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Supplemental Digital Content is available in the text., 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.

Malaltia renal en fase terminal; Trasplantament de ronyó Enfermedad renal en etapa terminal; Transplante de riñón End-stage renal disease; Kidney Transplant Background. There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx). Methods. We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up. Results. A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of −0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of −9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years. Conclusions. If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.

Trasplante renal de donante vivo; Tratamiento de la enfermedad renal Living donor kidney transplantation; Chronic kidney disease treatment Trasplantament renal de donant viu; Tractament de la malaltia renal El trasplante renal de donante vivo (TRDV) es la opción terapéutica con las mejores expectativas de supervivencia para el injerto y para el paciente con insuficiencia renal terminal; sin embargo, este tipo de trasplantes ha experimentado un descenso progresivo en los últimos años en España. Entre las posibles explicaciones del descenso de actividad se encuentra la coincidencia en el tiempo con un aumento en el número de donantes renales fallecidos, tanto por muerte encefálica como por asistolia controlada, que podría haber generado una falsa impresión de ausencia de necesidad del TRDV. Además, la disponibilidad de un mayor número de riñones para trasplante habría supuesto un incremento en la carga de trabajo de los profesionales que pudiera enlentecer los procesos de donación en vida. Otro posible argumento radica en un posible cambio de actitud hacia posturas más conservadoras a la hora de informar a pacientes y a familiares acerca de esta opción terapéutica, a raíz de los artículos publicados respecto al riesgo de la donación a largo plazo. Sin embargo, existe una importantísima variabilidad en la actividad entre centros y comunidades autónomas, no explicada por el volumen de trasplante procedente de otros tipos de donante. Este dato, unido a que la indicación de donación renal en vida se realiza de manera mayoritaria en situación de enfermedad renal crónica avanzada (ERCA) y que el tiempo en diálisis es un factor pronóstico negativo respecto a la supervivencia postrasplante, permite concluir que el descenso depende además de otros factores. Por este motivo, en la reunión anual de equipos de trasplante renal, celebrada en la sede de la Organización Nacional de Trasplantes (ONT) en 2018, se constituyó un grupo de trabajo formado por equipos de trasplante renal, el grupo de trasplantes de la Sociedad Española de Nefrología (SEN) (SENTRA), la Sociedad Española de Trasplantes (SET) y la ONT, con el objetivo de identificar otras causas que condicionaron el descenso de la actividad de este tipo de trasplantes en España y su posible relación con la gestión del proceso de donación de vivo. El grupo de trabajo diseñó un cuestionario de autoevaluación, que fue cumplimentado por las 33 unidades de trasplante renal de donante vivo activas en España. El cuestionario contiene preguntas sobre las diferentes fases del proceso de donación de vivo: información inicial, estudio del donante vivo e información de los riesgos, consentimiento, recursos humanos (RRHH), nefrectomía, trasplante y seguimiento posterior. El análisis de las respuestas ha dado como resultado la creación de un análisis de debilidades, amenazas, fortalezas y oportunidades (DAFO) del programa a nivel nacional y ha permitido elaborar recomendaciones específicas dirigidas a mejorar cada una de las fases del proceso de donación en vida. El documento, denominado Análisis de situación del trasplante renal de donante vivo y hoja de ruta ha sido también revisado por un panel de expertos en TRDV, representantes de varias sociedades científicas implicadas (Asociación Española de Urología [AEU], Sociedad Española de Enfermería Nefrológica [SEDEN], Sociedad Española de Inmunología [SEI/GETH]), el Grupo de Trabajo Enfermedad Renal Crónica Avanzada (ACERCA), la Asociación de Pacientes para la Lucha Contra la Enfermedad Renal (ALCER) y sometido posteriormente a consulta pública. Tras incluir las mejoras sugeridas, el documento final ha sido adoptado institucionalmente en el Consejo Interterritorial de Trasplantes (CIT) del Sistema Nacional de Salud. El trabajo realizado y las recomendaciones para optimizar el TRVD se describen a lo largo del presente artículo, organizados por los diferentes apartados del proceso de donación. 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.

