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

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.

Download Full-text

Oral and Salivary Changes in Patients with Chronic Kidney Disease

BANTAO Journal ◽

10.2478/bj-2014-0019 ◽

2014 ◽

Vol 12 (2) ◽

pp. 97-102 ◽

Cited By ~ 2

Author(s):

Ana Belazelkovska ◽

Mirjana Popovska ◽

Goce Spasovski ◽

Jelka Masin-Spasovska ◽

Svetlana Cekovska ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Transplant ◽

Negative Correlation ◽

Salivary Flow ◽

Clinical Findings ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Salivary Ph

Abstract Introduction. Kidney disease is associated with many abnormalities in the oral health status as well as with alterations in salivary flow and composition. The aim of this study was to evaluate and to correlate oral clinical findings, salivary flow (SF) and salivary pH values in patients with chronic kidney disease (CKD) not yet on hemodyalisis treatment, those undergoing hemodialysis and in kidney transplant recipients. Methods. In a cross-sectional study 90 patients were included. The cohort was composed of three groups: 30 patients with CKD (serum creatinine values under 120 μmol/L-group 1), 30 patients with CKD on hemodialysis (group 2) and 30 kidney transplanted patients (group 3). The control group consisted of 20 healthy individuals. Oral symptoms, signs and lesions: salivary volume, salivary pH and SF of stimulated and unstimulated saliva were evaluated. Results. Among patients with CKD without dialysis treatment inverse relationship was found between uremic fetor, unpleasant taste and unstimulated SF and also between xerostomia and stimulated SF. Negative correlation between thirst and unstimulated salivary flow was found in both groups, patients with CKD on dialysis and kidney transplant group. Furthermore, in kidney-transplant patients a negative correlation was found between petechiae and SF, while in group of patients with CKD on hemodialysis the same negative correlation was registered between uremic fetor and stimulated SF. Conclusions. Salivary flow was significantly lower in hemodialysis patients, while the highest was in the kidney-transplant recipients accompanied with improvement in the other oral clinical findings observed in our study.

Download Full-text

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.

Download Full-text

Long-term Glomerular Filtration Rate and Kidney Disease: Improving Global Outcomes Stage Stability After Conversion to Once-Daily Tacrolimus in Kidney Transplant Recipients

Transplantation Proceedings ◽

10.1016/j.transproceed.2018.04.076 ◽

2019 ◽

Vol 51 (1) ◽

pp. 147-152 ◽

Cited By ~ 2

Author(s):

F. Tinti ◽

I. Umbro ◽

L. Poli ◽

A. Cappoli ◽

M. Garofalo ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Kidney Transplant ◽

Filtration Rate ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Once Daily

Download Full-text

The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients

AJP Renal Physiology ◽

10.1152/ajprenal.00163.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. F9-F19 ◽

Cited By ~ 1

Author(s):

Alice Doreille ◽

Mélanie Dieudé ◽

Heloise Cardinal

Keyword(s):

Kidney Disease ◽

Kidney Transplant ◽

Interstitial Fibrosis ◽

Ischemia Reperfusion ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hla Antibodies ◽

Microvascular Injury ◽

Antibody Mediated Rejection ◽

Peritubular Capillaries

Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of profibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts, as well as modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the two main etiologies of microvascular damage in kidney transplant recipients. The presence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies, histological findings, such as diffuse C4d staining in peritubular capillaries, and the extent and severity of peritubular capillaritis, are commonly used clinically to provide both diagnostic and prognostic information. Complement-dependent assays, circulating non-HLA antibodies, or evaluation of the microvasculature with novel imaging techniques are the subject of ongoing studies.

Download Full-text

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.

Download Full-text