desempeño. CONCLUSIONES: Nuestro estudio sugiere que en pacientes mexicanos receptores de trasplante renal las mejores ecuaciones para estimar la TFG son CKD y MDRD.

Lipocalina asociada con gelatinasa del neutrófilo como predictor de disfunción del injerto a un año del trasplante renal.

INTRODUCCIÓN: Estudios recientes sugieren que la lipocalina asociada con la gelatinasa del neutrófilo urinaria (NGALu) es superior a la creatinina para la detección temprana de la disfunción del injerto renal, pero son pocos los estudios que evalúan su utilidad como predictor a largo plazo de dicha función. OBJETIVO: Explorar si los valores de NGALu en las primeras 48 horas después del trasplante renal predicen la función del injerto a largo plazo. MÉTODO: Cohorte prospectiva en la que se evaluaron los valores de NGALu a las 2, 12, 24 y 48 horas postrasplante renal. RESULTADOS: Se valoraron 79 pacientes trasplantados renales. Al año de seguimiento, 30.4 de los pacientes presentó disfunción del injerto. No se encontraron diferencias estadísticamente significativas entre los valores de NGALu y la función a un año del injerto renal (p = 0.65); el análisis multivariado mostró que ningún valor de NGALu fue un marcador predictor de disfunción del injerto a un año del trasplante renal. CONCLUSIÓN: Los valores de NGALu obtenidos en las primeras 48 horas postrasplante no se asociaron con disfunción del injerto a un año del trasplante renal. INTRODUCTION: Recent studies suggest that urinary neutrophil gelatinase-associated lipocalin (uNGAL) is superior to creatinine for renal graft dysfunction early detection, but there are only few studies assessing its usefulness as long-term predictor of said function. OBJECTIVE: To explore if uNGAL values within the first 48 hours after kidney transplantation predict graft function on the long term. METHOD: Prospective cohort, where uNGAL values were assessed at 2, 12, 24 and 48 hours post-kidney transplantation. RESULTS: Seventy-nine kidney transplant recipients were evaluated. At one year of follow-up, 30.4% of patients had graft dysfunction. No statistically significant differences were found between the uNGAL values and the renal graft function at one year (p = 0.65); the multivariate analysis showed that no uNGAL value was a predictor marker of graft dysfunction at one year of kidney transplantation. CONCLUSION: The uNGAL values obtained within the first 48 hours post-transplant were not associated with graft dysfunction at one year of kidney transplantation.

Characterization and rapid control of a vancomycin-resistant Enterococcus faecium (VREF) outbreak in a renal transplant unit in Spain: The environment matters.

OBJECTIVE: To describe a clonal outbreak due to vancomycin-resistant Enterococcus faecium (VREF) in the nephrology and renal transplant unit of a tertiary teaching hospital in Barcelona, Spain, and to highlight how active patient and environment surveillance cultures, as well as prompt and directed intervention strategies, mainly environmental, helped to successfully bring it under control. PATIENTS AND METHODS: A study was conducted on patients admitted to the nephrology ward with any culture positive for VREF over a 6-month period (August 2012-January 2013). Based on the identification of a clonal link between the isolates, weekly rectal screening using swabs was implemented for all patients, as well as environmental cultures and cleaning of medical equipment and the ward. VREF isolates were identified by MicroScan and confirmed by Etest. Bacterial identification was confirmed by MALDI-TOF MS. The presence of van genes, and esp and hyl virulence genes was determined using PCR. The clonal relationship between the isolates was studied first with DiversiLab (bioMérieux), and then by PFGE-Smal and MLST. A two-tier sequence of infection control measures was implemented. RESULTS: During the study period, VREF was isolated from 13 patients. All cases were colonized with no criteria for infection. VREF isolates were also extensively recovered from the environment and medical equipment. Isolates carried the vanA gene, and were multidrug-resistant, including high-level resistance (MIC >16mg/L) to vancomycin and teicoplanin. Molecular analysis showed that all VREF isolates belonged to sequence type 17 (ST17) carrying hyl virulence genes. After implementing infection control measures in a two-tier sequence, and reinforcing particularly environmental and medical equipment cleaning, no further cases were detected in the follow-up year. CONCLUSION: A clonal outbreak of VREF-ST17 involving only colonization is reported. The prompt implementation of aggressive infection control measures in patients and the environment was effective in controlling the outbreak and avoided the potential emergence of infection among patients.

Urinary tract infection in kidney transplant recipients.

Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence from 25% to 75%, varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought reviews the incidence and importance of urinary tract infection on graft survival, the microbiology with special emphasis on multidrug resistant microorganisms, the therapeutic management of UTI and the prophylaxis of recurrent UTI among solid organ transplant recipients, highlighting the need for prospective clinical trials to unify the clinical management in this population.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. / Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por el virus de la inmunodeficiencia humana.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients.

INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. OBJECTIVES: To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. METHOD: This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. RESULTS: Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. CONCLUSIONS: Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs.

Kidney stones in renal transplant recipients: A systematic review.

INTRODUCTION: Lithiasis in renal graft recipients might be a dangerous condition with a potential risk of organ function impairment. EVIDENCE ACQUISITION: A systematic literature search was conducted through February 2023. The primary objective was to assess the incidence of lithiasis in kidney transplant (KT) recipients. The secondary objective was to assess the timing of stone formation, localization and composition of stones, possible treatment options, and the incidence of graft loss. EVIDENCE SYNTHESIS: A total of 41 non-randomized studies comprising 699 patients met our inclusion criteria. The age at lithiasis diagnosis ranged between 29-53 years. Incidence of urolithiasis ranged from 0.1-6.3%, usually diagnosed after 12 months from KT. Most of the stones were diagnosed in the calyces or in the pelvis. Calcium oxalate composition was the most frequent. Different treatment strategies were considered, namely active surveillance, ureteroscopy, percutaneous/combined approach, or open surgery. 15.73% of patients were submitted to extracorporeal shock wave lithotripsy (ESWL), while 26.75% underwent endoscopic lithotripsy or stone extraction. 18.03% of patients underwent percutaneous nephrolithotomy whilst 3.14% to a combined approach. Surgical lithotomy was performed in 5.01% of the cases. Global stone-free rate was around 80%. CONCLUSIONS: Lithiasis in kidney transplant is a rare condition usually diagnosed after one year after surgery and mostly located in the calyces and renal pelvis, more frequently of calcium oxalate composition. Each of the active treatments is associated with good results in terms of stone-free rate, thus the surgical technique should be chosen according to the patient's characteristics and surgeon preferences.

Review and analysis of the results of kidney transplantation programs in Mexico.

OBJECTIVE: To know, analyze and compare kidney transplant programs; considering the survival of recipients at 1 and 5 years, from hospitals in Mexico. METHOD: A systematic review was carried out whose search focused on the survival of kidney transplant recipients. All publications found in PubMed and Google from 1963 to 2021 were included. The expectation-maximization algorithm was applied, proposing a mixture of normals, and hierarchical grouping to establish if there is any type of pattern and determine if there is a difference between the percentages. of survival at 1 and 5 years between the groups formed. RESULTS: Eight hospitals that published the survival of kidney transplant recipients were found. Survival rates ranged, at 1 year, from 94.7% to 100%, and at 5 years, from 85% to 96.2%. The methods used for their comparison indicated that there is a difference between survival at 1 and 5 years. CONCLUSIONS: In Mexico there is little information on the results of kidney transplant programs, and the information found shows great heterogeneity in said programs. Some strategies and actions are proposed to improve survival underreporting.

OBJETIVO: Conocer, analizar y comparar los programas de trasplante renal, considerando la supervivencia de los receptores a 1 y 5 años, en los hospitales en México. MÉTODO: Se realizó una revisión sistemática cuya búsqueda se centró en la supervivencia de los receptores de trasplante renal. Se incluyeron todas las publicaciones encontradas en PubMed y Google de 1963 a 2021. Se aplicó el algoritmo de expectation-maximization, proponiendo una mezcla de normales, y agrupamiento jerárquico para establecer si hay algún tipo de patrón y determinar si hay diferencia entre los porcentajes de supervivencia a 1 y 5 años entre los grupos formados. RESULTADOS: Se encontraron ocho hospitales que publicaron la supervivencia de los receptores de trasplante renal. Los rangos de las tasas de supervivencia fueron, a 1 año, del 94.7% al 100%, y a los 5 años, del 85% al 96.2%. Los métodos empleados para su comparación indican que hay diferencia entre la supervivencia a 1 y 5 años. CONCLUSIONES: En México se tiene poca información sobre los resultados de los programas de trasplante renal, y la información encontrada muestra gran heterogeneidad en dichos programas. Se proponen algunas estrategias y acciones para mejorar el subregistro de supervivencia.

Screening for tropical and imported infections in migrant kidney transplant candidates from the kidney transplant access consultation.