Background. The rapid identification of the viral load from hepatitis C virus (HCV) in seropositive donors enables the determination of their infection capacity and the subsequent design of a strategy to optimize the use of direct-action antivirals (DAA) in seronegative recipients. In 2017, we designed an optimization protocol; this study aims to assess its efficacy and safety. Methods. This is a prospective, multicenter observational study that complies with the Declarations of Helsinki and Istanbul. Donors were HCV seropositive. The HCV and human immunodeficiency virus loads were immediately determined in the donors. For viremic donors, recipients were treated with DAA for 8 weeks. For nonviremic donors, DAA was started if a viral load was detected during the follow-up period. The minimum follow-up period was 6 months posttransplant. Results. This study recruited 28 donors. Just over half of the donors (n = 15; 53.5%) had a nonactive history of injection drug use. Eight (22.4%) donors were viremic, and 20 (87.6%) were nonviremic; 13 (65%) had been treated previously. Nine grafts were ineligible for the protocol. We performed a total of 47 transplants. Procedure I (viremic donors) was performed in 13 recipients (27.7%). Posttransplant viremia was observed in 6 participants. Posttransplant viremia was low (

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes. ispartof: KIDNEY INTERNATIONAL vol:100 issue:1 pages:196-205 ispartof: location:United States status: published

Higher rates of severe COVID‐19 have been reported in kidney transplant recipients (KTRs) compared to non‐transplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score‐matching method to compare survival and severe disease‐free survival (defined as death and/or need for intensive care unit (ICU)) incidence in hospitalized KTRs and non‐transplant control patients between 26 February and 22 May 2020. Patients were matched for risk factors of severe COVID‐19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3‐73.1) in 3 French transplant centers. After a median follow‐up of 13 days (7‐30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow‐up of 8.5 days (2‐14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched non‐transplant patients with respective 30‐days survival of 62.9% and 71% (p=0.38) and severe disease‐free 30‐days survival of 50.6% and 47.5% (p=0.91). These findings suggest that severity of COVID‐19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Background and Aims A major complication primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of this relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in urine of native primary FSGS patients and have associated this feature to a prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. Method We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation (urinary ApoA-Ib positive) and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (No-FSGS, urinary ApoA-Ib negative). Results In ApoA-Ib positive recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells while in the No-FSGS patients ApoA-I was found along the cytoplasm of the tubular cells (Figure 1). Conclusion The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in the urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in the urine of native primary FSGS patients, this feature has been associated with prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study, we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (non-FSGS). In recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells, while in the non-FSGS patients, ApoA-I was found along the cytoplasm of the tubular cells. The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution.

BACKGROUND Preimplantation scores assist with correct kidney graft allocation, but macroscopic graft features have never been evaluated in this scenario. METHODS We designed a graft appraisal questionnaire, assessed its reproducibility by comparing the senior and junior surgeon responses and evaluated which features can predict transplant outcomes in 202 patients transplanted from 144 donors at a tertiary centre. We created new prediction models in combination with validated preimplantation scores. The primary outcome was graft loss or eGFR

