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Background Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. Methods In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. Results All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P Conclusions Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.

Purpose An outbreak of a novel respiratory disease due to coronavirus species was emerged in 2019 and named as Coronavirus Disease-2019 (COVID-19). Clinical and immunological factors affecting the course of COVID-19 in kidney transplant recipients (KTR) are not well-known. Methods In this prospective observational study, we presented 20 KTR with COVID-19 pnemonia and examined the factors predicting the severity of COVID-19. A total of 10 KTR without COVID-19 was used as control group. Lymphocyte subsets were determined by flow cytometry. In 13/20 patients, immunophenotyping was repeated 1 week later. Results Mean age of the patients was 50 ± 9 years. Patients were classified as mild–moderate (oxygen saturation: SO2 > 90%) and severe disease groups (SO2 ≤ 90%). Serum albumin and hemoglobin were lower and CRP, fibrinogen and peak d-dimer were higher in severe group. Peak CRP was inversely associated with nadir SO2 (r = − 0.68, p = 0.001). Neutrophil/lymphocyte ratio was higher in severe group (p = 0.01). CD3 + and CD4 + cells were lower and NK cell percentage (CD16 + 56 +) was higher in severe group. Percentage of spontaneously activated CD8 cells (CD8 + CD69 +) was higher in severe group. In comparison of KTR with and without COVID-19, CD8 + cells were lower but NK cell percentage was higher in KTR with COVID-19. Conclusion In this pilot study, increased NK cells, activated CD8 + cells and decreased CD3 + and CD4 + cells were associated with severity of COVID-19 in KTR. Peripheral immunophenotyping of lymphocyte subtypes may provide prognostic information about the clinical course of COVID-19 in KTR. Supplementary Information The online version contains supplementary material available at 10.1007/s11255-021-02947-y.

There is an information gap about the public's interest in nephrological diseases in the COVID-19 era. The objective was to identify public interest in kidney diseases during the pandemic. In this infodemiology study, Google Trends was queried for a total of 50 search queries corresponding to a broad spectrum of nephrological diseases and the term "nephrologist." Two time intervals of 2020 (March 15-July 4 and July 5-October 31) were compared to similar time intervals of 2016-2019 for providing information on interest in different phases of the pandemic. Compared to the prior 4 years, analyses showed significant decreases in relative search volume (RSV) in the majority (76%) of search queries on March 15-July 4, 2020 period. However, RSV of the majority of search queries (≈70%) on July 5-October 31, 2020 period was not significantly different from similar periods of the previous 4 years, with an increase in search terms of amyloidosis, kidney biopsy, hematuria, chronic kidney disease, hypertension, nephrolithiasis, acute kidney injury, and Fabry disease. During the early pandemic, there have been significant decreases in search volumes for many nephrological diseases. However, this trend reversed in the period from July 5 to October 31, 2020, implying the increased need for information on kidney diseases. The results of this study enable us to understand how COVID-19 impacted the interest in kidney diseases and demands/needs for kidney diseases by the general public during the pandemic.

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.

We compared the outcomes associated with plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption (IA) in the treatment of late antibody mediated rejection (AMR).Sixty-nine kidney transplantation (KTx) recipients with late AMR were retrospectively categorized according to management with PE (n = 30), DFPP (n = 22) or IA (n = 17). Allograft loss was compared across treatment groups by Kaplan-Meier analysis and Cox regression.Study groups were similar regarding age, sex, donor type, kidney function, donor specific antibodies, and post-KTx follow-up time. Five-year graft survival trended higher with IA (70.6%) compared to PE (36.7%) and DFPP (27.3%) (p = 0.06). In multivariate Cox regression, baseline eGFR (HR per ml/min/1.73 mThese results motivate the need for continued assessment of rituximab and plasmapheresis in larger studies.

BACKGROUND AND AIMS Galectin-9, interferon-inducible protein-10 (IP-10) and sialoadhesin (SIGLEC-1) are considered as potential biomarkers reflecting disease activity in patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum and urine galectin-9, IP-10 and SIGLEC-1 with disease activity in patients with SLE. Also, we compared the results with ANCA-associated vasculitis (AAV) to test the specificity of the biomarkers. METHOD A total of 63 patients with active SLE (31 renal and 32 extrarenal) were included in the study. A total of 30 patients with inactive SLE (15 renal and 15 extrarenal), 17 with renal active AAV and 32 healthy volunteers were selected as control groups. Serum (s) and urine (u) levels of galectin-9, IP-10 and SIGLEC-1 were tested using ELISA. Urine levels of biomarkers were normalized by urine creatinine. RESULTS Of 142 participants, 109 (76.7%) were female and median age was 36 (28.75–48) years. Groups were comparable with regard to sex and age distribution except for AAV. In AAV group, seven patients (41.1%) were female and median age was 60 (48–65.5) years. Proliferative lupus nephritis (LN) (class III/III + V and IV/IV + V) were found in 22 patients with active renal SLE (70.9%), while 6 patients (19.3%) had pure class V and 3 (9.7%) had class II LN. Levels of sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 were significantly higher in the active SLE group compared to the inactive SLE group (sIP-10; P = 0.046, uIP-10; P CONCLUSION sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 are associated with disease activity in SLE. None is able to discriminate active renal from active extrarenal disease. sIP-10 and uIP-10 are specific for active SLE compared to renal active AAV. sGalectin-9 may be a valuable biomarker to monitor response after treatment for active disease. Funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: TSA-2019–34 218.

