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Background Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63–17.21]} and female sex [OR 2.46 (CI 1.19–5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [−2.22 kg (95% CI −2.79 to −1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [−0.36% (95% CI −0.51 to −0.21)], serum uric acid [−0.44 mg/dl (95% CI −0.60 to −0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11–0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28–0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Few studies have described the clinical impact of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in renal transplant recipients (RTRs) in the context of omicron variant and the third vaccine dose. Antibody titer has been tried to relate to the prediction of outcomes related to SARS-CoV-2, but it results controversially in these populations.All patients with positive SARS-CoV-2 polymerase chain reaction followed at a RTRs reference center from March 15, 2020, to March 15, 2022, were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by nonantibodies (20 arbitrary unit [AU]/mL), low (20-100 AU/mL), and high antibody titers (100 AU/mL) against SARS-CoV-2 spike protein. Outcomes included pneumonia and mortality. We used logistic regression multivariable to assess for confounders.Among 186 RTRs with coronavirus disease 2019, 50.5% (n = 94) were vaccinated versus 49.5% (n = 92) unvaccinated. Of the vaccinated patients, 67.02% developed a high antibody titer (100 AU/mL) but 14.89% achieved a low antibody titer and 18.08%. Pneumonia-free survival (day 20) was 95% in high antibody titer but 40% in unvaccinated RTRs. Survival in RTRs at day 60 was similar in the unvaccinated group compared with nonantibodies breakthrough cases (82%) but 92% in the low antibody titer group (relative risk, 0.027; 95% confidence interval, 0.002-0.479; P = 0.014). Only patients with100 AU/mL showed a 100% survival on day 60 postinfection.Vaccinated RTRs who achieve at least a low antibody titer (20 AU/mL) had better results in terms of pneumonia and mortality than unvaccinated RTRs. Antibody titer100 AU/mL associate with even better results than patients with lower antibody titers.

BackgroundImmunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved.MethodsProspective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP). We evaluated anti-spike (by quantitative chemiluminescence immunoassay) and anti-nucleocapsid IgG (ELISA), percentage of TCD4+ and TCD8+ lymphocytes producing IFNγ against S-protein by intracellular flow cytometry after Spike-specific 15-mer peptide stimulation and serum neutralizing activity (competitive ELISA) at baseline and after vaccination.ResultsAmong COVID-19 naïve KTR, 54.2% developed cellular and humoral response after the third dose (vs 100% in DP and 91.7% in HV), 18% only showed cell-mediated response, 22.2% exclusively antibody response and 5.6% none. A correlation of neutralizing activity with both the IgG titer (r=0.485, p1000/mm3 [4.68 (1.72-12.73, p=0.003], eGFR>30 mL/min [7.34(2.72-19.84), pConclusionsKTR presented poor cellular and humoral immune responses following vaccination with mRNA-1273. The immunosuppression degree and kidney function of these patients play an important role, but the only modifiable factor with a high impact on humoral immunogenicity after a booster dose was an immunosuppressive therapy including a mTOR inhibitor. Clinical trials are required to confirm these results.

BACKGROUND AND AIMS The clinical effectiveness of COVID-19 vaccination in kidney transplant (KT) recipients is lower than in the general population. However, the evidence reported is limited so far. Our purpose is to analyze the characteristics and outcomes of a large series of KT with COVID-19 breakthrough infection and compare them with unvaccinated patients. As a secondary objective, we analyzed the evolution according to the type of mRNA vaccine administered. METHOD From April to October 2021, KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and type of vaccine were collected and outcomes of unvaccinated patients were compared with fully vaccinated patients. Univariable and multivariable Cox proportional hazard regression analyses were assessed for independent risk factors of COVID-19-related death. To avoid bias as much as possible, a sensitivity analysis was done exclusively in hospitalized patients. RESULTS During the period of the study, 481 KT recipients with COVID-19 were included in the registry: 351 fully vaccinated and 130 unvaccinated. Age, gender, KT vintage, diabetes as primary kidney disease, induction and maintenance immunosuppression and anti-COVID therapy were similar between both groups. Clinical picture was similar between fully vaccinated and unvaccinated patients: 10% versus 15.4% remained asymptomatic (P = 0.100), 56.7% versus 58.5% developed pneumonia (P = 0.720) and 66.1% versus 63.8% were hospitalized (P = 0.640), respectively. Survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated died (P = 0.776). In multivariable analysis, age (HR: 1.05, CI 95% 1.03–1.08, P Regarding the type of mRNA vaccine, 213 patients were vaccinated with the mRNA-1273 vaccine (Moderna) and 161 with the BNT162b2 (Pfizer-BioNTech), showing no differences in any of baseline and treatment-related variables analyzed. Patients vaccinated with the mRNA-1273 vaccine showed a significantly lower mortality than those who received BNT162b2 (16.4% versus 28.8%, P = 0.002), maintaining this difference in the multivariable analysis (reference mRNA-1273 vaccine: HR: 0.52, CI: 95% 0.31–0.85, P = 0.010). CONCLUSION COVID-19 severity in KT patients has remained high and has not improved despite receiving two doses of an mRNA vaccine. The mRNA-1273 vaccine has shown higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infection, so it could be considered as the first option in these patients.