The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C0), coefficient of variation of tacrolimus (CV-TAC-C0), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C0 at the time of biopsy as well as CV-TAC-C0, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score &ge, 1) in the first surveillance biopsy was associated with TAC-C0 (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50&ndash, 0.96, p = 0.027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1.05 and 95% CI: 1.01&ndash, 1.10, p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score &ge, 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41.2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0.48, 95% CI: 0.25&ndash, 0.92, p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24&ndash, 0.77, p = 0.005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissue.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Síndrome de dificultat respiratòria aguda; Trasplantament renal Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Síndrome de dificultad respiratoria aguda; Trasplante renal Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Acute respiratory distress syndrome; Renal transplantation Coronavirus disease 2019 (COVD-19) emerged as a pandemic in December 2019. Infection has spread quickly and renal transplant recipients receiving chronic immunosuppression have been considered a population at high risk of infection, complications and infection-related death. During this year a large amount of information from nationwide registries, multicentre and single-centre studies have been reported. The number of renal transplant patients diagnosed with COVID-19 was higher than in the general population, but the lower threshold for testing may have contributed to its better identification. Major complications such as acute kidney injury and acute respiratory distress syndrome were very frequent in renal transplant patients, with a high comorbidity burden, but further studies are needed to support that organ transplant recipients receiving chronic immunosuppression are more prone to develop these complications than the general population. Kidney transplant recipients experience a high mortality rate compared with the general population, especially during the very early post-transplant period. Despite the fact that some studies report more favourable outcomes in patients with a kidney transplant than in patients on the kidney waiting list, the higher mortality described in the very early post-transplant period would advise against performing a kidney transplant in areas where the spread of infection is high, especially in recipients >60 years of age. Management of transplant recipients has been challenging for clinicians and strategies such as less use of lymphocyte-depleting agents for new transplants or anti-metabolite withdrawal and calcineurin inhibitor reduction for transplant patients with COVID-19 are not based on high-quality evidence. The authors received grants from Red de Investigación Renal (REDinREN RD16/0009/0030) and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI 18/01704, PI 18/01382). B.C. is supported by a Vall d’Hebron Institute of Research grant. This article is part of a supplement supported by Fresenius Medical Care without any influence on its content.

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank

Introduction:Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time torecovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acutekidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidneytransplant recipients.Methods:We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treatedwith remdesivir. Outcomes and safety were assessed.Results:Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) requiredmechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged$65 years(45% vs. 3.2% in younger patients). Acute kidneyinjury was present in 27.7% of patients, but wasdiagnosed in 50% before treatment. No patients required remdesivir discontinuation because ofadverse events. We did notfind significant hepatoxicity or systemicsymptoms resulting from thedrug. Conclusion:In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renaland hepatic toxicity, but randomized trials are needed to assess its efficacy. The authors are indebted to the many physicians andnurses who take care of these patients and are facing theCOVID-19 pandemic in our country. This research wassupported by Rio Hortega contract CM19/00004 (ISCIII)(AB), and RD16/0009/0013 (ISCIII FEDER RedinRen). MJP-S is supported by a Spanish Society of Transplantscholarship

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D−/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D− (22 recipients from D− with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D−, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D−, P = .31), HIV breakthrough (4% D+ vs 6% D−, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84–3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21–0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D−/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

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 Mar 4 and Apr 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data was analyzed. The mean age was 60 years. Forty‐seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; p=0.04). Significant age differences were not found among patients developing and not developing ARDS (61.3yr vs 57.8yr, p=0.16). Seventy‐six (73%) patients were discharged while 28 (27%) died. Death was more common among the elderly (55yr and 70.8yr, p

Background The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. Methods Adult SOT recipients with laboratory PCR-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11th to April 25th 2020, were matched to controls (1:4) on the basis of sex, age and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit (ICU) and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and COVID-19 management medication were collected. Results Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (IQR) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (p=0.51).Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. Conclusions In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared to controls, although it was not statistically significant, and a notable propensity for DDI.