BACKGROUND AND AIMS There is not enough data on the post-COVID-19 (coronavirus disease 2019) period for peritoneal dialysis (PD) patients affected from COVID-19. We aimed to compare the clinical and laboratory data retrospectively obtained in the follow-up of PD patients after COVID-19 with a control PD group. METHOD This study, supported by the Turkish Society of Nephrology, is a national multicenter retrospectively case–control study involving adult PD patients with confirmed COVID-19, using data collected from 21 April 2021 to 11 June 2021. A control PD group was also formed from each PD unit, from patients with similar characteristics but who did not have COVID-19. Patients in the active period of COVID-19 were not included. Data at the end of the first month and within the first 90 days, as well as other outcomes, including mortality, were investigated. RESULTS A total of 223 patients (COVID-19 group: 113, control group: 110) from 28 centers were included. The duration of PD in both groups was similar [median (IQR):3.0 (1.88–6.0) years and 3.0 (2.0–5.6)], but the patient age of the COVID-19 group was lower than the control group [50 (IQR:40–57) years and 56 (IQR:46–64) years, P CONCLUSION Mortality in the first 90 days after COVID-19 in PD patients with COVID-19 is not different from the control PD group. However, some of these patients continue to experience significant problems, especially respiratory system symptoms, malnutrition, and hypervolemia.

Background This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. Methods We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell–mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. Results After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44–4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan–Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups. Conclusions Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.

Background We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN). Methods A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome. Results Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome. Conclusion Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.

Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS.Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed.Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient.Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) caused a pandemic that first discovered in Wuhan, China. While 10% of the patients have asymptomatic infection, 15-20% have lung involvement, 5-10% have multiple organ failure, and macrophage activation syndrome. Chronic respiratory diseases, diabetes mellitus, hypertension, and cancer are risk factors for mortality. Prognosis or optimal treatment strategy for renal transplant recipients in SARS-CoV-2 infection is still unknown. Besides fatal cases, there were also milder case reports. In addition, COVID-19 treatment and the maintenance immunosuppression strategy is still under debate. Antiviral therapies and drug interactions are special topics for these patients. To the best of our knowledge, favipiravir and anti-cytokine treatments have not been previously reported in a kidney transplant recipient with SARS-CoV-2 infection before. We report a case of SARS-CoV-2 infection in a kidney transplant recipient with fatal outcomes.