BACKGROUND AND OBJECTIVE: Kidney transplantation (KT) should be postponed in those people with active bacterial, fungal, viral and parasitic processes, since these must be treated and resolved previously. The objective of this study is to present the screening circuit implemented by the Nephrology clinic and describe the prevalence of tropical and imported infections in KT candidates born or coming from endemic areas. MATERIALS AND METHODS: Descriptive cross-sectional study, carried out in 2021. Sociodemographic and clinical variables, serological data of general infections and specific tests of tropical infectious diseases were collected. A descriptive analysis of the data was carried out. RESULTS: 67 TR candidates from Latin America (32.8%), North Africa (22.4%), Sub-Saharan Africa (14.9%) and Asia (29.9%) were included. 68.7% were men and the mean age was 48.9 ±â€¯13.5 years. After the general and specific studies, 42 (62.7%) patients were referred to the Infectious Diseases Service to complete this study or indicate treatment. 35.8% of the patients had eosinophilia, and in one case parasites were detected in feces at the time of the study. Serology for strongyloidiasis was positive in 18 (26.9%) cases, while positive serology for other tropical infections was hardly detected. 34.3% of patients had latent tuberculosis infection. CONCLUSIONS: The prevalence of tropical and imported infections in migrant candidates for RT was low, except for strongyloidiasis and latent tuberculosis infection. Its detection and treatment are essential to avoid serious complications in post-TR. To this end, the implementation of an interdisciplinary screening program from the KT access consultation is feasible, necessary and useful.

Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients. Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration-dose ratio.

BACKGROUND AND JUSTIFICATION: The strategy of the concentration-dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. MATERIALS AND METHODS: 425 kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divide patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into 3 metabolizer groups: fast (CYP3A5*1 carriers and CYP34A*1/*1), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). RESULTS: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values. CONCLUSION: Determination of the metabolizer phenotype according to CYP polymorphisms or the C/D ratio allows patients to be distinguished according to their exposure to Tac. Probably the combination of both classification criteria would be a good tool for managing Tac dosage for transplant patients.

[Tixagevimab-cilgavimab as pre-exposure prophylactic treatment against SARS-CoV-2 in kidney transplantation patients]. / Tixagevimab-cilgavimab como tratamiento profiláctico preexposición frente a SARS-CoV-2 en pacientes trasplantados renales.

INTRODUCTION: It has been reported that after vaccination with RNAm or viral vectors from SARS-CoV-2 a significant number of solid organ transplant recipients do not develop an effective immune response. In this scenario, the use of tixagevimab-cilgavimab was approved by the European Medicines Agency for COVID-19 prophylaxis in immunocompromised patients in March 2022. We present our experience with a group of kidney transplant recipients who received prophylactic treatment with tixagevimab-cilgavimab. MATERIAL AND METHODS: Prospective study from a cohort of kidney transplant recipients who had been previously vaccinated with 4 doses and did not achieve a satisfactory immune response to vaccination, presenting antibody titers lower than 260 BAU/mL when measured by ELISA. A total of 55 patients who received a single dose of 150mg of tixagevimab and 150mg of cilgavimab between May and September of 2022 were included in this study. RESULTS: No immediate or severe adverse reactions, including worsening of kidney function, were observed after administering the drug or during follow up. All patients who had received the drug 3 months prior presented positive antibody titers (>260 BAU/mL). Seven patients were diagnosed with COVID, and one of those patients had to be admitted to the hospital and died 5 days later from infectious complications and a suspected diagnosis of bacterial coinfection. CONCLUSIONS: In our experience, all kidney transplant recipients reached antibody titers higher than 260 BAU/mL 3 months after receiving prophylactic treatment with tixagevimab-cilgavimab with no severe or irreversible adverse reactions.

Does obesity really affect renal transplantation outcomes?

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with stage 5 chronic kidney disease (CKD). About 60% of CKD patients are overweight or obese at the time of kidney transplantation, and post-transplant obesity occurs in 50% of patients, with a weight gain of 10% in the first year and high risk of cardiovascular mortality. Obesity is associated with an increased risk of delayed graft function (DGF), acute rejection, surgical complications, graft loss and mortality. The aim of this study is to assess the clinical evolution of obese and overweight patients that have received a kidney transplant, based on short- and long-term complications associated with a higher BMI. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study was conducted with 104 kidney or pancreas-kidney transplant patients between March 2017 and December 2020, with a follow-up until April 2021. For comparative analysis, patients were grouped according to BMI. RESULTS: Mean age was of 56.65 years, 60.6% male and 39.4 % female. Overweight patients experienced prolonged surgeries, more surgical wound dehiscence, delayed graft function, hernias, proteinuria and more indications for renal biopsies. Additionally, obese patients displayed more DGF, indications for renal biopsies, proteinuria, development of diabetes mellitus, atrial fibrillation and needed prolonged hospital stays. CONCLUSIONS: Despite a high prevalence of comorbidity in the overweight and/or obese population, we found no reduction in patient and/or graft survival. However, longer follow-up is needed.

