bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1758TOCILIZUMAB TREATMENT IN DSA POSITIVE ANTIBODY MEDIATED REJECTION AMONG KIDNEY TRANSPLANT RECIPIENTS
Authors: Cseprekal Orsolya , Marton Adrienn , Molnar Sara , Patonai Attila , Fintha Attila , Micsik Tamás , Török Szilárd , Mathe Zsolt , Wagner Laszlo , Kobori Laszlo , Remport Adam 
Published: June 2020

Abstract

Background and Aims
Pretransplant or de novo donor specific antibodies (DSA) may lead to active or chronic active antibody mediated rejection (a and cABMR) as leading cause of graft loss after kidney transplantation. There is no treatment protocol approved for ABMR. Anti Il-6 tocilizumab (TCZ), inhibitor of DSA production, is a potential approach to stabilize kidney allograft function, however, evidence based results are not available.
In our retrospective case series analysis, we assessed the changes in DSA and eGFR during and at the end of treatment with TCZ.

Method
In our single center case series analysis, 10 kidney transplant patients with biopsy proven ABMR (aABMR 6, cABMR 4, age 43±10.5ys, 6 males, time since transplantation 18(2-119)months, 7 first transplant, serum creatinine 224±80 umol/L at baseline) were studied between January 2017 – June 2019. Total plasma exchange (PE) (5x) was followed by TCZ (8 mg/kg, 1x monthly for 6 months) in case of a and cABMR. Intravenous immunoglobulin (IVIG, 1gr/kg) was added in case of aABMR. Routine laboratory parameters and DSA were reported retrospectively.

Results
6 aABMR patients completed the treatment protocol. Class I DSA decreased significantly (MFI 4457(635-14084) vs. 877(595-5678); p=0.007), but Class II DSA remained the same during the treatment (MFI 4725 (586-17615) vs. 8097 (671-14636) p=NS). eGFR of aABMR patients and 1 cABMR patient were stabilized. 3 cABMR patients returned to dialysis. Reversible elevation of liver transaminases were detected in three patients. There was no any serious adverse event recorded.

Conclusion
The opportunely timed TCZ seems to be effective in reducing Class I DSA and stabilize graft function in patients with aABMR. Further studies are needed to prove the long-term efficacy and the exact role of TCZ in cABMR among kidney transplant patients.
P1759NEPHROTOXICITY OF CALCINEURIN INHIBITORS AS A RISK FACTOR FOR BK VIRUS REPLICATION AFTER KIDNEY TRANSPLANTATION
Authors: Krejčí Karel , Tichý Tomáš , Bednaříková Jana , Bartková Margita , Žamboch Kamil , Orság Jiří , Mrázek František , Zadražil Josef 
Published: June 2020

Abstract

Background and Aims
BK virus nephropathy (BKVN) represents a serious complication of kidney transplantation and is responsible for significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is considered a complication of immunosuppressive therapy and is closely related to its intensity. The aim of our prospective study was to evaluate the incidence of subclinical and clinically manifest nephrotoxicity of calcineurin inhibitors (CI) in repeated protocol kidney graft biopsies as a manifestation of excessive immunosuppression and to evaluate its relationship to the PCR confirmed active BKV replication and bioptically proven BKVN during the first year after transplantation.

Method
In a group of 161 newly transplanted patients we prospectively evaluated 457 consecutive protocol renal biopsies performed within the first year after transplantation. Using the CI nephrotoxicity score, the incidence of nephrotoxicity was monitored. Findings were correlated with laboratory (PCR) and histological evidence of active BK virus (BKV) replication and BKVN.

Results
When compared to the normal histology, nephrotoxicity was associated with more frequent significant BKV viraemia and viruria (P = 0.02 and P = 0.01, respectively) and more common occurrence of BKVN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of significant BKV viraemia and viruria (P = 0.03 and P = 0.01, respectively), independently of the initial BKV status of the monitored groups. Toxicity could also be used as a predictor of significant viraemia and viruria (P = 0.02 and P = 0.01, respectively) even in the absence of viral replication at the time of initial biopsy.

