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Given the increased COVID-19 observed in kidney transplant recipients (KTRs) and haemodialysis patients, several studies have tried to establish the efficacy of mRNA vaccines in these populations by evaluating their humoral and cellular responses. However, there is currently no information on clinical protection (deaths and hospitalizations), a gap that this study aims to fill.Observational prospective study involving 1,336 KTRs and haemodialysis patients from three dialysis units affiliated to Hospital Clínic of Barcelona, Spain, vaccinated with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccines. The outcomes measured were SARS-CoV-2 infection diagnosed by a positive RT-PCR fourteen days after the second vaccine dose, hospital admissions derived from infection, and a severe COVID-19 composite outcome, defined as either ICU admission, invasive and non-invasive mechanical ventilation, or death.Six per cent (18/302) of patients on haemodialysis were infected, of whom four required hospital admission (1.3%), only one (0.3%) had severe COVID-19, and none of them died. In contrast, 4.3% (44/1034) of KTRs were infected, and presented more hospital admissions (26 patients, 2.5%), severe COVID-19 (11 patients, 1.1%) or death (4 patients, 0.4%). KTRs had a significantly higher risk of hospital admission than HD patients, and this risk increased with age and male sex (HR 3.37 and 4.74, respectively).The study highlights the need for booster doses in KTRs. In contrast, the haemodialysis population appears to have an adequate clinical response to vaccination, at least up to four months from its administration.

The immunomodulatory effects of extracorporeal photopheresis (ECP) have been used for the treatment of T-cell mediated disorders, such as rejection in organ transplantation. Currently, it is an established therapy for heart and lung rejection, but not for kidney transplantation (KT), where experience is limited. In addition, some data suggest that ECP could generate an immune response against infections, thus being an alternative for the treatment of rejection in case of active or high-risk of infection. In the present study, we analyze four cases of use of ECP as concomitant therapy in patients with KT and high risk of opportunistic infections due to the high burden of immunosuppression throughout their renal diseases. Two patients had concomitant viral infection (cytomegalovirus and BK virus, respectively) and three patients were on treatment for graft rejection. In the two patients with active viral infection, the infection was successfully controlled during ECP treatment. In all cases, ECP has been shown to be a safe procedure, without complications.

Purpose: The protective role of Vitamin D as an immunomodulator has been demonstrated in different pathologies included the viral etiology. This effect has been described by different mechanisms among these acting as an immunoprotein inducer, participates in growth and cell differentiation and acts as a mediator of apoptosis. Some evidence suggests that it could influence the SARS-COV 2 infection and its prognosis. Kidney transplant (KT) patients are more susceptible to 25 (OH) VitD (Calcidiol) deficiencies. The purpose of this study is to evaluate the Vitamin D status in transplant patients who have been diagnosed with COVID-19 and its possible correlation with prognosis. Methods: It is an observational, retrospective, cross-sectional and descriptive study that includes kidney transplant patients diagnosed with COVID-19 and with serum 25 (OH) Vit D Results: 79 patients were evaluated. The mean age was 58 years, 60.8% were men. 86% were KT, 11% were simultaneous pancreas and kidney transplant (SPK). 39 (48%) presented neumonia, 22 (28%)flu-like syndrom. 14 (17%) asyntomatic and 2(2,5%) fever. From this patients 39,2% had not changes in the antiinflamatorie therapy, 20.3%, required increased dose of corticosteroids, and 30.4% required methylprednisolone bolus or initiation of anti-interleukin therapy. The mean of Vit D was 21.41+/- 11% we found that 52% has Vit D 30 ng / dl In 32 patientes who required intensification of treatment we found that 73% had Vit D levels

Background It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. Methods To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). Results Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). Conclusions This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P

Pre-implantation renal biopsies of expanded criteria donors are one of the criteria used for allocation decisions, but there are concerns about the impact of the interobserver variability and the technique to be used. The aim was (i) to compare the original report performed by on-call pathologists using frozen sections (FS) to a retrospective analysis carried out by a trained pathologist using the same frozen section, and (ii) to compare the same FS to subsequently obtained paraffin sections (PS) by the same pathologist. A total of 92 biopsies, 78 from transplanted and 14 from nontransplanted cases, were analyzed. Agreement between observers using the same FS was weaker than the correlation between FS and PS in all the examined parameters (Kendall's Tau b for the Remuzzi score 0.104 vs. 0.306). According to the Remuzzi score, the revised FS analysis would have resulted in a higher rate of organ discard (n = 19) than PS (n = 14) and the original report (n = 6). However, kidneys that would have been discarded according to the retrospective analysis showed adequate outcomes in terms of graft survival and function. Accordingly, the impact of interobserver and technique-related variability can be minimized by the use of a relatively low threshold (RS ≤ 4) for organ acceptance.

Background Systemic inflammation affects kidney function in a wide range of diseases. Even in kidney transplant recipients, higher levels of C-reactive protein (CRP) are invariably associated with both worse short- and long-term graft outcomes. However, little is known about systemic inflammation in kidney donors and, notably, brain death causes a strong systemic inflammatory response. Objective To analyze the role of systemic inflammation of brain-dead donors on short-term kidney graft outcomes (ie, delayed graft function [DGF], defined as the need of dialysis during the first week after transplantation). Materials and methods Retrospective analysis of clinical and biochemical characteristics of all brain-dead kidney donors generated in the Hospital Clinic of Barcelona in the 2006 to 2015 period (n = 194). Donors who were tested for CRP in the 24 hours before BD declaration were included (n = 97, 50% of initial population). Clinical and biochemical features of their respective recipients (n = 165) were analyzed, comparing recipients who developed DGF (n = 30) with recipients who did not (n = 135). Results Donors whose recipients later developed DGF had much higher CRP values (10.58 [5.1-18.21] vs 4.81 [1.42-12.2] mg/dL, P = .025). Other characteristics associated with the development of DGF were renal biopsy score and recipient dialysis vintage (P = .025 and P = .002, respectively). In logistic regression analysis, PCR maintained significance in the non–expanded criteria donor (ECD) group (odds ratio [OR], 1.102; P = .027), but it lost significance in the ECD group (P = .67). Conclusions Terminal donor CRP was associated with DGF in kidney transplant recipients and proved to be mostly significant in younger donors.

