bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1735USING PRONASE PRE-TREATMENT CDC-CROSSMATCH TO STUDY THE RITUXIMAB KINETICS IN KIDNEY TRANSPLANT CANDIDATES AND RECIPIENTS
Authors: Gandolfini Ilaria , Zanelli Paola , Palmisano Alessandra , Benigno Giuseppe Daniele , Fiaccadori Enrico , Maggiore Umberto 
Published: June 2020

Abstract

Background and Aims
Rituximab (RTX) is a monoclonal antibody that targets CD20 on B cells. It is often used in the desensitization before ABO- and HLA-incompatible kidney transplant (KT) and in the treatment of antibody-mediated rejection (ABMR), glomerulonephritis and post-transplant lymphoproliferative disorders (PTLDs) in KT recipients, however in most of these conditions the kinetics of the drug has not been widely investigated. Because of its intrinsic B cytotoxic property, its use can interfere with immunogenetic techniques such as B-cell complement mediated cytotoxic crossmatch (CDCXM). Low dose pronase pretreatment has been proposed to reverse this interference, cleaving the CD20 rituximab target from these cells. We wanted therefore to test the kinetics of rituximab in the serum of kidney transplant candidates or recipients using CDCXM with or without pronase pretreatment.

Method
We conducted a retrospective monocentric study on all KT candidates and recipients that underwent RTX therapy at the Parma Kidney Transplant Nephrology Unit (Parma, Italy) with serial biobanked frozen sera stored at the Immunogenetic Unit of Parma (Parma, Italy). B-cell CDCXM was performed in the presence or absence of low-dose (0.5 mg/mL) B-cells pretreatment. The difference between 2 intervals was analysed by Mann-Whitney test, groups analysis was analysed by Kruskal-Wallis test. The difference in the presence of absence of pronase pretreatment was analyzed by Wilcoxon test for paired data.

Results
We included 31 patients, 58% were male, the average age was 46+/- 13. The majority (74%) of the patients received a living donor KT and the most common indication for RTX was the desensitization for ABO- (58%) or HLA-(13%) incompatible living donor KT. Other indications were the treatment of glomerulonephritis (13%), ABMR (10%) or PTLD (6%). One patient received 2 doses of 1 g, the rest of the patients received 375 mg/m2 once (84%) or twice (16%). In 48% of the patients RTX therapy was followed by isolated plasmapheresis (PEX) or in combination with immunoadsorption (IA)(32%). In most of the patients B-cell CXCXM turned negative at 6 months after RTX treatment (p&lt;0.001)(Figure 1), however this cytotoxicity was more persistent (up to 12 months) in patients who did not underwent PEX+/-IA after RTX (Figure 2). The B-cell pretreatment with pronase was able to turn negative this reaction (p=0.002) in these patients.

Conclusions
The data of our study seem to suggest a persistence of RTX in the sera of KT patients among the 4 months of onlabel treatments, especially in the absence of PEX or IA treatment following RTX.
Moreover the use of B-cell CDCXM in the the presence or absence of pronase could be used to monitor circulating levels of RTX in different diseases.
P1737MICROBIOLOGICAL DIAGNOSIS OF DIARRHEA IN RENAL TRANSPLANT PATIENT BY MULTIPLEX PCR
Authors: Tiwari Vaibhav , Gupta Anurag , Anand Yogeshman , Bhargava Vinant , Malik Manish , Gupta Ashwani , Bhalla A K , Rana Devinder Singh 
Published: June 2020

Abstract

Background and Aims
Acute gastroenteritis is an unwelcome and harmful yet unavoidable complication in the renal transplant patient. Infections, especially atypical organisms like Norovirus, Cryptosporidium, along with typical microorganisms like E. coli and Giardia, form the significant players in the pathogenesis of diarrhea. Standard methods of staining and culture have reduced sensitivity as well as require considerable time for the reports. Stool Polymerase Chain Reaction (PCR)is a quick, sensitive, and hassle-free method that diagnoses more than 20 organisms within 1 hour. This study aims to determine the infective etiology of acute gastroenteritis in the transplant population as well to compare the yield of stool PCR with conservative methods.

