bluuebunny/crossref_metadata_2025 huggingface dataset:
P1723CLINICAL AND LABORATORY CHARACTERISTICS OF RENAL TRANSPLANT PATIENTS WITH AA AMYLOIDOSIS IN A TERTIARY CENTER IN TURKEY
Authors: Bilgic Ece , Eren Sadioğlu Rezzan , Eyüpoğlu Şahin , Kocaay Akın fırat , TUZUNER ACAR , Şengül Şule , Keven Kenan
Published: June 2020

Background and Aims

Despite improved therapeutic regimens, AA amyloidosis is still associated with higher risk of mortality after renal transplantation (RT). Moreover the clinical, laboratory characteristics and prognostic factors remain poorly understood. We aimed to identify predictive parameters of prognosis, investigate the etiology, clinical and laboratory features of renal transplant patients with biopsy proven AA amyloidosis.

Method

We conducted a retrospective study using twenty-eight renal transplant patients with AA amyloidosis and twenty-eight renal transplant control patients without amyloidosis matched for age and time after transplantation that were regularly followed in University of Ankara School of Medicine Nephrology Department between October 2018-October 2019. Causes of AA amyloidosis, treatment (colchicine and/ or anti-interleukin (IL) 1 treatment) and number of Familial Mediterranean Fever (FMF) attacks in the last year in case of FMF, biochemical values such as mean CRP, hemoglobin, serum albumin, proteinuria, glomerular filtration rate (GFR), serum creatinine levels were compared between groups.

Results

In amyloidosis and non-amyloiodosis group, the mean age was 44±13 and 44±12 years; 57% and 54% were males, mean time after transplantation was 95±64 and 93±12 month, respectively. FMF was found as the most common cause of AA amyloidosis (86%). All FMF patients received colchicine and eight (33%) FMF patients with AA amyloidosis with insufficient response to colchicine were treated with anti-IL-1 agents. The mean colchicine dose was 0,92±0,34 mg/day. The mean GFR were 63±24 ml/dk/1,73 m2 in amyloidosis and 71±19 ml/dk/1,73 m2 in non amyloidosis group, (p=0.195). The most important finding of present study was significantly higher CRP levels in patients with AA amyloidosis compared to non-amyloidosis group (15,12±15,16 mg/L vs 6,59±8,20 mg/L, p=0,011, respectively).

Conclusion

In this study, we found higher CRP levels in renal transplant patients with AA amyloidosis which indicates persistent ongoing chronic inflammation among these patients.

Figure

Clinical and Laboratory Characteristics of Patient Groups
P1724RISK FACTORS FOR BK VIRUS INFECTION AFTER KIDNEY TRANSPLANTATION IN THE CONTEMPORARY ERA: A SINGLE-CENTRE OBSERVATIONAL STUDY
Authors: Phagura Nuvreen , Thandi Karanjeet , Evison Felicity , Gallier Suzy , Sharif Adnan
Published: June 2020

Background and Aims

BK infection remains a risk factor for kidney transplant dysfunction and allograft loss. While many risk factors are reported in the literature, many are from historical cohorts and have never been validated in the contemporary era. The aim of this study was to explore risk factors for BK virus infection in the contemporary era of kidney transplantation and immunosuppression using a well-phenotyped clinical cohort.

Method

In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between January 1st 2007 and June 30th 2018. BK virus was checked in the context of any transplant dysfunction (indication-based) aligned with UK guidance. Positive BK virus results were defined as >200 copies/ml. Clinical outcomes extracted from electronic hospital records were linked with national datasets. Univariate analysis was undertaken to investigate the association between donor-, recipient- and transplant-related variables and risk for BK virus reactivation. Any variable with a p-value <0.15 in univariate

Results

Data was analysed for 1,770 kidney transplant recipients with median follow up 5.3 years (IQR 2.7 to 8.7 years). BK virus was associated with (versus without); male sex (8.3% versus 5.3% respectively, p=0.010), ABO-incompatible transplantation (12.7% versus 5.9% respectively, p=0.021) and delayed graft function (9.0% versus 6.3% respectively, p=0.032). In a multivariate analysis, including all variables in univariate analysis with p-value <0.15, the only independent variables associated with BK infection were recipient male sex (OR 2.051 [95% CI 1.196-3.519], p=0.009 and ABO-incompatible transplantation (OR 4.087 {95% CI 1.847-9.042], p=0.001). From an outcome perspective, recipients with BK viraemia had worse graft function at 1-, 3- and 5-year post kidney transplantation but no increased risk for death-censored graft loss.

