Donor-Derived Transmission of Cryptococcus gattii sensu lato in Kidney Transplant Recipients.
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ABSTRACT:
SUBMITTER: Santos DWCL
PROVIDER: S-EPMC7258454 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We compared 2 climate classification systems describing georeferenced environmental Cryptococcus gattii sensu lato isolations occurring during 1989-2016. Each system suggests the fungus was isolated in temperate climates before the 1999 outbreak on Vancouver Island, British Columbia, Canada. However, the Köppen-Geiger system is more precise and should be used to define climates where pathogens are detected.
| S-EPMC6711209 | biostudies-literature
Project description:African Americans are at greater risk to reach end-stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.Linking the five-yr patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13 692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function risks were estimated by Cox's regression (hazard ratio [HR] and 95% confidence interval) and logistic regression, respectively.Patients were 48 ± 14 yr old and included 39% women and 26% patients with diabetes. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with HR of 1.39 (1.09-1.78) for all-cause mortality, 1.80 (1.17-2.76) for cardiovascular mortality, 1.30 (1.03-1.64) for death-censored graft loss and 1.31 (1.10-1.57) for combined outcome over the six-yr observation period. In the non-African American recipient subcohort, but not in the African American recipient subcohort, African American donor race was associated with higher risk of death-censored graft loss (2.24 [1.44-3.49]) in our fully adjusted model.African American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.
| S-EPMC3593049 | biostudies-literature
Project description:Human adenovirus type 34 (HAdV-34) infection is a recognized cause of transplant-associated hemorrhagic cystitis and, in rare cases, tubulointerstitial nephritis. The source of such infections is often difficult to assess, that is, whether acquired as a primary infection, exposure to a pathogen in the transplanted organ, or reactivation of an endogenous latent infection. We present here 2 cases of likely transplant-acquired HAdV-34 infection from the same organ donor, manifesting as tubulointerstitial nephritis in 1.
| S-EPMC6411205 | biostudies-literature
Project description:BackgroundElevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR.MethodsDonor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33).ResultsThe median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA- patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%.ConclusionsThe combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.
| S-EPMC6133406 | biostudies-literature
Project description:The transmission of cancer from a donor organ is a rare event but has important consequences. Aim of this systematic review was to summarize all the published evidence on cancer transmission in kidney recipients. We reviewed published case reports and series describing the outcome of recipients with donor-transmitted cancer until August 2019. A total of 128 papers were included, representing 234 recipients. The most common transmitted cancers were lymphoma (n = 48, 20.5%), renal cancer (42, 17.9%), melanoma (40, 17.1%), non-small cell lung cancer (n = 13, 5.6%), neuroendocrine cancers comprising small cell lung cancer (n = 11, 4.7%) and choriocarcinoma (n = 10, 4.3%). There was a relative lack of glioblastoma and gastrointestinal cancers with only 6 and 5 cases, respectively. Melanoma and lung cancer had the worst prognosis, with 5-years overall survival of 43% and 19%, respectively; while renal cell cancer and lymphomas had a favorable prognosis with 5-years overall survival of 93 and 63%, respectively. Metastasis of cancer outside the graft was the most important adverse prognostic factor. Overall reporting was good, but information on donors' cause of death and investigations at procurement was often lacking. Epidemiology of transmitted cancer has evolved, thanks to screening with imaging and blood tests, as choriocarcinoma transmission have almost abolished, while melanoma and lymphoma are still difficult to detect and prevent.
| S-EPMC7701067 | biostudies-literature
Project description:BackgroundBK virus (BKV) is a significant cause of nephropathy in kidney transplantation. The goal of this study was to characterize the course and source of BKV in kidney transplant recipients.MethodsWe prospectively collected pretransplant plasma and urine samples from living and deceased kidney donors and performed BKV polymerase chain reaction (PCR) and immunoglobulin G (IgG) testing on pretransplant and serially collected posttransplant samples in kidney transplant recipients.ResultsAmong deceased donors, 8.1% (17/208) had detectable BKV DNA in urine prior to organ procurement. BK viruria was observed in 15.4% (6/39) of living donors and 8.5% (4/47) of deceased donors of recipients at our institution (P = .50). BKV VP1 sequencing revealed identical virus between donor-recipient pairs to suggest donor transmission of virus. Recipients of BK viruric donors were more likely to develop BK viruria (66.6% vs 7.8%; P < .001) and viremia (66.6% vs 8.9%; P < .001) with a shorter time to onset (log-rank test, P < .001). Though donor BKV IgG titers were higher in recipients who developed BK viremia, pretransplant donor, recipient, and combined donor/recipient serology status was not associated with BK viremia (P = .31, P = .75, and P = .51, respectively).ConclusionsDonor BK viruria is associated with early BK viruria and viremia in kidney transplant recipients. BKV PCR testing of donor urine may be useful in identifying recipients at risk for BKV complications.