It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted.

Background Induction therapy in renal transplantation reduces the incidence of acute rejection (AR) in expanded criteria donation (ECD) and donation after cardiac death (DCD). We compared the efficacy of Thymoglobulin (Sanofi-Aventis, Spain), ATG Fresenius (ATG-Fresenius, Spain), and Simulect (Novartis Farm, Spain) in a calcineurin-free protocol in ECD and DCD renal transplantation by evaluating patient survival, graft survival, and AR at 1 year and overall costs. Methods An observational retrospective study was performed using our database of 289 consecutive cadaveric ECD renal transplant recipients (n = 178) and DCD recipients (n = 111) from April 1999 to December 2011. Induction therapy consisted of Simulect, Thymoglobulin, and ATG Fresenius. Calcineurin-inhibitor (CNI)–free maintenance therapy consisted of mycophenolate mofetil or sodium and steroids. Results There were no differences in the patients' demographic characteristics or patient and graft survival. One-year AR rates were equivalent (ECD: 10%, 19.1%, 17.7% versus DCD: 14.3%, 7.1%, 16.7%). Leukopenia and thrombopenia were significantly more frequent in the ECD group treated with polyclonal induction. The average total cost of transplantation was higher in the ECD group but there were no significant differences in the average total cost between ECD and DCD: 39,970.31 ± 7,732€ versus 35,058.34 ± 6,801€ (P = NS). Conclusion Our study shows the same efficacy with polyclonal and monoclonal antibody induction and a CNI-free treatment regimen in ECD and DCD renal transplantation with no differences in overall costs at 1 year after transplantation.

In the recent years, more than 60% of available deceased donors are either older than 50 yr or have significant vascular comorbidities. This makes the acceptance and rejection criteria of renal allografts very rigorous, especially in cases of younger recipients, and at the same time encourages live donations. In our country, there is a lack of homogeneity in the percentages of use of expanded criteria donor (ECD) allografts between the different autonomous communities. Furthermore, the criteria vary greatly, and in some cases, great importance is given to the biopsy while in others very little. In this study, we present a unified and homogenous criteria agreed upon by consensus of a 10-member Panel representing major scientific societies related to renal transplantation in Spain. The criteria are to be used in accepting and/or rejecting kidneys from the so-called ECDs. The goal was to standardize the use of these organs, to optimize the results, and most importantly to provide for the maximum well being of our patients. Finally, we believe that after taking into account the Panel's thorough review of specific scientific literature, this document will be adaptable to other national renal transplant programmes.

Mammalian target of rapamycin inhibitors (mTORi) prevents cytomegalovirus (CMV) infection in kidney transplant (KT) patients. From May 2010 to December 2013, all KT recipients were retrospectively analysed. Maintenance immunosuppression regimen was divided into mTORi or calcineurin inhibitors (CNI)-based regimen. Since June 2011, CMV-seropositive recipients (R+) treated with high-intensity immunosuppression and mTORi did not receive anti-CMV prophylaxis. We analysed 350 consecutive patients, of which 95 (27%) received mTORi and 255 (73%) CNI-based immunosuppression. A Cox-regression multivariate analysis showed that the use of mTORi-based immunosuppression during all follow-up reduced the risk of CMV infection (HR 0.36, 95% CI 0.15-0.89, P = 0.028) and confirmed in a propensity score-matched cohort (HR 0.4, 95% CI 0.1-0.9, P = 0.047). Early discontinuation of mTORi increased the risk of CMV infection (HR 3.2; 95% CI 1.7-6.0) in univariate analysis. The incidence of CMV infection was not higher among CMV R+ patients on mTORi and requiring high-intensity immunosuppression when CMV prophylaxis was not given. The use of mTORi protected for CMV infection in KT patients, allowing to avoid antiviral prophylaxis for R+ patients receiving high-intensity immunosuppression. The increased risk of CMV infection after early discontinuation of mTORi warrants further research.

The aim of this study was to compare the group of patients receiving a new kidney transplant before starting dialysis again (pre-reTR) with a group of patients receiving a new kidney transplant after restarting dialysis (reTR).This retrospective cohort included all the kidney retransplantations (second transplantations) between 2000 and 2012 performed at our center and their follow-up until July 2014. We analysed graft and patient survival, rejection rates, and immunologic parameters of these patients.We studied 18 patients who had pre-reTR and 83 who had reTR. In the pre-reTR group no patient had panel-reactive assay (PRA)10% at any time. In the reTR group 26.5% had PRA10% at the time of transplantation (P = .014) and 54.2% had a historical highest PRA10% (P .001). The rejection rate was 11.1% in the pre-reTR group and 27.7% in the reTR group during the first year post-retransplantation (P = .227). Patient survival rate was 100% in the pre-reTR group at 5 years of follow-up, whereas in the reTR group at 1 year it was 95.2% and 85.9% at 5 years after retransplantation. Allograft survival at 1 and 5 years was 88% and 89%, respectively, in the pre-reTR group. On the other hand, in the reTR group it was 89% after the first year and 65% at 5 years post-retransplantation.Pre-emptive renal retransplantation is a feasible option that should be assessed in patients with kidney graft failure and may help to minimize the morbidity associated with dialysis reinitiation.

