scholarly journals Bringing Home The Bacon: Update on The State of Kidney Xenotransplantation

2018 ◽  
Vol 45 (1-3) ◽  
pp. 254-259 ◽  
Author(s):  
David K.C. Cooper ◽  
H. Iwase ◽  
L. Wang ◽  
T. Yamamoto ◽  
Qi Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Transplantation ◽  
Graft Survival ◽  
Cellular Response ◽  
Genetic Manipulation ◽  
Immunosuppressive Agents ◽  
Cross Reactivity ◽  
Genetically Engineered ◽  
Kidney Graft ◽  
Pig Kidney

Background: There is a continuing critical shortage of organs from deceased human donors for transplantation, particularly for patients awaiting kidney transplantation. Efforts are being made to resolve the donor kidney shortage by the transplantation of kidneys from genetically-engineered pigs. Summary: This review outlines the pathobiological barriers to pig organ xenotransplantation in primates, which include (i) antibody-dependent complement-mediated rejection, (ii) a T cell-mediated elicited antibody and cellular response, (iii) coagulation dysregulation between pigs and primates, and (iv) a persistent inflammatory response. As a result of increasing genetic manipulation of the pig and the introduction of novel immunosuppressive agents, pig kidney graft survival has increased from minutes to months, and even to >1 year in some cases. Aspects of the selection of the patients for a first clinical trial are discussed. Although there would appear to be some cross-reactivity between anti-human leukocyte antigen (HLA) antibodies and swine leukocyte antigens expressed in pigs, some HLA-sensitized patients will be at no disadvantage if they receive a pig kidney. Furthermore, the current limited evidence is that, even if the patient becomes sensitized to pig antigens (after a pig organ transplant), this would not be detrimental to a subsequent allotransplant. The potential risk of infection with a pig microorganism, and the function of a pig kidney in a primate are also discussed. Key Message: The recent encouraging results of pig kidney transplantation in nonhuman primates suggest the likelihood of a successful (and safe) initial clinical trial, with graft survival for months or possibly years.

scholarly journals Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas–Kidney Transplantation (SPKT)—A Landmark Analysis

2021 ◽  
Vol 10 (15) ◽  
pp. 3237
Author(s):  
Lukas Johannes Lehner ◽  
Robert Öllinger ◽  
Brigitta Globke ◽  
Marcel G. Naik ◽  
Klemens Budde ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Type I ◽  
Kidney Graft ◽  
Landmark Analysis ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

(1) Background: Simultaneous pancreas–kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Surgical and Medical Management of Tertiary Hyperparathyroidism

2010 ◽  
Vol 2 (3) ◽  
pp. 105-109 ◽  
Author(s):  
Yoshihiro Tominaga
Keyword(s):  
Clinical Trial ◽  
Kidney Transplantation ◽  
Cardiovascular Events ◽  
Graft Function ◽  
Controlled Clinical Trial ◽  
Kidney Graft ◽  
Common Complication ◽  
Surgical Indications ◽  
Tertiary Hyperparathyroidism ◽  
Persistent Hyperparathyroidism

ABSTRACT Persistent hyperparathyroidism (HPT) after successful kidney transplantation (RTx) (tertiary HPT; THPT) is a common complication in patients with RTx and may affect bone disease, deterioration of graft function and cardiovascular events. Parathyroidectomy (PTx) is the most successful treatment for resolving advanced HPT in patients with THPT. However, the surgical indications for THPT and timing of the operation are problematic because hypercalcemia can be resolved spontaneously. Subtotal and total PTx with autotransplantaion are widely accepted for THPT. The evidence to know which procedure is more appropriated could not be found. Recently the deterioration of kidney graft function after PTx for THPT has been reported and hypoparathyroidism after PTx may be avoided. Recently cinacalcet has been applied for patients with THPT and the medicine can dramaticaly control HPT and hypercalcemia. Possible risks of cinacalcet are hypocalcemia and increased calciuria and the approval for THPT remains highly controversial. A large number of prospective controlled clinical trial should be required.

scholarly journals A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Loss ◽  
Kidney Graft ◽  
Genotype Group ◽  
Transplant Survival ◽  
Increased Risk ◽  
The Impact

