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

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 Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

2020 ◽  
Vol 9 (6) ◽  
pp. 1911 ◽  
Author(s):  
Camilo G. Sotomayor ◽  
Charlotte A. te Velde-Keyzer ◽  
Martin H. de Borst ◽  
Gerjan J. Navis ◽  
Stephan J.L. Bakker
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Vascular Calcification ◽  
Graft Failure ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

Dynamic prediction models for graft failure in paediatric kidney transplantation

2020 ◽  
Author(s):  
Rémi Kaboré ◽  
Loïc Ferrer ◽  
Cécile Couchoud ◽  
Julien Hogan ◽  
Pierre Cochat ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Model ◽  
Kidney Graft ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Joint Models ◽  
Dynamic Prediction ◽  
Post Transplant

Abstract Background Several models have been proposed to predict kidney graft failure in adult recipients but none in younger recipients. Our objective was to propose a dynamic prediction model for graft failure in young kidney transplant recipients. Methods We included 793 kidney transplant recipients waitlisted before the age of 18 years who received a first kidney transplantation before the age of 21 years in France in 2002–13 and survived &gt;90 days with a functioning graft. We used a Cox model including baseline predictors only (sex, age at transplant, primary kidney disease, dialysis duration, donor type and age, human leucocyte antigen matching, cytomegalovirus serostatus, cold ischaemia time and delayed graft function) and two joint models also accounting for post-transplant estimated glomerular filtration rate (eGFR) trajectory. Predictive performances were evaluated using a cross-validated area under the curve (AUC) and R2 curves. Results When predicting the risk of graft failure from any time within the first 7 years after paediatric kidney transplantation, the predictions for the following 3 or 5 years were accurate and much better with the joint models than with the Cox model (AUC ranged from 0.83 to 0.91 for the joint models versus 0.56 to 0.64 for the Cox model). Conclusion Accounting for post-transplant eGFR trajectory strongly increased the accuracy of graft failure prediction in young kidney transplant recipients.

scholarly journals Long-Term Outcomes among Kidney Transplant Recipients and after Graft Failure: A Single-Center Cohort Study in Brazil

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Paula Rebello Bicalho ◽  
Lúcio R. Requião-Moura ◽  
Érika Ferraz Arruda ◽  
Rogerio Chinen ◽  
Luciana Mello ◽  
...  
Keyword(s):  
Cohort Study ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Cause Of Death ◽  
Chronic Rejection ◽  
Graft Failure ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. The results of kidney transplantation are impacted by the categories of events responsible for patient death and graft failure. The objective of this study was to evaluate the causes of death and graft failure and outcomes after graft failure among kidney transplant recipients. Methodology. A retrospective cohort study was conducted with 944 patients who underwent kidney transplantation. Outcomes were categorized in a managed and hierarchical manner. Results. The crude mortality rate was 10.8% (n=102): in 35.3% cause of death was infection, in 30.4% cardiovascular disease, and in 15.7% neoplasia and in 6.8%, it was not possible to determine the cause of death. The rate of graft loss was 10.6%. The main causes of graft failure were chronic rejection (40%), acute rejection (18.3%), thrombosis (17.3%), and recurrence of primary disease (16.5%). Failures due to an acute rejection occurred earlier than those due to chronic rejection and recurrence (p<0.0001). As late causes of graft loss, death with the functioning kidney occurred earlier than recurrence and chronic rejection (p=0.008). The outcomes after graft failure were retransplantation in 26.1% and death in 21.4%, at a mean of 25.5 and 21.4 months, respectively. Conclusion. It was possible to identify more than 90% of the events responsible for the deaths of transplanted patients, predominantly infectious and cardiovascular diseases. Among the causes of graft failure, chronic and acute rejections and recurrence were the main causes of graft failure which were followed more frequently by retransplantation than by death on dialysis.

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 Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Cox Regression ◽  
Carbonyl Stress ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
High Concentrations ◽  
Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

scholarly journals Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Event Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time To Event ◽  
Transplant Patients ◽  
Kaplan Meier ◽  
Lung Malignancy ◽  
Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

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.

Net Endogenous Acid Excretion and Kidney Allograft Outcomes

2021 ◽  
pp. CJN.00780121
Author(s):  
Stanley Yeung ◽  
Antonio Gomes-Neto ◽  
Maryse Osté ◽  
Else van den Berg ◽  
Jenny Kootstra-Ros ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Plasma Creatinine ◽  
Transplant Recipients ◽  
Acid Excretion ◽  
Kidney Transplant Recipients ◽  
Dietary Acid Load ◽  
Dietary Acid ◽  
Acid Load ◽  
Net Acid Excretion

Background and objectives: High dietary acid load may accelerate kidney function decline. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients and whether venous bicarbonate (HCO3−) mediates this association. Design, setting, participants and measurements: We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production (NEAP) was estimated using food frequency questionnaires (FFQ) and, alternatively, 24-hour urinary urea and potassium excretion to estimate NEAPUrine. We defined composite kidney endpoint as doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with kidney endpoint. We evaluated potential mediation effects of venous HCO3− , urinary HCO3− excretion, urinary ammonium (NH4+) excretion, titratable acid excretion, and net acid excretion on the association between NEAP and kidney endpoint. Results: Median NEAPFFQ and NEAPUrine were 40 (Interquartile range [IQR] 35-45) and 54 (IQR 44-66) mEq/day, respectively. During a median follow-up time of 5.3 (IQR 4.1-6.0) years, 121 (19%) participants reached kidney endpoint. After multivariable adjustment, NEAPFFQ and NEAPUrine (per SD higher) were independently associated with higher risk for kidney endpoint (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.12-1.57, P=0.001 and HR 95%CI, 1.44 [1.24-1.69], P<0.001 resp.). Baseline venous HCO3− mediated 20% of the association between NEAPFFQ and kidney endpoint. Baseline venous HCO3−, urinary NH4+ excretion and net acid excretion mediated 25%, -14% and -18% resp. of the association between NEAPUrine and kidney endpoint. Conclusion: Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous HCO3−, urinary NH4+ and net acid excretion.

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