The lack of donors is favoring living kidney donor (LKD) transplantation worldwide, quite often beyond the classic age-matching rules. We analysed renal function (RF) at 1 and 5 years in all donor and recipients as well as death-censored graft and patient survival. LKD recipients were divided into 4 subgroups: young recipients-young donors (YR-YD; N = 355), elderly recipients-young donors (ER-YD; N = 13), young recipients-elderly donors (YR-ED; N = 67), and elderly recipients-elderly donors (ER-ED; N = 38). "Elderly" was defined as ≥60 years. RF was better in those who received a young allograft (YR-YD/ER-YD) at any time (P .001). There was a trend toward higher proteinuria among the recipients of an old allograft (YR-ED/ER-ED) at any time (P = not significant [NS]). However, our population showed low levels of proteinuria and this was not a risk factor for graft failure. Logistic regression model showed that creatinine level at 1 year is a good predictor of graft losses. Graft survival was worse in the allografts from elderly donors (P .001). Analysing the young recipients, renal survival was inferior in those who received an old kidney (YR-ED; P .00005) as well as mortality rates at 14 years (P = .03). The RF of young (N = 295) and elderly donors (N = 98) was optimal with no progression to ESRD or deaths registered during follow-up. In conclusion, young recipients of elderly kidneys pay the price of a worse RF, allograft prognosis, and patient prognosis. The pair YR-ED is a doable option, but we recommend age matching when it is possible.

Ricart MJ, Oppenheimer F, Andres A, Morales JM, Alonso A, Fernandez C, on behalf of the Epi-trasplante Study, MIDATA Kidney–Pancreas Sub-study Group. Enteric-coated mycophenolate sodium in de novo and maintenance kidney–pancreas transplant recipients. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01526.x. © 2011 John Wiley & Sons A/S. Abstract: Background: Our objective was to describe efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) in de novo and maintenance recipients of kidney–pancreas transplant in the clinical practice. Methods: Observational, multicentre, prospective, 12-month study. Results: We included 24 de novo and 24 maintenance patients. EC-MPS mean (±SD) doses at initiation in de novo patients were 1440 ± 0 vs. 1268 ± 263 mg/d at month 12 (M12). Patient and renal graft survival at one yr were 100%, and pancreatic graft survival was 83.3% (two losses owing to technical failure and two owing to rejection). In the maintenance cohort, EC-MPS was introduced at a median (P25–P75) of 30 (6–71) months after transplant. Baseline doses were 585 ± 310 vs. 704 ± 243 mg/d at M12. In this group, a significant increase in creatinine clearance was observed (65 ± 22 at baseline vs. 74 ± 20 mL/min at M12, p = 0.011). Patient, renal, and pancreatic graft survival were 100%, 95.8%, and 100%, respectively (one kidney graft loss owing to rejection). During follow-up, one patient from each group discontinued EC-MPS. Conclusions: The efficacy of EC-MPS in the clinical practice of kidney–pancreas transplantation is good, with high patient and grafts survival at 12 months, and good safety profile. The maintenance group displayed an improvement in renal function.

Since the introduction of combined antiretroviral therapy (cART), solid organ transplantation (SOT) has become a therapeutic option for the HIV-positive population. In contrast with liver and kidney transplantation, only three simultaneous pancreas-kidney transplants (SPKT) have been reported among HIV-infected patients. Herein we have reported the first SPKT in an HIV-infected patient in Spain. The pancreas graft failed at 2 weeks and the patient died at 9 months because of a Pseudomonas aeruginosa infection. The three recipients reported in the literature lived, despite the failure of both the pancreas and kidney grafts in one subject. Despite the poor outcome of our case, HIV-1 infection was controlled after transplantation (stable CD4(+) cells and no AIDS-related events), and the kidney graft functioned with no episodes of rejection. The cART regimen used in the pretransplant period was switched at the time of transplantation to raltegravir and two nucleoside reverse transcriptase inhibitors (NRTI). Raltegravir has no interactions with immunosuppressive drugs. Target plasma levels of tacrolimus were achieved at a dose similar to that used in HIV-negative transplant recipients. The most adequate antiretroviral regimen for HIV-infected SOT recipients has not yet been established; however, one may consider switching protease inhibitors or non-NRTI-based regimens for a raltegravir-based regimen at the time of transplantation.

Increasing prevalence of infections caused by multiresistant gram-negative enteric bacilli due to synthesis of extended-spectrum beta-lactamase (ESBL) or to desrepressed chromosomic AmpC beta-lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3-year period was performed. ESBL-production was determined by phenotypic analysis based on the CLSI recommendations. A multi-variate logistic regression analysis was performed to identify independent variables associated with multi-resistant gram-negative bacilli infection. The study included 417 patients (61 double kidney-pancreas recipients). The incidence of ESBL-producing and desrepressed chromosomic AmpC beta-lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp(12/60 isolations). Double kidney-pancreas transplantation(OR 3.5, CI95% 1.6-7.8), previous use of antibiotics(OR 2.1,CI95% 1.1-4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5-6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2-14.9) were independent variables associated with these multiresistant gram-negative enteric bacilli infections. The incidence of ESBL-producing and desrepressed AmpC beta-lactamase gram-negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

The best immunosuppressive regimen in HIV-infected renal transplant recipients has not been established. Thymoglobulin has been associated with an increased risk of serious bacterial infections in HIV-negative patients and, for this reason, there is some concern over its use in the HIV-infected population. We describe three consecutive HIV-infected renal transplant recipients who received thymoglobulin as induction therapy, and we compared their progress with a cohort of 23 HIV-negative recipients. Median follow-up was 24 and 11 months, respectively. Nadir lymphocytopenia was observed at 1 week in both groups, and their absolute lymphocyte count recovery was similar. An early and deep (