Method
We retrospectively analyzed all renal transplant patients admitted between 2015 to 2018 with complaints of diarrhea (&gt;3 stools/day with loose consistency). The sample was tested for conventional microbiological methods, including a stool routine for microscopy and culture. A stool sample was also sent for Multiplex PCR, which was analyzed by Bio Fire FilmArray GI Panel, which identifies 22 enteropathogens. Endoscopic procedures were also undertaken in suspected cases for CMV colitis and pseudomembranous colitis.

Results
110 diarrheal events (admission for diarrhea) were recorded in 82 patients, with 181 organisms isolated in all samples. 16 events did not reveal any organisms in stool PCR. 85% sample yielded a positive result. The conventional method yielded a positive result in only 32.3% as compared to stool PCR. Co-infections were common, as 71.2% of events were associated with 2 or more organisms. Conventional methods failed to diagnose any co-infections. Norovirus G1/G2(20%) was the most common organism isolated from the stool, followed by Giardia (17%) and Enteropathogenic E. coli (16%). Giardia Lamblia with Norovirus G1/G2 was the most common co-infection in 19% of patients.

Conclusion
Stool PCR significantly improves the diagnostic yield in diagnosing enteric pathogens. Stool PCR is especially sensitive in detecting multiple organisms where conventional microbiological methods were completely unsuccessful. Norovirus is the most common enteropathogen, which is not picked by the conventional method. Giardia with Norovirus was the most common co-infection among post-transplant patients.
P1738COULD ADDING BORTEZOMIB HAVE BENEFIT FOR ANTIBODY MEDIATED REJECTION AFTER KIDNEY TRANSPLANTATION?
Authors: Dalili Nooshin , Nafar Mohsen 
Published: June 2020

Abstract

Background and Aims
Antibody Mediated Rejection (ABMR) is a severe complication that frequently occurs after kidney transplantation. The present RCT designed to evaluate the role of adding Bortezomib to standard regimen with plasma exchange, intravenous immunoglobulin and Rituximab in treatment of AMR after kidney transplantation.

Method
26 kidney transplant recipients (KTRs) with a biopsy proven diagnosis of AMR and positive DSA in a randomized clinical trial were compared: Thirteen KTRs treated with plasmapheresis, intravenous immunoglobulin and rituximab (PE-IVIG- RTX ) plus bortezomib versus 13 patients treated with standard of care regimen without bortezomib. We evaluated graft survival and DSA titer with MFI during a year after biopsy proven diagnosis.

Results
Statistical difference in graft survival between the two groups was noted: three out of 13 patients in the PE-IVIG-RTX group (23%) and 1/13 in the bortezomib group (7.5%) experienced loss of allograft function at a median time after diagnosis of 6 month and 12 month, respectively. DSA MFI titers 12 month after AMR diagnosis showed significant reducing slope in Bortezomib group. Regarding pathological changes micro vascular inflammation (glomerulitis + peritubular capillaritis score) reduced after PE-IVIG- RTX plus bortezomib in 7 out of 13 patients whom underwent protocol biopsies after treatment (53%) (Median score 3 in pre- treatment biopsy vs. 1 in post-treatment biopsy; P = 0.036).

Conclusion
Although DSA titer may not differ at 6 months after treatment of AMR between those who received standard regimen and those treated with adding Bortezomib, but at the end of one year patients treated with standard regimen plus Bortezomib reached lower MFI DSA titer. Adding Bortezomib to PE-IVIG- RTX for the treatment of AMR after kidney transplantation may enable clinicians to fight the DSA better and change the future of next generation of highly sensitized kidney transplant candidates.
P1740KINETICS OF B-CELL SUBSETS RECONSTITUTION FOLLOWING RITUXIMAB TREATMENT IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS
Authors: Li Yamei , Shi Yunying , Lin Tao , Wang Xianding , Yan Lin , Li Yi , Bai Yangjuan , Yang Cuili , Wan Zhengli , Wang Lanlan 
Published: June 2020

Abstract

Background and Aims
With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications.

