bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1606TIM-3/GAL-9 AS PREDICTORS OF COMPOSITE OUTCOMES AFTER KIDNEY TRANSPLANTATION: A COHORT STUDY
Authors: Yan Lin , Bai Yangjuan , Li Yamei , Li Yi , Wang Xianding , Shi Yunying , Wang Lanlan 
Published: June 2020

Abstract

Background and Aims
T cell immunoglobulin and mucin domain (Tim-3) and its ligand, galectin-9 (Gal-9), play an important role in immune regulation. Serum soluble Tim-3 (sTim-3) and Gal-9 (sGal-9) were observed to be correlated with renal function after kidney transplantation in our previous study, but whether these two could predict the adverse outcomes after transplantation is unknown.

Method
91 recipients receiving kidney transplantation were enrolled in this cohort study. 20 of all recipients suffered composite outcomes after kidney transplantation within two years. 71 recipients had stable renal function during this period. The expressions of sTim-3 and sGal-9 before and one month after transplantation were measured by ELISA.

Results
The level of sTim-3 before transplantation was significantly higher in recipients with stable renal function than composite outcomes (Median: range, 2275: 840-4236 pg/ml vs 1589: 353-3094 pg/ml, P=0.002, shown in Figure 1). The level of sGal-9 after transplantation was significantly lower in stable group than composite outcome group (Median: range, 4869: 1418-13080 pg/ml vs 6852: 4128-10760 pg/ml, P=0.003, shown in Figure 1). Area under curve (AUC) of sTim-3 before transplantation was 0.737 (P=0.002, shown in Figure 2) through the analysis of receiver operating characteristic curve (ROC curve). AUC of sGal-9 after transplantation was 0.751 (P=0.003, shown in Figure 2). After survival analysis, the percentage of recipients free from composite outcomes was significantly lower in patients with low level of sTim-3 than high sTim3 (P&lt;0.0001, shown in Figure 3), so was in patients with high sGal-9 than low sGal-9 (P=0.0004, shown in Figure 3).

Conclusion
Serum sTim-3 and sGal-9 could predict the adverse outcomes within two years after kidney transplantation.
P1609HLA EPITOPE MATCHING IN KIDNEY TRANSPLANTATION AND PRACTICAL APPLICATION
Authors: Rambabova Bushljetikj Irena , Spasovski Goce , Dimitrovski Koco 
Published: June 2020

Abstract

Background and Aims
HLA compatibility between donor and recipient is an important factor that influences graft outcomes after kidney transplantation. Increasing number of class I (HLA-AB) and class II (HLA-DR) mismatches are associated with an increased risk of acute rejection and graft loss. Recent developments have increased our understanding of the structural basis of HLA antigenicity and may allow accurate evaluation of the immunogenic potential of broad antigen HLA mismatches.
The immunogenicity of HLA antigens is determined by continuous and discontinuous short sequences of amino acids that form the antibody-accessible regions within each HLA allele known as epitopes. HLAMatchmaker, a computer algorithm that calculates the number of epitope mismatches between donors and recipients by considering each HLA allele as a combination of distinct epitopes known as triplets (continuous amino acid sequences) or eplets (closely located contiguous amino acid sequences).

Method
A total number of 55 adult patients with LDKT were included in the study. The inclusion criteria: first transplantation of one organ - kidney, use of living donor related or unrelated, emotionally related (spouses) donor. Data concerning donor - sex, age of the donor, type of donation (related or unrelated donor), and data concerning the recipients: sex, age, hemodialysis vintage, underlying disease, type of immunosuppressive therapy, were analyzed. The number of eplet HLA mismatches for each recipient and donor pair at HLA class I (HLA-AB) and class II (HLA-DR) loci was calculated using HLAMatchmaker (Version 1.2)

Results
In our study we have included 55 patients. 44 patients have related and 11 have unrelated donors. From the group of related donors 31 patients were haploidentycal, with 3 HLA miss match, in the group of unrelated donors-recipients 5 of them have 6 miss match. According HLA MM triplets Class 1 + 2 &lt; or&gt; 20 we have devided 2 groups, but no statistical difference on the graft function was observed in the follow up period.
Three acute rejections were reported in the group of patients with HLA miss match triplets Class 1 + 2&gt; 20.

