scholarly journals Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients

2020 ◽  
Vol 9 (2) ◽  
pp. 518 ◽  
Author(s):  
Tim J. Knobbe ◽  
Rianne M. Douwes ◽  
Daan Kremer ◽  
J. Casper Swarte ◽  
Michele F. Eisenga ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Microbial Fermentation ◽  
Main Role ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Fermentation Processes ◽  
Methanobrevibacter Smithii ◽  
Inflammatory Bowel ◽  
Insight Into

Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9–10.6] ppm vs. 16.0 [8.0–45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea.

scholarly journals Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eman H. Ibrahim ◽  
Mostafa G. Aly ◽  
Gerhard Opelz ◽  
Christian Morath ◽  
Martin Zeier ◽  
...  
Keyword(s):  
Renal Transplant ◽  
B Cell ◽  
Graft Function ◽  
Cell Subset ◽  
Immunosuppressive Drugs ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Significant Positive Association ◽  
Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

scholarly journals Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients

2020 ◽  
Vol 6 (4) ◽  
pp. 50
Author(s):  
Shelley Waters ◽  
Silvia Lee ◽  
Kylie Munyard ◽  
Ashley Irish ◽  
Patricia Price ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Immune Responses ◽  
Human Cytomegalovirus ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Hcmv Disease ◽  
Mirna Species

Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.

scholarly journals Evaluation of Serum Interleukin-6 Levels in the Renal Transplant Recipients: A Systematic Review and Meta-Analysis of Case-Control Studies

2019 ◽  
Vol 7 (1) ◽  
pp. 174-178 ◽  
Author(s):  
Hamidreza Omrani ◽  
Sayed Vahid Jasemi ◽  
Masoud Sadeghi ◽  
Sima Golmohamadi
Keyword(s):  
Renal Transplant ◽  
Meta Analysis ◽  
Elevated Serum ◽  
Cochrane Library ◽  
P Value ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Case Control Studies ◽  
Meta Regression Analysis

AIM: The purpose of this meta-analysis was the assessment of the serum IL-6 levels in the renal transplant recipients compared to the healthy controls. MATERIAL AND METHODS: Four databases including PubMed, Web of Science, Scopus, and Cochrane Library were searched up to July 2018 without language restriction. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). A continuous random-effects meta-analysis was used by RevMan 5.3 using the mean difference (MD) and 95% confidence intervals (CIs). Also, a regression model was done by Comprehensive Meta-Analysis version 2 (CMA v2). RESULTS: Out of 615 studies identified in the databases, 15 studies included and analysed in the meta-analysis. The studies were reported from 1994 to 2018. The meta-analysis included 1035 renal transplant recipients and 682 healthy controls. The pooled MD of the serum IL-6 levels in the transplant recipients compared to the healthy controls was 3.25 pg/mL [95%CI: 2.17, 4.32; P < 0.00001; I2 = 98% (P < 0.00001)]. Meta-regression analysis showed that one of the reasons of heterogeneity is the year of publication (Correlation coefficient (r) = 0.208, p-value = 0.00002). CONCLUSION: An elevated serum IL-6 level in the renal transplant recipients compared to the healthy controls showed that the serum level of this marker could be used for the evaluation of inflammation in ESRD patients undergoing renal transplantation.

scholarly journals Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients

2020 ◽  
Vol 9 (2) ◽  
pp. 525 ◽  
Author(s):  
Anna van der Veen ◽  
Isidor Minović ◽  
Martijn van Faassen ◽  
Antόnio W. Gomes-Neto ◽  
Stefan P. Berger ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Renal Disease ◽  
Urinary Excretion ◽  
Cox Regression ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Stage Renal Disease ◽  
End Stage

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs.

P6244Cytomegalovirus (CMV) burden may be used to enhance algorithms to predict future cardiovascular health in renal transplant recipients and healthy controls

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Affandi ◽  
S Lee ◽  
H Chih ◽  
E Brook ◽  
S Waters ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Adhesion Molecule ◽  
Pulse Wave ◽  
Healthy Adults ◽  
Intercellular Adhesion Molecule ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Vascular Health ◽  
Transplant Recipients ◽  
High Burden

