bluuebunny/crossref_metadata_2025 huggingface dataset:
P1746EFFICACY OF EXTRACORPOREAL PHOTOPHERESIS FOR THE TREATMENT OF RENAL CHRONIC ANTIBODY MEDIATED REJECTION: A PILOT STUDY
Authors: Pattonieri Eleonora Francesca , Gregorini Marilena , Viarengo Gianlcuca , Del Fante Claudia , Perotti Cesare , Grignano Maria Antonietta , Sepe Vincenzo , Libetta Carmelo , Abelli Massimo , Ticozzelli Elena , RAmpino Teresa
Published: June 2020

Background and Aims

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

The aim of this study was to describe the preliminary experience of ECP use to treat kidney cABMR.

Method

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

Results

We enrolled 6 KTR equally distributed in gender (3 M, 3 F) and aged 49.16 ± 7.15 years (mean±ds) .

Median follow up time was 12 months (min 12 – max 36).

All KTR had both class I and class II DSA with MFI > 5000 (min 5000 – max 36780).

In all patients no GFR deterioration was observed during follow up. UACR improved in 3 KTR while remained stable in the other 3 patients. No deaths or infections or cancer diagnosis or hospital admissions occurred. QoL ameliorated in all KTR.

DSA MIF decreased in all KTR and in 3 of them became even negative after 12 months of treatment.

Conclusion

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

Background and Aims

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

Method

In this study, 250 transplanted patients with calcineurin inhibitory (CNI) therapy and graft survival higher than 6 months and lower than 60 months were enrolled.

The patients were then divided in three groups: (MMF group) patients undergoing CNI therapy with CS (Ciclosporin) and MMF, (mTOR Inhibitors group) patients undergoing CNI, CS and mTOR Inhibitors therapy and (MMF to mTOR Inhibitors group) with patients shifting from MMF to mTOR Inhibitors therapy. Renal function, FGF-23, Klotho, PTH, 1-25OH-Vitamina D, arterial stiffness by Pulse Wave Velocity (PWV), left ventricular hypertrophy expressed by the MSV and endothelial function by Flow Mediated Dilation (FMD) were measured. PBMC were isolated by gradient centrifugation.

Results

Between the MMF group and the mTOR Inhibitors groups we did not find significant differences in renal function, PTH, 1-25OH-Vitamina D, PRA, DSA, PWV, FM e DFE. However, FGF23, Klotho, phosphate levels were significantly changed. (FGF-23 pg/ml; p=0,00001; Klotho p=0,01; fosfaturia p=0,03; MMF group vs mTOR Inhibitors group)

Interestingly, mTOR Inhibitors group patients showed a higher O2 consumption level associated to increased mitochondrial respiratory function. Pentraxin 3 (PTX-3) and p21 as inflammaging and senescence biomarkers were also detected to be significantly increased in MMF group compared to mTOR Inhibitors group (p=0,002).

Conclusion

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

Background and Aims

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

Method

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

Results

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

Conclusion:

The number of medications is positively associated with tacrolimus IPV in stable KTRs. There were also tacrolimus formulation-dependent differences in the assumed influence of several concomitantly received classes of medications, including steroids, diuretics, PPIs and statins, on the tacrolimus IPV.
P1771NOCARDIOSIS IN RENAL TRANSPLANT RECIPIENTS- TEN YEARS OF SINGLE CENTER EXPERIENCE
Authors: Singh Ravi Kumar , Bhalla A K , Gupta Anurag , Bhargava Vinant , Gupta Ashwani , Rana Devinder Singh
Published: June 2020

Background and Aims

Nocardiosis is a localized or disseminated bacterial infection caused by aerobic Actinomyces that commonly affects immunocompromised hosts. This study aimed to retrospectively review the clinical course and outcome of nocardiosis in renal transplant recipients at our center

Method

Data was obtained from hospital records retrospectively. Sixteen cases of nocardiosis were identified in a series of more than 1800 consecutive renal transplants performed at Sir Ganga Ram Hospital in the last decade from the year 2010 to 2019.