BACKGROUND AND AIMS SGLT2 inhibitors (SGLT2i) are the first-line therapy in patients with type 2 diabetes mellitus (DM2) and CKD, together with metformin according to most recent published guidelines. They are related to better renal and cardiovascular outcomes. SGLT2i could be potentially benefitial in terms of renal function preservation and cardiovascular outcomes in kidney transplantion (KT). Despite published data about SGLT2i in KT patients with DM2 or new-onset diabetes after transplantation are limited, their use seems to be common in everyday clinical practice. Our aim is to investigate if SGLT2i are safe and well tolerated in a cohort of KT recipients, as well as to analyze clinical and laboratory data at 6 months after SGLT2i initiation. METHOD Multicentre observational study in KT recipients with diabetes under SGLT2i treatment. RESULTS A total of 323 patients were included, and 284 completed a 6-month follow-up. Mean age was 61.2 ± 10.3 years old, 74.4% were men and 41% presented DM2. Previous antidiabetic therapies: insulin (48.1%), DPP4 inhibitors (36.1%) and metformin (33.1%). Empagliflozine was started in 55.8%, dapagliflozine in 23.2% and canagliflozin in 20.6%. After SGLT2i initiation, body weight reduction, an improvement in blood pressure and glycaemic control, higher haemoglobin levels and a decrease in cholesterol levels were observed. Also, a mild decrease in eGFR was detected while albuminuria was lower. These differences were statistically significant (Table 1). In 34 patients (10.5%), SGLT2i was stopped: 2.78% presented urinary tract infection (UTI), 1.5% balanitis and 1.2% important eGFR decreasing slope. During the study period, six patients presented a graft loss (one related to SLGT2) and six patients died (deaths not related to SGLT2i). CONCLUSION SGLT2i have a safe security profile in KT, and are related to a better glycaemic and blood pressure control, as well as to a decrease in albuminuria, and to an improvement in cardiovascular risk factors. Thus, SGLT2i should be prescribed in KT recipients with DM2 or NODAT with adequate eGFR. UTI surveillance is essential in these patients.

Trasplante renal de donante vivo; Tratamiento de la enfermedad renal Living donor kidney transplantation; Chronic kidney disease treatment Trasplantament renal de donant viu; Tractament de la malaltia renal El trasplante renal de donante vivo (TRDV) es la opción terapéutica con las mejores expectativas de supervivencia para el injerto y para el paciente con insuficiencia renal terminal; sin embargo, este tipo de trasplantes ha experimentado un descenso progresivo en los últimos años en España. Entre las posibles explicaciones del descenso de actividad se encuentra la coincidencia en el tiempo con un aumento en el número de donantes renales fallecidos, tanto por muerte encefálica como por asistolia controlada, que podría haber generado una falsa impresión de ausencia de necesidad del TRDV. Además, la disponibilidad de un mayor número de riñones para trasplante habría supuesto un incremento en la carga de trabajo de los profesionales que pudiera enlentecer los procesos de donación en vida. Otro posible argumento radica en un posible cambio de actitud hacia posturas más conservadoras a la hora de informar a pacientes y a familiares acerca de esta opción terapéutica, a raíz de los artículos publicados respecto al riesgo de la donación a largo plazo. Sin embargo, existe una importantísima variabilidad en la actividad entre centros y comunidades autónomas, no explicada por el volumen de trasplante procedente de otros tipos de donante. Este dato, unido a que la indicación de donación renal en vida se realiza de manera mayoritaria en situación de enfermedad renal crónica avanzada (ERCA) y que el tiempo en diálisis es un factor pronóstico negativo respecto a la supervivencia postrasplante, permite concluir que el descenso depende además de otros factores. Por este motivo, en la reunión anual de equipos de trasplante renal, celebrada en la sede de la Organización Nacional de Trasplantes (ONT) en 2018, se constituyó un grupo de trabajo formado por equipos de trasplante renal, el grupo de trasplantes de la Sociedad Española de Nefrología (SEN) (SENTRA), la Sociedad Española de Trasplantes (SET) y la ONT, con el objetivo de identificar otras causas que condicionaron el descenso de la actividad de este tipo de trasplantes en España y su posible relación con la gestión del proceso de donación de vivo. El grupo de trabajo diseñó un cuestionario de autoevaluación, que fue cumplimentado por las 33 unidades de trasplante renal de donante vivo activas en España. El cuestionario contiene preguntas sobre las diferentes fases del proceso de donación de vivo: información inicial, estudio del donante vivo e información de los riesgos, consentimiento, recursos humanos (RRHH), nefrectomía, trasplante y seguimiento posterior. El análisis de las respuestas ha dado como resultado la creación de un análisis de debilidades, amenazas, fortalezas y oportunidades (DAFO) del programa a nivel nacional y ha permitido elaborar recomendaciones específicas dirigidas a mejorar cada una de las fases del proceso de donación en vida. El documento, denominado Análisis de situación del trasplante renal de donante vivo y hoja de ruta ha sido también revisado por un panel de expertos en TRDV, representantes de varias sociedades científicas implicadas (Asociación Española de Urología [AEU], Sociedad Española de Enfermería Nefrológica [SEDEN], Sociedad Española de Inmunología [SEI/GETH]), el Grupo de Trabajo Enfermedad Renal Crónica Avanzada (ACERCA), la Asociación de Pacientes para la Lucha Contra la Enfermedad Renal (ALCER) y sometido posteriormente a consulta pública. Tras incluir las mejoras sugeridas, el documento final ha sido adoptado institucionalmente en el Consejo Interterritorial de Trasplantes (CIT) del Sistema Nacional de Salud. El trabajo realizado y las recomendaciones para optimizar el TRVD se describen a lo largo del presente artículo, organizados por los diferentes apartados del proceso de donación. Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis.Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Despite good long-term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard-criteria (SCD) (N = 366) and expanded-criteria (N = 247) brain-dead donors (ECD). One-, 5-, and 10-year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65-11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18-3.22), and in-hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09-2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long-standing kidney transplantation program, uDCD could help expand the kidney donor pool. post-print 1,71 MB

Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR], 1.1 to 10.5). Most episodes (96.4% [132/137]) were caused by Gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended‐spectrum β‐lactamase‐producing Enterobacterales [20.4%] and carbapenem‐resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [CI], 31.9% to 48.9%) for the whole cohort and 42.3% (95% CI, 31.2% to 54.0%) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR], 2.42; 95% CI, 1.11 to 5.29; P value = 0.027) and use of fosfomycin as salvage therapy (OR, 8.31; 95% CI, 1.67 to 41.35; P value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse events were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens., This study was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), and Spanish Network for Research in Renal Diseases (REDInREN RD16/0009) and cofinanced by the European Development Regional Fund entitled A way to achieve Europe. M.F.-R. holds a research contract (Miguel Servet, CP18/00073), from the Spanish Ministry of Science and Innovation, ISCIII.

