El crecimiento sostenido de la población con injerto funcionante en España, junto con la mejora de la supervivencia del injerto y del paciente, ha incrementado la complejidad y la carga asistencial asociadas al seguimiento postrasplante. En este contexto, la coordinación entre centros trasplantadores (CTR) y centros no trasplantadores (CnTR) constituye una estrategia fundamental para garantizar una atención eficiente, accesible y centrada en el paciente.El objetivo de este documento de consenso es establecer recomendaciones clínicas y organizativas para el seguimiento compartido del paciente trasplantado renal entre centros trasplantadores y centros no trasplantadores.El documento de consenso ha sido desarrollado por el grupo COMPARTE-TR, integrado por nefrólogos con experiencia en trasplante renal y seguimiento postrasplante de diferentes centros españoles. Las recomendaciones se fundamentan en la revisión de la evidencia científica disponible, en las guías nacionales e internacionales y en la experiencia clínica.Se proponen modelos organizativos para el seguimiento compartido entre CTR y CnTR, adaptables a las diferentes realidades asistenciales. Se establecen recomendaciones sobre criterios de derivación y retorno, propuestas organizativas, comunicación intercentros e información mínima necesaria para la transferencia asistencial. Asimismo, se define una propuesta de protocolo de seguimiento postrasplante que incluye la monitorización del riesgo inmunológico, infeccioso, cardiovascular, óseo-mineral y oncológico, así como la evaluación de la calidad de vida y la adherencia terapéutica. También se recogen estrategias de formación continuada, evaluación de resultados e investigación colaborativa.El seguimiento compartido entre CTR y CnTR constituye un modelo seguro y eficiente para la atención del paciente trasplantado renal. La implementación de protocolos consensuados y mecanismos estructurados de coordinación puede contribuir a homogeneizar la práctica clínica, mejorar la calidad asistencial y optimizar los resultados del trasplante renal.

BACKGROUND:Observational studies have shown that kidney transplant (KT) recipients who are cytomegalovirus (CMV)-seropositive (R+) but lack effective CMV-specific cell-mediated immunity (CMV-CMI) are at increased risk of CMV infection. METHODS:In this quasi-experimental study, an immune-guided prevention strategy based on early CMV-CMI assessment (1-2 posttransplant weeks) was evaluated in intermediate-risk KT recipients (R+ without lymphocyte-depleting induction). CMV-CMI was measured using the QuantiFERON assay (QTF-CMV). Recipients with nonreactive QTF-CMV received antiviral prophylaxis until either CMV-CMI reconstitution or month 6, while those with reactive QTF-CMV were managed with preemptive therapy. The primary outcome was the proportion of patients who developed CMV infection during the first posttransplant year. Secondary outcomes included CMV disease, CMV DNAemia requiring preemptive therapy, rejection, vascular events, and all-cause mortality. Outcomes were compared with a prospective preintervention cohort managed by standard-of-care preemptive therapy. RESULTS:We included 91 and 100 patients in the preintervention and intervention groups, with similar baseline characteristics. One-year incidence of CMV infection was similar between both groups (48.4% versus 50.0%; odds ratio [OR], 1.07; 95% confidence interval [CI], 0.61-1.89; P = 0.820). One-year incidence of CMV disease (secondary outcome) was lower in the intervention group (9.9% versus 3.0%; OR, 0.28; 95% CI, 0.07-1.08; P = 0.064), as confirmed in the per-protocol analysis (9.9% versus 2.2%; OR, 0.20; 95% CI, 0.04-0.97; P = 0.028). CONCLUSIONS:Although the tested QTF-CMV-based immune-guided strategy did not result in a reduction in the overall occurrence of CMV infection in intermediate-risk KT recipients, the lower incidence of CMV disease observed merits further research.