Introduction: There are not enough data on the post-CO-VID-19 period for peritoneal dialysis (PD) patients affected from COVID-19. We aimed to compare the clinical and laboratory data of PD patients after COVID-19 with a control PD group. Methods: This study, supported by the Turkish Society of Nephrology, is a national, multicenter retrospective case-control study involving adult PD patients with confirmed COVID-19, using data collected from April 21, 2021, to June 11, 2021. A control PD group was also formed from each PD unit, from patients with similar characteristics but without COVID-19. Patients in the active period of COVID-19 were not included. Data at the end of the first month and within the first 90 days, as well as other outcomes, including mortality, were investigated. Results: A total of 223 patients (COVID-19 group: 113, control group: 110) from 27 centers were included. The duration of PD in both groups was similar (median [IQR]: 3.0 [1.88-6.0] years and 3.0 [2.0-5.6]), but the patient age in the COVID-19 group was lower than that in the control group (50 [IQR: 40-57] years and 56 [IQR: 46-64] years, p < 0.001). PD characteristics and baseline laboratory data were similar in both groups, except serum albumin and hemoglobin levels on day 28, which were significantly lower in the COVID-19 group. In the COVID-19 group, respiratory symptoms, rehospitalization, lower respiratory tract infection, change in PD modality, UF failure, and hypervolemia were significantly higher on the 28th day. There was no significant difference in laboratory parameters at day 90. Only 1 (0.9%) patient in the COVID-19 group died within 90 days. There was no death in the control group. Respiratory symptoms, malnutrition, and hypervolemia were significantly higher at day 90 in the COVID-19 group. Conclusion: Mortality in the first 90 days after COVID-19 in PD patients with COVID-19 was not different from the control PD group. However, some patients continued to experience significant problems, especially respiratory system symptoms, malnutrition, and hypervolemia. © 2022 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7–7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Subclinical atherosclerosis and cardiovascular events are common even in young normotensive patients with autosomal dominant polycystic kidney disease (ADPKD). Our aim was to examine the relationship between serum fibroblast growth factor-23 (FGF-23) levels, left ventricular global longitudinal strain (LV-GLS), arterial stiffness (AS), and carotid intima-media thickness (CIMT) in patients with ADPKD with preserved kidney function. The relationship between albuminuria, AS, LV-GLS, CIMT, 24-hour ambulatory blood pressure measurement, and FGF-23 was examined in 52 normotensive and hypertensive patients with ADPKD and a matched control group of 35 subjects. AS was assesed with brachial-ankle pulse wave velocity, LV-GLS was measured with speckle-tracking echocardiography. FGF-23 was measured with enzyme-linked immunosorbent assay. The microalbumin/creatinine ratio was significantly higher in the ADPKD group than in the control group (p?0.001). Serum FGF-23 levels were similar between the study and control group. LV-GLS value tended to be impaired and CIMT to be higher in the ADPKD group compared to controls (?18.1?±?2.6 vs. -19.4?±?3.1?%, p?=?0.08; 0.75?±?0.1 vs. 0.68?±?0.1 mm, p?=?0.09, respectively). The augmentation index was significantly higher in the ADPKD group than in the control group (26.2?±?12.5 vs. 16.4?±?11.2 mmHg/mmHg, p?=?0.01). Our study supports subclinical impairment in arterial and cardiac functions in the early period of ADPKD. However, none of these factors was found to be associated with serum FGF-23 levels.

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN).A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining.Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021].An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Introduction Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. Method Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. Results A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7–30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). Conclusion Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.

Background:Infliximab (IFX) plays a key role in the management of severe and refractory manifestations of Behçet syndrome (BS). However we had previously shown that its sustained use may be limited due to adverse events and lack of patient compliance (1).Objectives:To assess the retention rate of IFX, adverse events, causes of discontinuation and outcome after cessation of IFX in a larger group of BS patients who were followed in a tertiary center.Methods:The charts of BS patients who were prescribed IFX between 2004 and 2020 were reviewed to determine demographic features, reasons for IFX use, previous and concomitant drugs, IFX duration, reasons for cessation of IFX and time to flare following cessation of IFX. Follow-up was censored on March 2020.Results:A total of 252 patients (195 men, mean age 40±10 years) received IFX for uveitis (n=122), vascular involvement (n=82), parenchymal neurologic involvement (n=32), gastrointestinal involvement (n=11), arthritis (n=10), mucocutaneous involvement (n=4), and secondary amyloidosis (n=1). Ten patients had more than 1 involvement requiring IFX.During a median follow-up of 52 (IQR: 30-88) months, 122 (48%) patients were still receiving IFX for a median period of 33 (IQR: 15-56) months while 130 (52%) patients had discontinued IFX after a median follow-up of 17 (IQR: 7-31) months. Reasons for discontinuation were remission in 25 (19%) patients, adverse events in 39 (30%), lack of efficacy in 23 (18%) (4 primary and 19 secondary), lack of patient compliance in 36 (28%), pregnancy in 4, and preparation for surgery in 3 patients.Adverse events (n=39) that required the cessation of IFX were infusion reaction (n=17), infection (n=7), hepatotoxicity (n=4), malignancy (n=4), palmoplantar psoriasis (n=3), lichen planus (n=1), drug induced lupus (n=1), splenic infarction (n=1), and a decrease in left ventricular ejection fraction (n=1).Among the 25 patients who discontinued IFX due to remission, 5 (20%) had a relapse after 4, 21, 26, 29, 38 and 46 months. The remaining patients did not experience a relapse during a median follow-up of 35 (IQR: 24-68) months.At the end of the follow-up, 2 patients had died due to lung adenocarcinoma during IFX treatment and 3 patients had died 1 year, 3 and 8 years after IFX discontinuation. The causes of death were with right heart failure due to pulmonary hypertension in 1, and severe nervous system involvement in 2 of the patients.Conclusion:Despite its successful use for the management of potentially organ and life-threatening manifestations in more than half of our patients with BS, long term maintenance was not possible in 42%, mainly due to adverse events, lack of patient compliance and inefficacy.Reference:[1]Esatoglu SN, Tukek B, Taflan SS, et al. SAT0258 Drug Retention Rate and Prognosis After Discontinuation of Infliximab in Patients with Behçet Syndrome. Annals of the Rheumatic Diseases 2020;79: 1071-1072.Reasons for infliximab treatmentNo of patientsNo (%) of patients who were still receiving infliximabNumber (%) of patients who discontinued infliximabReasons for discontinuationDuration of infliximab use(median (IQR) months)Eye involvement12259 (48)63 (52)Remission (n=17)Inefficacy (n=10)Lack of patient compliance (n=19)Adverse event (n=12)Others (n)=5)28 (12.5-52)Vascular involvement8240 (49)42 (51)Remission (n=10)Inefficacy (n=7)Lack of patient compliance (n=12)Adverse event (n=12)Others (n=4)18.5 (9-33.5)Parenchymal neurologic involvement3221 (66)11 (34)Adverse event (n=8)Inefficacy (n=2)Lack of patient compliance (n=1)25 (14.5-50)Gastrointestinal involvement114 (36)7 (64)Remission (n=1)Inefficacy (n=1)Adverse event (n=2)Lack of patient compliance (n=4)7 (2-17)Joint involvement102 (20)8 (80)Inefficacy (n=1)Adverse event (n=5)Lack of patient compliance (n=2)20 (4-35)Mucocutaneous involvement431Inefficacy (n=1)6, 10, 12, 104 monthsAA amyloidosis101Inefficacy (n=1)6 yearsDisclosure of Interests:None declared

