scholarly journals Gene Co-expression Networks Are Associated with Obesity-Related Traits in Kidney Transplant Recipients

2019 ◽  
Author(s):  
Rosario B Jaime-Lara ◽  
Abhrarup Abe Roy ◽  
Yupeng Wang ◽  
Ansley Stanfill ◽  
Ann K Cashion ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Weight Gain ◽  
Kidney Transplant ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Kidney Transplant Recipients ◽  
Microarray Expression Data ◽  
Transplant Patients ◽  
Clinical Trait ◽  
Kidney Transplant Patients

Abstract Background: Weight gain is often observed following kidney transplantation. Biological mediators of weight gain are not well understood in this population. Because subcutaneous adipose tissue can be easily obtained during kidney transplant surgery, it provides a unique avenue for studying the mechanisms of obesity for this group.Although differential gene expression patterns were previously profiled for kidney transplant patients, gene co-expression patterns can shed light on gene modules not yet explored on the coordinative behaviors of gene transcription in biological and disease processes. Methods: In this study, we collected 29 demographic and clinical variables and matching microarray expression data for 26 kidney transplant patients. We conducted Weighted Gene Co-expression Network Analysis (WGCNA) for 5,758 genes with the highest average expression levels and related gene co-expression to clinical traits. Results: A total of 35 co-expression modules were detected, seven of which showed association with clinical traits. Gene Ontology (GO) enrichment was found for five clinical trait-associated modules. One module consisting of 129 genes was enriched for metabolic and immune processes. The genes within this module were associated with multiple obesity-related traits, and is consistent with findings of previous studies in other clinically obese populations. Conclusions : Our study generatedgene coexpression modules associated with obesity-related traits in kidney transplant patients and provided new insights regarding the cellular biological processes underlying obesity. Trial Registration: N/A Keywords : co-expression modules, obesity, association, enrichment analysis, gene ontology, kidney transplant

scholarly journals Gene Co-expression Networks Are Associated with Obesity-Related Traits in Kidney Transplant Recipients

2020 ◽  
Author(s):  
Rosario B Jaime-Lara ◽  
Abhrarup Abe Roy ◽  
Yupeng Wang ◽  
Ansley Stanfill ◽  
Ann K Cashion ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Expression Patterns ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Microarray Expression Data ◽  
Transplant Patients ◽  
Clinical Trait ◽  
Kidney Transplant Patients ◽  
Microarray Expression ◽  
Subcutaneous Adipose

Abstract Background Obesity is common among kidney transplant recipients; However biological mediators of obesity are not well understood in this population. Because subcutaneous adipose tissue can be easily obtained during kidney transplant surgery, it provides a unique avenue for studying the mechanisms of obesity for this group. Although differential gene expression patterns were previously profiled for kidney transplant patients, gene co-expression patterns can shed light on gene modules not yet explored on the coordinative behaviors of gene transcription in biological and disease processes from a systems perspective. Methods In this study, we collected 29 demographic and clinical variables and matching microarray expression data for 26 kidney transplant patients. We conducted Weighted Gene Co-expression Network Analysis (WGCNA) for 5,758 genes with the highest average expression levels and related gene co-expression to clinical traits. Results A total of 35 co-expression modules were detected, two of which showed associations with obesity-related traits, mainly at baseline. Gene Ontology (GO) enrichment was found for these two clinical trait-associated modules. One module consisting of 129 genes was enriched for a variety of processes, including cellular homeostasis and immune responses. The other module consisting of 36 genes was enriched for tissue development processes. Conclusions Our study generated gene co-expression modules associated with obesity-related traits in kidney transplant patients and provided new insights regarding the cellular biological processes underlying obesity in this population.

scholarly journals Gene Co-expression Networks Are Associated with Obesity-Related Traits in Kidney Transplant Recipients

2020 ◽  
Author(s):  
Rosario B Jaime-Lara ◽  
Abhrarup Abe Roy ◽  
Yupeng Wang ◽  
Ansley Stanfill ◽  
Ann K Cashion ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Expression Patterns ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Microarray Expression Data ◽  
Transplant Patients ◽  
Clinical Trait ◽  
Kidney Transplant Patients ◽  
Microarray Expression ◽  
Subcutaneous Adipose

Abstract Background Obesity is common among kidney transplant recipients; However biological mediators of obesity are not well understood in this population. Because subcutaneous adipose tissue can be easily obtained during kidney transplant surgery, it provides a unique avenue for studying the mechanisms of obesity for this group. Although differential gene expression patterns were previously profiled for kidney transplant patients, gene co-expression patterns can shed light on gene modules not yet explored on the coordinative behaviors of gene transcription in biological and disease processes from a systems perspective. Methods In this study, we collected 29 demographic and clinical variables and matching microarray expression data for 26 kidney transplant patients. We conducted Weighted Gene Co-expression Network Analysis (WGCNA) for 5,758 genes with the highest average expression levels and related gene co-expression to clinical traits. Results A total of 35 co-expression modules were detected, two of which showed associations with obesity-related traits, mainly at baseline. Gene Ontology (GO) enrichment was found for these two clinical trait-associated modules. One module consisting of 129 genes was enriched for a variety of processes, including cellular homeostasis and immune responses. The other module consisting of 36 genes was enriched for tissue development processes. Conclusions Our study generated gene co-expression modules associated with obesity-related traits in kidney transplant patients and provided new insights regarding the cellular biological processes underlying obesity in this population.

