scholarly journals Circular RNAs in Urine of Kidney Transplant Patients with Acute T Cell-Mediated Allograft Rejection

2019 ◽  
Vol 65 (10) ◽  
pp. 1287-1294 ◽  
Author(s):  
Malte Kölling ◽  
George Haddad ◽  
Urs Wegmann ◽  
Andreas Kistler ◽  
Andrea Bosakova ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Allograft Rejection ◽  
Kidney Injury ◽  
Circular Rnas ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Kidney Rejection ◽  
Acute Kidney Rejection ◽  
And Control

Abstract BACKGROUND Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They are detectable in the blood of patients with acute kidney injury. We tested whether circRNAs were present in urine and could serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS A global circRNA expression analysis using RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients was performed. Dysregulated circRNAs were confirmed in a cohort of 62 patients with acute rejection, 10 patients after successful antirejection therapy, 18 control transplant patients without rejection, and 13 stable transplant patients with urinary tract infection. RESULTS A global screen revealed several circRNAs to be altered in urine of patients with acute rejection. Concentrations of 2 circRNAs including hsa_circ_0001334 and hsa_circ_0071475 were significantly increased. These were validated in the whole cohort of patients. hsa_circ_0001334 was upregulated in patients with acute rejection compared with controls. Concentrations of hsa_circ_0001334 normalized in patients with acute rejection following successful antirejection therapy. hsa_circ_0001334 was associated with higher decline in glomerular filtration rate 1 year after transplantation. CONCLUSIONS CircRNA concentrations are significantly dysregulated in patients with acute rejection at subclinical time points. Urinary hsa_circ_0001334 is a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

scholarly journals Long Noncoding RNAs in Urine Are Detectable and May Enable Early Detection of Acute T Cell–Mediated Rejection of Renal Allografts

2015 ◽  
Vol 61 (12) ◽  
pp. 1505-1514 ◽  
Author(s):  
Johan M Lorenzen ◽  
Celina Schauerte ◽  
Malte Kölling ◽  
Anika Hübner ◽  
Monika Knapp ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Noncoding Rnas ◽  
Kidney Injury ◽  
Long Noncoding Rnas ◽  
Cell Culture Supernatant ◽  
Transplant Patients ◽  
Inflammatory Conditions ◽  
And Control

AbstractBACKGROUNDLong noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. They are detectable in the blood of patients with acute kidney injury. We tested whether lncRNAs are present in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection.METHODSA global lncRNA expression analysis was performed with RNA from urine of patients with acute T cell–mediated renal allograft rejection and control transplant patients. Deregulated lncRNAs were confirmed in kidney biopsies and urine in a validation cohort of 62 patients with acute rejection, 10 of them after successful antirejection therapy, and 31 control transplant patients.RESULTSA global screen revealed several lncRNAs to be deregulated in urine of patients with acute rejection. Three intergenic lncRNAs, LNC-MYH13-3:1, RP11-395P13.3-001, and RP11-354P17.15-001, were most strongly altered. These were validated in the whole cohort of patients. RP11-395P13.3-001 and RP11-354P17.15-001 were upregulated in patients with acute rejection compared with controls. Only levels of RP11-354P17.15-001 normalized in patients with acute rejection after successful antirejection therapy. RP11-354P17.15-001 was associated with higher decline in glomerular filtration rate 1 year after transplantation. In vitro, in tubular epithelial cells, all lncRNAs were enriched by interleukin-6 treatment, but only RP11-395P13.3-001 and RP11-354P17.15-001 increased in cell culture supernatant, indicating that these lncRNAs might be secreted under inflammatory conditions.CONCLUSIONSlncRNAs are strongly altered in urine of patients with acute rejection. Urinary RP11-354P17.15-001 may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.