We aimed to investigate the effects of glomerular C3 deposition on clinical, histopathological features, and outcomes of patients with primary membranous nephropathy (MN).A total of 261 patients with biopsy-proven primary MN, who were on follow up for at least 6 months, were included in the study. The patients were grouped according to their C3 immunostaining in kidney biopsy samples at the time of diagnosis: Low intensity [LI; (C3 1 +)] and high intensity [HI; (C3 2 + or C3 3 +)]. The primary outcome was the development of kidney failure. Complete (CR) or partial remission (PR) was defined as secondary outcome.Sixteen patients reached the primary outcome after a median follow-up of 33.8 months. Patients in the high intensity group (119 cases) had lower eGFR and higher proteinuria at admission and last follow-up compared to patients in the low intensity group (142 cases). Also, more patients in the high intensity group reached the primary outcome compared to patients in the low intensity group: twelve patients (10.1%) in the high intensity group and four patients (2.8%) in the low intensity group reached the primary outcome (p = 0.015). Kaplan-Meier analysis demonstrated that patients in the high intensity group had a higher risk for kidney failure (p = 0.02). In multivariate logistic regression analysis, high intensity C3 deposition and initial estimated glomerular filtration rate (eGFR) indepenently predicted primary outcome.Extensive glomerular C3 deposition is a predictor of kidney failure in patients with MN.

Background and Aims Membranous nephropathy (MN) is the most common cause of glomerulonephritis in non-diabetic adults. B-cell dysfunction is an important pathway involved in pathogenesis. We, therefore, investigated effects of rituximab (RTX) on the outcome of patients with relapsed or refractory primary MN. Method In this retrospective analysis, 48 patients with primary MN were evaluated. Patients, who had relapsed or refractory biopsy-proven disease, with a nephrotic-range proteinuria despite at least six months of prior immunosuppressive therapy using corticosteroids, calcineurin inhibitors or mycophenolic acid derivatives, which were used according to KDIGO guidelines. All patients received at least 2 doses of 375 mg/m2 of RTX. Proteinuria and serum albumin levels of the patients were recorded at baseline, and 3,6,12,18 and 24 months. Results Of 48 patients who participated in this study, 27(56.3%) were male. Mean age was 45.3±17.2 years. Results of serum anti-phospholipase-A2-receptor (PLA2R) were available in 31 patients, 23 of whom (74%) were positive. Proteinuria levels at 3, 6, 12, 18, and 24 months after treatment with RTX showed a significant decrease when compared to baseline (p Conclusion Treatment with RTXiseffective in patients suffering from relapsed or refractory primary MN.

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.

