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1.
Cryptococcus gattii infection is a rare cause of severe pulmonary disease and meningoencephalitis that has only recently been detected in the southeastern United States. We describe an organ transplant-associated outbreak of C. gattii infection involving an HIV-negative immunosuppressed donor in this region who died following new-onset headache and seizure of unknown cause. Retrospective cryptococcal antigen (CrAg) testing of donor serum was positive. Two of the three transplant recipients developed severe C. gattii infection 11 and 12 weeks following transplantation. One recipient died from severe pulmonary infection, identified on autopsy, and the other ill recipient survived following treatment for cryptococcal meningitis. This outbreak underscores the importance of considering cryptococcosis in patients with clinical findings suggestive of subacute meningitis or other central nervous system (CNS) pathology, and the potential benefit of routine pre-transplant donor CrAg screening using lateral flow assay to guide recipient antifungal prophylaxis. The case also adds to emerging evidence that C. gattii is a potential threat in the southeastern United States.  相似文献   

2.
Preemptive kidney transplantation is the preferred initial renal replacement therapy, by avoiding dialysis and reportedly maximizing patient survival. Lead time bias may account for some or all of the observed survival advantage, but the impact of this has not been quantified. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included adult recipients of living donor kidney transplants during 1998‐2017. Patients were transplanted preemptively (n = 1435) or after receiving up to 6 months of dialysis (n = 712). We created a matched cohort using propensity scores, and accounted for lead time (dialysis and estimated predialysis) using left‐truncated Cox models with the primary outcome of patient survival. The median eGFR at transplantation was 6.9 mL/min per 1.73 m2 in the non‐pre‐emptive, and 9.6 mL/min per 1.73 m2 in the preemptive group. In the matched cohort (n = 1398), preemptive transplantation was not associated with a survival advantage hazard ratio (HR) for preemptive vs non‐pre‐emptive 1.12 (95% confidence interval [CI] 0.79‐1.61). Accounting for lead time moved the point estimates toward a survival disadvantage for preemptive transplantation (eg, HR assuming 4 mL/min per 1.73 m2/year eGFR decline, 1.21 [0.85, 1.73]), but in all cases the 95% CIs crossed 1. The optimal timing of preemptive living donor kidney transplantation requires further study.  相似文献   

3.
Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3–73.1) in three French transplant centers. After a median follow-up of 13 days (7–30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2–14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.  相似文献   

4.
A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001‐2016 to evaluate death‐censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15‐year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] = 0.730.770.82, P < .001), and was attenuated among African American donors (aHR 0.770.850.95; interaction: P = .01) and female recipients (aHR 0.770.840.91, P < .001). Although offspring kidney recipients had higher mortality (15‐year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR = 1.021.061.10, P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR = 0.930.971.01, P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.  相似文献   

5.
According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.  相似文献   

6.
The exact duration of viable SARS-CoV-2 shedding in kidney transplant recipients (KTRs) remains unclear. Here, we retrospectively investigated this issue using cell cultures of SARS-CoV-2 RT-PCR-positive nasopharyngeal samples (n = 40) obtained from 16 KTRs with symptomatic COVID-19 up to 39 days from symptom onset. A length of viable SARS-CoV-2 shedding >3 weeks from the onset of symptoms was identified in four KTRs (25%). These results suggest that a significant proportion of KTRs can shed viable SARS-CoV-2 for at least 3 weeks, which may favor the emergence of new variants. Based on these data, we recommend prolonging the isolation of KTRs with COVID-19 until negative SARS-CoV-2 RT-PCR testing.  相似文献   

7.
There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.  相似文献   

8.
Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). Anti-SARS-CoV-2 IgG seroprevalence was lower in KTR than in HCW (7% vs. 11.9%, = .001). Kidney transplant recipients with SARS-CoV-2 infection were younger (= .001) and received CNI-based immunosuppression more frequently (= .029) than seronegative KTR. Anti-SARS-CoV-2 IgG positive symptomatic KTR had a higher BMI (= .04) than asymptomatic KTR. Interestingly, anti-SARS-CoV-2 IgG levels were higher in KTR than in HCW (median 31 AU/ml, IQR 17–84 vs. median 15 AU/ml, IQR 11–39, < .001). The presence of moderate to severe symptoms in KTR was found to be the only independent factor affecting IgG levels (Beta coefficient = 41.99, 95% CI 9.92–74.06, p = .011) in the multivariable model. In conclusion, KTR exhibit a well-preserved symptom-dependent humoral response to SARS-CoV-2 infection.  相似文献   

9.
Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3+, CD3+/CD4+, CD3+/CD8+ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.  相似文献   

10.
Lack of donors hinders living donor kidney transplantation (LDKT) for African Americans. We studied the effectiveness of a transplant social worker intervention (TALK SWI) alone or paired with living donor financial assistance to activate African Americans’ potential living kidney donors. African Americans (N = 300) on the transplant waiting list were randomly assigned to usual care; TALK SWI; or TALK SWI plus Living Donor Financial Assistance. We quantified differences in live kidney donor activation (composite rate of live donor inquiries, completed new live donor evaluations, or live kidney donation) after 12 months. Participants’ mean age was 52 years, 56% were male, and 43% had annual household income less than $40,000. Most previously pursued LDKT. Participants were highly satisfied with TALK social workers, but they rarely utilized Financial Assistance. After 12 months, few (n = 39, 13%) participants had a new donor activation event (35 [12%] new donor inquiries; 17 [6%] new donor evaluations; 4 [1%] LDKT). There were no group differences in donor activation events (subdistribution hazard ratio [95% CI]: 1.09 [0.51–2.30] for TALK SWI and 0.92 [0.42–2.02] for TALK SWI plus Financial Assistance compared to Usual Care, p = 91). Alternative interventions to increase LDKT for African Americans on the waiting list may be needed. Trial registration: ClinicalTrials.gov (NCT02369354).  相似文献   