Background The high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading represents a challenge to haemodialysis (HD) units. While fast isolation of suspected cases plays an essential role to avoid disease outbreaks, significant rates of asymptomatic cases have recently been described. After detecting an outbreak in one of our HD clinics, wide SARS-CoV-2 screening and segregation of confirmed cases were performed. Methods The entire clinic population, 192 patients, underwent testing for SARS-CoV-2 detection by real-time reverse-transcriptase polymerase chain reaction . We used univariate and multivariate logistic regression to define variables involved in SARS-CoV-2 infection in our dialysis unit. Later, we analysed differences between symptomatic and asymptomatic SARS-CoV-2-positive patients. Results In total, 22 symptomatic and 14 of the 170 asymptomatic patients had a SARS-CoV-2-positive result. Living in a nursing home/homeless [odds ratio (OR) 3.54; P = 0.026], having been admitted to the reference hospital within the previous 2 weeks (OR 5.19; P = 0.002) and sharing health-care transportation with future symptomatic (OR 3.33; P = 0.013) and asymptomatic (OR 4.73; P = 0.002) positive patients were independent risk factors for a positive test. Nine positive patients (25.7%) remained asymptomatic after a 3-week follow-up. We found no significant differences between symptomatic and asymptomatic SARS-CoV-2-positive patients. Conclusions Detection of asymptomatic SARS-CoV-2-positive patients is probably one of the key points to controlling an outbreak in an HD unit. Sharing health-care transportation to the dialysis unit, living in a nursing home and having been admitted to the reference hospital within the previous 2 weeks, are major risk factors for SARS-CoV-2 infection.

Frailty is a concept that has been mainly developed in geriatrics and it came from the need of identifying subjects at risk to develop complications when they faced a stressful event. Frail patients have higher risk of mortality, poor outcomes and disability, and this is independent from their age or comorbidities. Chronic kidney disease patients present with high prevalence of frailty, especially those who are in renal replacement therapy. Frail or pre-frail patients on the kidney transplant waiting list represent 20–30%, and these patients are proven to have poorer results after the transplant, which is a stressful event itself. Tools for frailty assessment, both scales or indexes, may be useful to identify which subjects might be at risk for complications after transplant, and this is necessary to adapt our clinical practice and minimize morbidity. The most used frailty scale in kidney patients is Fried scale, which is based in five phenotypic items. Besides that, knowing frail population allows potential interventions such as prehabilitation while the patient is waiting for the kidney transplant, which the aim of improving their vulnerability prior to transplant and, therefore, optimizing results after transplant. More studies are needed amongst kidney patients to improve and prevent frailty. Resumen: El concepto de fragilidad ha sido desarrollado principalmente en el campo de la geriatría y surgió para identificar a aquellos pacientes que presentaban vulnerabilidad al enfrentarse a un evento clínico estresante. Los pacientes frágiles tienen mayor riesgo de mortalidad, complicaciones y discapacidad, independientemente de su edad o comorbilidades. Se ha descrito una alta prevalencia de fragilidad entre sujetos con enfermedad renal crónica, sobre todo en terapia renal sustitutiva. El porcentaje de pacientes frágiles o prefrágiles en lista de espera de trasplante renal se sitúa en torno a un 20–30% y se ha demostrado que estos pacientes tienen peores resultados tras el trasplante renal, que constituye un evento estresante. Las herramientas para evaluar la fragilidad, escalas e índices, pueden ser útiles para identificar qué pacientes están en riesgo de padecer más complicaciones postrasplante, lo que resulta necesario para adaptar nuestra práctica clínica y evitar morbilidad. La más utilizada en pacientes renales es la escala de Fried, que se basa en la detección de cinco dimensiones fenotípicas. Además, conocer la fragilidad de nuestros pacientes permite plantear intervenciones prehabilitadoras durante el tiempo que estén en lista de espera, con el objetivo de mejorar esta vulnerabilidad pretrasplante, y así optimizar los resultados postrasplante. Se necesitan estudios en población renal para mejorar y prevenir la fragilidad.