Conclusion
An increasing number of epitope HLA mismatches is associated with an increased risk of acute rejection. Triplet HLA mismatches may provide better risk stratification for acute rejection and graft survival among those who are otherwise classified as low immunological risk at the broad antigen level.
P1612CAN THE URINARY NITRATE TO CREATININE RATIO BE USED AS A MARKER FOR KIDNEY TRANSPLANT REJECTION?
Authors: Riddell Amy , Kirkwood John , Smallwood Miranda , Winyard Paul , Knight Bridget , Steer Karen , Puddicombe Lynette , Romanczuk Lidia , Shore Angela , Gilchrist Mark 
Published: June 2020

Abstract

Background and Aims
Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection, either at an earlier time point, or to inform earlier decision making to biopsy, could be transformative. Urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. Historically, assays for measurement of inorganic nitrate in biological fluids have been too time consuming to be useful in a clinical setting. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice.

Method
We conducted a prospective observational study, recruiting renal transplant participants over an 18 month period. We made no alterations to the patients’ clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance including routine attendances, unscheduled attendances for acute clinical indications, and on the day of attendance for biopsy, for those who underwent biopsy. We measured the urinary nitrate to creatinine ratio (uNCR) between patient groups including routine attendances, biopsy proven rejection and biopsy proven “no rejection”. uNCR was examined over time for those with transplant rejection. Groups were compared using a 2 tail t-test of unequal variance, for statistical significance.

Results
A total of 2656 samples were collected. uNCR during biopsy proven rejection, median 49 µmol/mmol, IQR 23-61, was not significantly different from that of routine samples, median 55 µmol/mmol, IQR 37-82 (p=0.56), or biopsy proven “no rejection”, median 39 µmol/mmol, IQR 21-89, (P=0.77). Overall uNCR was highly variable; median 52 µmol/mmol, IQR 31-81, with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection.

Conclusion
The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.
P1614ANTIAPOPTOTIC EFFECS OF CATECHIN AND GEMIGLIPTIN ON TACROLIMUS-INDUCED RENAL INJURY IN MICE
Authors: Kim Hyun Lee , SHIN BYUNG CHUL , CHUNG JONG HOON 
Published: June 2020

Abstract

Background and Aims
The aim of this study was to investigate the anti-apoptotic effects of catechin (CA) and dipeptidyl peptidase IV (DPP IV) inhibitor gemigliptin on tacrolimus (TAC)-induced nephropathy in mice.

Method
The mice (n=30) were divided into 5 groups (n=6/group); control group were intraperitoneally (IP) injected 0.9% saline, TAC group were IP injected TAC 2.5 mg/kg, DPP IV inhibitor group were given in addition gemigliptin 20 mg/kg (G20) by oral gavage. TAC-CA group were given TAC by IP injection and CA 100 mg/kg by subcutaneous injection. TAC-TA-G20 group were given with same dosages.

Results
The 24 hours urine protein amounts were significantly increased in TAC group (46.1±10.9mg/day) compared to control group (11.3 ±4.4mg/day) and significantly decreased in TAC-CA-G20group (13.1 ±5.9mg/day, P &lt;0.01) compared to TAC group. Serum creatinine levels were significantly increased in TAC group (1.03 ± 0.26 mg/dL) compared to control group (0.17 ± 0.02 mg/day) and significantly decreased in TAC-CA-G20group (0.23 ± 0.05 mg/day, p=0.008) compared to TAC group. In Western blot analysis of apoptotic protein, the BCL-2 protein expression by TAC was significantly suppressed by CA and gemigliptin injection but, the p53 protein expression by TAC was significantly resolved by CA and DPP IV inhibitor. There are proximal tubular edema and mild interstitial inflammation in the kidney of mice after TAC injection but no significant pathologic changes by CA injection and DPP IV inhibitor injected group.

