Fernando Escuin

Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection.

There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.

Sublingual administration of tacrolimus in a renal transplant patient

Tacrolimus is used in renal and other organ transplantations for immunossupression therapy. Bioavailability of enterally administered tacrolimus is poor, and further reduced by gastrointestinal failure or enteral nutrition. In these situations, intravenous administration is necessary to prevent treatment failure. However, intravenous administration should be done in a continuous manner and it has been implicated in anaphylaxis, torsades de pointes, cardiac arrhythmia and other serious adverse events. Also it is more expensive than other routes of administration. Sublingual administration of tacrolimus has been used in some cases, and literature reports show that it provides therapeutic tacrolimus levels in lung and liver transplant recipients. Here, we report a first case of sublingual administration of tacrolimus in kidney transplantation.

Resultados e impacto de una vía clínica para trasplante renal tras un año de desarrollo

Resumen Fundamento La disminucion de la variabilidad inapropiada en la practica clinica es una oportunidad de mejora de la calidad asistencial. Las vias clinicas representan una posible solucion para este tipo de variabilidad. El objetivo del estudio fue evaluar el impacto de una via clinica para trasplante renal. Metodos A los 3 meses de implantacion de la via se realizo un analisis preliminar. Tras la puesta en marcha de medidas de mejora se prosigue con la implantacion definitiva. Pasado 1 ano se evaluan los resultados y el impacto. Se revisa la documentacion de los pacientes atendidos mediante el analisis de la cobertura, las estancias, las variaciones, los sucesos adversos y la satisfaccion. Se comparan los resultados obtenidos con los 12 meses anteriores a la implantacion. Resultados Entre noviembre de 1999 y noviembre de 2000 fueron intervenidos 32 pacientes. La cobertura de la via fue del 97%. Las estancias hospitalaria y urologica se cumplieron por el 48,4% y el 62,1% de los pacientes. La estancia media hospitalaria fue de 18,9 dias frente a 22,1 en el periodo anterior a la via y represento una diferencia no significativa (p = 0,203), aunque se observa una importante disminucion de la variabilidad-desviacion estandar [DE]: 8,33 frente a 11,04 dias). El mayor numero de variaciones dependio del enfermo (68,2%). El porcentaje de sucesos adversos fue del 61,3% frente al 90,3% (p = 0,016). Se consideraron como predictores independientes de episodios adversos: la estancia (odds ratio [OR] = 1,32, p = 0,004) y la condicion pre-via (OR = 7,42, p = 0,017). La cobertura de la encuesta de satisfaccion fue del 68%. La satisfaccion con la atencion recibida fue del 94,5%. Conclusiones Se han detectado oportunidades de mejora, cumplimiento de estancias o cobertura de encuesta, pero la disminucion de la variabilidad en estancia, sin incremento de acontecimientos no deseados y su disminucion al controlar por estancia en pacientes con via, confirma que la via clinica de trasplante renal es una herramienta util para disminuir la variabilidad y mejorar la calidad cientificotecnica, la calidad percibida y la eficiencia en la practica clinica.

Revisión del trasplante renal ortotópico en nuestro centro

Resumen El trasplante renal ortotopico(TRO) es util en casos de aterosclerosis severa, trasplante heterotopico bilateral, anomalias vasculares pelvicas y en oclusion aortica, pero no esta disponible en todos los centros y solo se realiza de forma excepcional. Objetivo Revisar la indicacion, tecnica quirurgica y evolucion del TRO en nuestro hospital. Material y metodos Se recogieron todos los casos de TRO realizados desde enero-1990 hasta enero-2007, en total seis casos. Analizamos distintas variables: caracteristicas demograficas, caracteristicas del donante, tiempos de isquemia, evolucion de funcion renal y morbi-mortalidad asociada. Resultados TRO izquierdo se ha realizado en cuatro hombres y dos mujeres. La edad media de los pacientes fue 52±5 anos, todos los pacientes recibieron rinones de donante cadaver. La creatinina serica y urea media al mes fueron 2,2±0,72mg/dl y 103±17,2mg/dl y a los 6 meses fueron 1,8±0,69mg/dl y 78±14mg/dl respectivamente. De forma inmediata todos recibieron profilaxis con heparina de bajo peso molecular pero al alta a dos pacientes se indico antiagregacion, a tres anticoagulacion y a uno de ellos se decidio no anticoagular ni antiagregar por presentar historia de sangrados digestivos. Un paciente murio por episodio hemorragico a nivel del injerto renal a los seis meses del trasplante, estando en tratamiento con dicumarinicos, indicados por trombosis venosa profunda en miembro inferior derecho(MID). La supervivencia al ano es del 80% del injerto y del paciente. Solo dos pacientes requirieron ingreso posterior, uno de ellos por presentar un episodio de diverticulitis y otro por un cuadro de fracaso renal obstructivo que requirio colocacion de cateter pig-tail. Cuatro pacientes presentaron estenosis de vasos renales nativos detectada en la resonancia magnetica nuclear de control no sintomatica. Hay dos pacientes que llevan mas de tres anos trasplantados con funcion renal estable(creatinina 1,2mg/dl y 1,4mg/dl respectivamente). Conclusion TRO es una opcion adecuada en los pacientes con co-morbilidad aumentada por ateromatosis y que no pueden ser colocados en las fosas iliacas.UNLABELLED Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. AIM To review the indication, surgical technique and outcome of the ORT at our hospital. MATERIAL AND METHODS The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. RESULTS Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). CONCLUSION ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and that cannot be placed in the iliac fossaes.

The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES)

Background Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft’s life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term. Patients and Methods RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction. Results The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term. Conclusion RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.

La infección por citomegalovirus postrasplante renal y pérdida del injerto a largo plazo

BACKGROUND Despite the use of prevention strategies, cytomegalovirus (CMV) infection is the most common viral complication after renal transplant and its impact on long-term outcomes is still open to debate. OBJECTIVE To evaluate the incidence of CMV infection and disease during the use of prevention strategies in our centre and to analyse the association between CMV infection and long-term patient and graft survival and other potentially clinical events related with CMV. METHODS We reviewed the medical records of 377 recipients of kidney transplants performed between January 1998 and December 2008. Kaplain-Meier survival curve analysis was performed to analyse graft and patient survival by CMV infection/disease and Cox proportional hazards regression was used to identify factors associated with CMV infection/disease, graft loss and mortality. RESULTS The incidence of CMV infection was 34.7% and CMV disease was 9.5%. Patient and graft survival was significantly lower in patients with CMV infection/disease. CMV infection/disease was associated with a higher risk of graft loss (HR 1.91, 95% CI 1.09-3.36, p=0.023), but not with a higher mortality (HR 1.29, 95% CI 0.7-2.38, p=0.4). CONCLUSION CMV replication after renal transplant is a risk factor for long-term graft loss but not mortality. Prevention strategies decrease post-transplant CMV infection and disease.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.