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Background: Graft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study., Methods: Multicenter prospective observational cohort study., Setting and Participants: Seven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed-up for 10 years., Outcomes: Early graft loss and graft loss by thrombosis., Measurements: The presence of IgA anti-B2GP1 antibodies in pretransplant serum was examined using the same methodology in all the patients., Results: At transplantation, 288 patients were positive for IgA-B2GP1 (39%, Group-1) and the remaining were negative (Group-2). Graft loss at 6 months was higher in Group-1 (12.5 vs. 4.2% p  < 0.001), vessel thrombosis being the most frequent cause of early graft loss, especially in Group-1 (6.9 vs. 0.4% p  < 0.001). IgA-aB2GP1 was the most important independent risk factor for graft thrombosis (hazard ratio: 13.83; 95% CI: 3.17-60.27, p  < 0.001). Furthermore, the, presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. At 10 years, survival figures were also lower in Group-1: graft survival was lower compared with Group-2 (60.4 vs. 76.8%, p  < 0.001). Mortality was significantly higher in Group-1 (19.8 vs. 12.2%, p  = 0.005)., Limitations: Patients were obtained during a 3-year period (1 January 2000-31 December 2002) and kidneys were only transplanted from brain-dead donors. Nowadays, the patients are older and the percentage of sensitized and retransplants is high., Conclusion: In a prospective observational multicenter study, we were able to corroborate that pretransplant presence of IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Therefore, a prospective study is needed to evaluate the efficacy and safety of prophylactic anticoagulation to avoid this severe complication.

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., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

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.

Background: Cytomegalovirus (CMV) infection is an ongoing clinical problem in solid-organ transplantation (SOT). Pretransplant CMV serology is currently the only tool for assessing the risk of CMV infection, although cellular immune responses driven by CMV-specific CD4 and CD8 T lymphocytes are important for controlling viral replication. Therefore, the analysis of CMV-specific T cells may be useful for estimating the risk of infection., Methods: This is a prospective study of patients with kidney transplants and no prophylactic treatment for CMV replication. CD4 and CD8 T-cell responses to the major CMV pp65 and IE-1 antigens in 15 seropositive patients at intermediate risk of CMV infection were investigated, according to current algorithms. Intracellular flow cytometry was employed to determine IFN-γ production as a functional readout. The response was analyzed in pretransplant samples and prospectively at 1 and 6 months and at 1 year posttransplant., Results: It was observed that the CD8 responses to IE-1 antigen were practically absent pretransplant in patients who developed CMV infection posttransplant. Within the group of patients free of infection, CD8 responses to IE-1 were detected more frequently and were significantly higher (P=0.0083). In a receiver operating characteristics curve analysis (AUC=0.929; P=0.010; 95% CI: 0.078-1.0), low CD8 responses to IE-1 (≤0.05%) pretransplant predicted the development of CMV infection under the immunosuppressive regime after transplant with 100% specificity and 85.7% sensitivity., Conclusions: Assessment of IE-1-specific CD8 T-cell frequencies pretransplant may be a useful tool for identifying seropositive SOT patients at risk of developing CMV infection posttransplant.

Background: Kidney transplantation is the best option for the treatment of end-stage renal disease in terms of survival and quality of life. These results can be influenced by the pretransplant dialysis modality. The aim of this study was to evaluate whether the pretransplantation dialysis modality influences patient and allograft survival beyond 10 years and examine the potential risk factors associated with the outcomes., Methods: We conducted an observational, retrospective, single-center clinical study that included 236 patients [118 undergoing peritoneal dialysis (PD) and 118 undergoing hemodialysis (HD)] who proceeded to transplantation during the period December 1990-2002. Donor and recipient data were collected from our hospital's clinical registries. The follow-up period extended to the patient's death, the loss of the allograft, or loss to follow-up. The end date of the study was set at March 2012., Results: In the multivariate analysis, the long-term patient survival rate was higher for the PD group than for the HD group [HR = 2.62 (1.01-6.8); p = 0.04]; however, the allograft survival rate was not significantly different between the two groups [HR = 0.68 (0.41-1.10); p = 0.12]., Conclusion: Pretransplantation dialysis modality is associated with long-term patient survival, with outcomes favoring peritoneal dialysis over hemodialysis. However, the pretransplant dialysis modality does not influence long-term graft loss risk.

Background: Percutaneous biopsy of renal grafts is a diagnostic method for the assessment, management and clinical monitoring of renal transplant, so it is necessary to know its complications. There are few data in the literature regarding complications from biopsies in renal grafts., Objective: To evaluate the rate of complications in renal graft biopsies performed at our centre., Patients and Method: We performed a retrospective observational study, including data from patients who underwent renal graft biopsies from January 2000 to September 2012. Major complications were defined as: anemia requiring blood transfusion, intraparenchymal arteriovenous fistula or arterial bleeding requiring embolisation, nephrectomy, other surgery and exitus. And as minor complications: anemia without blood transfusion, intraparenchymal arteriovenous fistula without embolisation, haematomas or perirenal collections, hematuria and fever. Kidney biopsies were performed with ultrasound guidance and automatic devices., Results: We performed 390 kidney graft biopsies. 49 complications occurred. 22 were major: 12 per anemia that required blood transfusion, 6 requiring embolisation (5 arteriovenous fistulae and 1 arterial bleeding), 2 exitus, 1 trasplantectomy and 1 surgery (haematoma). 27 were minor: 12 perirenal collections, 9 arteriovenous fistulae without embolisation, 3 hematuria, 2 anemisation without blood transfusion and 1 fever., Conclusions: The rate of complications related to renal graft biopsy observed in our centre is similar to those described for native kidneys, therefore we believe it remains a safe and effective technique, and an important diagnostic tool.