Method
Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry.

Results
The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H).

Conclusion
Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.
P1742POTENTIAL TREATMENT METHOD OF RECURRENT URINARY TRACT INFECTION IN POSTMENOPAUSAL KIDNEY TRANSPLANT RECIPIENTS: THE RESULTS OF PILOT STUDY
Authors: Dolgolikova Anna , Huberskaya Maryna , Efimov Denis , Sadouski Denis , Viarshynin Pavel , Kalachyk Aleh 
Published: June 2020

Abstract

Background and Aims
Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI), especially recurrent UTI, is a common problem, with the prevalence up to 75% among kidney transplant (KTx) recipients. Older age, female gender and delayed graft function are among the independent risk factors for recurrent UTIs in renal transplant recipients*. Postmenopausal women with recurrent UTI after KTx especially caused by bacteria with multidrug antibiotic resistance (MDR) form a large and growing up group of patients with almost unachievable remission. The aim of the study was to assess the efficiency of different treatment schemes of recurrent UTI in postmenopausal female transplant recipients.
*prospective study presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy

Method
The randomized prospective pilot study was conducted to assess the efficiency of 3 different therapy schemes, study period: 2017-2019. Recurrent UTIs were defined as ≥2 UTIs in 6 months or ≥3 UTIs in 12 months. A UTI was diagnosed based upon the presence of pyuria defined as &gt;5 WBCs/high-power field and a urine culture of &gt;100,000 colonies/mL. All consecutive female patients with postmenopausal history who presented to the transplant clinic for follow-up over the study period of six months were prospectively randomized into 3 groups. The primary outcome was occurrence of UTI at 6 months.

Results
Escherichia coli was the responsible pathogen for recurrent UTI in 55% of cases. Other causative organisms include Klebsiella pneumoniae (35%) as well as Enterobacter spp (10%). The rate of resistance to all tested antibiotics was the highest in Klebsiella pneumoniae. The first episode of UTI occurred at 16 (8,5;42) week after KTx.
The total number of UTI episodes (per year) after treatment varies from 7 [5;8] in the 1st Group to 0 [0;0] at the 3rd Group (p&lt;0,001), in which 13 out of 15 patients achieved long-term remission during the observation period. Clinical data on the 1st check-up after treatment course and about UTI episodes are given bellow.

Conclusion
Frequent antibiotic usage often causes MDR as well as result in intestinal dysbacteriosis. Immunosuppression state, frequent antibiotic usage, intestinal disbiosis and also vaginal Ph decline form pathogenic vicious circle. Complex usage of fosfomycin that remains active against a considerable proportion of MDR gram-negative bacteria with bacteriophages, estrogen treatment and long-term probiotic supplement may reduce the UTI frequency in postmenopausal women after KTx.
P1744EFFECT OF TREATMENT WITH ALLOPURINOL ON BLOOD PRESSURE, CREATININ CLEARENCE AND PROTEINURIA IN ADULT RENAL ALLOGRAFT RECIPIENTS: A RANDOMIZED CONTROLLED TRIAL
Authors: Cingöz Mukaddes , Özdemir Orhan , Usalan Özlem , Usalan Celalettin 
Published: June 2020

Abstract

Background and Aims
Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in renal transplant patients. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in renal transplant patients and to investigate indirectly its effect on graft survival.

Method
A total of 105 Renal transplant recipients(RTRs) were included in this study. Patients were randomized to receive either placebo (n=51) or 300 mg/day allopurinol (n=54). We have examined uric acide, urinary albümin/Cr ratio, eGFR, CRP and blood pressure before and 24 weeks later after treatment in both group.