Background Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival. Methods We analyzed 279 adult renal transplant patients converted to an mTOR-i. CV was calculated using at least 3 blood trough levels between 3 and 18 months postconversion. Results The mean and median CV of the entire group was 25.54% and 23.7%, respectively. SRL and EVL mean CV was 23.8% and 27.1% (P = .03), respectively. The group of patients into the last tertile with CV> 28.52% presented a lower death-censored graft survival (75.26% vs. 93.01%, P Conclusion The CV of mTOR-i is correlated with long-term renal graft survival, so it should be considered a prognostic factor. SRL has a lower CV than EVL in renal transplant patients converted to mTOR-i in the stable posttransplant phase.

The +874 A/T polymorphism in the interferon gamma (IFNG) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient–, D+/R–) status (p-interaction = 0.01), with thymoglobulin induction therapy (p-interaction = 0.03) and with thymoglobulin anti-rejection therapy (p-interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R– and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy.

Posttransplant glomerulonephritis is a complication of kidney transplant that can impair graft function and long-term graft survival. De novo immunoglobulin A disease in kidney allografts appears to be much less common than the recurrent disease, and in most cases it is diagnosed in protocol biopsies with no clinical evidence of disease or in association with other renal transplant pathologies such as chronic rejection. We present a case of de novo immunoglobulin A nephropathy presenting with overt proteinuria, microscopic hematuria, and progressive deterioration of renal function 30 months after renal transplant.

Background The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant. Methods This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005–2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell’s c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias. Results Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11–5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009). Conclusions Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

En bloc pediatric transplantation (EBPT) began with the aim of increasing the donor pool due to the existing high demand for donors. At its inception, it was considered a type of suboptimal transplantation due to its association with a high incidence of vascular, urologic, and immunologic complications. The main objective of this study was to update information on EBPT with the largest case series that exists on a worldwide scale. In a retrospective study, the results obtained from brain-dead donors (BDDs; n = 770) were compared to those of EBPT (n = 100) from January 1990 to December 2012. The median of follow-up was 12.8 years (interquartile range 8.1 to 17.2). The variables collected for analysis were demographic factors (age and sex of recipients, age and weight of donors), renal function, graft survival, recipient survival, surgical complications (thrombosis, lymphocele, urologic complications, and renal artery stenosis and need for revascularization with angioplasty and/or stents). Subsequently in a second analysis, we studied the association between graft survival, thrombosis, angioplasty, stents, and appearance of lymphoceles with the different factors that were considered to be related in accordance with published literature and our own experience. Graft loss due to surgical complications was more frequent in EBPT than in BDD (15% vs 2.2 % in BDD; P < .001), and interstitial fibrosis and tubular atrophy were more frequent in BDD (13% vs 2%; P < .001). EBPT offers a good survival rate after overcoming the possible surgical complications that may arise.

Background Renal transplantation has been established as the treatment of choice for end-stage renal disease (ESRD) due to diabetic nephropathy. This study aimed to investigate the risk factors for recurrence of diabetic nephropathy (RDN) in renal allografts. Methods We studied 1,011 renal transplant patients from 1986 to 2003, of which 95 had ESRD due to diabetic nephropathy. We retrospectively analyzed the clinical characteristics and outcomes of RDN after renal transplantation. Results Of the 95 recipients with ESRD due to diabetic nephropathy, 41 developed RDN and 11 of those 41 underwent graft biopsy. The mean durations from transplantation to RDN and to renal replacement therapy was 81.58 months (range, 54–120 mo), and 109.66 months (range, 27–188.4 mo), respectively. At 5 years, treatment on statins and renin-angiotensin-aldosterone system (RAAS) blockers were associated with a higher survival free from RND (82.2% vs 63.2% [P = .070] and 100% vs 80% vs 0.6% [P = .013], respectively). Compared with cyclosporine, tacrolimus was associated with a higher risk for RND (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.75–5.13; P = .047). High doses of prednisone (>0.06 mg/kg) were also associated with a higher risk of RDN (OR, 3.03; 95% CI, 1.19–8.30; P = .029). The combination of calcineurin inhibitor and mammalian target of rapamycin inhibitor (mTORi) demonstrated the highest risk of RDN (OR, 14.08; 95% CI, 3.72–53.29; P Conclusions Treatment with tacrolimus and mTORi is the most diabetogenic immunosuppressive regimen. Treatment with tacrolimus entails a greater risk of RDN than with cyclosporine. The administration of statins or RAAS blockers could delay the progression of RDN.

Background The aim of this study was to determine the distribution of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) promoter region T-275A and C-2152T single-nucleotide polymorphisms (SNPs) in stable transplant patients and to investigate the impact of these SNPs on the evolution of this population after 10 years of follow-up. Methods White renal transplant recipients (n = 873) were studied. The median time of follow-up was 91.8 months (P25–75 46–146). Amplification with specific “primers” to delimit the study area was performed for each polymorphism. Amplification was performed with the use of real-time polymerase chain reaction. Results T-275A promoter mutation was detected in 13% of patients and C-2152T in 12% of patients. Survival analysis was performed on 873 renal transplants, carried out between 2004 and 2013. We found a higher frequency of death from cancer among polymorphism carriers ( P = .001). Conclusions It appears that carriers of T-275A and C-2152T SNPs of the UGT1A9 gene promoter region show a greater incidence of death from cancer, with a significantly higher cumulative incidence of death from gastrointestinal tumors.