Conclusion
Catechin and DPP IV inhibitor gemigliptin treatment has beneficial antiapoptotic effects on acute TAC-induced renal injury in mice.
P1624TORQUE TENO VIRUS FOR RISK STRATIFICATION OF GRAFT REJECTION AND INFECTION IN KIDNEY TRANSPLANT RECIPIENTS - A PROSPECTIVE OBSERVATIONAL TRIAL
Authors: Doberer Konstantin , Böhmig Georg A , Puchhammer-Stöckl Elisabeth , Bond Gregor 
Published: June 2020

Abstract

Background and Aims
The non-pathogenic and ubiquitous Torque Teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. This prospective observational trial was designed to assess the potential of TTV load for risk prediction of both, infection and rejection in the first year after transplantation. The objective of this trial was to provide TTV cut-off level to define an optimal TTV range as a basis for a randomised controlled interventional trial to test the efficacy of TTV-guided immunosuppression.

Method
Within this trial (DRKS00012335) all 386 adult (≥18 years of age) consecutive kidney graft recipients transplanted at the Medical University Vienna, Austria, between January 1st 2016 and June 31st 2018. were subjected to longitudinal per protocol TTV monitoring. In total 3265 TTV measurements were taken and 71 biopsy proven graft rejections (defined by BANFF classification) and 472 clinically relevant infections were documented in the first year post-transplant. After reaching steady state at the end of post-transplant month 3, peripheral TTV plasma load was analyzed in the context of subsequent rejection and infection by rt-PCR.

Results
Patients with allograft rejection had lower levels of TTV compared to patients without rejection (median 3.5x106 c/mL, IQR 1.7x105-1.3x108 c/ml vs. median 2.5x108 c/mL, IQR 5.8x106-9.3x108 c/mL; P = .028) in subsequent biopsies. TTV load in individuals experiencing an infectious event in the subsequent observation period was higher compared to patients without infection (median 3.9x108 c/mL, IQR 7.9x106-3.3x109 c/mL vs. median 2.6x107 c/mL, IQR 1.3x106-9.2x108 c/mL; P &lt; .001). Of note, TTV was quantified several weeks before rejection diagnosis and infection onset. Each log increase in TTV load decreased the odds for rejection by 22% (OR 0.78, 95% CI 0.62-0.97; P = .027) and increased the odds for infection by 11% (OR 1.11, 95% CI 1.06-1.15; P &lt; .001). The association of TTV and infection and rejection, respectively was not altered by confounding or effect modification. A TTV load between 106 and 108 copies/mL was defined as optimal range to minimize the risk for rejection and infection.

Conclusion
These data support the initiation of an interventional trial assessing the efficacy of TTV-guided immunosuppression to reduce infection and graft rejection in kidney transplant recipients.
P1632IMPACT OF RENAL TRANSPLANTATION ON THE FUNCTIONAL STATUS OF PATIENTS WITH END-STAGE RENAL FAILURE IN TACROLIMUS ERA
Authors: Ali Hatem Kaies Ibrahim Elsayed , Daoud Ahmed , Soliman Karim 
Published: June 2020

Abstract

Background and Aims
Survival after renal transplantation has improved significantly over the past 20 years. On the contrary, surprisingly little is known about the functional status post-transplant. A fundamental understanding of the functional status of patients surviving renal transplantation is of primary importance to clinicians and families alike, who often pursue renal transplantation with a principal hope that functional status will improve. The aim of our study is to assess the effect of renal transplantation on functional status of the patients in tacrolimus era

Method
Using data from the United States organ procurement and transplantation network, all renal transplant patients maintained on tacrolimus-based immunotherapy and had functional assessment at time of transplant and five-years post-transplant were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy on discharge were collected. Functional status was defined according to Karnofsky score measurements. Descriptive analysis was used to assess effect of renal transplantation on functional status. Outcome measured was functional status five-years post-transplant. Multiple logistic regression analysis was used to assess factors affecting functional status post-transplant.

Results
19704 patients were included in the study. Among patients with mild impairment at time of transplant, only 13.55% showed worsening of functional status. Among patients with moderate impairment at time of transplant, 65.5% showed improvement of functional status while only 3.92% showed worsening of functional status. Among patients with severe impairment at time of transplant, 88.56% showed improvement in functional status (64.57% showed improvement to mild impairment and 23.99% showed improvement to moderate impairment). Multiple logistic regression analysis showed that steroid withdrawal protocol is associated with improvement in functional status (OR=1.24, P=0.007, CI ranges from 1.06 to 1.45), while dialysis maintenance before transplantation was associated with abnormal functional status post-transplant (OR=0.73, P=0.003, CI ranges from 0.59 to 0.89).

