La incompatibilidad de grupo sanguíneo ABO y la sensibilización al HLA constituyen grandes barreras a vencer en pro de la óptima utilización de riñones de donante vivo. Describimos en nuestro medio ...el primer trasplante renal exitoso ABO incompatible en un paciente de 24 años, retrasplantado renal, altamente sensibilizado (PRA: 89%) y sin opción alguna en disponer de donantes cadavéricos ni familiares. Sin embargo, su único donante vivo HLA compatible era de grupo sanguíneo A incompatible con el grupo O del receptor. El paciente requirió de un régimen precondicionante consistente en recambios plasmáticos, rituximab, imunoglobulina y terapia inmunosupresora cuádruple, a fin de reducir los títulos elevados de isoaglutininas anti A de 1:128 a niveles de seguridad de 1:8, para el éxito del trasplante. Este fue realizado en Coordinación con la Unidad de Trasplante Renal del Hospital Clínic de Barcelona España (HCB). La ausencia de rechazo mediado por isoaglutininas muestra el potencial beneficio del protocolo al remover los anticuerpos anti grupo sanguíneo. A los dos años del trasplante, la función renal se mantiene estable con niveles de creatinina 1,5 mg%. Concluimos que el trasplante renal ABO incompatible (ABOi) es opción viable para pacientes cuyo único donante sea grupo sanguíneo incompatible, y entre nosotros representa esperanzadora fuente de órganos.
Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic ...factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.
Cystinosis is a rare lysosomal systemic disease that mainly affects the kidney and the eye. Patients with cystinosis begin renal replacement therapy during the first decade of life in absence of ...treatment. Prognosis of cystinosis depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment. Kidney disease progression, extra-renal complications and shorter life expectancy are more pronounced in those patients that do not follow treatment. The objective of this work was to elaborate recommendations for the comprehensive care of cystinosis and the facilitation of patient transition from paediatric to adult treatment, based on clinical experience. The goal is to reduce the impact of the disease, and to improve patient quality of life and prognosis.
Bibliographic research and consensus meetings among a multidisciplinary professional team of experts in the clinical practice, with cystinotic patients (T-CiS.bcn group) from 5 hospitals located in Barcelona.
This document gathers specific recommendations for diagnosis, treatment and multidisciplinary follow-up of cystinotic patients in the following areas: nephrology, dialysis,renal transplant, ophthalmology, endocrinology, neurology, laboratory, genetic counselling,nursing and pharmacy.
A reference document for the comprehensive care of cystinosis represents a support tool for health professionals who take care of these patients. It is based on the following main pillars: (a) a multi-disciplinary approach, (b) appropriate disease monitoring and control of intracellular cystine levels in leukocytes, (c) the importance of adherence to treatment with cysteamine, and (d) the promotion of patient self-care by means of disease education programmes. All these recommendations will lead us, in a second phase, to create a coordinated transition model between paediatric and adult care services which will contemplate the specific needs of cystinosis.
La combinación inmunosupresora más utilizada en trasplante renal de novo incluye un inhibidor de calcineurina (IC), tacrolimus, un derivado del ácido micofenólico y esteroides. La evidencia que ...sustenta esta práctica se basa en el ensayo clínico Symphony, de evolución controlada durante un año, en el que no existía ningún grupo comparador con IC asociado a un inhibidor de mTOR. Diversos ensayos clínicos de alta calidad sustentan la indicación del uso de everolimus como inmunosupresor básico asociado a una exposición reducida de un IC en pacientes que reciben un trasplante renal. Esta combinación podría mejorar las expectativas de resultados en salud.
Estas recomendaciones tratan de aportar la evidencia científica que apoya esta práctica, discuten las falsas creencias, mitos y realidades de la combinación y concretan pautas que permiten utilizarla con seguridad y evitar complicaciones.
The immunosuppressive combination most commonly used in de novo kidney transplantation comprises a calcineurin inhibitor (CI), tacrolimus, a mycophenolic acid derivative and steroids. The evidence which underlies this practice is based in the Symphony trial with controlled follow-up of one year, in which no comparator group included the combination CI-mTOR inhibitor. Different high-quality clinical trials support the use of everolimus as a standard immunosuppressive drug associated with reduced exposure of a CI in kidney transplantation. This combination could improve health related outcomes in kidney transplantation recipients.
The present recommendations constitute an attempt to summarise the scientific evidence supporting this practice, discuss false beliefs, myths and facts, and offer specific guidelines for safe use, avoiding complications.
Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.
In a multicenter noninferiority ...trial, we randomized 2037
kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m
at post-transplant month 12 using a 10% noninferiority margin.
In the intent-to-treat population (everolimus
=1022, MPA
=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%).
donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.
In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.
Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-β
1
(TGF-β
1
) is the main cytokine involved in the ...fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-β
1
production. Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-β
1
production in renal transplant patients. The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics, as well as TGF-β
1
and endothelin-1 (ET-1) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine. Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a random 2 × 2 crossover trial with amlodipine and losartan (6 wk with each therapy). Three studies were performed (at baseline and at the end of both treatment periods) to determine renal hemodynamics, TGF-β
1
, and ET-1. Both treatments controlled BP to a similar degree, but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction. In contrast, losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly. Losartan and amlodipine had opposite effects on TGF-β
1
. Amlodipine did not affect TGF-β
1
concentrations. In contrast, losartan reduced the plasma levels of TGF-β
1
by approximately by 50% (from baseline, 5.2 to 2.6 ng/ml;
P
= 0.01); the majority of the patients reached normal levels of TGF-β
1
. ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. The present study documents that with similar control of BP, losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-β1 concentrations. These differences could be important for the management of chronic allograft nephropathy.