Introduction Chronic allograft dysfunction (CAD) is the main cause of late transplant failure. Although several etiologies have been postulated, toxicity for calcineurin inhibitors (CNIs) is one of the most important causes of CAD, characterized by arteriolar hyalinosis, luminal narrowing, increased glomerulosclerosis, and tubulointerstitial damage. It’s known that in transplant patients with CAD, fibrogenic mediators such as transforming growth factor beta (TGF-β) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI. Aim This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus. Patients and methods We studied twelve renal transplant patients with CAD on CNI treatment. TGF-β in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment. Results TGF-β urine levels decreased from 24.7 ± 11.2 to 12.8 ± 5.1 ng/24 h ( P = .049). In plasma, a similar decrease trend was observed (22.2 ± 32 to 10.3 ± 3 ng/mL), although it was not significant ( P = .079). Endothelin-1 showed a decrease (8.1 ± 3 to 5.2 ± 1.1 pmol/L; P = .1) and VEGF in plasma increased from 34.3 ± 37 to 92.2 ± 86 pg/mL ( P = .051). Conclusions Patients undergoing conversion from CNI to sirolimus treatment for CAD presented a significant decrease in TGF-β urine levels, representing a decreased mediator of the CAD fibrogenic process.

To examine the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic) in renal transplant patients with diabetes mellitus, six- and 12-month data from three clinical trials with EC-MPS (Studies B301, B302, and myPROMS) were analyzed post hoc. Studies B301 (de novo patients) and B302 (maintenance patients) followed a randomized double-blind design whereas myPROMS was an open-label study in de novo and maintenance renal transplant patients in which all patients received EC-MPS as part of their immunosuppressive regimen. In studies B301 and B302, diabetic patients were compared against mycophenolate mofetil (MMF, CellCept), the reference drug. For myPROMS, data from diabetic and non-diabetic patients were compared. In total, 246 diabetic patients receiving EC-MPS were analyzed. In study B301, the efficacy failure rate [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up] in diabetics at 12 months was 17.6% (EC-MPS) vs. 26.2% (MMF), and of BPAR alone 14.7% vs. 19.0% (both n.s.). In de novo patients from myPROMS, the treatment failure rate was similar in diabetic (20.3%) and non-diabetic patients (27.1%), as was the incidence of BPAR (17.7% vs. 23.1%, both n.s.). The overall incidence, severity and pattern of AEs were comparable between EC-MPS and MMF in de novo patients. This was supported by the safety results assessed in maintenance patients (B302) indicating no increased safety risk with the use of EC-MPS in the diabetic patient population, if compared with MMF. Likewise, apart from a higher incidence of severe/serious infections in diabetics, the safety profile of EC-MPS was not different to non-diabetics in myPROMS. In conclusion, preliminary data suggest that EC-MPS in combination with cyclosporine (+/- steroids) can be used efficiently and safely for the prophylaxis of organ rejection in diabetic renal transplant patients. Moreover, diabetic patients can apparently be safely converted from MMF to EC-MPS. More data from prospective studies are needed to fully judge the efficacy and safety profile of EC-MPS in the diabetic transplant population.

We report the first case of a pregnancy in a renal transplant recipient with HIV infection. She underwent renal transplantation in 2005 and became pregnant in 2009. The patient underwent vaginal delivery and a healthy full-term, female baby was born. Almost 6 years after delivery, both mother and child were doing well. The management of concurrent renal transplantation, HIV infection and pregnancy was extremely challenging. Women with HIV infection who have undergone renal transplantation should be accurately informed of the potential health risks for them and their offspring. Multidisciplinary teams are mandatory in order to properly manage these patients.

Introduction Intron long-term graft function are uncertain. Although there have been a large number of successful pregnancies in renal graft recipients, the effects of pregnancy and type of immunosuppressant drugs. Objectives To analyze (1) the impact of pregnancy on the long term renal function and graft survival of kidney transplant recipients (KTx), and (2) the impact og the pregnancy in (KTx) immunosupressed with calcineurin inhibitors (CNI). Methods Retrospective analysis of two cohorts: one (PG) formed by all the KTx recipients from our institution that became pregnant between 1973 and 2004, and the other one (NPG) formed by, when possible, up two KTx patients of similar demographic and clinical characteristics: patient age, donor source, donor age, interval between KTx and pregnancy (or a matched interval for NPG), baseline renal function before pregnancy, hypertension, proteinuria >1 g, and CNI-based immunosuppression. but without pregnancies. Particular attention has been paid to long-term (5 and 10 years) renal function and graft survival. Males were selected to complete NPG if no matched women were available. Statistical analysis Assessment of baseline homogeneity between the two cohorts was performed by appropriate analysis. Time of survival of kidney was estimated by means Kaplan–Meier method and the Cox proportional hazard model was used to perform adjusted analysis. Results Fifty five pregnancies in 43 patients (PG) and 68 paired controls (NPG) were included in the study. The basal and functional characteristics of PG before pregnancy and NPG were not statistical and clinical significantly different. In a univariate Cox regression analysis, 10 years graft survival after pregnancy/study entry was significantly better in CG (79.9%) than PG (60.9%) ( P = 0.02). Multivariate analysis of graft survival showed an increased risk of long-term graft loss in pregnant women that had been treated with CNI as immunosuppressant drug compared with NP KTx that received CNIs (HR: 2.4, 95% CI, 1.17–5.00; P = 0.02). In a stratified analysis, evaluating separately the recipients that had received or not CNIs, the risk of graft loss was only increased among recipients that became pregnant post-transplantation treated with CNI compared with recipients that had received CNIs but had not become pregnant (HR: 3.3, 95% CI, 1.42–7.45; P = 0.005), but not among recipients that became pregnant post-transplantation and received other immunosuppressant agents (HR: 0.9, 95% CI, 0.24–3.80; P = 0.94). Conclusion Pregnancy in women receiving baseline immunosuppression with CNI significantly increases the risk of long-term graft loss, non observed in KTx patients treated with CNI that not became pregnant, nor in KTx patients that became pregnant but are treated with other immunosuppressant drugs . At our knowledge, this observation has not been previously reported