BACKGROUND:Chronic immunosuppression associated with certain lifestyle habits render kidney transplant (KT) recipients more susceptible to infection and cancer. We assessed the level of knowledge and adherence to safe living strategies to minimize the occurrence of posttransplant complications. METHODS:Consecutive KT recipients were offered a self-administered questionnaire covering the following areas: demographics and socioeconomic factors; generic hygiene habits; sun exposure; smoking and alcohol consumption; vaccination status; animal contact and gardening; international travelling; and food safety and habits. RESULTS:Between May 2019 and May 2021, 130 KT recipients responded the survey at a median of 61.5 posttransplant days (completion rate of 94.9%). Only 19.7% of participants visited the dentist at least every 3-6 months. Although the majority (88.5%) were aware of the need of sunscreen, only 23.3% used it throughout the year. Self-reported influenza vaccine uptake in the last session was 69.1%. Pet ownership was reported by 41.7% of participants, of which more than one-third had considered to give up the care of their animals. Gardening and international travel were uncommon. A notable proportion of participants acknowledged to consume the following products either "usually" or "often": raw or undercooked meat (12.4%), undercooked fish (24.8%), raw seafood (8.8%), homemade sausages or cured ham (51.5%), pâté or meat spreads (35.2%), and "ready-to-eat" salads (31.8%). Adherence was poorer among non-native-speaking patients and those with lower education and household incomes. CONCLUSION:There is room for improvement in health education and promotion practices among KT recipients, particularly those with potential cultural and socioeconomic barriers.

ABSTRACTBackgroundKidney transplant (KT) recipients at intermediate risk for cytomegalovirus (CMV) infection constitute a potential target for individualized prevention strategies informed by the CMV‐specific cell‐mediated immunity (CMV‐CMI). The optimal method for the functional assessment of CMV‐CMI in this group remains unclear.MethodsWe included 74 CMV‐seropositive KT recipients that did not receive T‐cell‐depleting induction and were managed by preemptive therapy. CMV‐CMI was monitored at baseline and months 1, 3, 6, and 12 by intracellular cytokine staining (ICS) and a interferon (IFN)‐γ‐release assay (QuantiFERON‐CMV [QTF‐CMV]). Both methods were compared for discriminative capacity (areas under the receiving operating characteristic curve [auROCs]) and diagnostic accuracy to predict protection against high‐level (≥1000 IU/mL) CMV DNAemia and/or disease.ResultsEighteen patients (24.3%) experienced high‐level CMV DNAemia or disease. There were no significant differences in the discriminative capacity to predict protection of CMV‐specific CD8+ (auROC: 0.719) and CD4+ T‐cell counts (auROC: 0.664) enumerated by ICS and IFN‐γ production measured by QTF‐CMV (auROC: 0.666). Optimal cutoff values of ≥9.8 CMV‐specific CD4+ T‐cells/µL and ≥5.7 CD8+ T‐cells/µL by ICS yielded excellent specificity (95.7% and 86.9%, respectively) and positive predictive values (PPVs) (>98.0%), but a sensitivity below 60%. A reactive QTF‐CMV (IFN‐γ ≥0.2 IU/mL) provided good sensitivity (81.6%) and PPV (92.5%), at the expense of a poor specificity (22.2%).ConclusionsThe discriminative capacity to predict immune protection against clinically relevant CMV infection among intermediate‐risk KT recipients was comparable for ICS and QTF‐CMV. A selected ICS threshold may provide better specificity than the interpretative cut‐off values currently recommended for QTF‐CMV. image

Herpesviruses are able to modulate adaptive T-cell-mediated responses to establish latency within the host. Reactivation of herpes simplex virus (HSV)-1/2 and varicella zoster virus (VZV) is a frequent and potentially serious complication among kidney transplant recipients (KTRs). The ability of clinical criteria to identify KTRs at increased risk of α-herpesvirus (HSV/VZV) infection is limited. We investigated the effect of two single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene in a single-center cohort of 204 KTRs. After a median follow-up of 3.1 years, 34 of them (16.7%) experienced 22 episodes of zoster and 15 episodes of HSV-1/2 infection. Homozygous carriers of the minor allele of rs231775 had a higher cumulative incidence of α-herpesvirus infection (23.5% for GG versus 7.6% for AA/AG carriers; P-value = 0.011) and a lower infection-free survival (log-rank P-value = 0.037). After multivariable adjustment by clinical factors (including use of valganciclovir prophylaxis and acute rejection as time-dependent variables), the GG genotype of CTLA4 (rs231775) SNP was associated to the study outcome (adjusted hazard ratio: 3.21; 95% confidence interval: 1.44-7.16). In conclusion, genetic polymorphisms in the co-inhibitory T-cell receptor CTLA-4 may be detrimental for the immune control of latent HSV/VZV infection in KTRs.