Introduction Improvement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exists about the effect of transforming growth factor beta 1 (TGF-beta1) on kidney transplant survival, since TGF-beta1 has profibrotic and protective effects. We therefore the impact of a recently discovered functional TGBF1 polymorphism on long term kidney graft survival. Methods We performed an observational cohort study analyzing recipient and donor DNA in 1,271-kidney transplant pairs from the University Medical Center Groningen in The Netherlands and associated a low-producing TGBF1 polymorphism (rs1800472 C>T) with 5, 10, and 15-year death-censored kidney graft survival. Results Donor genotype frequencies of s1800472 in TGBF1 differed significantly between patients with and without graft loss (P=0.042). Additionally, the low-producing TGBF1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (HR 2.13 for the T allele; 95%-CI 1.16-3.90; P=0.015). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 28.9% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGBF1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGBF1 polymorphism in the recipient and graft loss. Conclusion Kidney allografts possessing a low-producing TGBF1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGFbeta1 is beneficial, rather than harmful, for kidney transplant survival.

scholarly journals Dynamic predictions of kidney graft survival in the presence of longitudinal outliers

2020 ◽  
pp. 096228022094535
Author(s):  
Özgür Asar ◽  
Marie-Cécile Fournier ◽  
Etienne Dantan
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Random Effects ◽  
Survival Data ◽  
Kidney Graft ◽  
Validation Sample ◽  
Joint Models ◽  
Dynamic Prediction ◽  
Joint Modelling ◽  
Error Terms

In kidney transplantation, dynamic predictions of graft survival may be obtained from joint modelling of longitudinal and survival data for which a common assumption is that random-effects and error terms in the longitudinal sub-model are Gaussian. However, this assumption may be too restrictive, e.g. in the presence of outliers, and more flexible distributions would be required. In this study, we relax the Gaussian assumption by defining a robust joint modelling framework with t-distributed random-effects and error terms to obtain dynamic predictions of graft survival for kidney transplant patients. We take a Bayesian paradigm for inference and dynamic predictions and sample from the joint posterior densities. While previous research reported improved performances of robust joint models compared to the Gaussian version in terms of parameter estimation, dynamic prediction accuracy obtained from such approach has not been yet evaluated. Our results based on a training sample from the French DIVAT kidney transplantation cohort illustrate that estimates for the slope parameters in the longitudinal and survival sub-models are sensitive to the distributional assumptions. From both an internal validation sample from the DIVAT cohort and an external validation sample from the Lille (France) and Leuven (Belgium) transplantation centers, calibration and discrimination performances appeared to be better under the robust joint models compared to the Gaussian version, illustrating the need to accommodate outliers in the dynamic prediction context. Simulation results support the findings of the validation studies.

scholarly journals Simultaneous heart-kidney transplantation results in respectable long-term outcome but a high rate of early kidney graft loss in high-risk recipients – a European single center analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Oliver Beetz ◽  
Juliane Thies ◽  
Clara A. Weigle ◽  
Fabio Ius ◽  
Michael Winkler ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Kidney Transplantation ◽  
High Risk ◽  
Graft Survival ◽  
Patient Survival ◽  
Graft Loss ◽  
Organ Shortage ◽  
Kidney Graft ◽  
Long Term Outcome ◽  
Renal Graft

Abstract Background In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. Methods This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe’s largest transplant centers. Results Median follow-up was 100.33 (0.46–362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). Conclusions Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a “kidney-after-heart” program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.

scholarly journals POS-728 Infectious Complications Following Kidney Transplantation and Their Influence On Kidney Graft Survival

2021 ◽  
Vol 6 (4) ◽  
pp. S318
Author(s):  
C. IMEN ◽  
M. Hamouda ◽  
M. Ben Salem ◽  
M. Ben Salah ◽  
I. Handous ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Infectious Complications ◽  
Kidney Graft

scholarly journals Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hengcheng Zhang ◽  
Zijie Wang ◽  
Jiayi Zhang ◽  
Zeping Gui ◽  
Zhijian Han ◽  
...  
Keyword(s):  
Immune Response ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Serum Creatinine ◽  
Graft Survival ◽  
Rat Kidney ◽  
Combined Therapy ◽  
Graft Function ◽  
Kidney Graft ◽  
Term Survival

BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and MethodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

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