Background and Aims Although hematuria is the cardinal symptom of IgA nephropathy (IgAN), its effects on the outcome have not been studied extensively. We, therefore, aimed to analyze the association between microhematuria and clinicopathological features as well as outcome parameters in adult patients with IgAN. Method 129 adults with IgAN, diagnosed by kidney biopsy, and followed up for a median duration of 54.5 (IQR: 24.25-92.75) months, were included in this retrospective study. Urinary sediment analyses during the bouts of macrohematuria were not taken into consideration. For the purpose of this analysis, microhematuria was described as ≥5 red blood cells per high-power field (RBCs/hpf) and classified as mild (5-9 RBCs/hpf), moderate (10-19 RBCs/hpf), or severe (≥20 RBCs/hpf). Study outcome (event) was defined as at least a 50% reduction in baseline eGFR or development of stage 5 chronic kidney disease (eGFR Results Demographic, clinical, laboratory and histopathological features of patients at the time of diagnosis are summarized in the table. Usage of ACEi/ARBs [75/81 (92.5%) vs 45/48 (93.75%), p=0.803], fish oil [30/81 (37%) vs 19/48 (39.5%), p=0.773], azathioprine [16/81 (19.7%) vs 10/48 (20.8%), p=0.882] and mycophenolic acid derivatives [14/81 (17.2%) vs 11/48 (22.9%), p=0.434] were comparable among the patients with and without microhematuria. Corticosteroids were more frequently used in patients with microhematuria [41/81 (50.6%) vs 17/48 (35.4%)], although this difference was not statistically significant (p=0.093). Overall 30 patients (23.2%) reached the study outcome, and there were no differences between patients with (19, 23.4%) and without (11, 22.9%) microhematuria (p=0.944). Kaplan-Meier analysis revealed that event free survival rates were similar across study groups: 77.1% for patients without microhematuria; while 80% for mild, 77.3% for moderate, and 72.7% for severe microhematuria (p=0.436) (Figure). Microhematuria did not predict the study outcome when multivariable Cox regression analyses were performed [HR: 1.847 (95% CI: 0.696-4.904), p=0.218]. Throughout the follow-up, microhematuria disappeared (dropped below 5 RBCs/hpf) in 43 patients (53%), 8 of whom (18.6%) reached the study outcome as compared to 11 patients (28.9%) with persistent microhematuria (p=0.273). Disappearance of microhematuria was not a predictor of study outcome, as well [HR: 0.386 (95% CI: 0.068-2.180), p=0.281]. Conclusion Microhematuria is not associated with renal outcomes of adult patients with IgAN.

Background and Aims The largest data on the epidemiology of primary glomerular diseases (PGD) are obtained from the databases of countries or centers. Here, we presented the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD)Working Group. Method The data of patients who underwent renal biopsy and diagnosed as primary glomerular disease were recorded in the database prepared for the study. Between May 2009 and May 2019, a total of 4399 patients from 47 centers were evaluated. Basal data of 3875 patients were analyzed after exclusion of those lacking light microscopy and immunofluorescence findings. Results The mean age was 41.5 ± 14.9 years. Of the patients, 1690 were female (43.6%) and 2180 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGH was IgA nephropathy (25.7%), followed by membranous nephropathy (25.6%) and FSGS (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. Mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. Median proteinuria was 3300 (IQR: 1467-6307) mg / day, mean serum creatinine, estimated GFR and albumin values were 1.4 ± 1.5 mg / dl, 80.7 ± 39.1 ml / min and 3.2 ± 0.9 g / dl, respectively. Conclusion In Turkey, the incidence of IgA nephropathy patients have become more common than membranous nephropathy among PGD patients diagnosed with renal biopsy.

Objectives TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. Methods Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p Conclusion sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

Tuberculous mastitis is a rare presentation of tuberculosis, which is a major health problem in kidney transplant recipients due to its high incidence and prevalence, and difficulty in diagnosis as well as high risk of morbidity and mortality. In daily practice, physicians may frequently be led to a misdiagnosis such as breast carcinoma or abscess. We believe it is crucial for clinicians to recognize this important presentation of the disease. Therefore, we present a case of tuberculous mastitis in a kidney transplant recipient who was admitted with fever of unknown origin and successfully treated using standard anti-tuberculosis therapy without any complications.