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 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.

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 Is delayed graft function associated with ureteral stenosis in the kidney transplant recipient? A case-control study

2019 ◽  
Vol 13 (11) ◽  
Author(s):  
Axel Cayetano-Alcaraz ◽  
Juan Sebastian Rodriguez-Alvarez ◽  
Mario Vilatobá-Chapa ◽  
Josefina Alberú-Gómez ◽  
Bernardo Gabilondo-Pliego ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Kidney Transplant Recipient ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Control Study

Introduction: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. Methods: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008–2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. Results: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36–4.37) and ureteral duplication (OR 3.29; 95% CI 2.40–4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96–11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors. Conclusions: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

scholarly journals Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on Sirolimus In Vitro Metabolism and Trough Concentrations in Kidney Transplant Recipients

2013 ◽  
Vol 59 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Jean-Baptiste Woillard ◽  
Nassim Kamar ◽  
Sandra Coste ◽  
Lionel Rostaing ◽  
Pierre Marquet ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kidney Transplant ◽  
Calcineurin Inhibitor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Trough Concentrations ◽  
The Impact

BACKGROUND Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C&gt;T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C&gt;T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G&gt;A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = −0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.

scholarly journals Posttransplantation Anemia in Kidney Transplant Recipients

2019 ◽  
Vol 142 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Anat Gafter-Gvili ◽  
Uzi Gafter
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Hemoglobin Level ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Appropriate Treatment ◽  
Optimal Target ◽  
Kidney Transplant Patients ◽  
Anemia Treatment

Posttransplantation anemia (PTA) is common among kidney transplant patients. Early PTA is usually defined as anemia which develops up to 6 months after transplantation, and late PTA is defined as anemia which develops after 6 months. There are multiple causes, with iron deficiency being the major contributor. The occurrence of late PTA has been associated with impaired graft function. Early PTA has been shown to be a predictor of late PTA. PTA is associated with reduced mortality, reduced graft survival, and a decline in GFR. The association with mortality is related to the severity of the anemia and to specific causes of anemia. Treatment of PTA should probably begin as soon as possible after kidney transplantation. The optimal target hemoglobin level in kidney transplant recipients with anemia is higher than recommended in chronic kidney disease and should probably be up to 12.5–13 g/dL. In order to achieve this target, appropriate treatment with erythropoiesis-stimulating agents (ESA) and iron is indicated.

scholarly journals Establishing a tele-clinic service for kidney transplant recipients through a patient-codesigned quality improvement project

2019 ◽  
Vol 8 (2) ◽  
pp. e000427 ◽  
Author(s):  
Udaya Prabhakar Udayaraj ◽  
Oliver Watson ◽  
Yoav Ben-Shlomo ◽  
Maria Langdon ◽  
Karen Anderson ◽  
...  
Keyword(s):  
Quality Improvement ◽  
Kidney Transplant ◽  
Blood Test ◽  
Significant Proportion ◽  
Kidney Transplant Recipients ◽  
Test Quality ◽  
Improvement Project ◽  
Face To Face ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Kidney transplant patients in our regional centre travel long distances to attend routine hospital follow-up appointments. Patients incur travel costs and productivity losses as well as adverse environmental impacts. A significant proportion of these patients, who may not require physical examination, could potentially be managed through telephone consultations (tele-clinic). We adopted a Quality Improvement approach with iterative Plan–Do–Study–Act (PDSA) cycles to test the introduction of a tele-clinic service. We codesigned the service with patients and developed a prototype delivery model that we then tested over two PDSA improvement ramps containing multiple PDSA cycles to embed the model into routine service delivery. Nineteen tele-clinics were held involving 168 kidney transplant patients (202 tele-consultations). 2.9% of tele-clinic patients did not attend compared with 6.9% for face-to-face appointments. Improving both blood test quality and availability for the tele-clinic was a major focus of activity during the project. Blood test quality for tele-clinics improved from 25% to 90.9%. 97.9% of survey respondents were satisfied overall with their tele-clinic, and 96.9% of the patients would recommend this to other patients. The tele-clinic saved 3527 miles of motorised travel in total. This equates to a saving of 1035 kgCO2. There were no unplanned admissions within 30 days of the tele-clinic appointment. The service provided an immediate saving of £6060 for commissioners due to reduced tele-clinic tariff negotiated locally (£30 less than face-to-face tariff). The project has shown that tele-clinics for kidney transplant patients are deliverable and well received by patients with a positive environmental impact and modest financial savings. It has the potential to be rolled out to other renal centres if a national tele-clinic tariff can be negotiated, and an integrated, appropriately reimbursed community phlebotomy system can be developed to facilitate remote monitoring of patients.

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.

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