Pregnancy in Renal Transplant Recipients: Histopathology Provides New Insight.
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ABSTRACT:
SUBMITTER: Hendren EM
PROVIDER: S-EPMC8720824 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Pregnancy in Renal Transplant Recipients: Histopathology Provides New Insight.
Hendren Elizabeth M EM Reynolds Monica L ML
Kidney international reports 20211123 1
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Project description:Acute rejection threatens kidney allograft longevity. Cell-free DNA (cfDNA) is a real-time marker of organ injury and immune response. DNA methylation is an epigenetic marker that regulates gene expression. We aim to elucidate differential methylation of total plasma cfDNA between pediatric kidney transplant recipients in the presence compared to the absence of acute rejection. In doing so, we hope to exploit the property of cfDNA as a real-time biomarker and build on available testing to identify genes and processes participating in acute allograft rejection pathophysiology in kidney transplantation. Twenty plasma cfDNA samples from pediatric kidney transplant recipients were collected at the time of allograft biopsy. Using whole genome bisulfite sequencing (WGBS), differentially methylated cytosines were identified in presence vs absence of acute rejection. Separate analyses were performed comparing those with borderline rejection to those with rejection, and to those without rejection. Differentially methylated cytosines were then assessed for gene associations and pathway enrichments. Acute rejection was present in 7 biopsies, borderline rejection in 4 biopsies, and no rejection in 9 biopsies. In the comparison of acute rejection to non-rejection biopsies, there were 34,356 differentially methylated cytosines corresponding to 1,269 associated genes, and 533 enriched pathways. These numbers were all substantially greater (4x-13x) than the comparisons made between acute rejection against those with borderline rejection, and between non-rejection against borderline rejection. Prominently enriched pathways between samples of individuals with and without acute rejection were related to immune cell regulation, inflammatory response, lipid metabolism, and tryptophan-kynurenine metabolism. Our data suggest methylation plays a role in development of or response to acute kidney allograft rejection. Specifically, differentially methylated pathways associated with acute rejection include those related to immune and inflammatory responses.
2025-04-25 | GSE275017 | GEO
Project description:BackgroundKidney transplantation is a superior treatment for end-stage renal disease (ESRD), compared with hemodialysis, offering better quality of life and birth outcomes in women with ESRD and lower fertility rates.ObjectivesTo investigate the pregnancy, maternal, fetal, and graft outcomes following kidney transplantation in women with ESRD and evaluate the improvements in quality of life and associated risks.DesignA systematic review and meta-analysis performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines.Data sources and methodsA thorough search of multiple databases, including PubMed, Embase, Scopus, ATC abstracts, and Cochrane Central Register of Controlled Trials, was conducted to identify studies that analyzed pregnancy outcomes in kidney transplant patients. The search was conducted from the inception of each database to January 2023.ResultsThe study reviewed 109 studies that evaluated 7708 pregnancies in 5107 women who had undergone renal transplantation. Of these, 78.48% resulted in live births, 9.68% had induced abortion, and 68.67% had a cesarean section. Miscarriage occurred in 12.54%, preeclampsia in 20.87%, pregnancy-induced hypertension in 24.30%, gestational diabetes in 5.08%, and preterm delivery in 45.30% of cases. Of the 853 recipients, 123 had graft loss after pregnancy and 8.06% suffered acute rejection.ConclusionPregnancy after kidney transplantation is associated with risks for mother and fetus; however, live births are still possible. In addition, there are reduced overall risks of stillbirths, miscarriages, neonatal deaths, and gestational diabetes.RegistrationPROSPERO (CRD42024541659).
| S-EPMC11418342 | biostudies-literature
Project description:In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs.
| S-EPMC4886901 | biostudies-literature
Project description:Successful kidney transplantation offers patients with end-stage renal disease the greatest likelihood of survival. However, cardiovascular disease poses a major threat to both graft and patient survival in this cohort. Transplant recipients are unique in their accumulation of a wide range of traditional and non-traditional cardiovascular risk factors. Hypertension, diabetes, dyslipidaemia and obesity are highly prevalent in patients with end-stage renal disease. These risk factors persist following transplantation and are often exacerbated by the drugs used for immunosuppression in organ transplantation. Additional transplant-specific factors such as poor graft function and proteinuria are also associated with increased cardiovascular risk. However, these transplant-related factors remain unaccounted for in current cardiovascular risk prediction models, making it challenging to identify transplant recipients with highest risk. With few interventional trials in this area specific to transplant recipients, strategies to reduce cardiovascular risk are largely extrapolated from other populations. Aggressive management of traditional cardiovascular risk factors remains the cornerstone of prevention, though there is also a potential role for selecting immunosuppression regimens to minimise additional cardiovascular injury.
