scholarly journals A clinical evaluation of VO2 kinetics in kidney transplant recipients

Author(s):  
Alessandro Patti ◽  
Daniel Neunhaeuserer ◽  
Sara Ortolan ◽  
Fausto Roman ◽  
Andrea Gasperetti ◽  
...  

Abstract Purpose Aerobic exercise capacity is reduced in patients with chronic kidney disease, partly due to alterations at the muscular and microvascular level. This study evaluated oxygen uptake (VO2) kinetics as indicator of muscular oxidative metabolism in a population of Kidney Transplant Recipients (KTRs). Methods Two groups of KTRs enrolled 3 (n = 21) and 12 months (n = 14) after transplantation and a control group of healthy young adults (n = 16) underwent cardiopulmonary exercise testing on cycle-ergometer. The protocol consisted in two subsequent constant, moderate-load exercise phases with a final incremental test until exhaustion. Results The time constant of VO2 kinetics was slower in KTRs at 3 and 12 months after transplantation compared to controls (50.4 ± 13.1 s and 43.8 ± 11.6 s vs 28.9 ± 8.4 s, respectively; P < 0.01). Peak VO2 was lower in KTRs evaluated 3 months after transplantation compared to patients evaluated after 1 year (21.3 ± 4.3 and 26.4 ± 8.0 mL/kg/min; P = 0.04). Blood haemoglobin (Hb) concentration was higher in KTRs evaluated at 12 months (12.8 ± 1.7 vs 14.6 ± 1.7 g/dL; P < 0.01). Among KTRs, τ showed a moderate negative correlation with Peak VO2 (ρ = − 0.52) and Oxygen uptake efficiency slope (OUES) (r = − 0.57) while no significant correlation with Hb and peak heart rate. Conclusions KTRs show slower VO2 kinetics compared to healthy controls. Hb and peak VO2 seem to improve during the first year after transplantation. VO2 kinetics were significantly associated with indices of cardiorespiratory fitness, but less with central determinants of aerobic capacity, thus suggesting a potential usefulness of adding this index of muscular oxidative metabolism to functional evaluation in KTRs.

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Masanori Okamoto ◽  
Shintaro Yamanaka ◽  
Wataru Yoshimoto ◽  
Takashi Shigematsu

Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC) is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects) and a control group (group C: 7 subjects). Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1) the time-dependent change in bone mineral density (BMD) estimated with DEXA and (2) progression of abdominal AC, calculated twice as an index (ACI) using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% (P=0.015versus baseline), and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%), but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%,P=0.061). In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR.


2021 ◽  
Vol 7 ◽  
Author(s):  
Rainer Oberbauer ◽  
Matthias Edinger ◽  
Gabriela Berlakovich ◽  
Peter Kalhs ◽  
Nina Worel ◽  
...  

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR &lt;35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.


2021 ◽  
pp. 65-70
Author(s):  
I.A. Kozyro ◽  
◽  
А.V. Sukalo ◽  
О.A. Kondratenko ◽  

Damage of the cardiovascular system (cardiovascular disease, CVD) is the main cause of reduced life expectancy in children with chronic kidney disease (CKD). In the development of damage of the heart and blood vessels, both traditional factors and caused by impaired renal function, which appear already in the early stages of kidney disease, play a role. Purpose of the study: assessment of markers of the structure, function and metabolism of the heart and study of their changes in children, kidney transplant recipients. Materials and methods. 54 children, a kidney transplant recipients (Tx), who were under observation and treatment at the National Center for Pediatric Nephrology and Renal Replacement Therapy, Minsk 2nd Children's City Clinical Hospital, aged 3 to 17 years, were included in the study. The analysis of the data of the Tx group and conditionally divided subgroups: 1) with glomerular disease leading to the end stage of CKD (ESRD), n = 26; 2) with non-glomerular pathology, n = 27, in one patient the cause of ESRD was not specified. The control group consisted of healthy children from cardiology department without kidney pathology (n = 86). Results. Anamnestic, clinical, laboratory, immunological (serum concentration of T- and B-lymphocyte activation markers (RANTES and BAFF), proinflammatory (caspase 1, IL1fi and TNFa), vascular (VEGF) and tissue (TGF1p) growth factors), metabolic status (adyponectin, leptin, obestatin, vitamin D 25(OH)D), cardiospecific molecules (highly sensitive C-reactive protein (hsCRP), proBNP, transferrin, TSAT index), instrumental changes. Conclusion. Changes in the cardiovascular system in Tx are ambiguous. On the one hand, there is a significant improvement in the geometry of the myocardium and arterial hypertension, on the other hand, the atherogenic direction of metabolic changes and biochemical markers of CVD remains.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
R. L. Heilman ◽  
S. Nijim ◽  
H. A. Chakkera ◽  
Y. Devarapalli ◽  
A. A. Moss ◽  
...  