Conclusion

In the contemporary era, only recipient male sex and ABO-incompatible kidney transplantation are independently associated with risk for BK infection. Study limitations include lack of data regarding novel risk factors (e.g. BK virus serostatus). Association does not imply causality and we suggest further work is warranted to validate contemporary risk factors for BK infection in different kidney transplant population cohorts.
P1741TACROLIMUS FAST METABOLIZERS SHOW A HIGHER PROGRESSION OF INTERTITIAL FIBROSIS AND TUBULAR ATROPHY DURING THE FIRST YEAR AFTER RENAL TRASPLANTATION
Authors: Chamoun Huacon Betty , Torres Irina , Gabaldon Alejandra , Toapanta Néstor , Sellares Joana , Perello Manel , Moreso Francesc , Seron Micas Daniel
Published: June 2020

Background and Aims

Fast tacrolimus metabolizers (expressed as the blood concentration/ dose ratio; C / D; ng / mL * mg) showed poorer renal function at 2 years, a higher incidence of nephrotoxicity and BK polyomavirus infection. Greater variability of tacrolimus trough levels (CV) from six to twelve months is associated with the appearance of HLA antibodies, interstitial fibrosis / tubular atrophy (IFTA) progression and allograft loss. We evaluate the relationship between C / D, CV and IFTA progression.

Method

We evaluated a cohort of 87 low immunological risk renal transplants treated with prolonged-release tacrolimus, mycophenolate mofetil and steroids. We analyzed paired protocol biopsies at 4 and 18 months. Biopsies were evaluated according to the Banff classification and the progression of IFTA was defined as the difference of ci + ct score> 0 between 18 and 4 months. The C / D ratio was calculated as the average of the value recorded at 3, 6 and 12 months of follow-up. The tacrolimus CV between 6 and 12 months was calculated using all the available determinations.

Results

IFTA progression was observed in 36 cases (41%). In the univariate analysis, it was found that the progression of IFTA was associated with the ci + ct score at 4 months (0.92 ± 0.94 for progressors vs. 1.89 ± 1.26 not progressors, p = 0.0003), and with the average of the C / D ratio (1.70 ± 0.73 for progressors vs. 2.28 ± 1.25 not progressors; p = 0.0144, table 1). An independent association between the C/D ratio and the progression of IFTA was observed in the multivariate analysis (OR: 0.42; 95% CI: 0.22-0.82, p = 0.027).

Conclusion

The results of our work suggest that fast tacrolimus metabolizers (lower C / D ratio) are more susceptible to the nephrotoxic effect of tacrolimus.
P1743IMPORTANCE OF KIDNEY ALLOGRAFT REJECTİON IN BK VIRUS NEPHROPATHY
Authors: Demir Erol , Kayaş Kamil , Erel Cansu , Caparali Bilge , Ozler Tuba Elif , Dirim Ahmet Burak , Catikkas Nezahat Muge , Guller Nurana , Safak Seda , Ucar Ali Riza , Oto Ozgur Akin , Yazici Halil , Caliskan Yasar Kerem , Akgul Sebahat Usta , Temurhan Sonay , Ozluk Yasemin , Kilicaslan Isin , Yildiz Alaattin , Turkmen Aydin , Sever Mehmet Sukru
Published: June 2020

Background and Aims

Allograft rejection following BK virus nephropathy (BKVN) is an important cause of allograft loss in kidney transplant recipients. However, the effect of rejection type on allograft survival in patients with BKVN has not been described previously. This study aimed to investigate the relationship between allograft rejection type and graft survival in patients with BKVN.

