scholarly journals Detection of Antibody-Mediated Rejection in Kidney Transplantation and the Management of Highly Sensitised Kidney Transplant Recipients

10.5772/54735 ◽  
2013 ◽  
Author(s):  
Shyam Dheda ◽  
Siew Chong ◽  
Rebecca Lucy ◽  
Germaine Wong ◽  
Wai Hon
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection

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.

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 > 1.5xUNL) was seen in 48%, hypercalcemia (>10.3 mg/dL) in 18%, hypophosphatemia (<2.3 mg/dl) in 12%, and vitamin D deficiency (<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<0.001), and lower levels of phosphate (2.68 vs 3.18 mg/dL, p<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<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.

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

2019 ◽  
Vol 316 (1) ◽  
pp. F9-F19 ◽  
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.

scholarly journals 2658. Meningitis in Kidney Transplant Recipients: TransMéninges, a French Multicentric Retrospective Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Specific Population ◽  
Gram Negative ◽  
Wide Range

Abstract Background The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population. Methods We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected. Results Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%). The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively. Conclusion Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population. Disclosures All authors: No reported disclosures.

scholarly journals Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and Medicare

2021 ◽  
pp. CJN.10020620
Author(s):  
Winn Cashion ◽  
Walid F. Gellad ◽  
Florentina E. Sileanu ◽  
Maria K. Mor ◽  
Michael J. Fine ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Confidence Interval ◽  
Kidney Transplant ◽  
Veterans Health Administration ◽  
Veterans Health ◽  
Health Administration ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Administration Hospital

Background and objectivesMany kidney transplant recipients enrolled in the Veterans Health Administration are also enrolled in Medicare and eligible to receive both Veterans Health Administration and private sector care. Where these patients receive transplant care and its association with mortality are unknown.Design, setting, participants, & measurementsWe conducted a retrospective cohort study of veterans who underwent kidney transplantation between 2008 and 2016 and were dually enrolled in Veterans Health Administration and Medicare at the time of surgery. We categorized patients on the basis of the source of transplant-related care (i.e., outpatient transplant visits, immunosuppressive medication prescriptions, calcineurin inhibitor measurements) delivered during the first year after transplantation defined as Veterans Health Administration only, Medicare only (i.e., outside Veterans Health Administration using Medicare), or dual care (mixed use of Veterans Health Administration and Medicare). Using multivariable Cox regression, we examined the independent association of post-transplant care source with mortality at 5 years after kidney transplantation.ResultsAmong 6206 dually enrolled veterans, 975 (16%) underwent transplantation at a Veterans Health Administration hospital and 5231 (84%) at a non–Veterans Health Administration hospital using Medicare. Post-transplant care was received by 752 patients (12%) through Veterans Health Administration only, 2092 (34%) through Medicare only, and 3362 (54%) through dual care. Compared with patients who were Veterans Health Administration only, 5-year mortality was significantly higher among patients who were Medicare only (adjusted hazard ratio, 2.2; 95% confidence interval, 1.5 to 3.1) and patients who were dual care (adjusted hazard ratio, 1.5; 95% confidence interval, 1.1 to 2.1).ConclusionsMost dually enrolled veterans underwent transplantation at a non–Veterans Health Administration transplant center using Medicare, yet many relied on Veterans Health Administration for some or all of their post-transplant care. Veterans who received Veterans Health Administration–only post-transplant care had the lowest 5-year mortality.

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