Transplant renal artery stenosis: Study of incidence using doppler ultrasound, risk factors and analysis is effect in graft outcomes.

INTRODUCTION AND OBJECTIVES: Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation which estimated incidence is 13%. It could cause refractory arterial hypertension, kidney dysfunction and premature death in transplant recipients. METHODS: We carried out a retrospective study including every patient who underwent renal transplantation between 2014 and 2020. They were evaluated with a systematic post-transplant renal Doppler ultrasound. To identify independent risk factors for transplant renal artery stenosis we performed a multivariate analysis. RESULTS: Seven hundred twenty-four kidney transplants were included, 12% ​​were living donors and 88% were deceased donors. The mean age was 54.8 in recipients and 53 in donors. Transplant renal artery stenosis was diagnosed in 70 (10%) recipients, the majority in the first 6 months after surgery. 51% of patients with transplant renal artery stenosis were managed conservatively. The multivariate analysis showed diabetes mellitus, graft rejection, arterial resuture and donor body mass index as independent risk factors for transplant renal artery stenosis. Survival of the grafts with transplant renal artery stenosis was 98% at 6 months and 95% at two years. CONCLUSIONS: The systematic performance of Doppler ultrasound in the immediate post-transplant period diagnosed 10% of transplant renal artery stenosis in our cohort. Despite the above risk factors, an adequate monitoring and treatment could avoid the increased risk of graft loss in patients with transplant renal artery stenosis.

Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

Social determinants of health influencing the choice of dialysis modality in advanced chronic kidney disease: Need of an interdisciplinary approach.

INTRODUCTION: The influence of socioeconomic and cultural barriers in the choice of renal replacement therapy (RRT) techniques in advanced chronic kidney disease (ACKD) has been scarcely explored, which can generate problems of inequity, frequently unnoticed in health care. The aim of this study is to identify the "non-medical" barriers that influence the choice of RRT in an advanced chronic kidney disease (ACKD) consultation in Spain. MATERIAL AND METHODS: Retrospective analysis including the total number of patients seen in the ACKD consultation in a tertiary hospital from 2009 to 2020. Inclusion in the ACKD consultation began with an eligibility test and a decision-making process, conducted by a specifically trained nurse. The variables considered for the study were: age, sex, etiology of CKD, level of dependence for basic activities of daily living (Barthel Scale) and instrumental activities of daily living (Lawton and Brody Scale), Spanish versus foreign nationality, socioeconomic level and language barrier. The socioeconomic level was extrapolated according to home and health district by primary care center to which the patients belonged. RESULTS: A total of 673 persons were seen in the ACKD consultation during the study period, of whom 400 (59.4%) opted for hemodialysis (HD), 156 (23.1%) for peritoneal dialysis (PD), 4 (0.5%) for early living donor renal transplantation (LDRT) and 113 (16.7%) chose conservative care (CC). The choice of PD as the chosen RRT technique (vs. HD) was associated with people with a high socioeconomic level (38.7% vs. 22.5%) (p = 0.002), Spanish nationality (91% vs. 77.7%) (p < 0.001), to a lower language barrier (0.6% vs 10.5%) (p < 0.001), and to a higher score on the Barthel scale (97.4 vs 92.9) and on the Lawton and Brody scale (7 vs 6.1) (p < 0.001). Neither age nor sex showed significant differences in the choice of both techniques. Patients who opted for CC were significantly older (81.1 vs 67.7 years; p < 0.001), more dependent (p < 0.001), with a higher proportion of women (49.6% vs 35.2%; p = 0.006) and a higher proportion of Spaniards (94.7% vs 81%, p = 0.001) in relation to the choice of other techniques (PD and HD). Socioeconomic level did not influence the choice of CC. CONCLUSION: Despite a regulated decision-making process, there are factors such as socioeconomic status, migration, language barrier and dependency of the population that influence the type of RRT chosen. To address these aspects that may cause inequity, an intersectoral and multilevel intervention is required with interdisciplinary teams that include, among others, social workers, to provide a more holistic and person-centered assessment.