scholarly journals Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Femke C. C. van Rhijn-Brouwer ◽  
Bas W. M. van Balkom ◽  
Diana A. Papazova ◽  
Diënty H. M. Hazenbrink ◽  
Anke J. Meijer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Galactosidase Activity ◽  
Kidney Transplant Recipients ◽  
Paracrine Factors ◽  
Differentiation Capacity ◽  
Scratch Wound

Background. Cell-based therapies are being developed to meet the need for curative therapy in chronic kidney disease (CKD). Bone marrow- (BM-) derived mesenchymal stromal cells (MSCs) enhance tissue repair and induce neoangiogenesis through paracrine action of secreted proteins and extracellular vesicles (EVs). Administration of allogeneic BM MSCs is less desirable in a patient population likely to require a kidney transplant, but potency of autologous MSCs should be confirmed, given previous indications that CKD-induced dysfunction is present. While the immunomodulatory capacity of CKD BM MSCs has been established, it is unknown whether CKD affects wound healing and angiogenic potential of MSC-derived CM and EVs. Methods. MSCs were cultured from BM obtained from kidney transplant recipients (N=15) or kidney donors (N=17). Passage 3 BM MSCs and BM MSC-conditioned medium (CM) were used for experiments. EVs were isolated from CM by differential ultracentrifugation. BM MSC differentiation capacity, proliferation, and senescence-associated β-galactosidase activity was assessed. In vitro promigratory and proangiogenic capacity of BM MSC-derived CM and EVs was assessed using an in vitro scratch wound assay and Matrigel angiogenesis assay. Results. Healthy and CKD BM MSCs exhibited similar differentiation capacity, proliferation, and senescence-associated β-galactosidase activity. Scratch wound migration was not significantly different between healthy and CKD MSCs (P=0.18). Healthy and CKD BM MSC-derived CM induced similar tubule formation (P=0.21). There was also no difference in paracrine regenerative function of EVs (scratch wound: P=0.6; tubulogenesis: P=0.46). Conclusions. Our results indicate that MSCs have an intrinsic capacity to produce proangiogenic paracrine factors, including EVs, which is not affected by donor health status regarding CKD. This suggests that autologous MSC-based therapy is a viable option in CKD.

scholarly journals 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)

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.

scholarly journals Plasma Nitration of High-Density and Low-Density Lipoproteins in Chronic Kidney Disease Patients Receiving Kidney Transplants

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ahmed Bakillah ◽  
Fasika Tedla ◽  
Isabelle Ayoub ◽  
Devon John ◽  
Allen J. Norin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Sandwich Elisa ◽  
High Density ◽  
Hiv Protease ◽  
Lipid Lowering ◽  
Hiv Protease Inhibitors ◽  
Kidney Transplant Recipients

Background. Functional abnormalities of high-density lipoprotein (HDL) could contribute to cardiovascular disease in chronic kidney disease patients. We measured a validated marker of HDL dysfunction, nitrated apolipoprotein A-I, in kidney transplant recipients to test the hypothesis that a functioning kidney transplant reduces serum nitrated apoA-I concentrations.Methods. Concentrations of nitrated apoA-I and apoB were measured using indirect sandwich ELISA assays on sera collected from each transplant subject before transplantation and at 1, 3, and 12 months after transplantation. Patients were excluded if they have history of diabetes, treatment with lipid-lowering medications or HIV protease inhibitors, prednisone dose > 15 mg/day, nephrotic range proteinuria, serum creatinine > 1.5 mg/dL, or active inflammatory disease. Sera from 18 transplanted patients were analyzed. Four subjects were excluded due to insufficient data. Twelve and eight patients had creatinine < 1.5 mg/dL at 3 and 12 months after transplantation, respectively.Results. Nitrated apoA-I was significantly reduced at 12 months after transplantation (p=0.039). The decrease in apoA-I nitration was associated with significant reduction in myeloperoxidase (MPO) activity (p=0.047). In contrast to apoA-I, nitrated apoB was not affected after kidney transplantation.Conclusions. Patients with well-functioning grafts had significant reduction in nitrated apoA-I 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in chronic kidney disease.