Background:Vascular involvement is an important cause of morbidity and mortality in patients with Behçet syndrome (BS). TNF inhibitors have been reported to be effective for almost all serious manifestations of BS but data on vascular involvement is still limited.Objectives:To survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center.Methods:We reviewed the charts of all BS patients who used IFX and identified those who used this drug for vascular involvement. A standard form was used for extracting data on demographic and clinical features, type of vascular involvement, concomitant immunosuppressives, duration of IFX use, relapses, adverse events and outcome.Results:83 patients (67 men, 16 women, mean age 39.5 ± 8.4 SD years) had used IFX for vascular involvement. The number of patients with each type of vascular involvement as the main indication for IFX, and previous treatment modalities right before IFX are presented in the Table 1. 33 patients had more than 1 type of vascular lesion. Additional organ manifestations were eye involvement in 32, central nervous system involvement in 4 and gastrointestinal involvement in 3 patients. All but one patient used IFX at a dose of 5 mg/kg every 6-8 weeks. All patients used concomitant prednisolone and 51 received pulse methylprednisolone during induction. Other concomitant medications were azathioprine in 21 and mycophenolate mofetil in 4 patients. Outcome of IFX treatment at the end of a mean follow-up of 25.9 months (range 1-103) is tabulated according to arterial and venous involvement (Table 1). Overall, 57/83 (68%) patients obtained remission with no further relapses and IFX could be stopped in 12 (14%) of them. IFX was discontinued due to adverse events in 15 patients. These were allergic reactions in 8, tuberculosis, disseminated zona, lung adenocarcinoma, fibromyxoid sarcoma, heart failure, systemic lupus erythematosus, and palmoplantar pustulosis in 1 patient each. Three patients had died. Causes of death were lung adenocarcinoma in one patient and pulmonary hypertension related right heart failure due to pulmonary artery thrombosis in 2 patients.Conclusion:Infliximab seems to be beneficial in Behçet syndrome patients with vascular involvement, even in those who are refractory to immunosuppressives and corticosteroids. No further relapses occurred in 68% of the patients, and adverse events leading to discontinuation were observed in 18%.Arterial Involvement (n=36)Venous Involvement (n=47)Main reason for infliximab usePulmonary artery aneurysm and/or thrombosis, n=29Peripheral artery aneurysm, n=4Aortic aneurysm, n=3Vena cava superior and/or inferior thrombosis, n=5Lower extremity DVT, n=24Budd-Chiari syndrome, n=4Intracardiac thrombosis, n=2Dural sinus thrombosis, n=7Leg ulcer, n=5Previous treatmentFirst line infliximab413Corticosteroids3438Cyclophosphamide (CYC)25 (15/25 refractory to CYC; 10/25 for maintenance after CYC)11 (8/11 refractory to CYC; 3/11 for maintenance after CYC)Interferon-alpha-13Azathioprine2117Mycophenolate Mofetil12Cyclosporine A-2None due to non-compliance21OutcomeRemission, still on infliximab1623Discontinued due to remission48Discontinued due to adverse events59Discontinued due to relapse53Discontinued due to non-compliance53Died2 (1 had previously discontinued due to relapse)1Disclosure of Interests:None declared

Background:The causes of hospitalization may provide important information on the course of diseases and treatment-related adverse effects.Objectives:We aimed to determine the causes and outcome of hospitalizations among patients with Behçet Syndrome (BS) in a dedicated center.Methods:We surveyed hospitalization records in our clinic between January 2002 and December 2019 and identified those with a diagnosis of BS. The records of these patients were reviewed for demographic and clinical features, causes of hospitalization and outcome. We divided hospitalization causes into 2 as being BS related (organ involvement or deterioration) and non-BS related (treatment complication or others).Results:Three-hundred and thirty BS patients (75% men, mean age 37.7 ±11.4 SD years) were hospitalized for a total of 456 times during 18 years. The mean disease duration was 10.8± 8.8 SD years. Two-hundred and ninety-one (64%) patients were using immunosuppressives (IS) with or without corticosteroids (CSs) and 72 (16%) of them were under biologic treatment at the time of hospitalization. The mean duration of hospitalization was 12.7±10.7 SD days. The reasons for hospitalization were directly related to BS in 259 patients (57%) and non-related to BS in 191 (42%). Six patients were hospitalized for both BS and non-BS related reasons at the same time. The most common reasons were vascular involvement (n=169, 64%) for BS related reasons and infections (n=64, 32%) for non-BS related reasons (Table 1). Patients hospitalized for BS related causes were younger (35.2±10.6 vs 41.1±11.7, pConclusion:Vascular involvement is the leading cause of hospitalization among BS patients, followed by infections. The predominance of men among hospitalized patients underlines the relatively severe course of BS in men. The retrospective design and inclusion of patients who were hospitalized only in the rheumatology unit are limitations of this study.Table 1.Distributions of BS related and non-BS related reasons of hospitalizationsBS patients hospitalized with BS related reasons(n of pts=195, n of hospitalizations=265)*BS patients hospitalized with non-BS related reasons(n of pts=170, n of hospitalizations=197)*Causes of hospitalizations (per hospitalization)Vascular inv. (n=169, 64 %)Pulmonary artery inv. (n=64, 24 %)Deep vein thrombosis (n=39, 15 %)Budd-Chiari synd. (n=24, 9%)Vena cava inf. thrombosis (n=19, 7 %)Peripheral artery inv. (n=15, 6 %)Vena cava sup. thrombosis (n=14, 5 %)Aorta inv. (n=14, 5%)Coronary artery inv. (n=4, 2 %)Infection (n=64, 32%)Pneumonia (n=17, 8%)Tuberculosis (n=8, 4%)Urinary tract inf (n=7, 4%)Gastroenteritis (n=4, 2%)Osteomyelitis (n=3, 2%)Septic arthritis (n=3, 2%)Aspergillosis (n=2, 1%)Nocardia (n=1, 1%)Salmonella (n=1, 1%)Others (n=18, 9%)Neurologic inv. (n=50, 19 %)Parenchymal inv. (n=37, 14%)Dural sinus thrombosis (n=13, 5%)Drug side effects other than infections (n=29, 15 %)Interferon (n=10, 5%)Azathioprine (n=7, 4%)Cyclosporine (n=5, 3%)Steroid (n=3, 2%)TNF antagonists (n=3, 2%)IVIG (n=1, 1%)GI inv. (n=18, 7%)Additional rheumatologic diseases (n=17, 9%)Joint inv. (n=12, 5%)Renal disease (n=16, 8 %)Mucocutaneous inv. (n=10, 4%)Cardiovascular dis. (n=12, 6%)Eye inv. (n=8, 3%)Avascular necrosis (n=4, 2%)Others (n=8, 3%)Malignancy (n=11, 6%)Others (n=40, 20%)*Some patients were hospitalized more than one times and for both BS related and non-BS related reasons at different time and had more than one type of BS related and/or non-BS related reasons.Disclosure of Interests:None declared