Introducción: Varios países europeos disponen de programas de donación tras parada cardíaca controlada (cDCD). Veintidós centros participan en el grupo GEODAS, cuyos resultados clínicos presentamos desde una perspectiva nefrológica. Métodos: Estudio multicéntrico retrospectivo observacional con inclusión sistemática de todos los trasplantes renales (TR) procedentes de cDCD, siguiendo protocolos locales de extracción e inmunosupresión. Resultados: Se incluyó a 335 donantes tras cDCD (edad media 57,2 a˜nos) fallecidos mayoritariamente por eventos cardiovasculares. Se analizan 566 receptores (edad media de 56,5 años; el 91,9% con primer trasplante renal), con una mediana de seguimiento de 1,9 años.La terapia de inducción fue casi universal (timoglobulina 67,4%; simulect 32,8%) con mantenimiento con prednisona-MMF-tacrolimus (91,3%) o combinaciones con mTOR (6,5%). El tiempo medio de isquemia fría (CIT) fue 12,3 h. Hubo un 3,4% de fallo primario del injerto(n = 19), asociado fundamentalmente al tiempo de isquemia fría (solo el CIT ≥ 14 h se asoció a fallo primario del injerto). La función retrasada del injerto (DGF) fue 48,8%. Los factores de riesgo para la DGF fueron: CIT ≥ 14 h OR 1,6, procedencia de hemodiálisis (vs. diálisis perito-neal) OR 2,1 y edad del donante OR 1,01 (por año). Veintiún pacientes fallecieron con injerto funcionante (3,7%), con una supervivencia de paciente e injerto (censurada para muerte) al segundo año del 95% y del 95,1%, respectivamente. El filtrado glomerular estimado al año de seguimiento fue 60,9 ml/min. Conclusiones: El CIT es un factor modificable para mejorar la incidencia del fallo primario del injerto en trasplante renal procedente de cDCD. El trasplante renal con cDCD tiene mayor incidencia en la función retrasada del injerto, pero igual supervivencia de paciente e injerto que la referencia histórica para donación en muerte encefálica. Los resultados son satisfactorios para continuar promoviendo este tipo de donación, Introduction: Many European countries have transplant programmes with controlled donorsafter cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysedclinical results from a nephrological perspective.Methods: Observational, retrospective and multicentre study with systematic inclusion ofall kidney transplant recipients from cDCD, following local protocols regarding extractionand immunosuppression.Results: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due tocardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% firstkidney transplant) were analysed with a median of follow-up of 1.9 years. Induction the-rapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance withprednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischae-mia time (CIT) was 12.3 h. Approximately 3.4% (n = 19) of recipients experienced primarynon-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primarynon-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 hOR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (peryear). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerularfiltration rate at one year of follow-up was 60.9 ml/min. CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation., Este proyecto está auspiciado por el Grupo SENTRA de la SEN, la RedinRen 16/009/009 RETYC ISCIII, la Fundación Renal Iñigo Álvarez de Toledo y una beca colaborativa de Novartis, Astellas y Sanofi a través del Instituto de Investigación Sanitaria Puerta de Hierro-Segovia Arana

Background Substantial research has been conducted to develop limited-sampling strategies (LSS) to estimate the area under the curve (AUC(0-12h)) in patients treated with mycophenolate mofetil. However, no LSS has been validated for enteric-coated mycophenolate sodium (EC-MPS). Our aim was to develop an LSS to measure the AUC(0-12h) of mycophenolic acid in kidney recipients treated with tacrolimus and EC-MPS. Study design Thirteen serial blood samples were collected over 12 hours from 71 patients treated with tacrolimus and EC-MPS. Mycophenolic acid was measured in plasma using the enzyme-multiplied immunoassay. LSSs were developed and validated by multiple regression analysis using a 2-group method (test, n = 47; validation, n = 24). Results The best LSS obtained in the test group were for 3 and 4 time points AUC(0-12h) (mg·h(-1)·L(-1)) = 15.99 + 0.87C1 h + 0.68C2 h + 7.85C4 h and AUC(0-12h) (mg·h(-1)·L(-1)) =11.15 + 0.68C1 h + 0.45C1.5 h + 0.57C2 h + 8.16C4 h, respectively. When these LSS were tested in the validation group, the results were acceptable (adjusted r(2) = 0.71, bias =-0.214 [95% confidence interval (CI): -7.91 to 7.48], precision = 7.48 (95% CI: 3.69-19.39) for 3 time points and adjusted r(2) = 0.76, bias = -1.48 (95% CI: -8.23 to 5.27), precision = 7.68 (95% CI: 4.23-13.50) for 4 time points). Conclusions : An LSS using time points at C(1h)-C(2h)-C(4h) or C(1h)-C(1.5h)-C(2h)-C(4h) provides the most reliable and accurate estimation of the AUC(0-12h) of mycophenolic acid in stable renal transplant recipients treated with EC-MPS and tacrolimus.