Results
In the allopurinol group, the mean serum uric acid levels, eGFR, creatinine urinary albümin/Cr ratio significantly improved(P &lt; 0.001). However, blood pressure, CRP not statistically significant (P &gt; 0.05). No correlation was observed between changes in uric acide and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P &gt; 0.05). Multivariable regression analysis showed that uric acide was positively correlated with UACR (r= 0,473, β = 0.021, P = 0.002) and negatively correlated with eGFR ( r= -0554 β = 0.016, P = 0.001) in RTRs.

Conclusion
We bring indirect evidence that hyperuricemia increases urinary albümin/Cr ratio, and decreases eGFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of renal transplant recipients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and proteinuria.
P1746EFFICACY OF EXTRACORPOREAL PHOTOPHERESIS FOR THE TREATMENT OF RENAL CHRONIC ANTIBODY MEDIATED REJECTION: A PILOT STUDY
Authors: Pattonieri Eleonora Francesca , Gregorini Marilena , Viarengo Gianlcuca , Del Fante Claudia , Perotti Cesare , Grignano Maria Antonietta , Sepe Vincenzo , Libetta Carmelo , Abelli Massimo , Ticozzelli Elena , RAmpino Teresa 
Published: June 2020

Abstract

Background and Aims
Chronic antibody-mediated rejection (cABMR) is the main cause of kidney allograft failure. Currently there is no effective treatment. Extracorporeal photopheresis (ECP) is an immunomodulating therapy that acts increasing regulatory T cells and reducing effector T cells. ECP has been used with success to treat heart and lung rejection, acute and chronic Graft versus Host Disease and few cases of acute antibody mediated kidney rejection.
The aim of this study was to describe the preliminary experience of ECP use to treat kidney cABMR.

Method
This is an ongoing prospective observational study approved by the ethical committee of our institution. The study started in 2017 on kidney transplant recipients (KTR) with cABMR diagnosis bioptically proved. All patients received ECP in addition to the standard treatment. ECP schedule is reported in Figure 1. Serum and urine samples were collected at the beginning of the study and every 6 months during the follow up period. Analyzed variables were: glomerular filtration rate (GFR), urine albumin-creatinine ratio (UACR), Donor Specific Antibodies (DSA) measeured as Mean Intensity Fluorescence (MIF) by Luminex. Collected clinical data included: death, hospital admission number, cancer diagnosis, infections. Quality of life (QoL) scale was also recorded.

Results
We enrolled 6 KTR equally distributed in gender (3 M, 3 F) and aged 49.16 ± 7.15 years (mean±ds) .
Median follow up time was 12 months (min 12 – max 36).
All KTR had both class I and class II DSA with MFI &gt; 5000 (min 5000 – max 36780).
In all patients no GFR deterioration was observed during follow up. UACR improved in 3 KTR while remained stable in the other 3 patients. No deaths or infections or cancer diagnosis or hospital admissions occurred. QoL ameliorated in all KTR.
DSA MIF decreased in all KTR and in 3 of them became even negative after 12 months of treatment.

Conclusion
ECP is a safe and effective treatment to slow down the deterioration of kidney function in cABMR patients. Further studies are necessary to identify the responder patients and to better tailor the treatment schedule.
P1752THE ROLE OF MTOR INHIBITORS ON CARDIOVASCULAR AGING IN RENAL TRANSPLANT PATIENTS WITH CHRONIC GRAFT DYSFUNCTION
Authors: Infante Barbara , Castellano Giuseppe , Prisciandaro Concetta , Dilorenzo Adelaide , Bellanti Francesco , Coviello Nicola , Pontrelli Paola , Rascio Federica , FRANZIN ROSSANA , Gesualdo Loreto , Serviddio Gaetano , Grandaliano Giuseppe , Stallone Giovanni 
Published: June 2020

Abstract

Background and Aims
Chronic Kidney Disease (CKD) is strongly associated with increased circulatory complications that can lead to accelerated cardiovascular aging. During CKD, persistent oxidative stress triggered by mitochondrial dysfunction can affect Klotho protein levels together with circulating FGF23. mTOR pathway is involved in pro-survival mechanism and can be differently modulated by several available therapeutics, therefore exerting central function in senescence, autophagy and cellular regeneration. The aim of this study was to evaluate the beneficial effect of mTOR inhibition on cardiovascular aging in transplanted patient with Chronic Allograft Dysfunction.