Background and Aims Fast tacrolimus metabolizers (expressed as the blood concentration/ dose ratio; C / D; ng / mL * mg) showed poorer renal function at 2 years, a higher incidence of nephrotoxicity and BK polyomavirus infection. Greater variability of tacrolimus trough levels (CV) from six to twelve months is associated with the appearance of HLA antibodies, interstitial fibrosis / tubular atrophy (IFTA) progression and allograft loss. We evaluate the relationship between C / D, CV and IFTA progression. Method We evaluated a cohort of 87 low immunological risk renal transplants treated with prolonged-release tacrolimus, mycophenolate mofetil and steroids. We analyzed paired protocol biopsies at 4 and 18 months. Biopsies were evaluated according to the Banff classification and the progression of IFTA was defined as the difference of ci + ct score> 0 between 18 and 4 months. The C / D ratio was calculated as the average of the value recorded at 3, 6 and 12 months of follow-up. The tacrolimus CV between 6 and 12 months was calculated using all the available determinations. Results IFTA progression was observed in 36 cases (41%). In the univariate analysis, it was found that the progression of IFTA was associated with the ci + ct score at 4 months (0.92 ± 0.94 for progressors vs. 1.89 ± 1.26 not progressors, p = 0.0003), and with the average of the C / D ratio (1.70 ± 0.73 for progressors vs. 2.28 ± 1.25 not progressors; p = 0.0144, table 1). An independent association between the C/D ratio and the progression of IFTA was observed in the multivariate analysis (OR: 0.42; 95% CI: 0.22-0.82, p = 0.027). Conclusion The results of our work suggest that fast tacrolimus metabolizers (lower C / D ratio) are more susceptible to the nephrotoxic effect of tacrolimus.

Background and Aims Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib. Method The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry. Results No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients Conclusion ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS.

The clinical significance of renal transplant biopsies displaying borderline changes suspicious for T-cell mediated rejection (TCMR) or interstitial fibrosis and tubular atrophy (IFTA) with interstitial inflammation has not been well defined. Molecular profiling to evaluate renal transplant biopsies using microarrays has been shown to be an objective measurement that adds precision to conventional histology. We review the contribution of transcriptomic analysis in surveillance and indication biopsies with borderline changes and IFTA associated with variable degrees of inflammation. Transcriptome analysis applied to biopsies with borderline changes allows to distinguish patients with rejection from those in whom mild inflammation mainly represents a response to injury. Biopsies with IFTA and inflammation occurring in unscarred tissue display a molecular pattern similar to TCMR while biopsies with IFTA and inflammation in scarred tissue, apart from T-cell activation, also express B cell, immunoglobulin and mast cell-related genes. Additionally, patients at risk for IFTA progression can be identified by genes mainly reflecting fibroblast dysregulation and immune activation. At present, it is not well established whether the expression of rejection gene transcripts in patients with fibrosis and inflammation is the consequence of an alloimmune response, tissue damage or a combination of both.

Background: In December 2019, the novel SARS-CoV-2 virus triggered a large-scale pandemic of coronavirus disease 2019 (COVID-19) Kidney transplant recipients m

Background Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. Methods This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)–specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. Results Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30–9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31–59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89–237.96]). Conclusions Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell–depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. Clinical Trials Registration NCT02550639.

Lenvatinib has been approved for the treatment of advanced differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) following the results of the SELECT trial which demonstrated a significant increase in progression-free survival and a high response rates. The data reported for lenvatinib in RAI-refractory DTC (RAI-R DTC) are the most significant to date in this patient population, with a RECIST objective response rate above 60% and almost 80% reduction in the risk of disease progression. Because the first indication in oncology for lenvatinib is specifically in RAI-R DTC, a period of familiarisation with its safety and efficacy profile is required. This review includes a series of specific recommendations for optimising the management of RAI-R DTC with lenvatinib, as well as specific guidelines for minimising the incidence and severity of adverse events (AEs), which enable dose intensity to be increased and this way maximise the benefits of the drug in the patient population treated. These recommendations were defined at a meeting of experts of different specialities, reviewing available scientific evidence on the drug, as well as their own direct personal experience in daily clinical practice. For toxicity to be properly managed, a multidisciplinary approach is required in which the different medical services, nursing staff and the patient and their careers are all involved. It is essential to assess the suitability of patients who are candidates for lenvatinib, as well as their clinical and physiological status prior to treatment. They must then be closely monitored to prevent and detect possible AEs. The main objective should be to maintain the dose that obtains the maximum therapeutic effect, discontinuing the treatment only if the toxicity becomes unmanageable or there is no clinical benefit.