Method

We retrospectively analyzed the data of 159 kidney transplant recipients diagnosed BKVN and followed-up in our center between January 2009 and December 2019. BKVN was diagnosed by persistent viremia of more than 10000 copies/mL for four weeks or allograft biopsy. Vascular, obstructive or other non-parenchymal etiologies for allograft dysfunction were excluded. All patients were investigated for the presence of anti-HLA antibody at 6 and 12 months after BKVN diagnosis. Luminex solid-phase assay was used to investigate Class I and Class II PRA and MFI values greater than 1000 were accepted as positive. Allograft biopsy was performed in patients with progressive graft dysfunction or the presence of donor-specific antibodies (DSA) and analyzed according to the Banff Classification. The primary outcomes were defined as allograft loss or the allograft dysfunction which defined as was doubling serum creatinine levels.

Results

Patients were followed-up median 70 (IQR 13-198) months after kidney transplantation. Demographic data and clinical characteristics are provided in the table. 28 kidney transplant recipients suffered from allograft rejection after BKVN. Median rejection time to rejection after BKVN was 9 (IQR 5-164) months. 3 patients (18,8%) in the AMR group and 1 patient (8,3%) in the TCMR group experienced graft loss during follow-up. The mean serum creatinine levels at the last clinical visit were significantly higher in the AMR group compared to the TCMR group (1,9±0,8 vs 1,3±1,2 mg/dl; p=0,002). In multivariate analysis, AMR was an independent risk factor for allograft dysfunction (HR, 1,735; 95% CI 1,060 to 2,839; p=0,028).

Conclusion

The occurrence of AMR after BKVN is an important indicator of allograft dysfunction compared to TCMR. DSA screening should be routinely used in this group for early diagnosis and treatment of AMR.
P1745EFFECTS OF DESENSITIZATION THERAPY ON LYMPH NODES AND PERIPHERAL BLOOD TFH AND TFR CELLS IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS
Authors: Shi Yunying , Li Yamei , Lin Tao , Wang Xianding , Yan Lin , Li Yi , Bai Yangjuan , Yang Cuili , Wan Zhengli , Wang Lanlan
Published: June 2020

Background and Aims

Desensitization therapy has enabled successful transplantation of renal allografts across the ABO blood group barrier, which significantly expands the living donor pool. Whether the B cell depletion induced by rituximab would affect the proportions of peripheral blood (PB) and lymph nodes (LN) T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, whose survival depends on B cells, in ABO-incompatible kidney transplant recipients (ABOi-KTRs) is unknown.

Method

PB and LN samples were simultaneously collected on the day of transplantation from 14 ABOi-KTRs and 12 ABO-compatible KTRs (ABOc-KTRs) between January to October 2019. Additional PB from ABOi-KTRs was obtained before desensitization treatment (Rituximab+plasmapheresis+ immunosuppression). All recipients were undergone living donor transplantation. The frequency of B, Tfh (CD4+CXCR5+Foxp3-) and Tfr (CD4+CXCR5+Foxp3+) cells and the expression the PD-1, ICOS on Tfh and Tfr cells were quantified by flow cytometry.

Results

After desensitization treatment, significantly lower proportions of PB and LN B cells were observed in ABOi-KTRs (ABOi-a) when compared to ABOc and ABOi-b (ABOi-KTRs before desensitization) groups (Fig. A). Circulating Tfr cells decreased significantly after desensitization therapy, while no difference was found in LN Tfr cells (Fig. F). In addition, ABOi-a group showed higher expression of PD-1 on Tfr cell within PB, but lower within LN when compared to ABOi-b and ABOc groups, respectively (Fig. G). For Tfh proportion and its expression of PD-1 and ICOS within PB and LN, no significant difference was observed among groups (Fig. B-D). Significantly lower ratio of Tfr to Tfh was observed after ABO desensitization (Fig. E).

Conclusion

Our results indicated that ABO desensitization had significant suppression effects on B cells both within the PB and LN of ABOi-KTRs. In addition, the desensitization treatment mainly affected circulating Tfr cells, instead of Tfh cells, which shifted the balance between Tfr and Tfh cells towards Tfr cells in PB. Whereas, this treatment showed no influence on Tfh and Tfr populations within LN in ABOi-KTRs.
P1756ANTI-ABO ANTIBODY- VERSUS ANTI-HLA ANTIBODY-INDUCED ANTIBODY MEDIATED REJECTION IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT PATIENTS: RELATIVE INCIDENCE AND PHENOTYPE DIFFERENCE
Authors: Kong Jinmin , Kwon Hyukyong , Son Sung , Whang EUN
Published: June 2020

Background and Aims

Antibody-mediated rejection(AMR) in ABO incompatible(ABOi) kidney transplant(KT) patients can either be due to donor-specific anti-HLA antibody(DSA) or anti-blood group antibody. The relative frequency and possible phenotype difference of these two types of AMR in ABOi KT patients have not been reported.