BACKGROUND We analyzed our clinical experience with everolimus (EVL) and identified prognostic factors for a successful conversion. METHODS Retrospective study of 220 kidney recipients consecutively converted to EVL with calcineurin inhibitor elimination. We studied risk factors for proteinuria at 1 year after conversion, decline in renal function, and graft survival. RESULTS Baseline creatinine clearance was 52.4±17.8 mL/min vs. 53.4±20.1 mL/min 1 year after conversion (P=0.150). Median proteinuria increased from 304 mg/day (interquartile range 160-507) to 458 mg/day (interquartile range 238-892; P

A.I. Sanchez Fructuoso, N. Calvo, I. Perez-Flores, R. Valero, B. Rodriguez-Sanchez, D. Garcia de Viedma, P. Munoz, A. Barrientos. Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients. Transpl Infect Dis 2011: 13: 584–591. All rights reserved Abstract: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1–9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another. Results. We report our series of 15 renal transplant patients who underwent surgery between September 2004 and March 2010 and who developed BKV infection. The first 8 patients were treated with reduction of immunosuppression; 7 of these patients received cidofovir and 6 received intravenous immunoglobulin. The remaining 7 renal transplant recipients received mammalian target of rapamycin inhibitors (imTOR). In this group, we observed faster and more efficacious BKV clearance in plasma and urine and a steady improvement in allograft function, with no episodes of acute allograft rejection during follow-up. The polymerase chain reaction assay for BKV in urine became positive in 2 patients in whom imTOR were stopped due to severe side effects. Conclusions. The use of imTOR should be considered a first step in the treatment of renal transplant recipients with BKV infection. In our experience, this change in treatment was safe and resulted in viral clearance.

Resumen Introduccion Los antagonistas de los receptores de la an-giotensina II (ARA-II) son farmacos eficaces en el control de la presion arterial (PA), con demostrada accion anti-proteinurica. Aunque varios ARA-II han sido empleados con eficacia en la insuficiencia renal cronica (IRC), no hay estudios publicados sobre el efecto del olmesartan (ARA-II) en pacientes con IRC en estadio IV y V de la NKF. Objetivo El objetivo del estudio ha sido analizar la eficacia y la seguridad del empleo del olmesartan medoxo-milo en pacientes hipertensos con IRC en situacion de predialisis (PreD), y en tratamiento con hemodialisis (HD) y dialisis peritoneal (DP). En los pacientes en PreD y en DP con funcion renal residual (FRR) se ha estudiado tambien el efecto en la proteinuria y la funcion renal. Pacientes y metodos Se ha incluido a 32 pacientes (11 pacientes en PreD, 9 en HD y 12 en DP) a los que se anadio olmesartan (20-40 mg/dia) a su tratamiento antihi-pertensivo, y se estudio su efecto en la PA y distintos parametros analiticos a 1 y 3 meses de seguimiento: hemo-globina, hematocrito, tasa de filtracion glomerular (TFG), proteinuria, potasio (K), acido urico, AST, ALT, GGT, proteina C reactiva (PCR), albumina, transferrina, ferritina y fibrinogeno. Resultados Al mes del inicio de tratamiento con olmesartan, la PA se reduce de forma significativa de 156/88 a 138/76 mmHg (p Conclusiones El tratamiento con olmesartan en pacientes con IRC en estadio IV y V (tanto en DP como en HD) es eficaz en el control de la PA y muy bien tolerado. A pesar de la situacion de enfermedad renal severa, olmesartan reduce significativamente la proteinuria, sin empeorar la funcion renal ni la anemia. El prometedor efecto en los parametros de inflamacion necesita ser confirmado.

The −308G/A SNP oftumor necrosis factor-alpha (TNF-α) geneaffects TNF-αproduction. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-αproduction, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40–5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76–9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59–118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the −308G/ATNF-αpolymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens.

Background Inhibitors of mammalian target of rapamycin (mTORi) have been suggested as an alternative to calcineurin inhibitors (CNIs) to treat stable renal transplant recipients. However, their use has been significantly limited owing to a high incidence of side effects. Objective To compare the rate of dropout (mTORi elimination and CNI reintroduction) caused by side effects among renal transplant patients converted to everolimus (EVL) or sirolimus (SRL). Methods Between October 1999 and February 2010, 409 subjects were converted to an mTORi at least 3 months after transplantation, including 220 (53.8%) to EVL and 189 (46.2%) to SRL. Most patients were under CNI therapy. Patients were followed for a median of 35 months (interquartile range [IQR], 18–50 months). Results mTORi treatment was prematurely eliminated due to adverse events in 112 patients. The median time between the initiation of mTORi and discontinuation was 5.7 months (IQR, 1.9–15.7 months; range, 0.2–48 months): 5.5 (IQR, 1.6–16.3) in the EVL group and 7.4 (IQR, 2.6–15.6) in the SRL group. In the EVL group, the drug was stopped in 69 patients (31.4%), and in the SRL group in 43 patients (22.8%; P = .051). The most important causes of discontinuation were severe infections (2.3% in EVL group and 4.8% in SRL group; P = .17), pneumonitis (6.8 % in EVL group and 4.8 in SRL group; P = .38), acute rejection episode (4.1% in EVL group and 1.6% in SRL group; P = .13), proteinuria (4.1% in EVL group and 1.6% in SRL group; P = .13), renal function deterioration (2.3% in EVL group and 2.1% in SRL group; P = .91), and severe dermal eruption (2.3% in EVL group and 0.5% in SRL group; P = .14). Conclusions Although the overall incidence discontinuations due to side effects was higher in the EVL group, there was no greater frequency of severe side effects, such as pneumonitis, proteinuria, acute rejection episodes, renal function deterioration, or dermal eruptions.

Defining absolute psychiatric or neurological contraindications among kidney transplantation candidates is controversial, especially taking into account that graft outcomes are similar to other groups of patients. The social support network should be exhaustively evaluated to ensure adherence to immunosuppressive therapy and minimization of complications resulting from the neuropsychiatric disorder. We reviewed transplants (n = 668) in our center between January 2001 and August 2008 searching for patients with a diagnosis of neurological or psychiatric disease before renal transplantation. We also reviewed demographic data, social support networks, patient and graft survivals as well as transplant complications. Twelve patients were transplanted with neurological or psychiatric disorders: seven with cognitive impairment and five with psychiatric diseases. Nine patients had good social support networks. The mean follow-up time was 2.65 +/- 2.42 years. The graft loss rate was 34% (n = 4), including only one attributed to a mental disorder, namely, nonadherence to immunosuppressive therapy. Regarding complications, four were related to the neuropsychiatric disorder: hypoglycemia due to insulin overdose, aspiration pneumonia because of altered pharynx-larynx motility, hyponatremia related to diuretic abuse, and malnutrition plus dehydration. Patient survival in this period was 91.7%. The one patient died due to multiple organ failure secondary to respiratory sepsis with a functioning graft. In summary, neuropsychiatric disorders should not be considered to be contraindications for kidney transplantation although a social support network is essential and must be carefully evaluated.