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

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m2) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions and DSA at one year. The planned sample size was 25 patients per group. During 2012-2015, twenty-five patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2±14.4 vs. -6.6±12.0 mL/min/1.73 m2, p-value=0.475), increase of proteinuria (+0.9±2.1 vs. +0.9±2.1 g/day, p-value=0.378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA. This article is protected by copyright. All rights reserved.

Resumen Antecedentes y objetivo La calidad de vida relacionada con la salud (CVRS) se considera una medida de resultado del trasplante renal. En este estudio se evaluaron los cambios en la CVRS y los sintomas especificos de la enfermedad renal, ademas de los efectos de variables sociodemograficas y clinicas en la CVRS percibida por el paciente. Pacientes y metodo Se realizo un estudio longitudinal, con 5 momentos de evaluacion durante 2 anos despues del trasplante. Para evaluar la CVRS se administro el Kidney Disease Quality of Life Questionnaire Short Form , y el Hospital Anxiety and Depression Scale para evaluar el malestar emocional. Resultados A los 6 meses postrasplante, los pacientes tienen una CVRS similar a la poblacion general. La dimension de efectos de la enfermedad renal obtuvo un tamano de efecto grande (η 2 = 0,29), y un tamano medio la dimension de sobrecarga de la enfermedad renal (η 2 = 0,12), la dimension de actividad laboral (η 2 = 0,12) y la dimension de funcion sexual (η 2 = 0,13). El malestar emocional, la hemoglobina y la creatinina influyeron significativamente en la CVRS percibida por el paciente. Conclusiones Durante los 2 anos posteriores al trasplante renal se observo una mejora de la CVRS en cuanto a aspectos generales y sintomas especificos de la enfermedad.

Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.

Background Whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods In this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results We enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40–4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50–8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum β-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions Antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed.

Background: Prediabetes and post-transplant diabetes mellitus (PTDM) affect about 20-30% of renal transplant patients. PTDM is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. Methods: We analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated OGTTs up to 5 years and a long term survival evaluation. Findings: Prediabetes and PTDM were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was higher in patients with prediabetes, 28 (17%) or PTDM 20 (20%) than in normal subjects, 25 (7%), p = 0·001 and < 0·0001, respectively. The incidence of events was comparable between prediabetes and PTDM (p = 0·27). Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate COX survival analyses (HR:2·24 95% CI 1·11-4·52). Prediabetes at 3 months and HbA1c at 12 months were not significant. Interpretation: Prediabetes was a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Prediabetes is a potentially reversible condition, which offers the opportunity to prevent cardiovascular disease in this population. Funding Statement: Instituto de Salud Carlos III: The authors would like to acknowledge (a) the IMBRAIN project (FP7-RE6-POT-2012-CT2012- 31637-IMBRAIN) funded under the 7th Frameworks Programme (capacities), (b) the Instituto de Salud Carlos III (Fondo de Investigacioen Sanitaria: FIS) and Fondos FEDER for the following grants: PI 07/0732, the REDINREN RD/0021/0008 and PI10/02428 and (c) the funding of the Spanish Research Network for Kidney Diseases (REDINREN RD12/0021/0008). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of each hospital and followed the Declaration of Helsinki.

Health-related behaviours and psychological distress were examined after kidney transplantation. Patients were evaluated at 1 month, 6 months and 1 year after transplantation. Participants completed the Healthy Behaviours Questionnaire and the Hospital Anxiety and Depression Scale. No significant differences in Healthy Behaviours Questionnaire’s total score and psychological comorbidity were observed at three time points. However, there was an increase in drug-consumer habits ( p