Conclusion
This study revealed that renal transplantation is associated with substantial improvement in functional status of the patients. Steroid withdrawal protocols is associated with significant improvement in functional status while maintenance dialysis before transplantation is associated with worse outcomes. This study recommends using steroid withdrawal protocols and performing transplantation for the patients at the pre-dialysis state. Functional status at time of transplant shouldn’t be a hindrance to performing transplantation.
P1636THE IMPACT OF CALCINEURIN INHIBITOR WITHDRAWAL ON DE NOVO DSA PRODUCTION IN LIVING DONOR KIDNEY TRANSPLANTATION
Authors: HIRAMITSU Takahisa , Kanda Akiko , Futamura Kenta , Tomosugi Toshihide , OKADA Manabu , Norihiko Goto , Narumi Shunji , Watarai Yoshihiko 
Published: June 2020

Abstract

Background and Aims
Chronic antibody mediated rejection caused by de novo donor specific antibody (dnDSA) is one of the biggest reasons for graft failure. At present, because it is difficult to treat CAMR, prevention of de novo DSA production is important. We investigated the risk factor for dnDSA production in living donor kidney transplantation.

Method
807 patients underwent living donor kidney transplantation between January 2008 and December 2016. 159 recipients were excluded because of preformed DSA (58 recipients), pediatric transplantation (35 recipients), pancreas transplantation after kidney transplantation (4 recipients), and insufficient data on DSA after transplantation (62 recipients). 648 recipients were enrolled in this study. In 84 out of 648 recipients, dnDSA were detected until December 2018. With cox regression analysis, the risk factors for de novo DSA production were investigated between dn DSA positive and negative groups. The impact of donor characteristics including age and sex, and recipient characteristics including age, sex, hemodialysis vintage, cold ischemic time, past history of transfusion, pregnancy, and transplantation, HLA mismatch, pre-operative Flow PRA results, ABO incompatibility, rituximab induction, splenectomy, pre-operative plasmapheresis, transplantation from first-degree relatives, conversion of calcineurin inhibitor (CNI), conversion of mycophenolate mofetil, mizoribin, and everolimus, CNI used for induction, induction with mycophenolate mofetil, mizoribin, and everolimus, CNI withdrawal, withdrawal of mycophenolate mofetil, mizoribin, and everolimus, and rejection within 6 months after transplantation were investigated.

Results
In the univariate analysis, male recipient, male donor, and CNI withdrawal were the significant risk factors (P=0.020, HR 1.795, 95%CI 1.095-2.942; P=0.027, HR 0.568, 95%CI 0.344-0.938; P&lt;0.001, HR 6.346, 95%CI 2.560-15.730, respectively). In the multivariate analysis, calcineurin inhibitor withdrawal was significant risk factor with P&lt;0.001, HR 6.374, 95%CI 2.567-15.828.

Conclusion
Calcineurin inhibitor withdrawal was the significant risk factor for de novo DSA production in living donor kidney transplantation
P1644SAPS AND EPTS SCORES AS PREDICTORS OF RENAL FUNCTION IN RECENT RENAL TRANSPLANTATION
Authors: Sanchez Gil Jimmy Reinaldo , Coca Armando , Rodriguez Portela Guadalupe , Aller Aparicio Carmen , Mendiluce Alicia 
Published: June 2020

Abstract

Background and Aims
The risk scores used in Critical Care Units estimate the severity and mortality of patients. The SAPS (Simplified Acute Physiologic Score) and its SAPS II and SAPS III variants calculate the severity by collecting the values recorded in the first 24 hours. The EPTS (Estimated Post-Transplant-Survival) is used as a reference for the allocation of organs in the US by the OPTN. The objective is to determine its use in recent renal transplant units as estimator of subsequent renal function, in services where patients move from the operating room to a nephrological intermediate care unit.