Mammalian target of rapamycin (mTOR) inhibitors induce pneumonitis, an unusual but potentially fatal side effect of this drug group. We retrospectively collected the cases of pneumonitis induced by sirolimus or everolimus among 1471 adult cadaveric renal transplant recipients who were grafted at our institution from 1980-2008. Due to chronic transplant dysfunction or tumor, 205 patients were switched from calcineurin inhibitors to sirolimus (n = 88) or to everolimus (n = 117). Six patients (2.9%) developed pneumonitis: 1 was associated with sirolimus and 5 with everolimus (5 males and 1 female; median age, 60 years [range, 47-73 years]). Median times from conversion to pneumonitis onset were 34 days in 4 patients (range, 24-46 days) and 491 days in 2 subjects (range, 454-528 days). The mean drug trough level at presentation was 8.2 microg/L (range, 5.5-13.8 microg/L). The most common symptoms were dry cough (n = 6), fever (n = 5), and dyspnea (n = 4). Imaging tests revealed lower lobe involvement in all patients. Bronchoalveolar lavage performed in 4 patients showed lymphocytic alveolitis. All patients completely recovered after drug withdrawal. Five patients received steroids, 5 were switched to a calcineurin inhibitor, and 1 was switched to the other mTOR inhibitor. In conclusion, mTOR inhibitor-associated pneumonitis is a rare disease. Sirolimus did not cause more cases of pneumonitis than everolimus. Pneumonitis development was not dependent upon the drug blood level. Lower lobe involvement and lymphocytic alveolitis were usually present. Discontinuation of the mTOR inhibitor with steroid prescription resulted in adequate outcomes. A change to the other mTOR inhibitor should be contemplated if patient circumstances require this type of immunosuppression.

It is well know that anti-HLA antibodies are an important obstacle in kidney transplantation. Our aim was to study the clinical impact of pretransplant donor specific anti-HLA antibodies (HLA-DSA), in highly sensitized (HS) patients. We analyzed retrospectively the day-of-transplant sera by Luminex Single Antigen Assay (LSA) in HS patients, and the results were correlated with episodes of humoral and cellular rejection as well as with graft and patient survival. All HS subjects received the same induction therapy and rejection episodes were biopsy proven. Thirteen patients (56.5%) preformed HLA-DSA, and we observed higher incidence of acute rejection in aforementioned patients than in the pre-transplant negatives DSA recipients (77% versus 30%, P = 0.03). The one-year graft survival was significantly reduced in positive pre-transplant HLA-DSA patients (60% versus 100%, P = 0.01 Breslow). The positive predicted value of HLA-DSA in relation to rejection reached 100% if patients lost their previous graft in the first year after transplant. Among anti-HLA antibodies present in patients before transplant, HLA-DSA were significantly associated with high risk of acute humoral and cellular rejection and reduced graft survival in posttransplant outcome. The negative impact of these antibodies was even higher when patients suffered an early loss of the previous transplant.

Objectives We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. Methods We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. Results Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P = .004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P = .035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. Conclusion There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of these entities, which are related to poor cardiovascular outcomes.

Introduction. The incidence of candiduria in renal transplant recipients is unknown. In clinical practice, the indications for antifungal therapy are not well established. Furthermore, there is the problem of the choice of the antifungal drug since some of them may select resistant Candida species, or interact with immunosuppressive agents or only be used intravenously. Aim. We sought to study the incidence, clinical repercussions and effectiveness of antifungal treatment to prevent recurrence of candiduria. Materials and methods. We examined all episodes of Candida-positive urine cultures (>50,000 cfu/mL) in 996 recipients over 2 years. We considered the Candida species, administered treatment, presence of fever, requirement for hospital admission versus outpatient case, occurrence of simultaneous bacterial urinary tract infection (UTI), antibiotic use during the week before candiduria, and presence of an indwelling urinary catheter. Results. Among 996 subjects, 34 displayed 83 episodes of candiduria, yielding an accumulated incidence of 3.4% after 2 years. The frequency was higher among women (6.3% vs 1.7%, P < .001). Of the 45 outpatient episodes (54.2%), 17 were treated and one required hospitalization (5.9%). Of the 28 nontreated outpatients, two were hospitalized (7.1%, P = .68 vs treated patients). All cases of hospital admission presented simultaneous bacterial UTI, none developed candidemia, and two patients did not receive any antifungal therapy. With respect to the first episodes of each patient (n = 34), 5/11 treated (45.5%) and 4/23 untreated (17.4%) patients developed recurrences (P = .095). Selection of more resistant Candida species was not observed. Fifty cases (60%) were associated with antibiotic therapy and 34 (41%) the presence of a urinary catheter. Conclusions. It does not seem necessary to treat candiduria in this setting. Antifungal therapy was not associated with either a reduction in recurrence or the appearance of more resistant species in this study. We observed no important clinical repercussions.