Background Data are scarce on cytomegalovirus (CMV) and BK virus (BKV) infection after antibody-mediated rejection (ABMR). Objectives We hypothesized that the immunological response in patients with ABMR or the immune modulation associated with its treatment could predispose to CMV and BKV infection. Our objective was to investigate this hypothesis. Study design We conducted a single-center, matched case-control study (1:2 ratio) to analyze CMV and BKV replication during the first year after the ABMR diagnosis in kidney transplant recipients. Adult recipients with a histopathological diagnosis of ABMR between 2007–2015 were included as cases. Controls were kidney recipients who underwent transplantation immediately before and after the index case. Results Fifty-eight patients diagnosed with ABMR (33 chronic active ABMR and 25 acute ABMR), with their matched controls (116) were included. Forty-four cases received treatment for ABMR, including plasmapheresis (41), immunoglobulins (40), and rituximab (31). Within 1 year after ABMR, cases showed CMV replication more often than controls (9/58, 15.5% vs 7/116, 6%, OR = 4.21, CI 1.10–16.16, p = 0.04). Over the study period, CMV PCR determinations were requested more frequently in cases than controls (46/58, 79.3% vs 63/116, 54.3%, OR = 4.58, CI 1.92–10.9, p = 0.001). On multivariate analysis adjusted for CMV PCR determinations, retransplantation, antithymocyte globulin treatment and methylprednisolone treatment for acute rejection, CMV replication remained more common in cases than in controls (OR = 2.41, CI 0.49–11.73, p = 0.28). There were no differences in BKV replication in either urine or blood. Conclusions ABMR may be a risk factor for CMV but not for BKV replication in kidney transplant recipients.

Background The incidence of cutaneous infections by dematiaceous fungi is rising in our environment due to the high number of solid organ transplant recipients (SOTR). Objective To review our experience in the management of cutaneous phaeohyphomycoses in a Spanish reference centre for dermatological care of SOTR. Methods Retrospective clinical, histopathological and microbiological review of all SOTR diagnosed of a phaeohyphomycosis in a 7-year period. Results Eleven SOTR were identified (8 lung and 3 kidney). The lesions were solitary in six patients and multiple in five, affecting mostly the lower extremities. Early lesions showed epidermal hyperplasia and a diffuse dermal suppurative granulomatous infiltrate that was progressively substituted by fibrosis when the lesions were treated. Septated fungal structures with refractile walls were identified. DNA sequencing confirmed the presence of Alternaria spp (8 cases), Cladosporium cladosporioides, Microsphaeropsis arundinis and Exophiala oligosperma. Three patients with single lesions were treated with surgery, while the other 8 required long-term antifungal therapy, including itraconazole, voriconazole and/or terbinafine, combined with surgery and reduction in tacrolimus doses. Conclusion A clinical, histopathological and microbiological correlation is essential to corroborate this diagnosis. Solitary lesions are easily treated with surgery, but larger or multiple lesions may require long medical treatments combined with surgery and modification of immunosuppressive medication. The list of dematiaceous fungi implicated in cutaneous infections is expanding, in line with the availability of more sophisticated identification methods and the increasing number of immunosuppressed patients.

Reactivation of Chagas disease in the chronic phase may occur after solid organ transplantation, which may result in high parasitemia and severe clinical manifestations such as myocarditis and meningoencephalitis. The aim of the present study is to describe the prevalence of Chagas disease among solid organ–transplanted patients in a tertiary hospital from a nonendemic country. A cross-sectional study was performed at Vall d’Hebron University Hospital (Barcelona, Spain) from April to September 2016. Chagas disease screening was performed through serological tests in adult patients coming from endemic areas that had received solid organ transplantation and were being controlled in our hospital during the study period. Overall, 42 patients were included, 20 (47.6%) were male and median age was 50.5 (23–73) years. Transplanted organs were as follows: 18 kidneys, 17 lungs, and 7 livers. Three patients had Chagas disease, corresponding to a prevalence among this group of solid organ–transplanted patients of 7.1%. All three patients were born in Bolivia, had been diagnosed with Chagas disease and received specific treatment before the organ transplantation. We highly recommend providing screening tests for Chagas disease in patients with or candidates for solid organ transplantation coming from endemic areas, early treatment with benznidazole, and close follow-up to prevent clinical reactivations.

