scholarly journals The Pre-Transplant Drop in Panel-Reactive Antibodies Titer Evaluated Using Complement-Dependent Cytotoxicity (PRA-CDC) and the Risk of Early Acute Rejection in Sensitized Kidney Transplant Recipients

Medicina ◽  
2018 ◽  
Vol 54 (5) ◽  
pp. 66
Author(s):  
Aureliusz Kolonko ◽  
Beata Bzoma ◽  
Piotr Giza ◽  
Beata Styrc ◽  
Michał Sobolewski ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Multiple Logistic Regression Analysis ◽  
Graft Function ◽  
Study Groups ◽  
Cytotoxicity Test ◽  
Kidney Transplant Recipients ◽  
Complement Dependent Cytotoxicity ◽  
Transplant Candidates ◽  
The Relationship

Background: The panel-reactive antibodies that use the complement-dependent cytotoxicity test (PRA-CDC) are still a standard method for monitoring the degree of immunization in kidney transplant candidates on active waiting lists in some countries, including Poland. The aim of this study was to analyze the relationship between the maximum and the last pre-transplant PRA titer on the percentage of positive cross-matches and rate of early acute rejection episodes. Material and methods: The retrospective analysis included 528 patients from two transplant centers. All patients were divided into three groups, depending on their peak and last pre-transplant PRA titers. There were 437 (82.8%) patients with peak PRA <20% (non-sensitized group, non-ST) and 91 (17.2%) patients with peak PRA >20%. Among the latter group, 38 had maintained PRA level >20% at the time of transplantation (sensitized patients, ST), whereas 53 had pre-transplant PRA ≤20% (previously sensitized patients, prev-ST). Results: The percentages of positive crossmatches were 76.9% in ST and 53.7% in prev-ST groups versus 18.4 in non-ST group (both p < 0.001). The acute rejection rates were 18.9, 17.6 and 6.8%, respectively (p < 0.001 for ST or prev-ST versus non-ST). The pre-transplant PRA titer drop did not decrease the risk of early acute rejection [OR = 1.09 (95% CI: 0.31–3.85)] in a multiple logistic regression analysis. The occurrences of primary graft non-function and delayed graft function were similar in all study groups. Conclusions: Previously immunized kidney transplant candidates even with substantial decrease in pre-transplant PRA-CDC levels are still at high immunological risk when compared with non-immunized patients, and they should receive lymphocyte-depleting induction therapy.

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Clara Pardinhas ◽  
Rita Leal ◽  
Francisco Caramelo ◽  
Teofilo Yan ◽  
Carolina Figueiredo ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Graft Function ◽  
Delayed Graft Function ◽  
First Year ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p&lt;0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p&lt;0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p&lt;0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p&lt;0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p&lt;0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients

2002 ◽  
Vol 87 (02) ◽  
pp. 194-198 ◽  
Author(s):  
Torsten Slowinski ◽  
Ingeborg Hauser ◽  
Birgit Vetter ◽  
Lutz Fritsche ◽  
Daniela Bachert ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Function ◽  
Factor V Leiden ◽  
Factor V ◽  
Transplant Recipients ◽  
Graft Dysfunction ◽  
Kidney Transplant Recipients ◽  
Factor V Leiden Mutation

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.

scholarly journals A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection

2019 ◽  
Vol 30 (8) ◽  
pp. 1481-1494 ◽  
Author(s):  
Weijia Zhang ◽  
Zhengzi Yi ◽  
Karen L. Keung ◽  
Huimin Shang ◽  
Chengguo Wei ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Peripheral Blood ◽  
Expression Profiles ◽  
Graft Function ◽  
Gene Signature ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Targeted Expression ◽  
Independent Cohort

BackgroundIn kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies.MethodsWe examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort.ResultsStudy participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss.ConclusionsOur targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.

scholarly journals Long-Term Outcomes after Acute Rejection in Kidney Transplant Recipients: An ANZDATA Analysis

2019 ◽  
Vol 30 (9) ◽  
pp. 1697-1707 ◽  
Author(s):  
Philip A. Clayton ◽  
Stephen P. McDonald ◽  
Graeme R. Russ ◽  
Steven J. Chadban
Keyword(s):  
Cardiovascular Disease ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Graft Function ◽  
High Rate ◽  
Sensitivity Analyses ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

BackgroundDeclining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients.MethodsTo understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics.ResultsAR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results.ConclusionsAR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.

scholarly journals THE RELATIONSHIP BETWEEN URIC ACID LEVELS AND GRAFT FUNCTION IN RENAL TRANSPLANT PATIENTS WHO DISCONTINUED STEROID THERAPY

2021 ◽  
Author(s):  
Hulya Colak ◽  
Sibel Ersan ◽  
Mehmet Tanrisev ◽  
Banu Yilmaz ◽  
Orcun Ural ◽  
...  
Keyword(s):  
Uric Acid ◽  
Acute Rejection ◽  
Graft Survival ◽  
Significant Relationship ◽  
Laboratory Data ◽  
Graft Function ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Before And After ◽  
The Relationship

Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients from among 678 RT patients transplanted from living donors between 1999-2020 were included. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications (d.a. use of immunosuppressive, antihypertensive), laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure [BP], body mass index, late acute rejection (LAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between LAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. In conclusion, per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

Comparison of FOXP3 and Interleukin 35 Expression Profiles in Kidney Transplant Recipients With Excellent Long-Term Graft Function and Acute Rejection

2021 ◽  
Vol 19 (11) ◽  
pp. 1142-1148
Author(s):  
Mahsa Torabijahromi ◽  
Jamshid Roozbeh ◽  
GhanbarAli Raeesjalali ◽  
Maryam Shafiee ◽  
Nakisa Rasaei ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Expression Profiles ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients

2021 ◽  
Vol 10 (9) ◽  
pp. 1934
Author(s):  
Domingo Hernández ◽  
Teresa Vázquez ◽  
Juana Alonso-Titos ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Graft Function ◽  
Human Leukocyte ◽  
Subclinical Inflammation ◽  
Kidney Transplant Recipients ◽  
Protocol Biopsy ◽  
Recipient Age ◽  
The Impact ◽  
Hla Mismatches

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

scholarly journals Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients

2021 ◽  
Vol 10 (13) ◽  
pp. 2854
Author(s):  
Fernanda Rodrigues ◽  
J. Swarte ◽  
Rianne Douwes ◽  
Tim Knobbe ◽  
Camilo Sotomayor ◽  
...  
Keyword(s):  
Small Bowel ◽  
Kidney Transplant ◽  
Surrogate Marker ◽  
Bacterial Overgrowth ◽  
Dietary Factors ◽  
Multivariable Logistic Regression Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
The Relationship

Background: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H2 and diarrhea in KTR, and explored potential clinical and dietary determinants. Methods: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H2 and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. Results: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m2) had a median exhaled H2 of 11 (5.0–25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H2 ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H2 was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07–2.14 per log2 ppm, p = 0.02). Polysaccharide intake was independently associated with higher H2 (std. β 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. β 0.16 p = 0.05). Conclusion: Higher exhaled H2 is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation.

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