| S-EPMC6603974 | biostudies-literature
Project description:Socioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant than less-deprived individuals. This qualitative study aimed to identify reasons for the observed socioeconomic disparity in live-donor kidney transplantation.A qualitative study using face-to-face in-depth semistructured interviews.A UK tertiary renal referral hospital and transplant centre.Purposive sampling was used to select deceased-donor transplant recipients from areas of high socioeconomic deprivation (SED) (19 participants), followed by a low SED comparison group (13 participants), aiming for maximum diversity in terms of age, gender, ethnicity, primary renal disease and previous renal replacement therapy.Participants were interviewed following their routine transplant clinic review. Interviews were digitally audio-recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using the constant comparison method described in Grounded Theory.Themes common and distinct to each socioeconomic group emerged. 6 themes appeared to distinguish between individuals from areas of high and low SED. 4 themes were distinct to participants from areas of high SED: (1) Passivity, (2) Disempowerment, (3) Lack of social support and (4) Short-term focus. 2 themes were distinct to the low SED group: (1) Financial concerns and (2) Location of donor.Several of the emerging themes from the high SED individuals relate to an individual's lack of confidence and skill in managing their health and healthcare; themes that are in keeping with low levels of patient activation. Inadequate empowerment of socioeconomically deprived individuals by healthcare practitioners was also described. Financial concerns did not emerge as a barrier from interviews with the high SED group. Interventions aiming to redress the observed socioeconomic inequity should be targeted at both patients and clinical teams to increase empowerment and ensure shared decision-making.
| S-EPMC4785291 | biostudies-other
Project description:Experiments in preclinical transplant models have indicated that preoperative administration of donor-derived M regs to transplant recipients may promote beneficial regulatory responses to a subsequent allograft. This contention is supported by results from the TAIC-I and –II clinical studies, which demonstrated that infusion of a crude cell preparation containing regulatory macrophages was both safe and could promote a state of donor-specific hyporesponsiveness. In an extension of this work, two patients were treated with donor-derived M regs prior to receiving a living-donor kidney transplant. Keywords: Classification of clinical samples
2011-11-28 | GSE24172 | GEO
Project description:Allograft tolerance, in which a graft is accepted without long-term immunosuppression, could overcome numerous obstacles in transplantation. Human allograft tolerance has been intentionally induced across HLA barriers via combined kidney and bone marrow transplantation (CKBMT) with a regimen that induces only transient chimerism. Tregs are enriched early after CKBMT. While deletional tolerance contributes to long-term tolerance, the role of Tregs remains unclear. We have optimized a method for identifying the donor-specific Treg repertoire and used it to interrogate the fate of donor-specific Tregs after CKBMT. We expanded Tregs with several different protocols. Using functional analyses and T cell receptor sequencing, we found that expanding sorted Tregs with activated donor B cells identified the broadest Treg repertoire with the greatest potency and donor specificity of suppression. This method outperformed both alloantigen stimulation with CTLA4Ig and sequencing of CFSElo cells from the primary mixed lymphocyte reaction. In 3 tolerant and 1 nontolerant CKBMT recipients, we sequenced donor-specific Tregs before transplant and tracked them after transplant. Preexisting donor-specific Tregs were expanded at 6 months after CKBMT in tolerant patients and were reduced in the nontolerant patient. These results suggest that early expansion of donor-specific Tregs is involved in tolerance induction following CKBMT.
| S-EPMC6302945 | biostudies-literature
Project description:Background:Hereditary renal hypouricemia (HRH) is a genetically heterogenetic disease. Patients with HRH are almost asymptomatic; but some may experience exercise-induced acute kidney injury (EAKI) and nephrolithiasis which may bring concerns regarding the risk-benefit ratio as marginal kidney donors. This study examined the pathogenic mutations of hypouricemia in two recipients after receiving kidney transplantation, providing preliminary evidence for the mechanism of hypouricemia. Methods:Two participants underwent detailed biochemical examinations. DNA and RNA were extracted from transplant specimens for sequencing. The whole-genome sequencing and polymerase chain reaction (PCR) amplification were performed to confirm the pathogenic genes. Functional effects of mutant proteins were verified by bioinformatics analysis. RNA-sequencing (RNA-seq) was used to study the transcriptome of hypouricemia. Results:Both of the recipients had the low serum uric acid (UA) (45-65 µmol/l), high fraction excretion of UA (44% and 75%) and an increase in the UA clearance (35.9 and 73.3 mL/min) with a functioning graft. The sequencing analyses revealed 7 kinds of potential mutational genes in this case, two novel mutations p.R89H and p.L181V in SLC22A12 gene which were revealed by bioinformatics could be pathogenic in nature. Conclusions:Two novel mutations of SLC22A12 were identified. Preliminary functional analysis revealed a potential deleterious effect of these mutations in the grafts derived from the donor and sequencing analysis expand the molecular mechanisms of renal hypouricemia.
| S-EPMC7186701 | biostudies-literature