Introduction End-stage renal disease (ESRD) is a major public health problem in the Spanish health system. Kidney transplantation is the treatment of choice, offering better survival and cost-effectiveness than other alternatives. This study aimed to compare the cost of living-donor kidney transplantation (LDKT) during the first year after transplantation with that of hemodialysis (HD). Method A prospective, descriptive study of cost and efficacy was performed in the Hospital Clinic in Barcelona from January to December 2011. We included 106 patients (57 undergoing HD and 49 receiving a LDKT). The costs of LDKT (donor and recipient) and HD were calculated based on our economic database program. Results The mean age of recipients and donors was 46 ± 15 and 52 ± 10 years, respectively, and 67% of the recipients were men. In HD patients, the mean age was 67 ± 11 years and 62% were men. The total cost of LDKT was €29,897.91 (€8,128.44 for donors and €21,769.47 for recipients). The total cost of HD was €43,000.88 (€37,917 for HD and related procedures plus €5,082 for transport). LDKT represented a savings of €13,102.97 per patient/year and the payback period was less than 1 year. Quality-adjusted life years were higher in LDKT than in HD patients. Conclusion LDKT is cost effective during the first year after transplantation and is associated with enhanced quality of life. From both the medical and economic points of view, pre-emptive LDKD should be encouraged in Spain to reduce the health budget for ESRD.

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p

The relationship between anticalcineurin (CNI) drugs and the development new-onset diabetes mellitus after kidney transplantation (NODAT) is well established. Among these agents cyclosporine shows lesser diabetogenicity than tacrolimus. It has been described that conversion from tacrolimus to cyclosporine improves glycemic control; however, there are no studies showing whether this reduced risk is maintained upon long-term follow-up.To evaluate whether CNI drugs conversion from tacrolimus to cyclosporine helps to maintain better glycemic control.We retrospectively evaluated the evolution of glucose metabolism at 5 years after conversion from tacrolimus to cyclosporine in eight patients (six men) with NODAT. Mean age was 42.8 ± 15 years, and time after transplantation to conversion 128 ± 40 months. We analyzed fasting serum glucose, lipid metabolism, renal function, and cyclosporine levels at 0, 6, 12, 24, 36, 48, and 60 months after conversion.At 6 months after conversion, improved glucose metabolism was observed (268 ± 161 versus 121 ± 31 mg/dL; P.01) although it was minimal in one case with persistent high blood glycemic levels. Only two patients maintained a normal glucose at the end of follow-up. Five subjects showed increased glycemia at 12 to 24 months after conversion requiring antidiabetic therapy: three patients, insulin and two oral antidiabetic agents. Two patients lost their allografts due to chronic rejection at 32 and 50 months respectively. Among the other six patients, renal function remained stable (1.9 ± 0.6 versus 2.11 ± 0.97 mg/dL; P = NS). There was no significant differences among the other variables. Cyclosporine levels remained stable during the follow-up.Conversion of renal transplant patients with NODAT from tacrolimus to cyclosporine improves glucose metabolism in the short term but glycemia increases thereafter.

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Background. Acute rejection remains a major problem in renal transplantation. Immunoprophylaxis with basiliximab (Simulect) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression. This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine (USP Modified, Neoral), mycophenolate mofetil, and steroids. Methods. In a randomized, double-blind, placebo-controlled, multicenter study, 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation (day 0) and 20 mg on day 4 (n=59), or placebo (n=64). All received triple-drug immunosuppression and were followed for 6 months. Results. Tolerability of basiliximab was equivalent to placebo, with no increase in serious adverse events, infection, malignancy, or posttransplant lymphoproliferative disorder. At 6 months, there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection (15.3% vs. 26.6%, P=NS) and of acute rejection treated with antibody (5.1% vs. 15.6%, P=NS). Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection, biopsy-confirmed rejection, rejection episodes treated with antibody therapy, and treatment failure. Renal function improved more rapidly in the basiliximab group, with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo (P=0.034). At 12 months, patient survival was 100% in both groups; graft survival was 94.9% with basiliximab and 92.2% with placebo. Conclusions. Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.

Introduction The aim of this study was to evaluate the experience of a renal transplantation unit in the management of human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Methods A prospective study was performed between 2005 and 2010 among 23 patients with ESRD. Results In this study 83% of HIV- infected patients with ESRD were included on the waiting list for renal transplantation with 4 patients in a clinical evaluation phase. During the follow-up, 52% of waiting list patients (n = 11) received a renal transplant, and 1 patient underwent a simultaneous kidney-pancreas transplantation. Among the waiting list group we observed a significant later exclusion (43%; n = 3). Among the transplanted group there was a high but clinically inconsequential prevalence of acute tubular necrosis (36%; n = 4) and acute rejection episodes (36%; n = 4). The renal function showed a serum creatinine of 1.1 mg/dL at a follow-up of 24 + 12 months. All patients on the waiting list and after the transplantation are prescribed combined antiretroviral treatment (cART) with a low viral load 200. Conclusions HIV-infected patients with ESRD should be considered to be candidates for renal transplantation if they meet the HIV inclusion criteria. Renal transplantation in adequately selected HIV-infected patients is a safe procedure with acceptable patient and graft survivals.