We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID‐19) in Spain until 13 ...July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range IQR: 52‐70), and 66% were male. The incidence of COVID‐19 in SOT recipients was two‐fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18‐131). Infection was hospital‐acquired in 13% of cases. No donor‐derived COVID‐19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon‐β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow‐up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio OR: 2.5; 95% CI: 1.4‐4.6), age >60 years (OR: 3.7; 95% CI: 2.5‐5.5), and hospital‐acquired COVID‐19 (OR: 3.0; 95% CI: 1.9‐4.9).
The authors report the Spanish nationwide experience with solid organ and hematopoietic stem cell transplant recipients diagnosed with COVID‐19, revealing a higher incidence and more aggressive course of infection than in the general population.
TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus‐based regiMen) was a 24‐month, prospective, open‐label trial in 2037 de novo renal transplant recipients randomized (1:1) within ...24 hours of transplantation to receive everolimus (EVR) with reduced‐exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard‐exposure CNI. Consistent with previously reported 12‐month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy‐proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = −0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2) in both arms. The incidence of de novo donor‐specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on‐treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R− high‐risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard‐of‐care up to 24 months. Clinicaltrials.gov number: NCT01950819.
Two‐year follow‐up findings from TRANSFORM, the largest study in de novo renal transplantation to date, demonstrate that everolimus‐facilitated calcineurin inhibitor reduction provides a valid alternative to standard‐of‐care immunosuppression comprising mycophenolate with standard calcineurin inhibitor by offering comparable antirejection efficacy, stable renal function, and significant benefit in protecting from viral infections.
Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID‐19). However, risk factors for relevant outcomes remain uncertain in this population. This is a ...multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty‐seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy‐six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.
This multicenter study of kidney transplant recipients with COVID‐19 analyzes the clinical course and immunosuppression adjustments during infection and investigates risk factors for severe forms.
La cistinosis es una enfermedad lisosomal minoritaria de expresión sistémica con especial afectación renal y oftalmológica, en la que los pacientes inician terapia renal sustitutiva en la primera ...década de la vida en ausencia de tratamiento. El pronóstico de la cistinosis depende del diagnóstico precoz, la pronta instauración del tratamiento con cisteamina y el buen cumplimiento terapéutico. La progresión de la enfermedad renal y de las complicaciones extrarrenales y una menor supervivencia, son más acentuadas en pacientes no adherentes.
El objetivo de este trabajo fue la elaboración de unas recomendaciones para la atención integral de la cistinosis y la transición del adolescente a la medicina del adulto, basadas en la experiencia clínica, con el fin de reducir el impacto de la enfermedad y mejorar la calidad de vida y el pronóstico del paciente.
Búsqueda bibliográfica y reuniones de consenso de un equipo multidisciplinar de expertos en la práctica clínica con pacientes afectos de cistinosis (Grupo T-CiS.bcn), procedentes de 5 hospitales localizados en Barcelona.
El documento recoge recomendaciones específicas y necesarias para el diagnóstico, tratamiento y seguimiento multidisciplinar de la cistinosis en las siguientes áreas: nefrología, diálisis, trasplante renal, oftalmología, endocrinología, neurología, laboratorio, consejo genético, enfermería y farmacia.
Disponer de un documento de referencia para la atención integral de la cistinosis constituye una herramienta de soporte para los profesionales de la salud que asisten a estos pacientes. Los principales pilares en los que se sustenta son: a) el enfoque multidisciplinar, b) la adecuada monitorización de la enfermedad y control de los niveles de cistina intraleucocitarios, c) la importancia de la adherencia al tratamiento con cisteamina y d) la promoción del autocuidado del paciente mediante programas de educación en la enfermedad. Todo ello conducirá, en una segunda fase, a la elaboración de un modelo de transición coordinado entre los servicios de pediatría y de adultos que contemple las necesidades específicas de la cistinosis.
Cystinosis is a rare lysosomal systemic disease that mainly affects the kidney and the eye. Patients with cystinosis begin renal replacement therapy during the first decade of life in absence of treatment. Prognosis of cystinosis depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment. Kidney disease progression, extra-renal complications and shorter life expectancy are more pronounced in those patients that do not follow treatment.
The objective of this work was to elaborate recommendations for the comprehensive care of cystinosis and the facilitation of patient transition from paediatric to adult treatment, based on clinical experience. The goal is to reduce the impact of the disease, and to improve patient quality of life and prognosis.
Bibliographic research and consensus meetings among a multidisciplinary professional team of experts in the clinical practice, with cystinotic patients (T-CiS.bcn group) from 5 hospitals located in Barcelona.
This document gathers specific recommendations for diagnosis, treatment and multidisciplinary follow-up of cystinotic patients in the following areas: nephrology, dialysis, renal transplant, ophthalmology, endocrinology, neurology, laboratory, genetic counselling, nursing and pharmacy.
A reference document for the comprehensive care of cystinosis represents a support tool for health professionals who take care of these patients. It is based on the following main pillars: a) a multi-disciplinary approach, b) appropriate disease monitoring and control of intracellular cystine levels in leukocytes, c) the importance of adherence to treatment with cysteamine, and d) the promotion of patient self-care by means of disease education programmes. All these recommendations will lead us, in a second phase, to create a coordinated transition model between paediatric and adult care services which will cover the specific needs of cystinosis.
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