Method

Of 111 ABOi KT patients between 2007 and 2019 in our center, 15(13.5%) patients developed acute AMR diagnosed by indication biopsy. Since there is no histologic distinction between DSA- and anti-ABO-induced AMR, we assumed the causative antibody in each case based on anti-ABO level and DSA, measured in serum collected at the time of AMR.

Results

Of these 15 cases of acute AMR, 5 were attributable to anti-ABO(ABO-AMR) since anti-ABO titer was higher (≥16) and DSA was undetectable at the time of rejection. Five cases were attributable to DSA(DSA-AMR) since DSA was detectable and anti-ABO was lower during rejection. Another 3 cases with lower anti-ABO titer and undetectable DSA were also assumed to be DSA-induced, since this low level of anti-ABO is unlikely to cause rejection and DSA can be undetectable in DSA-induced AMR by adsorption of Ab on graft, as frequently seen in ABO-compatible patients Two cases with both higher anti-ABO titer and detectable DSA was regarded as undetermined. The onset of acute AMR was within 2 weeks in all cases(median 7.0 days) and comparable between DSA- and ABO-AMR. Initial anti-ABO titer was also not statistically different; median(range) 256(64-4096) in ABO-AMR and 64(16-256) in DSA-AMR. All the 5 patients with ABO-AMR had negative PRA before KT, whereas 5 of 8 patients with DSA-AMR had positive PRA before KT, and two DSA-AMR patients had preformed DSA before KT. There was no difference in peak creatinine and response to treatment. All the AMR were recovered by treatment and no graft was lost to rejection. No patient with ABO-AMR developed chronic AMR whereas one of DSA-AMR patients developed chronic AMR.

Conclusion

In summary, among 15 cases of acute AMR, 5 were ABO-AMR, 8 were DSA-AMR and 2 were undetermined. There was no difference in clinical feature between DSA- and ABO-AMR. No patient with ABO-AMR developed chronic AMR.
P1757RITUXIMAB FOR RECURRENCE OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS AFTER KIDNEY TRANSPLANTATION: RESULTS OF A NATIONWIDE STUDY
Authors: Lanaret Camille , Anglicheau Dany , Vincent Audard , Lambert Celine , Couzi Lionel , Buchler Matthias , Ohlmann Sophie , Bertrand Dominique , Jean-Philippe Rérolle , Thierry Antoine , Maillard Nicolas , Schvartz Betoul , Golbin Leonard , Pernin Vincent , Ducloux Didier , Bouvier Nicolas , Poulain Coralie , Heng Anne Elisabeth , Greze Clarisse , Malvezzi Paolo , Martinez Frank , Kamar Nassim , Garrouste Cyril
Published: June 2020

Background and Aims

The indication of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation (KT) remains controversial. The objective of our study was to evaluate the benefit and tolerability of adding RTX to the standard of care (SOC) comprising plasmapheresis (PP), corticosteroids, and high-dose anticalcineurins for the treatment of FSGS recurrence after KT.

Method

This retrospective, multicenter study reports on 148 patients, transplanted between 31 December 2004 and 31 December 2018, aged 39.9 + 13.4 years, who developed FSGS recurrence at 7 [3–23] days. In all 109 patients received a SOC (Group 1). RTX was introduced in this group after more than 28 days of SOC for failure or for therapeutic intensification (n = 19, Group 1a), or for early discontinuation of PP (n = 12, Group 1b); 39 patients received RTX associated at the outset with SOC (Group 2).

Results

We observed 46.6% complete remission (CR) and 33.1% partial remission (PR). Ten-year graft survival was 65.6% [51.4–76.6] and 13.4% [3.4–30.0] in responders and non-responders respectively. There was no difference in CR + PR rate between G1 (82.5%) and G2 (71.8%), p = 0.08, confirmed by propensity score +4.3% (95% CI [−9.0%-17.5%], p = 0.53). Following addition of RTX (Group 1a), we observed a CR rate of 26.3% and a PR rate of 31.6%. Patients with and without RTX experienced similar rejection rates (18.6% and 28.2%, p = 0.17) and infection rates (71.4% and 79.5%, p = 0.40). In multivariate analysis, the infections were associted with hypogammaglobulinemia <5g/l (OR = 8.04, 95% CI [1.65,39.25], p = 0.01).