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW).Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups.Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P<.0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39–24.2) and between the SR and control group (HR 4.22, 95% CI 1.30–13.7).Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW.


2019 ◽  
Vol 9 (1) ◽  
pp. e08-e08
Author(s):  
Heshmatollah Shahbazian ◽  
Ali Ghorbani ◽  
Fatemeh Hayati ◽  
Seyed Seifollah Beladi Mousavi ◽  
Leila Sabetnia ◽  
...  

Introduction: Thymoglobulin is a lymphocyte-depleting polyclonal antibody, administered for induction therapy at the time of kidney transplantation to reduce the risk of acute allograft rejection. The appropriate dosage and duration of therapy is controversial. The higher dosages are associated with infection and malignancy. Objectives: In this study efficacy and safety of lower dosage (in comparison with previous studies) of thymoglobulin in kidney transplant recipients was evaluated. Patients and Methods: In this clinical trial, 106 adult kidney transplant recipients, were randomized before transplantation in two groups (case and control). The case group (53 patients) were received induction therapy with thymoglobulin (1.5 mg/kg/d for 3 days) and the control group (53 patients) were received non-induction regiment. Delayed graft function (DGF), glomerular filtration rate (GFR), acute allograft rejection and thymoglobulin complications were evaluated during the first post-transplantation year. Results: Around 106 kidney transplant recipients were enrolled (71 or 66.98% deceased donor) to the study. No significant statistical differences were found in GFR at the time of discharge from hospital (P=0.399) and at 1 year (P=0.851) and acute allograft rejection (P= 0.304) between two groups. Graft survival (73.5% in case group versus 81.1% in control group, P=0.392) at month 12th was similar among groups. Additionally, no significant differences of acute allograft rejection in recipient from deceased or living donor between two groups were detected. There was a higher incidence of DGF in the control group (26.4%) than the thymoglobulin group (5.8%) and the difference was statistically significant (P= 0.004). Thrombocytopenia (17% versus 49.1%, P<0.001) and leukopenia (11.3% versus 50.9%, P<0.001) were also significantly higher in the case group. Conclusion: While the incidence of DGF was reduced in thymoglobulin group, the short-term acute allograft rejection rate was not reduced compared to the control group. However, our results require further consideration with larger samples


2019 ◽  
Vol 30 (4) ◽  
pp. 692-709 ◽  
Author(s):  
Marianne Delville ◽  
Baptiste Lamarthée ◽  
Sylvain Pagie ◽  
Sarah B. See ◽  
Marion Rabant ◽  
...  

BackgroundAlthough anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti–HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.MethodsWe conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.ResultsWe identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti–endothelial cell Abs—angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs—did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.ConclusionsOur findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 884-884
Author(s):  
Tara O’Brien ◽  
Karen Rose ◽  
Alai Tan