INTRODUCTION:The increased risk of tuberculosis (TB) reactivation in solid organ transplant recipients supports the recommendation of screening for latent tuberculosis infection (LTBI). Adherence to available screening tests has not been studied in the kidney transplant (KT) population. We aimed to assess screening compliance within the ATALANTA-DOS population study. METHODS:ATALANTA-DOS studied an intervention bundle aimed at preventing infection in KT recipients. We compared LTBI screening rates between the pre-intervention (February 2016 - September 2017) and intervention (February 2018 - September 2019) cohorts and evaluated adherence rates between the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST). RESULTS:A total of 307 KT recipients were included (155 in the pre-intervention cohort; 148 in the intervention cohort). A systematic assessment of screening compliance by an infectious disease specialist on day +30 post-KT improved LTBI screening adherence (82.6% [114/138] vs 1.3% [2/155]; p-value <0.001). In the intervention cohort, compliance was higher with IGRA (83.3% [52/62]) than with TST (68.1% [49/72]). Two cases of LTBI were detected in the pre-intervention cohort and five in the intervention cohort (4.4% [5/114]). All patients completed LTBI treatment after ruling out active TB. No cases of active TB were identified during follow-up. CONCLUSIONS:Systematic evaluation of LTBI screening compliance significantly increased screening completion rates among KT recipients. IGRA-based strategies increased screening compliance, supporting their implementation over TST for LTBI screening among KT recipients. Increased adherence would allow a more targeted and effective treatment of LTBI.

ABSTRACTThe impact of human cytomegalovirus (HCMV) infection on the mid‐ and long‐term balance between pro‐inflammatory and anti‐inflammatory cytokines among kidney transplant recipients (KTRs) remains unclear. We measured plasma levels of 12 Th1/Th2‐type cytokines (granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, interleukin [IL]‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐12p70, IL‐13, IL‐18 and tumor necrosis factor‐α) in a cohort of 290 KTRs at four time points through month 12 after transplantation. Cytokine levels at each point were compared according to the previous documentation of HCMV replication by two approaches: “cumulative exposure” from the time of transplantation and “recent exposure” within the 2–3 months preceding cytokine assessment. Significance levels were Bonferroni‐corrected for multiple pairwise comparisons. Plasma levels of IL‐6, IL‐10, and IL‐12p70 at month 1 were significantly increased in KTRs that had experienced HCMV infection during the first 30 days. By month 3, IL‐6 and IL‐10 remained increased in KTRs with cumulative exposure through day 90. Cumulative exposure to HCMV replication through day 180 was also associated to increased IL‐10 levels at month 6. In addition, KTRs with recent HCMV exposure had increased IL‐10 levels at months 3 and 6. After multivariable adjustment, cumulative exposure to HCMV infection and/or the area under curve of HCMV DNAemia during the corresponding period were associated to IL‐10 levels within the highest quartile at months 1, 3, and 6. Preceding HCMV infection induces sustained changes in the plasma cytokine milieu of KTRs, with elevated IL‐6 and IL‐10 levels throughout the first 6 months after transplantation.

Abstract Background and Aims This study explores a personalized delisting strategy enabling kidney transplantation in highly sensitized patients with preformed donor-specific anti-HLA antibodies (DSA) trying to minimize the risk of antibody-mediated rejection (ABMR). Method Retrospective single-centre analysis of 50 kidney transplant recipients with preformed DSA (preDSA) after employing a delisting strategy to enhance their access to transplantation, and without received a pre-transplant or immediate post-transplant desensitization protocol. The delisting approach focused on allowing less deleterious antibodies according to their mean fluorescence intensity (MFI), anti-HLA class and C1q study results. The strategy consisted on eliminating as prohibited HLA antigens those recognized by antibodies with the lowest MFI in the following order: 1st- MFI < 5000; 2nd- MFI < 10000; 3rd-Any MFI. Additionally, delisting prioritized a single locus in the following order: 1st- one of the HLA class I loci (A, B, or Cw); 2nd- the rest of the class I loci; 3rd- HLA-DP, followed by DR. C1q studies were performed before delisting and transplantation was contraindicated in the presence of DSA detected in the C1q assay. Two comparative cohorts included 50 sensitized recipients without pre-transplant DSA (SwoDSA) and 50 non-sensitized recipients (NS). Results The delisting strategy allowed transplantation with preformed DSA and demonstrated comparable rejection rates to SwoDSA and NS groups (16%, 14% and 8%, respectively; log-rank = 0.28). However, the occurrence of acute ABMR was 12% in the preDSA group, significantly higher than in SwoDSA (1%) and NS (0%) (log-rank = 0.0093). The immunological risk assumed in delisting correlated with ABMR incidence (patients with ABMR had significantly higher sum MFI [mean ± SD: 9301 ± 6340 vs 4492 ± 5641; p = 0.049]), emphasizing the importance of tailored strategies. DSA persistence after transplantation correlated with higher MFI and increased ABMR risk. Of note, 16% of preDSA patients developed de novo DSA versus only the 4% of SwoDSA and 0% of NS patients (p = 0.004). After a mean follow-up of 3.1 ± 2.1 years, the 1-, 3- and 5-year death-censored allograft survival rates were 100%, 90% and 78%, respectively, in the preDSA group; 98%, 84% and 84% in the SwoDSA group and 100% in NS group (log-rank = 0.02). Conclusion The present study demonstrates the feasibility and acceptable outcomes of kidney transplantation in highly sensitized patients with preformed DSA through a personalized delisting strategy without using desensitization protocols.

