scholarly journals Integrative Analyses of Circulating Small RNAs and Kidney Graft Transcriptome in Transplant Glomerulopathy

2021 ◽  
Vol 22 (12) ◽  
pp. 6218
Author(s):  
Canan Kuscu ◽  
Manjari Kiran ◽  
Akram Mohammed ◽  
Cem Kuscu ◽  
Sarthak Satpathy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Transplant ◽  
Small Rna ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Tissue Integration ◽  
Transplant Patients ◽  
Mrna Targets ◽  
Transplant Glomerulopathy

Transplant glomerulopathy develops through multiple mechanisms, including donor-specific antibodies, T cells and innate immunity. This study investigates circulating small RNA profiles in serum samples of kidney transplant recipients with biopsy-proven transplant glomerulopathy. Among total small RNA population, miRNAs were the most abundant species in the serum of kidney transplant patients. In addition, fragments arising from mature tRNA and rRNA were detected. Most of the tRNA fragments were generated from 5′ ends of mature tRNA and mainly from two parental tRNAs: tRNA-Gly and tRNA-Glu. Moreover, transplant patients with transplant glomerulopathy displayed a novel tRNA fragments signature. Gene expression analysis from allograft tissues demonstrated changes in canonical pathways related to immune activation such as iCos-iCosL signaling pathway in T helper cells, Th1 and Th2 activation pathway, and dendritic cell maturation. mRNA targets of down-regulated miRNAs such as miR-1224-5p, miR-4508, miR-320, miR-378a from serum were globally upregulated in tissue. Integration of serum miRNA profiles with tissue gene expression showed that changes in serum miRNAs support the role of T-cell mediated mechanisms in ongoing allograft injury.

scholarly journals Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure

2018 ◽  
Vol 29 (9) ◽  
pp. 2279-2285 ◽  
Author(s):  
Elena G. Kamburova ◽  
Bram W. Wisse ◽  
Irma Joosten ◽  
Wil A. Allebes ◽  
Arnold van der Meer ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Hla Antibodies ◽  
Transplant Patients ◽  
Increased Risk ◽  
Positive Serum

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

scholarly journals Acute and Chronic Changes in Gene Expression After CMV DNAemia in Kidney Transplant Recipients

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard Ahn ◽  
Joanna Schaenman ◽  
Zachary Qian ◽  
Harry Pickering ◽  
Victoria Groysberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Transplant ◽  
Time Course ◽  
Cell Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Cmv Dnaemia

Cytomegalovirus (CMV) viremia continues to cause significant morbidity and mortality in kidney transplant patients with clinical complications including organ rejection and death. Whole blood gene expression dynamics in CMV viremic patients from onset of DNAemia through convalescence has not been well studied to date in humans. To evaluate how CMV infection impacts whole blood leukocyte gene expression over time, we evaluated a matched cohort of 62 kidney transplant recipients with and without CMV DNAemia using blood samples collected at multiple time points during the 12-month period after transplant. While transcriptomic differences were minimal at baseline between DNAemic and non-DNAemic patients, hundreds of genes were differentially expressed at the long-term timepoint, including genes enriching for pathways important for macrophages, interferon, and IL-8 signaling. Amongst patients with CMV DNAemia, the greatest amount of transcriptomic change occurred between baseline and 1-week post-DNAemia, with increase in pathways for interferon signaling and cytotoxic T cell function. Time-course gene set analysis of these differentially expressed genes revealed that most of the enriched pathways had a significant time-trend. While many pathways that were significantly down- or upregulated at 1 week returned to baseline-like levels, we noted that several pathways important in adaptive and innate cell function remained upregulated at the long-term timepoint after resolution of CMV DNAemia. Differential expression analysis and time-course gene set analysis revealed the dynamics of genes and pathways involved in the immune response to CMV DNAemia in kidney transplant patients. Understanding transcriptional changes caused by CMV DNAemia may identify the mechanism behind patient vulnerability to CMV reactivation and increased risk of rejection in transplant recipients and suggest protective strategies to counter the negative immunologic impact of CMV. These findings provide a framework to identify immune correlates for risk assessment and guiding need for extending antiviral prophylaxis.