Method
In this study, 250 transplanted patients with calcineurin inhibitory (CNI) therapy and graft survival higher than 6 months and lower than 60 months were enrolled.
The patients were then divided in three groups: (MMF group) patients undergoing CNI therapy with CS (Ciclosporin) and MMF, (mTOR Inhibitors group) patients undergoing CNI, CS and mTOR Inhibitors therapy and (MMF to mTOR Inhibitors group) with patients shifting from MMF to mTOR Inhibitors therapy. Renal function, FGF-23, Klotho, PTH, 1-25OH-Vitamina D, arterial stiffness by Pulse Wave Velocity (PWV), left ventricular hypertrophy expressed by the MSV and endothelial function by Flow Mediated Dilation (FMD) were measured. PBMC were isolated by gradient centrifugation.

Results
Between the MMF group and the mTOR Inhibitors groups we did not find significant differences in renal function, PTH, 1-25OH-Vitamina D, PRA, DSA, PWV, FM e DFE. However, FGF23, Klotho, phosphate levels were significantly changed. (FGF-23 pg/ml; p=0,00001; Klotho p=0,01; fosfaturia p=0,03; MMF group vs mTOR Inhibitors group)
Interestingly, mTOR Inhibitors group patients showed a higher O2 consumption level associated to increased mitochondrial respiratory function. Pentraxin 3 (PTX-3) and p21 as inflammaging and senescence biomarkers were also detected to be significantly increased in MMF group compared to mTOR Inhibitors group (p=0,002).

Conclusion
In conclusion these data suggest that the use of mTOR Inhibitors in transplanted patients could prevent the occurrence of circulating complication and reduce the cardiovascular aging risk.
P1770HIGH PILL BURDEN INCREASES INTRAPATIENT TACROLIMUS TROUGH LEVELS VARIABILITY IN STABLE KIDNEY TRANSPLANT RECIPIENTS
Authors: Giza Piotr , Kolonko Aureliusz , Chudek Jerzy , Ficek Rafał , Dwulit Tomasz , Wiecek Andrzej Jan 
Published: June 2020

Abstract

Background and Aims
High intrapatient variability (IPV) of tacrolimus trough levels is associated with poor long-term outcome after transplantation. Polypharmacy, related to the high co-morbidity, may affect the pharmacokinetics of tacrolimus in a substantial proportion of kidney transplant recipients (KTRs). We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV.

Method
We studied 152 tacrolimus-treated KTRs with mean post-transplant time 6.0±3.1 years, without dosing changes over the consecutive 2 years. The coefficient of variation (CV) as a measure IPV was calculated in each patient. Data concerning the type (generic name) and number of currently prescribed medications were collected. The participants were divided into 4 groups, based on the number of regularly prescribed drugs (≤3; 4-6; 7-9; ≥10).

Results
The median daily pill burden was 6.2±2.5 (ranged 2 to 15). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (IQR 0.08-0.14); group 2: 0.14 (0.01-0.17); group 3: 0.17 (0.14-0.23); group 4: 0.17 (0.15-0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503; p&lt;0.001], age [rpartial = -0.150; p=0.07] and eGFR [rpartial = -0.140; p=0.09] independently influenced the tacrolimus IPV (R2=0.30). Concomitant steroids or diuretics use increased IPV only in Advagraf-treated KTRs, whereas PPIs or statin use increased IPV in Prograf, but not Advagraf group.

Conclusion:
The number of medications is positively associated with tacrolimus IPV in stable KTRs. There were also tacrolimus formulation-dependent differences in the assumed influence of several concomitantly received classes of medications, including steroids, diuretics, PPIs and statins, on the tacrolimus IPV.