Abnormal Nailfold Capillaries in Patients after Hand Transplantation

Background: The development of graft vasculopathy may play a role in the long-term deterioration of hand grafts. The aim of study was to examine the patterns of the nailfold capillaries in hand transplant recipients. Methods: the study was performed on six patients who received hand transplantation. To normalize for the effect of immunosuppression an age- and sex-matched group of 12 patients with active kidney transplant was selected. As an additional control group, 12 healthy volunteers were recruited. Nailfold videocapillaroscopy was performed in all participants. Additionally, serum concentrations of vascular endothelial growth factor (VEGF) were measured. Results: Videocapillaroscopic examination of the hand allografts revealed significant abnormalities: including capillary disorganization and microhaemorrhages. The number of capillaries was reduced, the vessels were enlarged and branched. Surprisingly, similar, albeit slightly less pronounced, changes were seen in the nailfolds of healthy hands of the limb transplant recipients. In kidney transplant recipients the capillaroscopic pattern was general normal and comparable to healthy individuals. Moreover, serum concentrations of VEGF in all participants correlated with average capillary diameter in capillaroscopy. Conclusions: in hand transplant recipients advanced microvascular abnormalities are found in nailfold capillaroscopic pattern in both transplanted and own extremities connected with elevated levels of VEGF.

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Alendronate as an Effective Treatment for Bone Loss and Vascular Calcification in Kidney Transplant Recipients

Journal of Transplantation ◽

10.1155/2014/269613 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Masanori Okamoto ◽

Shintaro Yamanaka ◽

Wataru Yoshimoto ◽

Takashi Shigematsu

Keyword(s):

Bone Loss ◽

Effective Treatment ◽

Kidney Transplant ◽

Vascular Calcification ◽

Secondary Osteoporosis ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Mineral Density ◽

Group A

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.

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A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

Frontiers in Medicine ◽

10.3389/fmed.2020.634260 ◽

2021 ◽

Vol 7 ◽

Author(s):

Rainer Oberbauer ◽

Matthias Edinger ◽

Gabriela Berlakovich ◽

Peter Kalhs ◽

Nina Worel ◽

...

Keyword(s):

Bone Marrow ◽

Kidney Transplant ◽

Graft Function ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Donor Bone Marrow ◽

Living Donor Kidney Transplant

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 <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.

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THE STATE OF THE CARDIOVASCULAR SYSTEM IN CHILDREN OF KIDNEY TRANSPLANT RECIPIENTS

Medical Journal ◽

10.51922/1818-426x.2021.3.65 ◽

2021 ◽

pp. 65-70

Author(s):

I.A. Kozyro ◽

◽

А.V. Sukalo ◽

О.A. Kondratenko ◽

Keyword(s):

Kidney Disease ◽

Cardiovascular System ◽

Kidney Transplant ◽

Clinical Laboratory ◽

Pediatric Nephrology ◽

Control Group ◽

Healthy Children ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Activation Markers

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.

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Impact of Acute Rejection on Kidney Allograft Outcomes in Recipients on Rapid Steroid Withdrawal

Journal of Transplantation ◽

10.1155/2011/583981 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

R. L. Heilman ◽

S. Nijim ◽

H. A. Chakkera ◽

Y. Devarapalli ◽

A. A. Moss ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Control Group ◽

Steroid Withdrawal ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Protocol Biopsy ◽

And Control ◽

The Impact

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.

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Comparison of clinical outcome of induction immunosuppressive therapy with thymoglobulin and standard therapy in kidney transplantation; a randomized double-blind clinical trial

Journal of Nephropathology ◽

10.15171/jnp.2020.08 ◽

2019 ◽

Vol 9 (1) ◽

pp. e08-e08

Author(s):

Heshmatollah Shahbazian ◽

Ali Ghorbani ◽

Fatemeh Hayati ◽

Seyed Seifollah Beladi Mousavi ◽

Leila Sabetnia ◽

...