scholarly journals Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Event Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time To Event ◽  
Transplant Patients ◽  
Kaplan Meier ◽  
Lung Malignancy ◽  
Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

scholarly journals 530. COVID-19 in kidney transplant recipients: Single-center experience and case-control study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S332-S332
Author(s):  
Anna Hardesty ◽  
Aakriti Pandita ◽  
Yiyun Shi ◽  
Kendra Vieira ◽  
Ralph Rogers ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Case Control Study ◽  
Clinical Course ◽  
Case Series ◽  
Case Fatality ◽  
Case Control ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Control Study

Abstract Background Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34–65) years; 5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1–203) months. Two KTR, both transplanted >10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were >1,000 (normal: < 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were >10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%; 7.6% in KTR on IS; 9% in hospitalized KTR on IS). Four controls died (CFR: 9%; state CFR: 5.2%; inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Table 1 Table 2 Conclusion Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. Disclosures All Authors: No reported disclosures

scholarly journals Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Amudha Palanisamy ◽  
Paul Persad ◽  
Patrick P. Koty ◽  
Laurie L. Douglas ◽  
Robert J. Stratta ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Hematologic Malignancy ◽  
Deceased Donor ◽  
Myeloid Sarcoma ◽  
Kidney Transplant Recipients ◽  
Systemic Involvement ◽  
Transplant Patients ◽  
Single Donor ◽  
Allograft Nephrectomy ◽  
One Year

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescencein situhybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

scholarly journals Effect of Remdesivir on COVID-19 PCR Positivity and Cycle Threshold in Kidney Transplant Recipients

2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cycle Threshold ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Polymerase Chain ◽  
New Diagnosis ◽  
The Impact ◽  
Median Change

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.

Long-term protein intake control in kidney transplant recipients: Effect in kidney graft function and in nutritional status

2003 ◽  
Vol 41 (3) ◽  
pp. S146-S152 ◽  
Author(s):  
Annamaria Bernardi ◽  
Franco Biasia ◽  
Tecla Pati ◽  
Michele Piva ◽  
Angela D'Angelo ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Kidney Transplant ◽  
Protein Intake ◽  
Graft Function ◽  
Kidney Graft ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Intake Control

Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes

2021 ◽  
pp. CJN.03290321
Author(s):  
Simon Ville ◽  
Marine Lorent ◽  
Clarisse Kerleau ◽  
Anders Asberg ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Ischemia Reperfusion ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Deceased Donor ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Heart Beating ◽  
Deceased Donor Kidney Transplant

BackgroundThe recognition that metabolism and immune function are regulated by an endogenous molecular clock generating circadian rhythms suggests that the magnitude of ischemia-reperfusion and subsequent inflammation on kidney transplantation, could be affected by the time of the day. MethodsAccordingly, we evaluated 5026 first kidney transplant recipients from deceased heart-beating donors. In a cause-specific multivariable analysis, we compare delayed graft function (DGF) and graft survival according to the time of kidney clamping and declamping. Participants were divided into clamping between midnight and noon (AM clamping group, 65%) or clamping between noon and midnight (PM clamping group, 35%), and similarly, AM declamping or PM declamping (25% / 75%). ResultsDGF occurred among 550 participants (27%) with AM clamping and 339 (34%) with PM clamping (adjusted OR = 0.81, 95%CI: 0.67 to 0.98, p= 0.03). No significant association of clamping time with overall death censored graft survival was observed (HR = 0.92, 95%CI: 0.77 to 1.10, p= 0.37). No significant association of declamping time with DGF or graft survival was observed. ConclusionsClamping between midnight and noon was associated with a lower incidence of DGF whilst the declamping time was not associated with kidney graft outcomes.

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