123 Trends in Prevalence of Chronic Kidney Disease in Kidney Transplant Recipients

2011 ◽  
Vol 57 (4) ◽  
pp. B47
Author(s):  
Yihung Huang ◽  
Anca Tilea ◽  
Brenda Gillespie ◽  
Neil Powe ◽  
Laura Plantinga ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals The Protective Role of Protocol Biopsy for Allograft Kidney Maintenance in Kidney Transplantation

2021 ◽  
Author(s):  
Okjoo Lee ◽  
Kyo Won Lee ◽  
Jae Berm Park ◽  
Jung Eun Lee ◽  
Na Young Hwang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Function ◽  
Protective Role ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Protocol Biopsy ◽  
Kidney Disease Progression

Abstract Many studies have reported that protocol biopsy (PB) may help preserve kidney function in kidney transplant recipients. Early detection and treatment of subclinical rejection may reduce the incidence of chronic allograft nephropathy and graft failure. However, no consensus has been reached regarding PB effectiveness, timing, and policy. This study aimed to evaluate the protective role of routine PB performed 2 weeks and 1 year after kidney transplantation. We reviewed 854 kidney transplant recipients at the Samsung Medical Center between July 2007 and August 2017, with PBs planned at 2 weeks and 1 year after transplantation. We compared the trends in graft function, chronic kidney disease progression, new-onset chronic kidney disease, infection, and patient and graft survival between the 504 patients who underwent PB and 350 who did not undergo PB. The PB group was again divided into two groups: the single PB group (n = 207) and the double PB group (n = 297). In the PB group, the donors and recipients were significantly older and there was a greater presence of recipient diabetes mellitus and donor hypertension, donor-specific antigen, and a higher proportion of ABO-incompatible kidney transplantations. The PB group was significantly different from the no-PB group in terms of the trends in graft function (estimated glomerular filtration rate). The Kaplan-Meier curve showed that PB did not significantly improve graft survival or overall patient survival. However, in the multivariate Cox analysis, the double PB group had advantages in graft survival, chronic kidney disease progression, and new-onset chronic kidney disease. PB can play a protective role in the maintenance of kidney grafts in kidney transplant recipients.

scholarly journals Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

2021 ◽  
Vol 11 (1) ◽  
pp. 148
Author(s):  
Lukas Buchwinkler ◽  
Claire Anne Solagna ◽  
Janosch Messner ◽  
Markus Pirklbauer ◽  
Michael Rudnicki ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Antibody Response ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Factors Associated

Most trials on mRNA vaccines against SARS-CoV-2 did not include patients with chronic kidney disease (CKD), hemodialysis (HD) patients, or kidney transplant recipients (KTR). However, those patients have a higher risk for a severe course of COVID-19 disease and mortality. Available literature has demonstrated a reduced efficacy of mRNA vaccines in HD patients and KTR, while data on CKD patients is scarce. Additionally, factors associated with non-response are poorly understood and not well characterized. We assessed antibody (AB) response (n = 582, 160 CKD patients, 206 patients on HD, 216 KTR) after the administration of two doses of a mRNA-vaccine with either BNT162b2 or mRNA-1273. AB measurements were carried out after a median of 91 days after first vaccinations, demonstrating non-response in 12.5% of CKD patients, 12.1% of HD patients, and 50% of KTR. AB titers were significantly higher in CKD patients than in HD patients or KTR. Factors associated with non-response were treated with rituximab in CKD patients, the use of calcineurin inhibitors in HD patients and older age, and the use of BNT162b2, mycophenolic acid, or glucocorticoids and lower hemoglobin levels in KTR. This study contributes to the understanding of the extent and conditions that predispose for non-response in patients with impaired kidney function.

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