Background The occurrence of anti-HLA antibodies plays a well established role in solid organ rejection. The development of x-MAP multiple bead technology (Luminex) has enabled more accurate detection and definition of these alloantibodies. Methods In 267 kidney transplant patients with stable allograft function for ≥3 years, we analyzed the presence of anti-HLA antibodies by Luminex technology. These patients had no alloantibodies before transplantation, and the immunosuppression treatment was: tacrolimus, cyclosporine, mycophenolate mofetil, prednisone, everolimus, and/or sirolimus. Results Fifteen of the 267 patients showed anti-HLA class I antibodies and 12 showed anti-HLA class II antibodies, Seven patients had donor-specific antibodies (DSA): 1 anti-HLA class I, 5 anti-HLA class II, and 1 with both classes. No differences were found between DSA and the use or not of any specific therapy. However, in the retrospective review, we found a higher incidence of acute rejection episodes in the immediate posttransplant period among patients who developed class II DSA than those without DSA. Conclusions The prevalence of patients with normal renal function who develop DSA beyond 3 years after transplantation was relatively low. Steroid or withdrawal replacement of calcineurin inhibitors with inhibitors of mammalian target of rapamycin seem to not be risk factors to increase the development of DSA. The finding that patients who developed DSA showed a higher rate of previous acute rejection episodes suggested that they should be monitored more frequently for HLA antibodies.

Introduction. The clinical utility of predose levels of mycophenolic acid (MPA) monitoring among patients treated with mycophenolate mofetil (MMF) has been questioned. The aim of this study was to evaluate the impact of adequate MPA levels in the incidence of acute rejection episodes among a cohort of kidney transplant recipients. Material and Methods. In this retrospective study of 314 consecutive cases treated with tacrolimus, MMF, and steroids, evaluated 12-hour trough MPA samples during the first week as well as at 1, 3, 6, and 12 months as median values. Results. During the first week, the median values of MPA were 1.6 μg/mL (p25-75 0.7-2.7 μg/mL) on mean doses of 1.84 ± 0.38 g/d. The incidence of acute rejection was 28%. The mean MPA levels during the first week were significantly lower among patients who developed rejection than in nonrejectors (1.5 ± 0.1 vs 2.1 ± 0.1 μg/mL; P < .001). There were no significant differences in trough tacrolimus levels between rejectors and nonrejectors (11.2 ± 0.4 vs 11.6 ± 1.2 μg/mL; P < .78). Logistic regression analysis showed that one of the predictive factors of acute rejection was a 12-hour trough MPA

Persistent hyperparathyroidism is observed in 17% to 50% of patients at 1 year after renal transplantation. In 10% of these patients, hypercalcemia is also present. This condition increases the risk of vascular calcification, correlating with inferior graft function among patients with interstitial calcification in the renal allograft. Hypertension is appears in 60% to 90% of patients after transplantation, favoring progressive graft dysfunction. Hypercalcemia per se causes hypertension. Parathyroid hormone can potentiate the pressor effects of hypercalcemia. Fourteen renal transplant recipients were included based upon: total serum calcium > 10.0 mg/dL, intact parathyroid hormone levels > 70 pg/mL, graft function > 6 months, creatinine clearance > 50 mL/min, and stable immunosuppressive therapy. We also examined blood pressure and antihypertensive treatment. Initially patients received 30 mg of cinacalcet once a day. The follow-up was up to 6 months. The mean cinacalcet dose was 40 mg/24 h. Five patients received 60 mg/24 h. Both serum calcium and iPTH decreased significantly from 10.6 (DE 0.4) to 9.8 (DE Both serum calcium and iPTH decreased significantly from 10.6 (DE 0.4)to 9.8 (DE 0.6) mg/dL (P < .001) and from 195.0 (DE 140.0) to 118.62 (DE 102.2; P < .0001). There were no significant changes in renal function, proteinuria, or tacrolimus levels. Mean blood pressure diminished from 94.1 (DE 12.0) to 88.0 (DE 7.5) mm Hg (P < .019) with no changes in antihypertensive treatment. Cinacalcet was suspended in one patient because of gastrointestinal discomfort and in another one because the iPTH was reduced to 51 pg/mL. Cinacalcet is an effective treatment for persistent hyperparathyroidism associated with hypercalcemia among renal transplant patients and may be helpful for hypertension control.

The immune monitoring of transplant patients may allow us to minimize adverse events of immunosuppression and predict risks of rejection. Herein we have evaluated the capacity of an immune cell function assay to predict episodes of rejection and infections as well as its correlation with immunosuppressive drug trough levels and CD4, CD8, CD25, and DR cell counts.This prospective study of 38 kidney transplant patients was performed from January to June 2008. Blood samples were obtained at several times posttransplantation until the sixth month. We measured intracellular adenosine triphosphate (iATP) levels following CD4 cell activation for comparison with the clinical courses.Patients withor=525 ng/mL levels of iATP in the first week posttransplantation were 6.6 times more likely to develop an acute rejection episode (ARE) than those with lower immune response values (P = .014). Those who had an ARE with iATP525 ng/mL were generally highly sensitized (4/5). Statistically significant variations in iATP levels were observed among patients who had an ARE (P = .006). There was a relationship between infections and iATP levels also. Infections were more frequent with iATPor= 225 ng/mL (P = .048); patients with severe infections displayed lower iATP levels (180 +/- 143 vs 416 +/- 180 ng/mL; P = .01). There were no associations with CD4, CD8, CD25, or DR cell counts or with immunosuppressive drug trough levels.iATP levels may be considered to be a reliable marker of cellular immune status among renal graft recipients possibly identifying patients with a high risk of infection or rejection.