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age-matched patients with chronic kidney disease without history of cardiovascular events. Twenty-four-hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.

Objective To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. Patients and methods A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. Results During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. Conclusions The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function.

Resumen Objetivo Analizar y evaluar nuestra experiencia en el tratamiento quirurgico mediante abordaje abierto de las estenosis ureterales complejas postrasplante renal de adulto en un centro de tercer nivel en los ultimos 7 anos. Se revisan las diferentes alternativas quirurgicas utilizadas. Pacientes y metodos Desde enero de 2005 hasta diciembre de 2012 se han realizado un total de 589 trasplantes renales de adulto consecutivos. Un 1,1% del total presentaron algun grado de uropatia obstructiva sintomatica que, tras derivacion urinaria inicial, requirieron de abordaje quirurgico abierto utilizando la via urinaria nativa ipsilateral o contralateral. Se presentan las caracteristicas de los pacientes, clinica, exploraciones realizadas asi como tecnica quirurgica llevada a cabo y sus resultados. Resultados Durante el periodo evaluado se llevaron a cabo un total de 7 cirugias reparativas en 5 varones y 2 mujeres que presentaban estenosis ureterales postrasplante renal mediante ureteropielostomia abierta utilizando ureter nativo ipsilateral en 6 casos y contralateral en el restante. En un caso de realizo anastomosis ureterocalicilar por retraccion pielica extrema. No ha habido complicaciones relevantes ni se ha requerido de nefrectomia de rinon nativo por complicacion posterior. La totalidad de los pacientes intervenidos presentaron cifras de creatinina plasmatica optimas con resolucion de la dilatacion previa. Conclusiones La nefrostomia percutanea inicial seguida de la correccion quirurgica abierta mediante la utilizacion de ureter nativo representa una alternativa definitiva, valida y optima en terminos de seguridad y preservacion de la funcion renal.

Background: The majority of studies suggesting that online hemodiafiltration reduces the risk of mortality compared to hemodialysis (HD) have been performed in dialysis-prevalent populations. In this report, we conducted an epidemiologic study of mortality in incident dialysis patients, comparing post-dilution online hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to correct indication bias. Methods: Our study cohort comprised 3,075 incident dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between January 2009 and December 2012. The primary outcome of this study was to investigate the impact of the type of renal replacement on all-cause mortality. An analysis of cardiovascular mortality was defined as the secondary outcome. To achieve these objectives, patients were followed until December 2016. Patients were categorized as high-flux HD patients if they underwent this treatment exclusively. If >90% of their treatment was with online hemodiafiltration, then the patient was grouped to that modality. Results: After PSM, a total of 1,012 patients were matched. Compared with patients on high-flux HD, those on online hemodiafiltration received a median replacement volume of 23.45 (interquartile range 21.27–25.51) L/session and manifested 24 and 33% reductions in all-cause and cardiovascular mortality (all-cause mortality hazards ratio [HR] 0.76, 95% CI 0.62–0.94 [p = 0.01]; and cardiovascular mortality HR 0.67, 95% CI 0.50–0.90 [p = 0.008]). Conclusions: This study shows that post-dilution online hemodiafiltration reduces all-cause and cardiovascular mortality compared to high-flux HD in an incident HD population.

The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo-interstital inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC-C0 target at 1-year 6-10 ng/mL) and reduced MMF dose (500 mg bid at 1-year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC-C0 (target 3-7 ng/mL) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C0 in the early (OR: 0.75, 95%CI: 0.61-0.92; p=0.006) and late biopsies (OR: 0.69, 95%CI: 0.50-0.95; p=0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95%CI: 0.83-0.98; p=0.0101) and with low TAC-C0 in late biopsies (OR: 0.77, 95%CI: 0.61-0.97; p=0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC-C0 or MMF dose in the multivariate analysis. Our data suggest that in TAC and MMF based regimens, TAC-C0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose. This research has been accepted and published in Transplant International. © 2017 Wiley