Conclusion
Early histological detection of CI nephrotoxicity followed by pre-emptive CI dose reduction might prevent significant BKV reactivation in the risky first posttransplant year. The evaluation whether a regression of histological signs of nephrotoxicity after a CI dose reduction leads to a reduction in BKV replication, and whether a more frequent occurrence of rejection does not complicate further posttransplant course, will be the subject of our further investigation.
Supported by grant of Ministry of Health, Czech Republic DRO (FNOL 00098892) – 87-68.
P1761SIDE EFFECTS OF MTOR INHIBITORS DEPEND ON THE BASELINE METABOLIC STATUS OF KIDNEY TRANSPLANT RECIPIENTS
Authors: Cucchiari David , Molina-Andujar Alicia , Montagud-Marrahi Enrique , Rovira Jordi , Diekmann Fritz 
Published: June 2020

Abstract

Background and Aims
Biologically, the cellular activity of the mTOR complexes depends on the balance between the catabolic and the anabolic inputs. Hence, we hypothesized that the metabolic side effects of mTOR inhibitors (mTORi) in kidney transplantation depend on the baseline metabolic status of the patient.

Method
The analysis included all the patients that have been transplanted in our Center between June 2013 to December 2016, completed one year of follow-up and did not change medication during the first year after kidney transplantation (per-protocol population, n=298). Outcomes chosen include de novo diabetes, 1-year difference from baseline in glycated hemoglobin (HbA1c), triglycerides and total cholesterol. Kidney transplant recipients were treated either with an mTORi (either Sirolimus or Everolimus, n=134) or Mycophenolic Acid (MPA, n=164). Both drugs were always accompanied by tacrolimus and steroids. Patients were stratified according to the treatment received (mTORi versus MPA) and the baseline metabolic status (diabetes mellitus type 2 and obesity). Differences among groups were analyzed with exact Fisher test and ANOVA test with LSD post-hoc analysis.

Results
We observed a strong difference for 1-year change in HbA1c depending on the baseline metabolic status of the patients (P&lt;0.001 between groups, Figure 1a). The worst results were observed for patients with baseline diabetes. Among these, obese patients treated with mTORi had the higher increase in HbA1c (3.04 ± 1.18% from baseline, P&lt;0.01 with all groups at post-hoc analysis). De-novo diabetes was more frequent in patients taking mTORi (23.4 vs. 13.1%), albeit not significantly (P=0.100) and without differences taking into account obesity as a covariate. Triglycerides increased substantially in patients without baseline diabetes and treated with mTORi (P&lt;0.05). Surprisingly, in diabetic patients no differences were observed in triglycerides between mTORi and MPA groups (Figure 1b). There were no differences in the increase in total cholesterol among groups (P=0.155) (Figure 1c).

Conclusion
We observed that the 1-year increase in HbA1c and triglycerides attributable to mTORi after kidney transplantation depends on the baseline metabolic status of the patients. We propose that the metabolic side effects of mTORi depend on the balance between anabolic and catabolic inputs of every kidney transplant recipient.
P1762THE EFFECT OF IMMUNOSUPPRESSIVE THERAPY ON THE CLINICAL FOLLOW-UP OF BK VIRUS IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Yilmaz Gulay , Polatkan Volkan , Ozdemir Ebru , Erturk Turker , Tatli Emel , Berber Ibrahim , Cakir Ulkem 
Published: June 2020

Abstract

Background and Aims
BK virus nephropathy occurs in up to 10% of kidney transplant recipients and can result in graft loss. The reactivation of BK virus is largely asymptomatic, and routine surveillance especially in the first 12-24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and antiviral treatment in the early stages may be effective in stopping BK virus replication. This study is designed to investigate the effect of management in immunosuppressive therapy on BK virus titers and graft functions in our kidney transplant group.

Method
A total of 370 kidney transplant recipients between the ages of 18-69 years and receiving a triple immunosuppressive therapy (Tacrolimus+Mycophenoloic Acid+Prednisolone) were included in the study. Demographic characteristics, BK virus titers, serum creatinine and immunosuppressive drug (Tacrolimus, Everolimus) levels were measured at regular intervals in the first 24 months. Among these patients 43 of them were found to have BK virus positivity. At the time of the detection of BK virus positivity, patients were divided into three groups regarding the change in the immunosuppressive protocols: Group I: Tacrolimus + Everolimus + Prednisolone, Group II: Everolimus + Prednisolone, Group III: Tacrolimus + Prednisolone. BK virus titers and graft functions of all three groups were compared with each other. SPSS 15 for Windows was used for statistical analysis.

Results
The mean age of the patients was 45.3 years, and the mean duration of transplantation was 16.3 months at the time of the BK virus positivity. During the follow-up, mean Tacrolimus levels were found to be in their highest value (14.1 ng/mL) in the posttransplant three months while BK virus titer reached the highest value (1.1x106 copies/ml) in the posttransplant seven to nine months. Increased creatinine values two months after BK virus positivity were strongly correlated (p = 0.02, p = 0.008, p = 0.05, p = 0.002 at 6th, 9th, 12th and 24th months, respectively). A significant decrease in BK virus titers was observed in all three groups due to reductions in immunosuppressive treatment protocol (p = 0.005, p = 0.003, p = 0.028, in groups I, II, III respectively).