Background:Infliximab (IFX) is increasingly used in the management of severe, relapsing or refractory manifestations of Behçet Syndrome (BS). Emergence of de novo manifestations have been reported during IFX treatment, despite efficacy for the initial manifestation that required IFX use1.Objectives:We aimed to survey a sizeable cohort of BS patients treated with IFX for the development of de novo manifestations during treatment.Methods:A chart review was conducted to identify all BS patients who were given IFX in our Behçet Disease Research Center between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant drugs, prior treatments, and outcomes were recorded. De novo manifestations were defined as new BS manifestations that had not occurred before IFX treatment.Results:A total of 252 patients used IFX with the main indications being uveitis in 122, vascular involvement in 82, parenchymal central nervous system involvement in 32, gastrointestinal involvement in 11, arthritis in 10, mucocutaneous involvement in 4, and secondary amyloidosis in 1. Of these patients, 17 (6%) had developed a total of 21 de-novo manifestations during a mean follow-up of 38.4 ± 92 (SD) months (Table 1). Vascular involvement was the main indication for IFX in the majority (n=12; 71%) of these 17 patients followed by eye involvement (n=3; 18%), central nervous system involvement (n=1), and joint involvement (n=1). Concomitant medications were prednisolone in 14 patients, azathioprine in 6 patients, mycophenolate mofetil, cyclosporine-A and methotrexate in 1 patient each. Thirteen patients (76%) were in remission for the main indication when de-novo manifestations emerged. In 10 patients IFX treatment was intensified either by increasing the dose to 10 mg/kg (2 patients) or by shortening the infusion intervals to 4 weeks (2 patients) along with the addition of corticosteroids or immunosuppressives. In the remaining 7 patients IFX was switched to another agent (cyclophosphamide in 5, adalimumab in 1 and anakinra in 1). At the time of this survey 8/17 patients were still on IFX for a mean follow-up of 32.5 ± 24.6 (SD) months, with concomitant low dose prednisolone in 5, azathioprine in 3 and mycophenolate mofetil in 3. In addition to the 7 patients who discontinued IFX at the time of de-novo manifestations, 2 more patients had discontinued IFX due to allergic reactions.Conclusion:De novo manifestations developed during IFX treatment in 6% of BS patients, despite efficacy for the initial manifestation. Appearance of de novo manifestations mostly in patients with vascular involvement is noteworthy. Intensification of IFX treatment was efficacious in managing de novo manifestations in more than half of these patients.References:[1]Hamuryudan V et al. Semin Arthritis Rheum. 2015;45(3):369-73.Table 1.Distribution of de novo manifestations that have emerged in 17 patientsDe-novo manifestations21Pulmonary artery aneurysm1Pulmonary artery thrombosis2Coronary artery involvement3Superficial thrombophlebitis5Arthritis5Erythema nodosum3Gastrointestinal involvement1Central nervous system involvement1Disclosure of Interests:None declared

Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation.A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively.The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P .05). However, no differences were found according to genotype distribution in all groups (P.05).Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates.Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex).Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042).In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Background The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. Methods Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. Results All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) ( P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/μL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/μL [log10: 3.34 ± 0.27]) ( P P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53–0.85) for serum Gd-IgA1 ( P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group ( P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] ( P = .224). Conclusions This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Pregnancy-associated thrombotic microangiopathy is a very rare condition; however, it significantly increases fetal or maternal morbidity and mortality. Pregnancy may trigger atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. The risk for pregnancy-associated aHUS is highest during the second pregnancy. The outcome is usually poor with 50–60% mortality; renal dysfunction and hypertension are the rule in those who survive the acute episode. After the development of complement regulation mechanisms and aHUS pathogenesis, eculizumab has been widely used as a first-line treatment in aHUS. Eculizumab has been produced to minimize immunogenicity and Fc-mediated functions, including recruitment of inflammatory cells and complement activation, and using eculizumab in first-line treatment improves kidney function. Recent studies showed that early diagnosis and rapid use of eculizumab in first-line treatment improve outcomes. We demonstrate a case with pregnancy-triggered aHUS occurring in the second trimester, who was successfully treated and delivered a healthy baby under eculizumab treatment.