Background. Renal re-transplants are increasing in number, due to many first renal transplant patients coming back to dialysis treatment. There are controversial opinions about the evolution of these re-transplanted patients. The aim of our study is to analyse the prognosis of patients and grafts under a renal re-transplant.Methods. This was a retrospective study of 579 renal re-transplants realized in 15 Spanish different centres in the years 1990, 1994, 1998 and 2002 including all renal re-transplants realized in the above-mentioned centres during the same periods.Results. During the follow-up period, 8.81% of patients died. The actuarial patient survival was 85% at 10 years and 80% at 15 years. Principal reasons of death were the same as normal for the renal transplanted patient: cardiovascular (30.77%), infectious (13.46%) and neoplastic (13.46%). During the period of follow-up, 28.6% of the grafts were lost. The actuarial graft survival was 75% at 10 years and 58% at 15 years. Causes of graft loss are very similar to those described in literature.Conclusion. Renal re-transplant is a kind of substitute renal treatment with excellent clinical results that allow to take it as a first-order modality of treatment when the first renal transplant has failed.

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.

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.

Background: Posttransplant lymphoproliferative disorders (PTLDs) are almost always of B-cell derivation and have a strong association with Epstein-Barr virus (EBV). Only rare cases of CD30 (Ki-1)-positive anaplastic large cell (ALC) lymphomas in transplant recipients have been described. EBV has been studied in few of these cases. Pleural effusion is an uncommon clinical manifestation of both PTLDs and CD30-positive ALC lymphoma., Case: A 60-year-old, male renal transplant recipient presented with fever and pleural effusion. Cytologic examination of the effusion revealed a large cell lymphoma. Immunocytologic studies disclosed a T-cell phenotype. Subsequently a cutaneous lesion and an accessory spleen were observed, and cervical lymphadenopathies developed. Fine needle aspiration of lymph nodes confirmed the presence of lymphoma. Histologic and immunohistochemical studies of the lymph nodes, skin and accessory spleen revealed the presence of CD30-positive, T-cell, ALC lymphoma. No EBV DNA was detected by polymerase chain reaction analysis. Despite chemotherapy, the patient died seven months after the initial cytologic diagnosis of lymphoma., Conclusion: CD30-positive ALC lymphomas are an uncommon variant of PTLDs that should be considered in the differential diagnosis of neoplastic disorders arising in immunosuppressed patients. Cytology and immunocytochemistry are useful diagnostic procedures for their early detection.

Three I.M. injections of hepatitis B vaccine (Merck Sharp & Dohme) were administered, according to the recommended schedule (0, 1, 6 mos), to seronegative individuals of one renal dialysis unit (33 patients, 58 health care personnel) and, according to a shorter regimen (0, 1, 3 mos), in another unit of similar characteristics (30 patients, 53 health care personnel). Staff members and renal patients received, respectively, 20 y 40 mcg of vaccine per injection. In the early vaccination phase, the two regimens did not lead to a difference in seroconversion rates nor in anti-HBs titers. After a 9-month surveillance, lower seroconversion rates, although not significant, were observed with the accelerated regimen among staff members (84.2%) and renal patients (79.2%) as compared with 93% and 87.5%, respectively, following the normal schedule. At the same time, anti-HBs titers were significantly lower (p less than 0.001) in the staff (316 RIA U) and patients (93 U) vaccinated according to the short regimen than in their respective counterparts (4196 and 1047 U) assigned to the normal schedule. A fourth dose of vaccine given to subjects with low and no anti-HBs titers significantly increased seroconversion and anti-HBs levels, although with little success among the former non-responders.

We report on a patient with gastric adenocarcinoma and severe renal failure caused by hemolytic uremic syndrome with predominantly vascular involvement. Evolution was favorable with partial recovery of renal function after tumor excision and administration of fresh plasma. Although microangiopathic hemolytic anemia is frequently associated with solid tumors, the appearance of a typical hemolytic uremic syndrome with carcinoma is exceptional.

Dermatofibrosarcoma protuberans has been considered to be of fibrohistiocytic or fibroblastic origin. The purpose of this paper is to identify the original cell strain from which this neoplasm derives, using tissue culture and electron microscopic methods. Thirteen cases of DFSP characterised by clinical, topographical, histological and behavioral criteria were explanted. The emigrating cells were bipolar with two opposed processed and showed a radial arrangement in respect to the explants. After the second week the distal processes tended to curve back towards the cell body forming flame-like structures. This cell morphology and cellular orientation persisted during the whole life of the culture. Electron microscopy was performed in three cases; the newly grown cells maintained an electron microscopic picture similar to that found in the original tumors. This pattern of behaviour is characteristic of fibroblastic tumors and has been found in explants of normal fibroblasts, of fibromatosis and of fibrosarcomas used as controls. On this basis, we believe that DFSP is a fibrosarcoma of the skin of low grade malignancy.