Increased circulating concentrations of interleukin 2 receptor during rejection episodes in heart- or kidney-transplant recipients

1990 ◽  
Vol 36 (12) ◽  
pp. 2106-2109 ◽  
Author(s):  
G C Zucchelli ◽  
A Clerico ◽  
R De Maria ◽  
M Carmellini ◽  
R Di Stefano ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Interleukin 2 ◽  
Clinical Markers ◽  
Kidney Transplant Recipients ◽  
Interleukin 2 Receptor ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Mean

Abstract Concentrations of interleukin 2 receptor (sIL-2R) have been suggested as a marker of rejection episodes after organ transplantation. To evaluate the analytical performance of a "sandwich-type" enzyme immunoassay method for sIL-2R and to verify whether increased concentrations of sIL-2R might be a useful marker of allograft rejection, we quantified sIL-2R in serum samples from heart- or kidney-transplant patients. The mean (+/- SD) pre-transplant value of sIL-2R (592 +/- 209 kilo-units/L) in heart-transplant patients was significantly higher (P less than 0.01) than that observed in controls (350 +/- 101 kilo-units/L). After heart transplantation, the concentrations of sIL-2R slowly decreased to baseline in successfully treated patients but increased significantly (1129 +/- 215 kilo-units/L; P less than 0.01) during acute rejection crisis. However, severe infections were also associated with a significant increase of sIL-2R, so the sIL-2R test is not specific for allograft rejection. The mean pre-transplant concentration of sIL-2R was also increased (1943 +/- 878 kilo-units/L) in 26 renal-transplant patients; after transplantation, this value returned to normal, as did that for creatinine, but persisted steadily high in five patients who experienced acute tubular necrosis. In this group of patients, the sIL-2R concentration increased by 1.5- to fourfold, both during acute rejection episodes and in clinically evident infection; thus measurement of creatinine and sIL-2R concentrations can help to distinguish between rejection, infection, and cyclosporine toxicity. In two episodes of mild cyclosporine-induced nephrotoxicity, we observed slight increases in serum creatinine (which returned to baseline when the cyclosporine dose was decreased) not associated with an increase in sIL-2R. We conclude that systematic monitoring of sIL-2R together with other biochemical and clinical markers may be useful in the management of kidney-transplant patients.

scholarly journals Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Maria Prendecki ◽  
Tina Thomson ◽  
Candice L Clarke ◽  
Paul Martin ◽  
Sarah Gleeson ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
T Cell Responses ◽  
Cellular Responses ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Background Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in kidney transplant patients, assessing both serological and cellular responses. Methods 920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion. Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83. Conclusions. Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies

2001 ◽  
Vol 27 (6) ◽  
pp. 987-991 ◽  
Author(s):  
R. Sabat ◽  
C. Höflich ◽  
W.D. Döcke ◽  
F. Kern ◽  
H.-D. Volk ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Transplant Patients ◽  
Kidney Transplant Patients

scholarly journals CD4 + T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients

2020 ◽  
Vol 34 (9) ◽  
Author(s):  
Tilo Freiwald ◽  
Stefan Büttner ◽  
Nardos T. Cheru ◽  
Despina Avaniadi ◽  
Simon S. Martin ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Pneumocystis Pneumonia ◽  
Cd4 T Cell ◽  
Transplant Patients ◽  
T Cell Lymphopenia ◽  
Kidney Transplant Patients

scholarly journals A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients’ Lives and Allografts

2020 ◽  
Vol 9 (9) ◽  
pp. 2986 ◽  
Author(s):  
Smaragdi Marinaki ◽  
Stathis Tsiakas ◽  
Maria Korogiannou ◽  
Konstantinos Grigorakos ◽  
Vassilios Papalois ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Distress Syndrome ◽  
Kidney Injury ◽  
Deceased Donor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Male Predominance ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Mean

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

scholarly journals CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

2019 ◽  
Vol 8 (8) ◽  
pp. 1147 ◽  
Author(s):  
Lemerle ◽  
Garnier ◽  
Planchais ◽  
Brilland ◽  
Subra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Kidney Transplant ◽  
Cd8 T Cells ◽  
De Novo ◽  
Predictive Biomarkers ◽  
Transplant Patients ◽  
History Of ◽  
Kidney Transplant Patients ◽  
A Prospective Study

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

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