Background/Aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM– C3–, IgM+ C3–, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77–8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3–27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3– and IgM– C3– groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349–8.344, p = 0.009). Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.

Background: TWEAK, MCP-1 and NGAL, mediators in pathogenesis of systemic lupus erythematosus (SLE), are proinflammatory cytokines/chemokines that are thought as potential biomarkers reflecting disease activity (1). Objectives: In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and non-renal SLE. Methods: Thirty active patients with SLE (15 renal and 15 non-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 non-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results: Sixty-one SLE patients, 51 (83.6%) of whom were female, with a median disease duration of 83 (23.5-135) months and a median age of 35 (27-47.5) were included in the study. Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared with the inactive SLE (n=31) group (sTWEAK: p=0.005; uTWEAK: p=0.026; sNGAL: p Conclusion: sTWEAK, uTWEAK, sNGAL and uNGAL are significant biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV. sTWEAK may be of use for discriminating active nephritis from non-renal active disease in SLE. Further studies are awaited to confirm these results (This study was funded by Istanbul University with the project number TTU-2017-24738 and Turkish Society for Rheumatology). Reference [1] Mok CC. Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol. 2010;2010:638413. Disclosure of Interests: None declared

Introduction Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. Methods All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. Results There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti–oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. Discussion Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.

Introduction Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. Materials and Methods Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. Results One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. Conclusion The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Ozluk, Yasemin/0000-0002-7191-0488; WOS: 000394441100004 PubMed: 27776435 Background: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR. Methods: Fifty-two patients suffered from AMR (30 male; mean age 39 +/- 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification. Results: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 +/- 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p =.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p = .017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p = .004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival. Conclusions: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.

Background:Oral ulcers, the hallmark lesion of Behçet’s syndrome (BS) can be disabling and impair eating, drinking and speaking. Despite recent advances in systemic medications for the treatment of oral ulcers, some patients do not achieve complete remission. Topical agents may help such patients by decreasing the pain and duration of oral ulcers. Pentoxyfilline (PTX) is a methylxanthine derivative that inhibits phosphodiesterase and is thought to have immunomodulatory effects in addition to improving blood flow which is its main reason for use in peripheral vascular disorders.Objectives:The aim of this study is to assess the efficacy and safety of PTX gel for oral ulcers in patients with BS. We also aimed to explore the best tools for the assessment of treatment response to topical agents in randomized controlled trials (Clinicaltrial.gov ID: NCT 03888846).Methods:This was an open-label, randomized, parallel group study comparing PTX gel in addition to colchicine (PTX-COL) with colchicine alone (COL). Patients with BS who were treated with colchicine and not using any other systemic medications for BS, having at least one oral ulcer that appeared during the last 48 hours were included. PTX 5% gel with a dose of 1000 mg/day was applied in 4 divided doses per day for 14 days. Patients were contacted daily for 14 consecutive days. Photographs were taken every 24 - 48 hours and graphical processing software was used to calculate the area of the index ulcer. Duration of the index ulcer, time to start of index ulcer shrinkage, time to 50% reduction in oral ulcer pain on a 10 mm visual analog scale (VAS), change from baseline in the area of the index ulcer over time, total number of oral ulcers and adverse events were evaluated.Results:A total of 41 patients were randomized, 39 patients (18 in the PTX-COL group and 21 in the COL group) completed the study and 2 patients in PTX-COL group withdrew from the study due to unacceptable dysgeusia and nausea. Mean duration of index ulcer, time to start of index ulcer shrinkage, time to 50% reduction in oral ulcer pain, and number of patients with no detectable ulcers on day 4 in each group were lower in the PTX-COL group as presented in the Table. Change from baseline in the area of index ulcer and pain score over time is shown in the Figure. There were no serious adverse events. Fifteen (75%) patients reported nausea, 11 (55%) reported dysgeusia and 2 reported vomitting in the PTX-COL group, while 2 patients (10%) reported nausea in the COL group.Conclusion:This pilot phase 2 open label, randomized controlled study supports the hypothesis that topical PTX in addition to colchicine accelerates the healing of BS oral ulcers compared to colchicine alone. A phase 3 controlled study with a higher number of patients is planned with improving the taste for tolerability of the product.Disclosure of Interests:Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker, Berna Yurttas: None declared, Zekayi Kutlubay: None declared, Tim Cote Employee of: Silk Road Therapeutics is in Washington, DC, USA, Şemsi Burak Derkunt Employee of: Silk Road Therapeutics is in Washington, DC, USA, Yusuf Yazici: None declared, Hasan Yazici: None declared