scholarly journals Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation

2020 ◽  
Vol 32 (5) ◽  
pp. 335-346 ◽  
Author(s):  
Haruka Higuchi ◽  
Daisuke Kamimura ◽  
Jing-Jing Jiang ◽  
Toru Atsumi ◽  
Daiki Iwami ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Therapeutic Target ◽  
Allograft Rejection ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Tubular Cells ◽  
Chronic Allograft Rejection ◽  
Antibody Mediated Rejection

Abstract Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection.

scholarly journals Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 413
Author(s):  
Theerawut Klangjareonchai ◽  
Natsuki Eguchi ◽  
Ekamol Tantisattamo ◽  
Antoney J. Ferrey ◽  
Uttam Reddy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Pharmacological Intervention ◽  
Diabetic Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Post Transplant ◽  
Glucose Management

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

scholarly journals Outcomes of Kidney Transplantation in Fabry Disease: A Meta-Analysis

Diseases ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 2
Author(s):  
Maria L. Gonzalez Suarez ◽  
Charat Thongprayoon ◽  
Panupong Hansrivijit ◽  
Juan Medaura ◽  
Pradeep Vaitla ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Fabry Disease ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Graft Failure ◽  
Current Therapy ◽  
Transplant Recipients ◽  
Lysosomal Storage ◽  
Kidney Transplant Recipients ◽  
Enzyme Replacement

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

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

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

Factors that Influence the Durability of Transplanted Kidneys in South Africa

2019 ◽  
Vol 21 (2) ◽  
Author(s):  
Hillary Ndemera ◽  
Busisiwe R. Bhengu
Keyword(s):  
South Africa ◽  
Kidney Transplant ◽  
Lifestyle Modification ◽  
P Value ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Factors Influencing ◽  
Allograft Loss ◽  
Transplanted Kidneys

Kidney transplantation is the cornerstone for renal treatment in patients with end-stage renal failure. Despite improvements in short-term outcomes of renal transplantation, kidney allograft loss remains a huge challenge. The aim of the study was to assess factors influencing the durability of transplanted kidneys among transplant recipients in South Africa. A descriptive cross-sectional study design was used. A random sampling was used to select 171 participants. Data were collected through structured face-to-face interviews developed from in-depth consideration of relevant literature. Data were coded and entered into the SPSS software, version 24. The entered data were analysed using descriptive and inferential statistics. The results revealed that the average durability of transplanted kidneys was 9.07 years among selected kidney transplant recipients in South Africa. Factors associated with the durability of transplanted kidneys included age, the sewerage system and strict immunosuppressive adherence, all with a P-value = .000, followed by the mode of transport (P-value = .001) and support system (P-value = .004). Other variables including demographics, the healthcare system, medication and lifestyle modification engagement were not associated with the durability of transplanted kidneys. Understanding the factors influencing the durability of transplanted kidneys among kidney transplant recipients in South Africa is crucial. The study revealed associated factors and gaps which may be contributory factors to kidney allograft loss. This study provides an opportunity to introduce specific interventions to nephrology professionals to promote prolonged graft durability. It is recommended that a specific intervention model be developed, which targets South African kidney recipients taking into account the significant variables in this study and the socio-economic status of the country.

scholarly journals Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
H. Tejeda-Mora ◽  
J. G. H. P. Verhoeven ◽  
W. Verschoor ◽  
K. Boer ◽  
D. A. Hesselink ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Flow Cytometric Analysis ◽  
Principal Component ◽  
Circulating Endothelial Cells ◽  
Clinical Markers ◽  
Kidney Transplant Recipients ◽  
Post Transplant

AbstractThe diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.

FC 124PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER KIDNEY TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Kidney Transplantation ◽  
Bone Turnover ◽  
Kidney Transplant ◽  
Renal Osteodystrophy ◽  
Bone Disease ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Steroid Dose ◽  
Bone Biopsies

Abstract Background and Aims Bone disease after kidney transplantation is an issue of growing concern, as prolonged graft survival and older age of recipients necessitate focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo disturbances of mineral metabolism all contribute to bone disease in kidney transplant recipients. The current pattern of renal osteodystrophy after kidney transplantation is not well characterized. This study reports histomorphometric findings of protocolled bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. Method Histomorphometric analysis of transiliac bone biopsies with prior tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical measurements included bioactive parathyroid hormone (PTH), total calcium, phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed rank tests were used to evaluate differences across categories and between groups, respectively. Stepwise multivariate linear regression was performed to identify key demographic and biochemical determinants of bone turnover (bone formation rate, BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr). Results Mean age was 57±11 years, 71% were men, and all were Caucasian. Mean eGFR was 49±16 (range 19 to 106) ml/min/1.73 m². Hyperparathyroidism (PTH &gt; 1.5xUNL) was seen in 48%, hypercalcemia (&gt;10.3 mg/dL) in 18%, hypophosphatemia (&lt;2.3 mg/dl) in 12%, and vitamin D deficiency (&lt;15 ng/mL) in 4% of patients. Categorization of bone turnover, mineralization, and volume is shown in Figure 1. Bone turnover was normal in the vast majority (71%). Patients with low turnover (26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low turnover; p=0.02). Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had higher levels of PTH (124 vs 53 ng/L, p&lt;0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p&lt;0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3 mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients with normal mineralization. Patients with low bone volume tended to be older (61 vs 56 years, p=0.07). Independent determinants of BFR were PTH (β=0.68, p&lt;0.001) and cumulative steroid dose (β = -0.22, p=0.02). Determinants of Mlt were phosphate (β=-0.48, p=0.001) and cumulative steroid dose (β=0.18, p=0.004), and determinants of BAr were age (β=-0.15, p=0.002), and BMI (β=0.33, p=0.002). Conclusion Bone turnover is normal in the majority of kidney transplant recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism. Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone mineralization in kidney transplant recipients.

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