Conclusion
Our study favors the benefits of the prospective screening for BK virus to identify early viral replication, permit intervention, and prevent progression to nephropathy or allograft loss. The best studied treatment for BK viremia and nephropathy is careful reduction of immunosuppression
P1765COMBINING THE BEST OF TWO OPTIONS: A SPLIT STRATEGY WITH PROPHYLAXIS OR PRE-EMPTIVE THERAPY TO PREVENT CYTOMEGALOVIRUS AFTER KIDNEY TRANSPLANTATION
Authors: Hellemans Rachel , Wijtvliet Veerle , Bergs Kristof , Philipse Ester , Vleut Rowena , Massart Annick , Couttenye Marie-Madeleine , Mattheeussens Veerle , Abramowicz Daniel 
Published: June 2020

Abstract

Background and Aims
Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for either high risk CMV-seronegative recipients of a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). A split strategy according to CMV risk, however, is not specifically mentioned.

Method
We evaluated a split strategy to prevent cytomegalovirus infection after kidney transplantation. D+/R- patients received valganciclovir (VGC) prophylaxis during 200 days and R+ patients were treated pre-emptively according to CMV DNAemia.

Results
Between April 2014 and March 2018, 40 D+/R- and 92 R+ patients underwent kidney transplantation. Forty-six % received antithymocyte globuline (ATG) induction and 98 % were treated with calcineurin inhibitors, mycophenolic acid (MPA) and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200 days), 15 % developed late-onset disease. Fifty-three % developed neutropenia during prophylaxis, including 16/40 (40 %) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30 %) and/or VGC (30 %), and occasional need for granulocyte colony stimulating factors (5 %). In the R+ group, 40 % received antiviral therapy for a median duration of 21 days. Five percent developed CMV disease. Only 5 % developed neutropenia. D+/R+ status (hazard ratio (HR) 2.09, P 0.004) and ATG use (HR 2.81, P &lt; 0.0001) were risk factors for CMV reactivation.

Conclusion
Prophylaxis leads to acceptable CMV control in high risk patients, but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk for CMV.
P1766EFFECT OF EVEROLIMUS AND REDUCED CALCINEURIN INHIBITORS ON BIOPSY PROVEN BK VIRUS ASSOCIATED NEPHROPATHY-
Authors: Zaky Ziad 
Published: June 2020

Abstract

Background and Aims
BK virus-associated nephropathy (BKVAN) is a clinically important entity that results in an allograft loss in kidney transplant recipients (KTRs). Mammalian target of rapamycin inhibitors (mTOR-i) have been proposed as possible immunosuppressive therapy in BK virus infection because of their antiviral capacity. However, the effect on biopsy (bx) proven BKVAN is still unclear.

Method
This a retrospective single center review of 27 (KTRs) on triple immunosuppression regimen (CNI/MMF/prednisone), who developed BK viremia and had bx proven BKVAN (n=13, 48%). Patients were converted to Everolimus, reduced/or no CNI and prednisone. We present the renal allograft function, BK viremia status and histological data after a mean follow up period of 28.4±17.9 months post-transplant.

Results
We reviewed 27 KTRs (17 males, 11 AA) transplanted between 2012 and 2019, who developed BK viremia, 23/27 patients (85%) underwent surveillance & for cause bx (n=55). All patients were switched to Everolimus, reduced CNI (one patient was on Cyclosporin) and prednisone regimen. Median time from transplant to BK viremia was 2.5 months (min 0.7-max 76.7). After a mean follow up period of 17.9±12 months post conversion, the mean serum creatinine remained relatively stable (1.54 mg/dl ±0.47; 1.79 mg/dl±0.82; P=0.17). The mean BK viral load was statistically significantly reduced (P=0.045), pre/post conversion median BK levels were (35900 (655-2.5 million copies) and 752 (0-92150) respectively), 13/27 (48%) patients had undetectable BK viral load. 13/27 (48%) had bx proven BKVAN, with 4/13 (31%) had no follow up bx, 4/13 (31%) had follow up bx proven resolved BKVAN and 5/13 (38%) had bx proven persistent BKVAN (figure 1). Post conversion 3/27 (11%) patients were treated for borderline acute cellular rejection with pulse steroids and had negative DSA.