Despite the advances in immunosuppressive therapy and in patient care, about 20-30% of patients will have lost their grafts after 3 years and this loss will continue by 3-4% per year. These patients are included in maintenance dialysis programmes and account for 4 to 10% of those admitted every year for maintenance dialysis therapy. Among those patients who loss their grafts 40-60% are included in transplant waiting lists. This increases the number of patients waiting for a graft and raises the dilemma about the rights to be included in deceased donor programmes. A common characteristic of these patients waiting for a second or even third transplant is the presence in the blood of antibodies to HLA antigens. A new transplant is the best therapeutic option for these patients, and the results are quite close to those achieved for the first graft. Moreover, a new transplant improves patient outcome when compared with those remaining in the waiting list. The best results are obtained in diabetic patients and in those between 18 to 50 years old (Evidence C). However, the percentage of patients retransplanted has not varied in the last years, possibly due to the wider criteria adopted on candidate selection that increases the waiting lists (Evidence B). In the second transplant, mismatched HLA-A,B antigens could be repeated if the recipient has not developed specific antibodies to these antigens. Recent cross-match has to be negative. Immunosuppressive therapy is similar to that used with first transplants. Lymphoproliferative diseases, BK virus nephropathy and primary glomerulonephritis do not preclude a second transplant (Evidence C).

The early diagnosis of the graft intolerance syndrome or a subclinical state of chronic inflammation due to a failed kidney allograft, is one of the goals that the nephrologists must fulfill to take a series of measures directed to solve this situation. Fever, haematuria, local pain and/or tenderness are the main clinical criteria to make a diagnosis. However, oftenly there are not any clinical symptoms and only the presence of parameters of chronic inflammation (elevated C-reactive protein, erythrocyte sedimentation rate, hypoalbuminemia and anemia resistant to erythropoietin therapy) are signs of this entity. Maintenance of immunosuppressive treatment is not advisable due to the risk of infections as well as the increase in cardiovascular risk (level evidence A). Transplantectomy is the best treatment if there are some associated complications such as allograft infection, neoplasia or high risk of graft rupture. However, surgical treatment is not exempt from risks and it is associated to a considerable rate of complications, with the consequent prolongation of the hospitalization stay. Therefore it is desirable to use less invasive procedures, such as embolization. This could be the first step unless the conditions enumerated in point 3 come up (Level evidence B). It is desirable to use prophylactic antibiotic before the embolization to avoid infectious complications (Level evidence B).

In peritoneal dialysis (PD) patients, we analyzed the relationship between residual renal function (RRF) and well-known predictors of mortality such as anemia, inflammation, and nutrition. We also investigated possible associations between the foregoing parameters and cardiovascular comorbidity, peritoneal transport rate, statin and antihypertensive treatments, and ultrafiltration volume. Our study enrolled 24 patients (17 men, 7 women; mean age: 56 +/- 12 years) who had started PD at our hospital between 1998 and 2004. Patients who had been hospitalized or had had peritonitis before the study were excluded. Nutrition status, inflammation, anemia, RRF and dialysis adequacy were assessed after 1-2 months. We found that RRF was positively correlated with normalized protein equivalent of nitrogen appearance (nPNA: r = 0. 52, p = 0. 03) and negatively correlated with C-reactive protein (CRP: r = -0.47, p0.01) and peritoneal ultrafiltration (r = -0.42, p0.05). Only the nPNA and CRP correlations remained statistically significant on multivariate logistic regression analysis (CRP: r = 0.8, p = 0.011; nPNA: p = 0.013). Moreover, as compared with patients without inflammation, patients with inflammation had significantly lower hemoglobin (Hgb) levels (11.8 +/- 1.1 g/dL vs. 13.2 +/- 1.2 g/dL, p0.02), serum prealbumin levels (27.3 +/- 8 mg/dL vs. 36.6 +/- 9 mg/dL, p0.05), and serum transferrin levels (168 +/- 34 mg/dL vs. 202 +/- 31 mg/dL, p0.05), and a higher erythropoietin resistance index (ERI: 10 +/- 4 vs. 6 +/- 3.5, p0. 02). We observed no differences in RRF or nutrition status between the patients with high and with low peritoneal transport. Regarding comorbidity, patients with pre-existing cardiovascular disease had higher CRP levels (0.8 +/- 0.4 mg/dL vs. 0.4 +/- 0.4 mg/dL, p0.05) and lower mean Hgb levels (13.3 +/- 1 g/dL vs. 14.4 +/- 1 g/dL, p0.05) than did patients without such pre-existing disease. A strong, predictable association exists between RRF and inflammation and nutrition status in incident patients on PD. Serum CRP is a good indicator of inflammation, which correlates well with nutrition status, anemia, and responsiveness to erythropoietin therapy.

Patients returning to hemodialysis (HD) after failure of their kidney transplant suffer from high morbidity and mortality rates. It is common practice to keep failed kidney transplants in place. It is not known if these failed kidney transplants induce an inflammatory state that contributes to morbidity and mortality. In a single facility, patients starting on HD with failed kidney transplant were identified (Group A) and screened for the presence of chronic inflammatory state. Those with clinical symptoms attributed to the failed allograft (Group A1) were not offered transplant nephrectomy unless deemed necessary during follow-up. Their clinical and laboratory data were followed up for 6 months. Similar data were obtained from a group of incident HD patients (Group B). Forty-three patients had a failed Kidney transplant (Group A). Of these, 29 comprised Group A1 and 14 Group A2. Group B comprised 121 patients. In comparison with Group B, Group A exhibited worse anemia and erythropoietin resistance index (ERI), had lower serum albumin and prealbumin, and higher CRP. Group A1 had lower Hb and higher ferritin, CRP, and ESR in comparison with Group A2. Following transplant nephrectomy, Group A1 had improvement in ERI, serum albumin, prealbumin, ferritin, fibrinogen, CRP, and ESR. At 6 months, Group A1 had higher Hb and serum albumin levels, and lower CRP and ERI in comparison with Group A2. Group B parameters showed no change during follow-up. Patients returning to HD following failure of their kidney transplant suffer from a chronic inflammatory state. Resection of failed transplants in symptomatic patients is associated with amelioration of markers of chronic inflammation. Transplant nephrectomy should be considered a treatment option for patients with failed kidney transplants, especially if they exhibit signs and symptoms of chronic inflammatory state.