11.
12.
T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV‐specific peptide‐based enzyme‐linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN‐γ) binding spot‐forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early‐1 (IE‐1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R?] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92‐360) posttransplant. A cutoff value of >40 sfu/2.5 × 105 cells for either IE‐1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post‐EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV‐specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.  相似文献   

13.
While trimethoprim‐sulfamethoxazole is considered first‐line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim‐sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty‐two patients (35%) had 48 trimethoprim‐sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non‐immune‐mediated and 17% were immune‐mediated. Significantly more patients underwent trimethoprim‐sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; = .0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self‐limiting with only 1 recurrence of an immune‐mediated reaction. After protocol implementation, aerosolized pentamidine‐associated costs were reduced. The introduction of a standard approach to trimethoprim‐sulfamethoxazole rechallenge in the context of both prior immune and non‐immune‐mediated reactions was safe and successful in improving the uptake of first‐line Pneumocystis pneumonia prophylaxis in renal transplant recipients.  相似文献   

14.
The SARS‐Cov‐2 infection disease (COVID‐19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID‐19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti‐retroviral and tocilizumab. Short‐term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D‐dimer, C‐reactive protein, and IL‐6 at their first tests. COVID‐19 is frequent among the elderly KT population and associates a very early and high mortality rate.  相似文献   

15.
Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1–10 × 106 Treg per kg at Day +5 posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort). Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard immunosuppression. Treg therapy may provide an exciting opportunity to minimize immunosuppression therapy and improve long-term outcomes.  相似文献   

16.
SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.  相似文献   

17.
Patients who undergo kidney transplantation are at increased risk of cancer due to the long‐term use of immunosuppressive treatment. Postrenal transplant cancers usually originate from recipient cells, but donor‐related cancers have been rarely reported. We report the case of 49‐year‐old woman who developed multiple myeloma of donor origin 7 years after kidney transplantation. The donor was the mother of the recipient and also developed multiple myeloma 1 year after kidney donation. The diagnosis of multiple myeloma was based on IgG lambda monoclonal protein and the infiltration of plasma cells in bone marrow. The renal biopsy did not reveal plasmacytoma in the transplanted kidney. Epstein‐Barr virus DNA load was negative in peripheral blood. The patient responded to lenalidomide and dexamethasone, and subsequently received autologous stem cell transplantation. Donor chimerism was detected in the recipient marrow by short tandem repeat analysis; however, studies of Ig gene rearrangement were inconclusive due to insufficient DNA quality. The chromosomal abnormalities in the two myelomas were different. This case suggests that donor cells with myeloma‐initiating potential can be transferred to a recipient via a renal graft and can lead to the development of donor‐derived multiple myeloma in the recipient under immunosuppression.  相似文献   

18.
Kidney transplant recipients (KTR) may be at increased risk of adverse COVID-19 outcomes, due to prevalent comorbidities and immunosuppressed status. Given the global differences in COVID-19 policies and treatments, a robust assessment of all evidence is necessary to evaluate the clinical course of COVID-19 in KTR. Studies on mortality and acute kidney injury (AKI) in KTR in the World Health Organization COVID-19 database were systematically reviewed. We selected studies published between March 2020 and January 18th 2021, including at least five KTR with COVID-19. Random-effects meta-analyses were performed to calculate overall proportions, including 95% confidence intervals (95% CI). Subgroup analyses were performed on time of submission, geographical region, sex, age, time after transplantation, comorbidities, and treatments. We included 74 studies with 5559 KTR with COVID-19 (64.0% males, mean age 58.2 years, mean 73 months after transplantation) in total. The risk of mortality, 23% (95% CI: 21%–27%), and AKI, 50% (95% CI: 44%–56%), is high among KTR with COVID-19, regardless of sex, age and comorbidities, underlining the call to accelerate vaccination programs for KTR. Given the suboptimal reporting across the identified studies, we urge researchers to consistently report anthropometrics, kidney function at baseline and discharge, (changes in) immunosuppressive therapy, AKI, and renal outcome among KTR.  相似文献   

19.
The aim of this study was to determine if natural killer cell number (CD3?/CD16±/CD56±) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty‐nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (= .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74‐0.90; < .0001) but not natural killer number (OR 0.96, 95% CI 0.93‐1.00; = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.  相似文献   

20.
The fatality of novel coronavirus disease 2019 (COVID‐19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID‐19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36‐year‐old man who underwent KT 3 years ago. He was diagnosed with COVID‐19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID‐19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug‐to‐drug interaction. The second case was developed in a 56‐year‐old man without any symptoms. He received a second KT from an ABO‐incompatible donor 8 years ago. He was diagnosed with COVID‐19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.  相似文献   

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