Conclusion
Conversion to mTOR-i-based therapy could provide an added benefit in BK viremia as well as BKVAN and could be an effective strategy for the decrease of the viremia and increase of graft survival in selected patients. In the medium-term follow up, the BK viral load was statistically significantly lower even in bx proven persistent BKVAN, and almost half (4/9) of the bx proven BKVAN have resolved. The median time for conversion for patients with resolved BK nephropathy was 25 days (range 19-38) vs 263 days (range 17-931) in patients with persistent BK nephropathy (P&lt;0.001), pointing to possible benefit of rapid conversion to mTOR-i based regimen in the setting of BK viremia.
P1768EFFECTS OF HIGH INTENSITY INTERVAL TRAINING ON CIRCULATING LYMPHOCYTES, MONOCYTES AND CYTOKINES IN RENAL TRANSPLANT RECIPIENTS
Authors: Hutchinson Ganisha , Billany Roseanne E , Bishop Nicolette , Cooper Andrea , Smith Alice 
Published: June 2020

Abstract

Background and Aims
High intensity interval training (HIIT) has been shown to improve traditional and non-traditional cardiovascular risk factors in the general population and in chronic diseases. However, intense exercise has the potential to suppress immune function and promote systemic inflammation. Renal transplant recipients (RTRs) are immunologically vulnerable and therefore thorough understanding of the effects of different exercise regimes is required to inform exercise advice and guidelines. The aim of this study was to explore the immune and inflammatory effects of HIIT in comparison to moderate intensity continuous training (MICT) in RTRs.

Method
Renal transplant recipients (n = 24, age (years) = 48 ± 13, BMI = 27.2 ± 5.6 kg.m2, eGFR (mL·min· 1.73 m2) = 58 ± 19) were randomised into one of three thrice-weekly 8 week exercise programmes: HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%–90% of peak oxygen uptake (V̇O2 peak), HIIT B (4 × 4 min interval training at 80%–90% V̇O2peak) or MICT (∼40 min cycling at 50%–60% V̇O2peak). Peripheral blood mononuclear cells were isolated at baseline, mid-training, post-training and three months post-training and stained for lymphocyte and monocyte phenotypic and activation markers. Plasma cytokines (IL-6, IL-10 and TNF-α) were measured by affinity ELISA kits.

Results
Friedman’s ANOVA was used to assess within-group differences and a Kruskal-Wallis H test was used to assess between-group differences; any significant findings were followed up using a post-hoc test. There were no differences in circulating lymphocyte or monocyte lineage markers within or between groups over time (P &gt; 0.05). Cytokines did not change in relation to exercise within or between groups over time (P &gt; 0.05).

Conclusion
This is the first study to investigate the effects of HIIT on immune parameters and inflammation markers longitudinally in RTRs or other immunosuppressed populations. Our data do not indicate any evidence for adverse effects of HIIT on circulating lymphocytes, monocytes or cytokines and suggest that such exercise regimes may be immunologically safe for immunosuppressed patients. We recommend further investigations involving larger sample size to confirm our results.
P1773BENEFITS OF CONTROL RENAL BIOPSIES IN THE ASSESSMENT OF ANTI-REJECTION THERAPY EFFICACY IN PATIENTS WITH HISTOLOGICAL LESIONS DIAGNOSED EITHER BY PROTOCOL OR BY “FOR CAUSE” BIOPSIES
Authors: Affatato Stefania , Sandrini Silvio , Fisogni Simona , Bossini Nicola , Valerio Francesca , Movilli Ezio , Maffei Camilla , Possenti Stefano , Scolari Francesco 
Published: June 2020

Abstract

Background and Aims
Efficacy of acute rejection (AR) therapy has always been evaluated based upon improvement of renal function. On the contrary, the degree of histological lesion (HL) regression has rarely been considered for this purpose.
The main goal of this study was to evaluate the percentage of failures in HLs regression after treatment aimed at both “subclinical” and “clinical” AR. Treatment efficacy was therefore evaluated with control renal biopsies (CBs) performed 30-60 days after anti-rejection therapy. In addition, the correlation between graft function and histological data was assessed. The results of treatment for “subclinical" and "clinical” AR were considered separately.