We sought to determine the frequency, risk factors, and clinical impact of recurrent urinary tract infections (UTI) in kidney transplant recipients. Of 867 patients who received a kidney transplant between 2003 and 2010, 174 (20%) presented at least one episode of UTI. Fifty-five patients presented a recurrent UTI (32%) and 78% of them could be also considered relapsing episodes. Recurrent UTI was caused by extended-spectrum betalactamase (ESBL)-producing Klebsiella pneumoniae (31%), followed by non-ESBL producing Escherichia coli (15%), multidrug-resistant (MDR) Pseudomonas aeruginosa (14%), and ESBL-producing E. coli (13%). The variables associated with a higher risk of recurrent UTI were a first or second episode of infection by MDR bacteria (OR 12; 95%CI 528), age >60 years (OR 2.2; 95%CI 1.15.1), and reoperation (OR 3; 95%CI 1.37.1). In addition, more relapses were recorded in patients with UTI caused by MDR organisms than in those with susceptible microorganisms. There were no differences in acute rejection, graft function, graft loss or 1 year mortality between groups. In conclusion, recurrent UTI is frequent among kidney recipients and associated with MDR organism. Classic risk factors for UTI (female gender and diabetes) are absent in kidney recipients, thus highlighting the relevance of uropathogens in this population.

Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11-8.33) and 0.56 (0.11-14.3), respectively (p0.0001). According to the post transplant period (1-3, 4-6 and6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations. These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Background Secondary hyperparathyroidism (SHPT) is a relevant problem in patients undergoing dialysis, and cinacalcet hydrochloride seems to be the best option for controlling it. After kidney transplantation (KTx), moderate to severe SHPT may persist and cause hypercalcemia and hypophosphatemia, among other deleterious effects. The number of patients receiving cinacalcet before KTx is increasing. Objective To evaluate the evolution of calcemia, phosphatemia, and intact parathyroid hormone (iPTH) after KTx in patients with SHPT receiving cinacalcet on dialysis. Patients and Methods The study included 19 patients (15 men and 4 women; mean [SD] age, 52 [13] years) undergoing dialysis and receiving cinacalcet before KTx. Mean duration of dialysis before KTx was 33 (25) months, and cinacalcet dose was 45 (15) mg/d. Creatinine, calcium, phosphorus, alkaline phosphatase, and iPTH concentrations were evaluated at baseline (day of surgery), at 15 days after surgery, and then monthly for 6 months. In all patients, cinacalcet therapy was discontinued on the day of surgery. Results After the first month post-KTx, mean (SD) serum creatinine concentration was 1.6 (0.4) mg/dL and remained stable during follow-up. Calcium and phosphorus concentrations were normal in 13 patients after KTx; however, in 6 patients, hypercalcemia (calcium concentration, 11 [1.3] mg/dL) or hypophosphatemia (phosphorus concentration, 1.7 [0.6] mg/dL) developed, with iPTH concentration of 557 (400) pg/mL and alkaline phosphatase concentration of 307 (114) IU/mL. Treatment with cinacalcet resulted in correction of calcium and phosphorus concentrations (10.1 [0.4] mg/dL and 1.7 [0.7] mg/dL, respectively). Patients in whom hypercalcemia or hypophosphatemia developed were receiving cinacalcet, 60 mg/d or more, during dialysis therapy. Patients who received cinacalcet, 30 mg/d, before KTx did not exhibit hypercalcemia or hypophosphatemia after KTx. Conclusion In patients with HPT undergoing dialysis and receiving cinacalcet, 60 mg/d or more, this drug therapy should be continued after KTx to avert development of hypercalcemia or hypophosphatemia.

Introduction. Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. Methods. We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. Results. At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 ± 0.7 vs 1.8 ± 0.8 mg/dL, P

Background Mutiresistant bacterial infections are an emerging problem in the nosocomial setting. Our objectives were to describe the incidence, outcome, and risk factors for acquisition of multiresistant bacteria among renal transplant recipients. Methods We prospectively followed patients undergoing kidney transplantation over a 3-year period. We collected demographic features, underlying chronic diseases, and main transplant characteristics and complications. Multiple antibiotic resistance was defined for the most important bacteria: Enteric gram-negative bacilli resistant to betalactamics, cephalosporins, and quinolones; Staphylococcus aureus resistant to methicillin, cotrimoxazole, and clindamcin; Enterococcus spp resistant to ampicillin and quinolones; nonfermentator bacilli resistant to all antibiotics except aminoglycosides and collistin. Results Overall, 416 patients included 65 double transplants (62 kidney-pancreas and three kidney-liver) of mean age 48.5 years, and 57% men. Infection with multiresistant bacteria was observed in 58 patients (14%). Most frequent multiresistant bacteria were: Escherichia coli ( n = 33), Klebsiella spp ( n = 15), Citrobacter spp ( n = 8), Enterobacter spp ( n = 5), Morganella morganii ( n = 2), Pseudomonas aeruginosa ( n = 16), Acinetobacter baumanii ( n = 2), Enterococcus spp ( n = 9) and methicillin-resistant S. aureus (MRSA, n = 2). Age greater than 50 years, hepatitis C virus infection, double kidney-pancreas transplantation, requirement for posttransplant hemodialysis, surgical reoperation, and requirement for nephrostomy were independent variables associated with multiresistant bacterial infection. Most used antibiotics for treatment were: carbapenems (65%), amikacin (12%), linezolid, piperacillin-tazobactam, vancomycin, collistin, and fosfomycin. Infection with multiresistant bacteria was associated with a worse prognosis (graft loss or death, 19% vs 8%, P = .009). Conclusions The incidence of infection with multiresistant bacteria in our renal transplant cohort was high, being most frequently cephalosporin-resistant enteric gram-negative bacilli and multiresistant P aeruginosa . Methicillin-resistant S. aureus incidence was low. Infection with multiresistant bacteria conferred a worse prognosis.