Conclusion

Rituximab could be used in cases of SOC failure or in remission patients for early weaning of plasmapheresis, without increasing infectious risk.
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

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

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

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<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<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<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

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

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 < 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

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<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

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 > 0.05). Cytokines did not change in relation to exercise within or between groups over time (P > 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

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

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<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<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.
P1788FACTORS AFFECTING EGFR SLOPE IN KIDNEY TRANSPLANT RECIPIENTS DURING 48 MONTHS AFTER TRANSPLANTATION
Authors: Rambabova Bushljetikj Irena , Dohcev Saso , Mojsova Mijovska Maja , Stavridis Sotir , Stankov Oliver , Spasovski Goce
Published: June 2020

Background and Aims

After the first year following kidney transplantation approximately 3-5% of grafts fail each consecutive year. Many factors have impact on the graft function and only a few may be modifiable. Monitoring of the graft function by serum creatinine concentrations and estimated glomerular filtration rate (eGFR) are recommended methods for evaluation. The aim of the study was to assess the decline of graft function defined by change in the annual eGFR slope and factors that might affect it.

Method

A total number of 55 adult patients with living donor kidney transplant (LDKT) were included in the study. The inclusion criteria were: first transplantation of one organ - kidney, use of living donor related or unrelated (emotionally related - spouses) donor. Clinical and biochemical variables, serum creatinine, BUN, protein status, 24 hours proteinuria and body weight were analyzed at 12, 24, 36 and 48 months after transplantation. The Nankivell equation for estimating glomerular filtration rate was used to calculate the slope of renal function over time (1 to 4 years post-transplantayion) by linear regression analysis.

Results

Out of 55 kidney transplant recipients 18 (33.3%) were female. The majority of transplants had good function (eGFRNankivell ≥ 60 ml/min) at 1 year.

The average GFR at 12 months was 67.81±16.7 mL/min/1.73 m2 with majority of patients at stage 2 of chronic kidney disease classification. Thirty eight patients had eGFR slope <5ml/min/year and 12 patients had a higher slope ( >5ml/min/year).

Only 5 patients (∼ 9%) have graft failure during the period of follow up of 48 months. The average slope decline calculated with linear regression analysis was -3.42 ± 3.2 mL/min/year (range -12.38 – 3.29 ) (slope ± standard error). Proteinuria was predictive for worsening of the graft function. Rapid progressors have been associated with a higher proteinuria at 24 and 48 months: 0.35 ± 0.39 g/24h, median 0.24 (range 0.11 – 0.43 g/24h) and 0.49 ± 0.59 g/24h, median 0.31 (range 0.14 – 0.48 g/24h), (p=0.044 and p=0.021, respectively).

Younger patients have more rapid eGFR slope decline (slope (-7.81 ± 2.12 vs. -2.40 ± 1.3, mL/min/year, p=0,0001). The mean recipient age in the group with stabile eGFR slope was 37.59± 8.7, and in the group with rapid progression was 29.1 ± 8.6 years (p=0.0046).

Conclusion

Proteinuria after kidney transplantation has been identified as a risk factor associated with poor graft survival. Younger renal transplant recipients are associated with more rapid decline of the graft function that could be partially explained with their more potent immune response
P1789DE NOVO INFLAMMATORY BOWEL DISEASE AFTER KIDNEY TRANSPLANTATION - REPORT OF THREE CASES
Authors: Obrencevic Katarina , Petroviä‡ Marijana , Vavic Neven , Petrovic Stanko , Tufegdzic Ivana , Rabrenovic Violeta , Tadiä‡ Jelena , Mijuskovic Mirjana
Published: June 2020

Background and Aims

Inflammatory bowel disease (IBD) are not common after kidney transplantation. Development of IBD in the patient on immunosuppression is unexpected, because IBD is believed to be the result of inappropriate and ongoing activation of the mucosal immune system and immunosuppressive drugs are used in the treatment of IBD. The aim of our study was to evaluate the occurrence of de novo IBD, ulcerative colitis and Crohn’s disease, in the patients who received kidney transplant in our hospital, the time after transplantation and the immunosuppression therapy when diagnosis was made.