Abstract Background Cytomegalovirus (CMV) has been implicated in accelerated cardiovascular changes and may warrant inclusion in predictive algorithms. This is addressed here in healthy older adults and in renal transplant recipients (RTR) stable on therapy as they retain a high burden of CMV. Methods RTR (n=45) stable >2 years after transplantation and 58 age-matched healthy adults were recruited in 2014 and returned in 2017. Venous blood samples and saliva were collected, frozen and stored. Plasma proteins linked with inflammation [soluble interferon a receptor 2 (sIFNaR2), sTNFR1, sCD14, C-reactive protein (CRP)], vasculopathy [p-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1)], and metrics of CMV burden [antibodies reactive with CMV lysate, gB or IE-1 (by ELISA), CMV DNA in saliva (by PCR) and T-cell IFNg responses to CMV antigens (by ELISpot)] were assessed in 2014. In 2017, vascular endpoint measurements included brachial artery flow mediated dilatation (FMD), pulse wave analysis [augmented index corrected to heart rate of 75 beats per minute (Aix@75)] and pulse wave velocity (PWV). Results In 2017, RTR had lower FMD % (p<0.001), higher PWV (<0.001) and slightly higher Aix@75 values (p=0.14) compared with healthy adults, indicating inferior vascular health. In a multivariable regression model (adjusted R2=0.42) predicting 2017 FMD in RTR (adjusted for age, sex, BMI, eGFR, sCD14, CMV gB Ab and saliva CMV DNA), each 1AU/mL increase of CMV gB Ab (p=0.03) predicted a 5% increase in FMD – associating with better vascular outcomes, but detectable saliva CMV DNA (p=0.02) associated with a 3% increase in FMD. In healthy adults, however, while predicting 2017 FMD (adjusting for p-selectin, ICAM-1, age, sex, BMI, eGFR; adjusted R2=0.22), a 1 ng/mL increase in p-selectin (p=0.03) predicted a 0.04% increase in FMD, and 1 ng/mL increase in ICAM-1 (p=0.03) associated with 0.03% lower FMD. From the pulse wave analyses of RTR, every 1ng/mL increase of sIFNaR2 (p=0.06) marginally predicted 1.4 unit decrease in Aix@75 (adjusted for CMV IE-1 Ab, sIFNaR2, age, sex, BMI and eGFR; adjusted R2=0.37). However in healthy adults, each 1ng/mL increase of sIFNaR2 levels (p=0.04) associated with 3.5 units worsening of Aix@75 (p=0.04) (adjusted R2 = 0.40). Each 1 AU/mL increase in CMV IE-1 Ab levels associated with 0.08 units decrease in PWV (p=0.02) (adjusting for CMV IE-1 Ab, sCD14, age, sex, BMI and eGFR adjusted R2=0.55). Conclusions Overall measures of a high burden of CMV, predicted a low FMD marking poor peripheral vascular health in RTR several years after assessment, with more potency than was achieved with plasma markers of systemic and vascular inflammation, which was observed in healthy controls. CMV antibodies can predict future measures of arterial stiffness such as Aix@75 and PWV in healthy controls, but need further investigation in larger cohorts.

scholarly journals Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

2020 ◽  
Vol 9 (2) ◽  
pp. 386 ◽  
Author(s):  
J. Casper Swarte ◽  
Rianne M. Douwes ◽  
Shixian Hu ◽  
Arnau Vich Vila ◽  
Michele F. Eisenga ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Gut Microbiome ◽  
Linear Models ◽  
Immunosuppressive Drugs ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Microbiome Composition ◽  
Intestinal Dysbiosis

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5–12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.

scholarly journals Urinary Excretion of N1-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients

2019 ◽  
Vol 8 (11) ◽  
pp. 1948 ◽  
Author(s):  
Carolien P.J. Deen ◽  
Anna van der Veen ◽  
Martijn van Faassen ◽  
Isidor Minović ◽  
António W. Gomes-Neto ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Dietary Intake ◽  
Urinary Excretion ◽  
Vitamin B6 ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Kidney Donors ◽  
Long Term Outcome ◽  
All Cause Mortality

Renal transplant recipients (RTR) commonly suffer from vitamin B6 deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B6 is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of N1-methylnicotinamide (N1-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B6 status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7–6.1) years and 275 healthy kidney donors, 24-h urinary excretion of N1-MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of N1-MN excretion with mortality were investigated by Cox regression analyses. Median N1-MN excretion was 22.0 (15.8–31.8) μmol/day in RTR, compared to 41.1 (31.6–57.2) μmol/day in healthy kidney donors (p < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; p = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; p < 0.001), plasma vitamin B6 (29.0 (17.5–49.5), and 42.0 (29.8–60.3) nmol/L; p < 0.001), respectively. N1-MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45–0.71; p < 0.001), independent of potential confounders. RTR excrete less N1-MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B6 status. Importantly, lower 24-h urinary excretion of N1-MN is independently associated with a higher risk of premature all-cause mortality in RTR.

scholarly journals BK Virus Infection:A Hidden Threat for Renal Transplant Recipients

2018 ◽  
Vol 43 (3) ◽  
pp. 101-107
Author(s):  
Afzalun Nessa ◽  
Nustrat Mannan ◽  
Shahina Tabassum ◽  
Sharimin Sultana ◽  
K.M Shahidul Islam
Keyword(s):  
Renal Transplant ◽  
Serum Creatinine ◽  
Graft Loss ◽  
Bk Virus ◽  
Urine Samples ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Transplant Patients

BK virus (BKV) infection has become an important concern for renal transplant recipients, as it may cause nephropathy in transplant patients receiving immunosuppressive therapy resulting in renal dysfunction and possibly, graft loss. This crosssectional study was carried out at the Department of Virology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2015 to June 2016, aimedto detect the incidence of BKV infection among transplant recipients from Bangladesh. A total of 30randomly selected adult renal transplant recipients and 15 healthy controls were included in this study.Their blood and urine samples were collected at 4 and 12 weeks of post transplantation, and tested for BKV DNA by quantitative real-time polymerase chain reaction. The serum creatinine levels were measured along with other routine investigations at the Department Biochemistry, BSMMU.Virological analysis showed, 8 (26.6%) patients had detectable BKV DNA at 4 weeks (1 month). Of them, 23.3% (7/30) had viruria and 3.3% (1/30) had viraemia. No BKV DNA was detected either in blood or in urine samples of healthy controls. Incidence of BKV infection found significantly higher (p<0.02) in transplant patients than healthy controls. However, their serum creatinine value was not significantly higher than that of the BKV DNA negative patients. At third month (12 weeks post transplantation), BKVviruria and/or viraemia were detected among 23.3% (7/30) patients where 13.3% (4/30) patients were newly detected who were previously ( at 4 weeks of transplant) negative; only 1 (3.3%) patient had both viraemia and viruria. There was significant variation (p<0.05) in mean serum creatinine value of BKV DNA positive and BKV DNA negative recipients at third month follow-up.Significantly higher incidence of BKV infection among transplant patients indicates thatit is very likely occurring in transplantation recipients, andBKV screening test should be included in routine postoperative follow-up investigations for early detection; and thus prevent the graft loss due to BKV nephropathy.

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