Introduction. Tolerance to immunosuppresant treatment has considerable impact on adherence to therapy and on the outcome of renal transplantation. Recent data indicate better gastrointestinal tolerance to enteric-coated mycophenolate sodium (EC-MPS) than to the classic mycophenolate mofetil (MMF) formulation. Aim. This study assessed the effect of conversion therapy from MMF to EC-MPS on gastrointestinal tolerance and quality of life in renal transplant recipients. Methods. This open observational study analyzed the outcomes of conversion from MMF to EC-MPS among renal transplant patients with gastrointestinal complaints. At baseline (B) and at 8 weeks postconversion patients were assessed by the Gastrointestinal Quality of Life Index (GIQLI) questionnaire as well as by clinical evaluation (acute rejection, infection) and analytical determinations. Results. We analyzed 18 recipients of cadaveric renal transplants of mean age of 54 ± 9 years including 61% men and one retrasplant. Our patients had stable renal function with mean creatinine of 1.9 ± 0.7 mg/dL. Baseline treatment included cyclosporine-MMF-prednisone (33%) or FK-MMF-prednisone (66%). Bioequivalent conversion was carried out at 50 ± 29 months posttransplantation. Conversion to EC-MPS resulted in an improvement in overall quality of life (total score: baseline 106.61 vs 8 weeks 116.89; P < .01). Improvements were observed in the following GIQLI subscales: gastrointestinal symptoms (3.12 vs 3.48, P

Introduction Infections represent a major cause of morbidity and mortality among renal transplant recipients. Our aim was to analyze the incidence and etiology of infection-related mortality among a large cohort of renal transplant recipients. Methods From 1995 to 2004, we collected all causes of mortality among patients receiving a renal transplantation. The date of transplant, the last follow-up/death, type of transplant, age, and cause of death were tabulated into a database. The incidence rate of mortality was calculated in events per 10,000 transplant months. Results Among the 1218 renal transplants performed in the study period the causes of mortality were: cardiovascular, 65 (38%); infection, 49 (29%); cancer, 21 (12%); other causes, 18 (10.5%); and unknown, 18 (10.5%). Infection-related mortality were: sepsis = 17 (35%), bacterial pneumonia = 9 (18%), abdominal bacterial infection = 2 (4%), invasive viral infection = 12 (24%), and invasive fungal infection = 9 (18%). There were no differences in the global causes of mortality according to the year of transplantation. The incidence rate of infection-related mortality was higher among aged patients and similar to cardiovascular-related mortality. Comparing the periods 1995 to 1999 with 2000 to 2004, bacterial infection-related mortality remained stable (57% vs 57%), while viral infection-related mortality decreased (31% vs 7%) and fungal infection-related mortality increased (11% vs 36%; P = .06). Conclusions In the last decade, infection-related mortality among renal transplant recipients has not decreased. Although better control of invasive viral infections has been achieved, bacterial and fungal invasive infections remain important causes of mortality in this population.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P.05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P.001), body mass index (BMI)30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P.001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Background.Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. Methods. From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). Results. Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (

The increased incidence of Kaposi’s sarcoma (KS) in organ transplantation has been related to the KS herpes virus and the permissive effect of immunosuppressive therapy. We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection. Methods In this estudy we performed a retrospective chart review of 7 caucasian renal transplant recipients affected by KS to determine demographic data, etiology of ESRD, immunologic risk factors, immunosuppressive treatment, KS disease follow-up, and renal function before and after SRL conversion. Results All seven patients were under calcineurin inhibitor treatment at the onset of KS which was limited to the skin, without regression despite attempts to minimize immunosuppression. After conversion to SRL, six patients showed progressive regression of KS lesions, with only hyperpigmented atrophic cutaneous lesions remaining after a mean time of 8.1 months (2–18 months). The seventh patient has completed 9 months follow-up with a near complete regression of KS lesions. One patient returned to hemodialysis after 13 months following irreversible acute renal failure not directly related to SRL conversion; in the other six, renal function was stable. The mean serum creatinine was 1.87 ± 0.64 versus 1.74 ± 0.68 mg/dL, pre-conversion versus the end of follow up, respectively. Mean SRL blood level was 9.2 ± 2.0 ng/mL. Conclusion After SRL conversion, patients with KS showed progressive regression without an increased risk of acute rejection. SRL offers a promising approach to the management of posttransplantation KS and probably other malignancies in organ transplant recipients.