The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and de novo cancer. The association between IFN-γ production and outcomes was analyzed as “low” immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; P-value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; P-value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation.

Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.

Abstract Background and Aims Kidney transplantation (KT) provides an opportunity to increase fertility in women with chronic kidney disease and gestational desire. Lack of knowledge about obstetric complications and implications for the graft may lead to discourage pregnancy for these women. Although the incidence of pregnancy is rising in women receiving KT, the impact that it may have on the graft function is unknown. Method We conducted an observational, retrospective, single-centre study of a cohort of kidney transplant recipients (KTR) who became pregnant between 2007 and 2022. Clinical and analytical parameters were evaluated before, during and after pregnancy. The main aim was to assess the long-term impact of pregnancy on the graft by analysing renal function 3 years after pregnancy. Results We included 25 women receiving a KT between 1990 and 2018, among which 72% (n = 18) were transplanted from a deceased donor. 2 women (8%) received a combined liver-kidney transplant and 2 women (8%) a simultaneous pancreas-kidney transplant. Maintenance immunosuppression before conception included teratogenic drugs in 68% of cases [12 of them (48%) received mycophenolate mofetil and 5 of them (20%), mTOR inhibitors]. Planned withdrawal was only applied in 50.0% of pregnancies (n = 15). 30 pregnancies were identified (5 patients had 2 post-transplant pregnancies). Median age at gestation was 35 years [interquartile range (IQR) 33-39]. 5 conceptions required assisted reproductive technology. The main complications were gestational hypertension in 4 KTR (13.3%) and preeclampsia in 7 pregnancies (23.3%). 60% of neonates (n = 18) were preterm births (36 [IQR 34-37] weeks of pregnancy at birth) and 44% (n = 12) had low birth weight (2530 [IQR 2283-2950] grams). No foetal malformations were described. Due to physiological changes, a significant increase in estimated glomerular filtration rate (eGFR) was observed in the first and the second trimester of pregnancy (61 [IQR 50-91] ml/min and 70 [IQR 50-90] ml/min, respectively vs. baseline eGFR 59 [IQR 47-77] ml/min; p 0.001]. However, eGFR was equal to the previous one in the third trimester of pregnancy (60 [IQR 44-69] ml/min vs. 59 [IQR 47-77] ml/min; p 0.322). Median proteinuria remained below 0.5 g/day throughout pregnancy, without significant variation. Immunosuppression regimen during pregnancy was mainly based on a combined therapy of steroids, calcineurin inhibitors and azathioprine (21 KTR, 70%). Tacrolimus dose increase (median 63.6% [IQR 33.3-90.0%]) was necessary to maintain proper drug levels throughout gestation. Kidney graft function showed a decline in the first and second year after pregnancy compared to baseline function (54 [IQR 35-77] ml/min and 55 [IQR 36-75] ml/min vs. 59 [IQR 47-77] ml/min; p 0.018 and p 0.021, respectively]. Nevertheless, by the third year post-pregnancy, eGFR was similar to the baseline function (62 [IQR 43-73] ml/min vs. 59 [IQR 47-77] ml/min; p 0.365]. Likewise, annual eGFR variation was comparable during 3 years before (+1.0 ml/min/year) and 3 years after pregnancy (−0.9 ml/min/year), hence no worsening was observed after gestation (p 0.78). No differences were observed in proteinuria either (baseline proteinuria 0.17 [IQR 0.13-0.3] g/day vs. third-year proteinuria 0.21 [IQR 0.15-0.34] g/day; p 0.938). Only 5 women had a baseline serum creatinine above current recommendations for pregnancy (&gt;1.5 mg/dl) and only 3 women presented baseline proteinuria &gt; 0.5 g/day. In this group (n = 7), pregnancy occurred later after KT (96.0 [IQR 80.9-213.0] vs. 46.0 [IQR 16.0-67.5] months; p 0.024). The only 2 graft losses in the cohort were in this group. Both were attributed to transplant glomerulopathy, and they occurred at years 3 and 5 after pregnancy. On the other side, in this group there were no other baseline differences or obstetrical complications [Table 1]. Conclusion Pregnancy does not normally affect graft function and it stabilises within 3 years after gestation. It is important to increase data on women with suboptimal graft function to determine the direct implications that pregnancy may have on these KTRs.