Method

We used an electronic medical archival system to identify the patients with IBD. Between 1996 and 2018 a total of 462 kidney transplantations were done in Military Medical Academy. Analysis in this study included 400 patients who were regulary controlled in our hospital. Demographic data and clinical findings including age, sex, primary renal disease, type of kidney donor, and immunosuppressive therapy were evaluated. The time of the occurrance of the IBD after transplantation, the colonoscopy and pathologic findings were also noted.

Results

de novo IBD was observed in three patients 19, 11 and 7 years after kidney transplantation respectively. In all patients end-stage renal disease was due to chronic glomerulonephritis without histology verification. Family history was negative in all. They were male, age 40, 42 i 47 years respectively when diagnosis was made. Their immunosuppressive regimen included prednisone, mycophenolate mofetil (MMF) and tacrolimus with a trough level between 5 and 7 ng/ml. They all developed constitutional symptoms with significant weight loss and fever, abdominal pain and cramps, diarrhoea which was in one case bloody. Infectious and other etiology was excluded. Colonoscopy showed ulcerative colitis in two patients and Crohn’s disease in one. The patients with ulcerative colitis responded on maintenance therapy combined with 5-aminosalicylic acid, but one of them had common flare-ups with mild clinical picture. The patient with Crohn’s disease was successfully treated with azathioprine instead of MMF with high-dose steroids.

Conclusion

We concluded that new onset of IBD can develop after kidney transplantation despite use of immunosuppressive therapy. It should be considered in all transplanted patients who develop gastrointestinal complaints. The future studies could answer why the immunosuppressive therapy is not effective for IBD in these group of patients.
P1795ASSOCIATION BETWEEN T CELL INFILTRATION IN BIOPSY PROVEN ACUTE T CELL MEDIATED REJECTION AND RESPONSE TO THERAPY
Authors: Dalili Nooshin , Ahmadpoor Pedram , Einollahi Behzad , Azhdari Tehrani Hamed
Published: June 2020

Background and Aims

Renal transplantation is considered as the best replacement therapy for advanced ESRD patients. An allograft rejection happens as a result of post transplant immune reactions, which change the outcome of the organ transplantation. Today a major challenge in the field of transplantation is the identification of easy, reliable and non-invasive markers or methods that being able to predict the probability of organ rejection. One of the possible methods is looking for type of infiltrated cells in tissue obtaining by biopsy stained with specific cellular markers and assesses the infiltration of these cells in different types of rejection. Here the severity of CD3, CD20, Th17 and FOXP3 infiltration in patients with biopsy proven acute cellular rejection was evaluated based on IHC staining, whether these specific infiltrations can show an association with graft outcome or not.

Method

50 patients with biopsy proven Acute T Cell Mediated Rejection (ATCMR) recruited. Previous clinical data and 1 year clinical follow up collected. The entire specimen assessed for infiltration of CD3, CD20, FOXP3 Tregs and Th17 with IHC. Patients divided into subgroups: stable graft function versus impaired graft function based on serum creatinine course in one year follow up after rejection therapy and appropriate response to treatment versus failure to response, based on allograft function throughout the course of admission.

Results

In impaired graft function arm, FOXP3 (7.88 vs. 8.02 with P-value 0.96) and Th17 cells were higher (5.01 vs. 10.2 with P-value 0.24) but with non-significant values. FOXP3/Th17 ratio was higher in stable group (1.4 vs. 1.12 with P-value 0.22). In failure to response to therapy group both FOXP3 (9.95 vs. 6.63 with P-value 0.1) and Th17 (11.3 vs. 8.3 with P-value 0.15) cells were higher. FOXP3/Th17 ratio was higher in proper response group (1.19 vs. 1.15 with P-value 0.8). No significant difference was obtained between CD3 and CD20 infiltration in these two groups.

Conclusion

Final results showed that Th17 has more important role in predicting the graft outcome and response to treatment and FOXP3 infiltration had a minor part. This may be in controversial with previous facts about the role of FOXP3 cells, which drive the allograft into stable condition.