Introduction. Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients. Objective. The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients. Methods. We studied a group of 12 recipients (6 men and 6 women of mean age 55 ± 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoAl, ApoB, and Lp(a) levels. Results. The change to tacrolimus resulted in significant decreases in TC levels, 213 ± 30 (B) versus 185 ± 27 (12s) (P

Behcet's disease (BD) is a chronic, relapsing, inflammatory disorder, and the underlying histophatological lesion is vasculitis of unknown cause. Some case reports of BD with positive C-ANCA titers have been reported, but only 2 case reports have documented the association of ANCA-associated glomerulonephritis (GN) and BD, and no renal transplantation cases have been described. We report such a case. A 27-year-old male was referred for consultation due to acute renal failure. Seven years before, BD was diagnosed. At the time of consultation he suffered from uveitis and generalized arthralgias. The serum creatinine was 14 mg/dl and urinalysis showed 4+ protein and microscopic hematuria. Results of serological tests were normal. The ANCA PR 3 titer was 1:100 of cytoplasmic pattern. A renal biopsy showed a rapidly progressive type III glomerulonephritis. In spite of immunosuppressive therapy with cyclophosphamide and high steroid doses, renal function did not recover and hemodialysis therapy was initiated. One year later, the patient underwent a renal transplantation. Follow-up was absolutely normal, and 5 years after transplantation, renal function persisted to be normal, without urinary abnormalities and signs of reactivation of original disease, except for occasional arthralgias. C-ANCA titer was decreased and remained stable (

The introduction of cyclosporine in kidney transplantation rapidly improved short and medium term graft and patient survival rates. Initially many trials used cyclosporine monotherapy to avoid steroid toxicity, but high acute rejection rates lead to a change in the immunosuppressant scheme. The use of prophylactic steroids significantly decreased acute rejection rates, but the long-term benefit of such a reduction has not been assessed. Methods Retrospective analysis of the impact of early acute rejection on long-term outcome (10 years) in 264 consecutive renal transplants performed in a single institution between 1986 and 1993 using cyclosporine monotherapy (CM) (n = 139) versus cyclosporine and prednisone (CS) (n = 125). Different protocols were used for elderly or immunological high-risk patients and for transplants with delayed graft function and therefore these patients are not included. The incidence and severity of acute rejection episodes and long-term patient and graft survivals were analyzed. Results At 1 year, acute rejection episodes showed significantly higher frequency in the CM group than in the CS group (72.66% vs 46.40%). Nevertheless, graft and patient survival rates were similar at 1, 5, and 10 years (Graft: 96.38%, 78.77%, and 59.84% vs 92.59%, 75.62%, and 53.44%; Patient: 99.27%, 95.06%, and 84.76% and 95.9%, 93.09%, and 88.28%). Conclusion The addition of prophylactic steroids decreases the incidence of acute rejection but does not improve the long-term graft survival. These findings suggest that in an era of new immunosuppressants, fewer acute rejection episodes will be evident requiring more effort to detect and treat subclinical rejections.

Osteoporosis is a frequent complication after renal transplantation. Some workers have shown that bisphosphonates may be effective to prevent and treat corticosteroid-induced osteoporosis in these patients. In this study we report our experience with administration of the biphosphonate alendronate to treat renal transplanted patients with established osteoporosis.Twelve to 24 months after transplantation (9 women, 5 men) 14 renal transplant patient were treated with alendronate and 12 patients (7 women, 5 men) were untreated. All patients displayed an iPTH240 pg/mL and a bone mineral density (BMD) t-score-2.5. All patients received cyclosporine and prednisone therapy. Biochemical measurements, BMD, and X-rays of the lumbar spine were measured during study. Patients in the treatment group received alendronate 10 mg/d (po) and vitamin D plus calcium (800 UI cholecalciferol and 2.5 g of CaCO(3)) per day while those in the control group only received vitamin D plus calcium, at the same dose.There was no difference in mean age, weight, time after transplantation, or immunosuppression between the treatment and control groups. There were no significant differences in the biochemical parameters during the study period. Over the 1-year study period, patients receiving alendronate displayed a greater increase in BMD. Lumbar spine BMD increased 4.3 +/- 6.1% in the treatment group versus 0.55 +/- 5.30% in controls. Femoral neck BMD increased 10.3 +/- 11.9% and 2.2 +/- 5.7%, respectively, in the treatment and control groups. Patients receiving alendronate frequently experienced intestinal disconfort.The bisphosphonate alendronate is effective to treat renal transplant patients suffering from established osteporosis.

Urinary tract infections (UTIs) are frequent after renal transplantation, but their impact on short-term graft outcome is not well established. All kidney transplants performed between July 2003 and December 2010 were investigated to evaluate the impact of UTI on graft function at 1 year after transplantation. Of 867 patients who received a kidney transplant, 184 (21%) developed at least one episode of UTI, at a median of 18 days after transplantation. The prevalence of acute graft pyelonephritis (AGP) was 15%. The most frequent pathogens identified were Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa, 37% of which were considered to be multidrug-resistant strains. Thirty-eight patients (4%) lost their grafts, 225 patients (26%) had graft function impairment and the 1-year mortality rate was 3%; however, no patient died as a consequence of a UTI. Surgical re-intervention and the development of at least one episode of AGP were independently associated with 1-year graft function impairment. Moreover, the development of at least one episode of AGP was associated with graft loss at 1 year. Patients with AGP caused by a resistant strain had graft function impairment more frequently, although this difference did not reach statistical significance (53% vs. 36%, p 0.07). Neither asymptomatic bacteriuria nor acute uncomplicated UTI were associated with graft function impairment in multivariate analysis. To conclude, UTIs are frequent in kidney transplant recipients, especially in the early post-transplantation period. Although AGP was significantly associated with kidney graft function impairment and 1-year post-transplantation graft loss, lower UTIs did not affect graft function.

THERE IS A HIGH prevalence of cardiovascular disease among long-term renal transplant recipients. Its etiology is multifactorial, though hyperlipidemia has been identified as one of the most important risk factors. The atherogenic capacity of the lipoproteins is conditioned by the fatty acid composition of their lipid component. The balance in the concentration of polyunsaturated and monounsaturated fatty acids in low-density lipoproteins (LDL) influences the susceptibility of the LDL particles to oxidation. The fatty acid content of the various lipid fractions has not been extensively studied in renal transplant recipients. The aim of the study was to analyze the fatty acid distribution in the LDL fraction of renal transplantation patients treated with cyclosporine-neoral.