Abstract Daily walking activities are associated with improving cardiovascular and well-being in older kidney transplant recipients. Multicomponent interventions using technology and goal setting holds promise for sustaining daily walking activity among this population. The purpose of this randomized controlled trial pilot study was to evaluate the feasibility of a multicomponent intervention called SystemCHANGE™ + activity tracker for daily walking activity in older (age 60 and over) kidney recipients from baseline to 12 months. The intervention group implement a personal-system solution and wore a mobile activity tracker daily for 12 months. The attention-control group received educational information on healthy living as a transplant recipient and was asked to wear a mobile activity tracker daily for 12 months. Participants were randomized 1:1 to the intervention or control group. The sample consisted of 53 participants (n = 27 intervention, and n = 26 control). At the 12-month follow-up visit, the total study attrition rate was 23%. The adherence rates at 12 months were 96.5% in the intervention group and 80.8% in the attention- control group. The intervention group increased their steps from baseline to 12 months by 334 steps per day. The attention-control group demonstrated a decrease in steps by 563 steps per day. We found a mean difference of 1041± 2440 (Cohen’s d = 0.43) in daily steps between the groups from baseline to 12 months. The data suggests SystemCHANGE™ in combination with activity trackers may be feasible for older kidney transplant recipients to enhance and sustain physical activity with daily walking.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamed Jahromi ◽  
Torki Al-Otaibi ◽  
Osama Ashry Gheith ◽  
Nashwa Farouk Othman ◽  
Tarek Mahmoud ◽  
...  

AbstractNew Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (− 174)C, macrophage mediator; IL-4 C (− 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (− 174) C, IL-4 C (− 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S28-S29
Author(s):  
Anna Hardesty ◽  
Elizabeth Klein ◽  
Kendra Vieira ◽  
Dimitrios Farmakiotis

Abstract Background Organ transplant recipients may not mount an adequate immune response to COVID-19 infection, and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAb), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. Methods We identified KTR with COVID-19 between 3/1/2020 and 4/30/2021. Patients were excluded if they had multiorgan transplant or hospital-acquired COVID-19. Data were analyzed by Cox regression with mAb administration as time-dependent variable, and the day of symptom onset as baseline. Results We studied 95 KTR; 20 received mAb. Comorbidities and immunosuppression were balanced between the two groups. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15 vs. 76%, P&lt; 0.001). This association remained significant after adjustment for confounders and by analyzing mAb administration as a time-dependent variable (Table: adj. HR 0.2, P=0.04). No KTR who received mAb died or required mechanical ventilation. Black or Hispanic KTR were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER (Table). Table Factors significantly associated with hospitalization or ER visit. Conclusion In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, were exacerbated by the COVID-19 pandemic. Acknowledging the nonconcurrent control group as a limitation, we found a strong signal for benefit from mAb treatment. Antiviral mAb are a promising therapeutic modality for immunosuppressed patients. Disclosures Dimitrios Farmakiotis, M.D., Astellas (Grant/Research Support)Merck (Grant/Research Support)Viracor (Grant/Research Support)


Author(s):  
Alessandro Patti ◽  
Daniel Neunhaeuserer ◽  
Andrea Gasperetti ◽  
Veronica Baioccato ◽  
Marco Vecchiato ◽  
...  

The overshoot of the respiratory exchange ratio (RER) during recovery from exercise has been found to be reduced in magnitude among patients with heart failure. The aim of this study is to investigate whether this phenomenon could also be present in patients with peripheral, and not cardiac, limitations to exercise such as kidney transplant recipients (KTRs). In this retrospective cross-sectional study, KTRs were evaluated with maximal cardiopulmonary exercise testing (CPET) assessing the RER overshoot parameters during recovery: the RER at peak exercise, the maximum RER value reached during recovery, the magnitude of the RER overshoot (RER mag = (RER max-peak RER)/peak RER%) and the linear slope of the RER increase after the end of exercise. A total of 57 KTRs were included in the study (16 females), all of them showing a significant RER overshoot (RER mag: 28.4 ± 12.7%). Moreover, the RER mag showed significant correlations with the fitness of patients (peak VO2: ρ = 0.57, p < 0.01) and cardiorespiratory efficiency (VE/VCO2 slope: r = −0.32, p < 0.05; oxygen uptake efficiency slope (OUES): r = 0.48, p < 0.01). Indeed, the RER mag was significantly different between the subgroups stratified by Weber’s fitness class or a ventilatory efficiency class. Our study is the first to investigate recovery of the RER in a population of KTRs, which correlates well with known prognostic CPET markers of cardiorespiratory fitness, determining the RER mag as the most meaningful RER overshoot parameter. Thus, the RER recovery might be included in CPET evaluations to further improve prognostic risk stratifications in KTRs and other chronic diseases.


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