Method
Real-time ultrasound-guided CBs were performed in an outpatient setting using 16G tru-cut needles. The HLs considered were: interstitial inflammation (i), tubulitis (t), glomerulitis (g), arteritis (v), capillaritis (ptc). Each lesion was graded from 0 to 3 (sec Banff 2013-2017). For this study, only HLs with a score ≥2 were considered. Therapy failure was determined both by the percentage of patients (pts) with persistence of HLs and by the change of HLs score after treatment, in the control biopsies. Anti-rejection therapy varied according to AR type and severity. In patients failing AR therapy, serum creatinine was evaluated before and after the treatment.

Results
111 BCs were performed after treatment either for subclinical (n = 47) or for clinical (n = 64) AR. Before therapy, HLs (with score ≥2) present in subclinical and clinical AR were: i: 23% and 52%; t: 30% and 30%; g: 34% and 41%; ptc: 11% and 28%; v: 15% and 19%.
After therapy, in the setting of subclinical AR, HLs were still present with a range between 29% (v) and 81% (g) with stable or improved histological score. In this scenario, renal function resulted stable and satisfactory (Tab 1).
In the case of clinical AR, the persistence of histological lesions ranged from 25% (v) to 92% (g), also with stable or improved histological scores. In this case, therapy was always followed by an improvement in renal function (Tab 2).

Conclusion
After AR therapy, only the morphological data obtained with histological analysis can disclose failures of anti-rejection therapy, both in presence of subclinical and clinical AR.
The high rate of treatment failure may explain the correlation between AR and worse graft survival.
Our results could lead us to consider the need for a more aggressive anti-rejection treatment.
Control renal biopsies after AR therapy should always be considered on clinical grounds.
P1774CONVERSION FROM TWICE-DAILY TACROLIMUS (TAC-IR) TO ONCE-DAILY EXTENDED RELEASE TACROLIMUS (LCPT) IN EVEROLIMUS TREATED STABLE KIDNEY TRANSPLANT RECIPIENTS
Authors: Cseprekal Orsolya , Marton Adrienn , Török Szilárd , Patonai Attila , Földes Katalin , Wagner Laszlo , Molnar Miklos Zsolt , Mathe Zoltan , Kobori Laszlo , Remport Adam 
Published: June 2020

Abstract

Background and Aims
Stable kidney transplant patients (KTX) treated according to TRANSFORM study protocol (TAC-IR + everolimus (EVR) + corticosteroid) were converted from twice daily TAC-IR to novel (MELT-dose) once-daily tacrolimus formulation (LCPT) on a 1:0.7 total daily dose (TDD) basis. Tolerability, safety, and trough level (Co) – TDD characteristics of the conversion (CV) was analyzed in a single center retrospective observational study.

Method
Between Sep. 2017 and Aug. 2018 38 KTX recipients were included. Pre- and post-CV TAC TDD, Co and TAC Co/D as well as EVR TDD and Co data were evaluated 4, 2 weeks before and 4 consecutive times after CV (94 (74-112 median IQR) post-transplant days). Pre- and post-CV eGFR, routine lab parameters and occurrence of adverse events were also investigated.

Results
In one patient 2 weeks after CV EVR was stopped due to infection, 37 KTX (males 22 (58%), age 54 (42-63) years) finished the entire observational period. According to CV protocol the median TDD of LCPT was lower than pre-CV TAC-IR at each visit: 4.5(3.5-7) mg/day pre-CV versus 3.5 (2.5-5), 3.6 (2.5-5), 3.5 (2.5-5) and 3.5 (2-5) (p&lt;0.001) post-CV. Mean TAC Co decreased from pre-CV Co 7.8 (6.4-9.5) ng/ml to 6.7 (4.8, 8.6), 7.0 (5.2, 9.6), 6.5 (5.7, 8.4) and 7.2 (5.4, 8.7) (p&lt;0.001). LCPT Co /TDD did not change: 1.6 (1.1-2.5) pre- and 2.1 (1.1- 2.9), 2.1 (1.1- 4.1), 1.6 (1.3- 3.5), 2.0 (1.4-4.1) (p = 0.18) post-CV. EVR Co /TDD (1.6 (1.3-2.1), 1.6 (1.3; 2.3), 1.6 (1.3-2.0), 1.6 (1.2-2.2)) remained similar to pre-CV: 1.6 (1.4- 2.4) (p = 0.65). There was no change in eGFR, hemoglobin levels and no drug related adverse event was observed during the study period.

Conclusion
Conversion from TAC-IR to LCPT in everolimus treated stable KTX recipients resulted in a significant post-CV decrease in TAC- Co, whilst Co/TDD remained unchanged. The conversion was safe and had no effect on EVR Co and TDD. Further investigations are needed to define optimal TAC-IR to LCPT conversion dose rate.