| S-EPMC6482292 | biostudies-literature
Project description:Hepcidin is a small peptide with a critical role in cellular iron homeostasis, as it regulates utilization of stored iron and antimicrobial defense in inflammation (bacterial and fungal). Since it was isolated in 2000, and especially in the last decade, numerous studies aimed to evaluate the clinical use of plasma and urine hepcidin as a marker of anemia, especially anemia of chronic disease and post-transplant anemia (PTA). Hepcidin regulation is delicately tuned by two inflammatory pathways activated by interleukin-6 (IL-6) and bone morphogenic proteins (BMPs) and iron regulated pathway sensitive to circulating transferin-iron (TR-Fe) complex. BMP-mediated pathway and TR-Fe sensitive pathway seem to be connected by hemojuveline, a BMP co-factor that interacts with transferine receptor 2 (TRF2) in cases of high TR-Fe circulatory concentration. In addition to these regulatory mechanisms other regulators and signaling pathways are being extensively researched. ?Hepcidin has been identified as an important contributor to morbidity and mortality in end stage renal disease (ESRD) but no such association has jet been found in case of PTA. However, there is an association between higher doses of erythropoiesis-stimulating agents (ESA) and mortality in the posttransplant period and the assumption that hepcidin might play a role in ESA resistance in PTA. Thus the review's main goal was to summarize papers published on the association of hepcidin with PTA, give up-to-date information on hepcidin regulation and on potential therapeutics that optimize hepcidin regulation. We also compared the performances of tests for hepcidin determination and reviewed research on immunosuppressants' (IS) effect on hepcidin concentration.
| S-EPMC4783088 | biostudies-other
Project description: Not available
| S-DIXA-D-1025 | biostudies-other
Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug.
2010-12-22 | GSE14630 | GEO
Project description:Cohort study of 137 renal transplant recipients and 29 non-immunosuppressed controls, looking at clinical influences upon monocytic HLA-DR density (mHLA-DRd) and associated clinical outcomes (namely, malignancy development)
2022-06-02 | GSE205122 | GEO
Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug. For microarray analysis, we studied 5 randomly selected patients included in the training group. Patients included in this group were, at the time of enrollment (T0), on standard maintenance immunosuppression with Cyclosporine (Neoral, Novartis, Basel, mean±SD of daily dose: 160.1±37.1mg), prednisone (5 mg daily) and Azathioprine (50 mg daily). Twenty patients, at T0, were switched from Azathioprine to EC-MPS (Myfortic, Novartis, Basel, 720 mg bid) for their need of allopurinol therapy (EC-MPS group). However, to avoid confounding factors, allopurinol treatment did not start until the end of our study (3 months). For the microarray analysis, we randomly selected 5 patients from the EC-MPS group. PBMC both at T0 and at T1 (3 months after the switching of the therapy) were immediately isolated from 20 ml of whole blood by Ficoll–Hypaque (Flow Laboratories, Irvine, UK) density gradient centrifugation. Total RNA was extracted by RNeasy mini kit (QIAGEN Inc., Valencia, CA) according the manufacturer’s instructions. Total RNA was processed and hybridized to the Affymetrix GeneChips Human Genome U133 Array Set HG-U133A (Affymetrix)(Affymetrix, Santa Clara, CA)
2010-12-22 | E-GEOD-14630 | biostudies-arrayexpress
Project description:Urinary tract infection (UTI) is the most common complication following kidney transplantation (KT), which could result in losing the graft. This study aims to identify the prevalence of bacterial UTI among KT recipients in Yemen and to determine the predisposing factors associated with post renal transplantation UTI. A cross sectional study included of 150 patients, who underwent KT was conducted between June 2010 and January 2011. A Morning mid-stream urine specimen was collected for culture and antibiotic susceptibility test from each recipient. Bacterial UTI was found in 50 patients (33.3%). The prevalence among females 40.3% was higher than males 29%. The UTI was higher in the age group between 41-50 years with a percentage of 28% and this result was statistically significant. Predisposing factors as diabetes mellitus, vesicoureteral reflux, neurogenic bladder and polycystic kidney showed significant association. High relative risks were found for polycystic kidney = 13.5 and neurogenic bladder = 13.5. The most prevalent bacteria to cause UTI was Escherichia coli represent 44%, followed by Staphylococcus saprophyticus 34%. Amikacin was the most effective antibiotic against gram-negative isolates while Ciprofloxacin was the most effective antibiotic against Staphylococcus saprophyticus. In conclusion, there is high prevalence of bacterial UTI among KT recipients in Yemen. Diabetes mellitus, vesicoureteral reflux, neurogenic bladder, polycystic kidney and calculi were the main predisposing factors.
| S-EPMC4675517 | biostudies-other