This study investigates kidney transplant outcomes in highly sensitised patients after implementing a delisting strategy aimed at enabling transplantation despite preformed donor‐specific antibodies (preDSA), with the goal of reducing acute antibody‐mediated rejection (aAMR) risk. Fifty‐three sensitised recipients underwent kidney transplant after delisting prohibited HLA antigens, focusing initially in low MFI antibodies (<5000), except for anti‐HLA‐DQ. If insufficient, higher MFI antibodies were permitted, especially for those without an immunogenic eplet pattern assigned. Delisting of Complement‐fixing antibodies (C1q+) was consistently avoided. Comparison cohorts included 53 sensitised recipients without DSA (SwoDSA) and 53 non‐sensitised (NS). The average waiting time prior to delisting was 4.4 ± 1.8 years, with a reduction in cPRA from 99.7 ± 0.5 to 98.1 ± 0.7, followed by transplantation within 7.2 ± 8.0 months (analysed in 34 patients). Rejection rates were similar among preDSA, SwoDSA, and NS groups (16%, 8%, and 11%, respectively; p = 0.46). However, aAMR was higher in the preDSA group (12%, 4%, and 2%, respectively; p = 0.073), only presented in recipients with DSA of MFI >5000. The highest MFI DSA were against HLA‐DP (Median: 10796 MFI), with 50% of preDSA aAMR cases due to anti‐DP antibodies (n = 3). Graft survival rates at 1 and 5 years in preDSA group were 94%, and 67%, comparable to SwoDSA (94%, and 70%; p = 0.69), being significantly higher in the NS group (p = 0.002). The five‐year recipient survival rate was 89%, comparable to SwoDSA and NS groups (p = 0.79). A delisting strategy enables safe kidney transplant in highly sensitised patients with preDSA, with a slight increase in aAMR and comparable graft and patient survivals to non‐DSA cohorts.

BACKGROUND:Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT. METHODS:A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation. RESULTS:The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups. CONCLUSIONS:A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.

Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs.

We measured cytomegalovirus (CMV)-specific antibodies that neutralize epithelial cell infection (CMV-AbNEIs) in 101 CMV-seropositive kidney transplant recipients (KTRs) at baseline and posttransplant months 3 and 6. All the patients received antithymocyte globulin and 3-month valganciclovir prophylaxis. There were no significant differences in pretransplant AbNEIs titers between KTRs that developed or did not develop any-level CMV infection or the composite of high-level infection and/or disease. One-year CMV infection-free survival was comparable between KTRs with or without pretransplant CMV-AbNEIs. No differences were observed by months 3 and 6. We observed no protective role for CMV-AbNEIs among CMV-seropositive KTRs undergoing T-cell-depleting induction.

The best method for monitoring cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) among high-risk kidney transplant (KT) recipients remains uncertain. We assessed CMV-CMI by intracellular cytokine staining (ICS) by flow cytometry and a commercial interferon (IFN)-gamma release assay (QuantiFERON (R)-CMV [QTF-CMV]) at posttransplant months 3, 4, and 5 in 53 CMV-seropositive KT recipients that had received induction therapy with antithymocyte globulin (ATG) and a 3-month course of valganciclovir prophylaxis. The discriminative capacity (areas under receiver operating characteristics curve [auROCs]) and diagnostic accuracy to predict immune protection against CMV infection from the discontinuation of prophylaxis to month 12 were compared between both methods. There was significant although moderate correlations between CMV-specific IFN-gamma-producing CD8(+) T-cell counts enumerated by ICS and IFN-gamma levels by QTF-CMV at months 3 (rho: 0.493; p = 0.005) and 4 (rho: 0.440; p = 0.077). The auROCs for CMV-specific CD4(+) and CD8(+) T-cells by ICS were nonsignificantly higher than that of QTF-CMV (0.696 and 0.733 vs. 0.678; p = 0.900 and 0.692, respectively). The optimal cut-off of >= 0.395 CMV-specific CD8(+) T-cells yielded a sensitivity of 86.4%, specificity of 54.6%, positive predictive value of 79.2% and negative predictive value of 66.7% to predict protection. The corresponding estimates for QTF-CMV (IFN-gamma levels >= 0.2 IU/mL) were 78.9%, 37.5%, 75.0%, and 42.9%, respectively. The enumeration of CMV-specific IFN-gamma-producing CD8(+) T-cells at the time of cessation of prophylaxis performed slightly better than the QTF-CMV assay to predict immune protection in seropositive KT recipients previously treated with ATG.