Method
The SAPS (II and III) and OPTN scores were applied in 87 (N = 87) consecutive renal transplanted patients. The point value of each of the scales was evaluated with the creatinine values at hospital discharge, and one month after the transplant. The scores obtained on the SAPS scales were divided as follows (SAPSIIA &lt;20 points, SAPSIIB ≥20 points) (SAPSIII A &lt;30 points, SAPSIIIB ≥30 points). In the EPTS scale, two cut-off points were used to divide the groups (20% Score; EPTS-IA ≤20%, EPTS-IB&gt; 20%), (Score 40%; EPTS-IIA ≤40%, EPTS -IIB&gt; 40). The sérum creatinine means of each of the groups were compared. Data were analyzed with SPSS 20.0.0

Results
Significant differences were found in serum creatinine levels in renal function at the first month of transplantation in the SAPS II groups (SAPS IIA 1.38 mg / dl, SAPS IIB 1.79 mg / dl; P = 0.017 95% CI). With an area under the ROC curve of 0.65 (P = 0.017 95% CI). In the SAPS III groups no significant differences were found. In the EPTS scales, there were also significant differences in creatinine one month after the transplant in the group with a score of 40% (EPTS-IIA ≤40% 1.42 mg / dl, EPTS-IIB&gt; 40 1.81 mg / dl; P = 0.024 95% CI) With an Area under the ROC curve of 0.64 (P = 0.037 95% CI).

Conclusion
The SAPSII and EPTS scores can be a useful tool in estimating renal function one month after renal transplantation, giving a prognosis of renal graft function. The combined use of these scales together with other functional graft tests could have an important relevance in the management and follow-up of recent renal transplantation. Other studies with larger sample sizes are necessary to establish the appropriate cut-off points for the scales.
P1647CHANGES IN CAUSES OF EARLY GRAFT LOSS IN LIVING DONOR KIDNEY TRANSPLANT RECIPIENTS, 1972-2018
Authors: Futamura Kenta , Norihiko Goto , Fukuhara Hiroki , Nawano Takaaki , Kanda Akiko , Tomosugi Toshihide , OKADA Manabu , Tsujita Makoto , HIRAMITSU Takahisa , Narumi Shunji , Watarai Yoshihiko 
Published: June 2020

Abstract

Background and Aims
In living donor kidney transplantation, the progress of immunosuppressants in recent decades has led to an average graft survival period more than 15 years. However, the rate of graft loss (GL) within 5 years is still about 5%. Since the incidence of early GL is low, clinical evidence of causes and risk factors are limited and it remains unclear whether early GL was predictable before transplantation. Our purposes were to characterize a patient population with GL, to identify risk factors associated with early (&lt;5 years) GL.

Method
The subjects were 1,779 patients who underwent living donor kidney transplantation at Japanese Red Cross Nagoya Daini hospital and Masuko Memorial Hospital from January 1, 1972 to December 31, 2018 (former group (1972-1999) : 503, latter group (2000-2018) : 1,276). We retrospectively examined patient characteristics, timing and causes of GL in 445 cases with GL by December 31, 2019 (GL cases in former group : 335, GL cases in latter group : 110).

Results
The 5- and 10-year graft survival rates were on an increasing trend, with 74.7% and 58.3% in former group and 95.2% and 88.7% in latter group, respectively. In latter group, T cell-mediated rejection and recurrence of primary diseases were significantly more frequent in GL cases within 5 years after transplantation than over 5 years (10% vs 0%, p=0.02 and 6% vs 0%, p=0.04). Although not significant, GL due to antibody-mediated rejection tended to more frequent in over 5 years after transplantation (22% vs 45%). Compared the causes of GL within 5 years after transplantation between GL cases in former group and latter group, rate of allograft rejection significantly reduced (88％ vs 44%, p&lt;0.001), and infections (especially BK polyomavirus infection), medication nonadherence and recurrence of primary diseases tended to increase (0%, 4% and 3% vs 8%, 16% and 8%, respectively).

Conclusion
Our analysis suggests that management of infections, medication nonadherence and recurrence of primary diseases have become more important for living donor kidney transplant recipients in recent years with improved immunosuppressants.