Keyword(s):

Clinical Trial ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Induction Therapy ◽

Allograft Rejection ◽

Control Group ◽

Case Group ◽

Transplant Recipients ◽

Acute Allograft Rejection ◽

Kidney Transplant Recipients

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

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Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens

Journal of the American Society of Nephrology ◽

10.1681/asn.2018080868 ◽

2019 ◽

Vol 30 (4) ◽

pp. 692-709 ◽

Cited By ~ 24

Author(s):

Marianne Delville ◽

Baptiste Lamarthée ◽

Sylvain Pagie ◽

Sarah B. See ◽

Marion Rabant ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Kidney Transplant ◽

Hla Antigens ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serum Samples ◽

Hla Antibodies

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.

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Physical Activity Adherence Rates in Older Kidney Transplant Recipients: A Pilot Randomized Controlled Trial

Innovation in Aging ◽

10.1093/geroni/igaa057.3263 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 884-884

Author(s):

Tara O’Brien ◽

Karen Rose ◽

Alai Tan

Keyword(s):

Kidney Transplant ◽

Controlled Trial ◽

Intervention Group ◽

Attention Control ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Activity Tracker ◽

Walking Activity ◽

Attention Control Group

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.

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Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant

Scientific Reports ◽

10.1038/s41598-021-84400-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mohamed Jahromi ◽

Torki Al-Otaibi ◽

Osama Ashry Gheith ◽

Nashwa Farouk Othman ◽

Tarek Mahmoud ◽

...

Keyword(s):

Kidney Transplant ◽

Transforming Growth Factor ◽

Interferon Γ ◽

Cytokine Profile ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Onset Diabetes ◽

Metabolic Complication ◽

New Onset

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.

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39. Anti-Spike Monoclonal Antibody Therapy for Kidney Transplant Recipients with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.039 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S28-S29

Author(s):

Anna Hardesty ◽

Elizabeth Klein ◽

Kendra Vieira ◽

Dimitrios Farmakiotis

Keyword(s):

Kidney Transplant ◽

Cox Regression ◽

Organ Transplant ◽

Passive Immunization ◽

Time Dependent ◽

Therapeutic Modality ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Research Support

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< 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)

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INCREASING PHYSICAL ACTIVITY POST-KIDNEY TRANSPLANT: A PILOT RANDOMIZED CONTROLLED TRIAL

Innovation in Aging ◽

10.1093/geroni/igz038.1919 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S521-S521

Author(s):

Tara O’Brien ◽

Cynthia Russell ◽

Donna Hathaway

Keyword(s):

Physical Activity ◽

Kidney Transplant ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Randomized Controlled ◽

Activity Trackers ◽

Pilot Randomized Controlled Trial

Abstract Older kidney transplant recipients are at risk for graft failure and death due to lack of physical activity. Physical activity after transplant is the most modifiable non-pharmacological factor for improving physical function. One personal system intervention called, SystemCHANGE™ in combination with activity trackers, holds promise for increasing physical activity among this population. The purpose of this pilot randomized controlled trial was to evaluate the efficacy of SystemCHANGE™ on increasing average daily steps in older (age 60 and over) kidney transplant recipients from baseline to 6 months. The intervention group met monthly to implement a successful personal system solution based on their daily routines and step-data collected from the activity tracker. The control group received monthly educational information on healthy living with a transplant. Participants were randomized 1:1 to the intervention or control group. The sample consisted of 31 participants (n = 15 intervention, and n = 16 control). No significant differences were found at baseline among the groups for demographics, self-efficacy and health outcomes (blood pressure, weight, waist circumference, 6 minute Walk Test). However, the intervention group had greater increase in the average daily steps from baseline to 6 months (mean ± SD: 1511 ± 2320) as compared to the control group (181 ± 2419). The between-group difference was of medium effect size (d = .56).The data suggests SystemCHANGE™ in combination with activity trackers may be feasible for older kidney transplant recipients to enhance daily steps.

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