Abstract Background and Aims Torque teno virus (TTV) is a non-pathogenic anellovirus whose replication kinetics reflects the overall state of immunosuppression. Although chronic kidney disease (CKD) induces a well-stabilised dysfunction of the immune system, long-term use of renal replacement therapies (RRT) itself could also modify the immune response. Method We analyzed TTV DNA loads at baseline (in the pre-transplant assessment), day 7 and months 1, 3,6 and 12 after kidney transplantation (KT). Recipients were categorized according to their RRT status: pre-emptive KT (pre-KT), hemodialysis (HD) and peritoneal dialysis (PD). TTV DNA load was measured by real-time polymerase chain reaction. Results A total of 221 CKD patients were analyzed. The mean age was 53.9 ± 15.7 years, 72.4% were males, and hypertension (85.1%) and diabetes (30.1%) were the most common comorbidities. According to the pre-transplant TTR status, 159 (72.0%) were on HD, 35 (15.8%) on PD and 27 (12.2%) received pre-KT. There were no differences in baseline comorbidities or age between patients according to their RRT status, except for residual diuresis (P <0.01). HD patients had higher serum albumin levels than patients receiving pre-KT or PD (4.4 ± 0.5 vs. 4.1 ± 0.6 vs. 3.9 ± 0.4 g/dL, respectively, P <0.01). PD patients exhibited higher TTV DNA load (3.4 ±1.2 log10 copies/mL) than HD (2.8 ± 1.6 log10 copies/mL) or pre-KT patients (2.4 ± 2.1 log10 copies/mL), although the differences were not statistically significant. PD patients had lower time on dialysis than HD patients (18.4± 16.2 vs. 37.5± 53.6 months, respectively; P = 0.038). Although PD patients had higher TTV DNA load during the post-transplant follow-up than HD and pre-KT patients, viral kinetics were comparable across these three groups by month 12 after transplantation. Time on dialysis was not associated with TTV DNA load (P = 0.18). RRT status was not associated with the incidence of post-transplant infection or a composite of opportunistic infection and/or de novo malignancy. Conclusion TTV DNA load could be useful identifying KT recipients at high risk of immunosuppression-related complications. Although PD patients presented a non-significant higher TTV DNA load, we did not find differences according to the modality of prior RRT or the time on dialysis.

The case discussed involves a 69-year-old Thai woman who underwent orthotopic heart transplantation 9 months before this event. She presented with fever without localizing signs or symptoms. However, her chest images revealed mass-like consolidation in the left upper lobe. Blood culture and lung tissue identified Rhodococcus equi. She was successfully treated with a combination of antimicrobial therapy, optimization of immunosuppressants, and surgical resection.

Previous reports hypothesized that cytomegalovirus (CMV) may predispose to non-CMV infection after kidney transplantation (KT). We analysed the incidence of non-CMV infection (overall, bacterial and opportunistic) in 291 KT recipients according to the previous development of any level or high-level (≥1,000 IU/ml) CMV viremia. Exposure to CMV replication was assessed throughout fixed intervals covering first the 30, 90, 180 and 360 post-transplant days (cumulative exposure) and non-overlapping preceding periods (recent exposure). Adjusted Cox models were constructed for each landmark analysis. Overall, 67.7 and 50.5% patients experienced non-CMV and CMV infection, respectively. Patients with cumulative CMV exposure had higher incidence of non-CMV infection beyond days 30 (p-value = 0.002) and 90 (p-value = 0.068), although these associations did not remain after multivariable adjustment. No significant associations were observed for the remaining landmark models (including those based on high-level viremia or recent CMV exposure), or when bacterial and opportunistic infection were separately analysed. There were no differences in viral kinetics (peak CMV viremia and area under curve of CMV viral load) either. Our findings do not support the existence of an independent association between previous CMV exposure and the overall risk of post-transplant infection, although results might be affected by power limitations.