Results

Thirteen out of Sixteen patients(81.25%) had developed nocardiosis within a 1-year post-renal transplant. The diabetic population constituted 31.3%. CMV disease was present in 25% of patients six months prior to the diagnosis of Nocardiosis.56.3% of patients were on Trimethoprim-sulfamethoxazole prophylaxis while they were diagnosed with nocardiosis. Pleuropulmonary nocardiosis was the most common form of infection(68.75%). Primary cutaneous nocardiosis was identified in one patient(6.25%). cerebral nocardiosis and disseminated nocardiosis was diagnosed in two patients each(12.5%).In the last 3 years with the introduction of MALDI-TOF led to the identification of the subspecies of Nocardia which was not possible earlier. In the last 3 years, 6 patients were diagnosed with nocardiosis, in which 4 were infected with Nocardia farcinica, one patient with Nocardia Asiatica and one with Nocardia cyrigeorgica. Nocardia farcinica was resistant to cotrimoxazole, which used to be first-line therapy against Nocardiosis before subspecies identification and sensitivity testing. With the help of proper identification of subspecies by MALDI-TOF and antibiotic susceptibility by E-testing, 5 out of 6 patients could be treated while earlier 6 out of 10 patients could be treated.

Conclusion

Nocardiosis is a rare, difficult-to-diagnose-and-treat infection following kidney transplantation. Trimethoprim-sulfamethoxazole prophylaxis was not effective in the prevention of disease. The Subspecies identification and modification of the plan of management according to antibiotic sensitivity results in improved outcomes.
P1772CONVERSION TO BELATACEPT IMPROVES RENAL GRAFT FUNCTION OF PATIENTS WITH SEVERE HISTOLOGICAL AND FUNCTIONAL INVOLVEMENT. LONG-TERM UNICENTRIC EXPERIENCE
Authors: Lopez-Oliva Maria Ovidia , Alvarez Garcia Laura , Perez Robles Tamara , Vaca Gallardo Marco Antonio , Juan Santacruz , Gonzalez Garcia Elena , Selgas Rafael , Jimenez Carlos
Published: June 2020

Background and Aims

Belatacept selectively blocks the costimulation signal of T cells. Its use, both de novo and in conversion, is associated with a better renal graft function compared to the regimens that include a calcineurin inhibitor (CNI). We expose our experience with belatacept as a rescue therapy in patients who present moderate-severe dysfunction after renal transplantation and compare the evolution with those patients who received the contralateral kidney graft without change to belatacept.

Method

Adult kidney transplanted patients, with graft dysfunction and renal biopsy with CNI toxicity or chronic vascular lesions who are changed from CNI to belatacept were included. Efficacy (creatinine, proteinuria, TFGe, acute rejection tested by biopsy, anti HLA) and safety (adverse events, tumors or infections) variables were recorded before and after the change.

Results

11 patients were included. The change to belatacept was made at a median of 13 months from the transplant (range 1-62 months) and the duration of the treatment ranged between 6 and 74 months. Renal function improved from a mean creatinine of 3.04±1.34 mg/dl before the change to 1.9±0.3 mg/dl at 6 and 12 months after conversion (p = 0.016), being the last average creatinine (December 2019) of 1.7±0.3 mg/dl.

Belatacept was withdrawn in one case, at one year, due to the development of specific donor antibodies without evidence of acute rejection. There were no cases of post-transplant lymphoproliferative syndrome. Two patients developed VBK replication controlled with immunosuppression modification and three patients developed CMV infection controlled with valganciclovir. There was no episode of acute rejection after conversion.

In 5 cases the contralateral kidney graft was not implanted, while in 6 cases it was implanted in another recipient who was not given belatacept and was taken on CNI therapy. The last average creatinine (December 2019) of patients without belatacept was 3.3±1.6 mg/dl vs. 1.6±0.2 mg/dl in patients with belatacept (p = 0.03).

Conclusion

The change to belatacept improves the renal function of all patients, even in those with severe histological and functional involvement. The improvement of renal function remains stable in the medium/long term and is significantly better than the renal function of patients with CNI.
P1776HLA TYPING BY NGS ENHANCES MISMATCH DETECTION IN LIVING KIDNEY TRANSPLANTATION
Authors: Pehnke Sarah , Lindner Tom H , Popp Bernt , Doxiadis Ilias , Landgraf Ramona , Lehmann Claudia , Halbritter Jan , Münch Johannes
Published: June 2020

Background and Aims

Antibody mediated rejection (ABMR) due to the development of donor specific HLA antibodies is the most common cause for graft loss in kidney transplant recipients. Therefore, a low count of HLA mismatches is favorable in the course of transplantation. Hitherto, several techniques for HLA typing have been adapted in parallel, e.g. serological or low-resolution PCR. In this single-center study, we aimed to perform “HLA re-typing” by next generation sequencing (NGS) in a living kidney transplant cohort (n=143), in order to identify HLA mismatches in donor/recipient pairs, that were missed by previous HLA typing methods.

Method

We isolated DNA of 102 donor/recipient pairs, that received a living kidney transplantation at the University Hospital Leipzig (Germany) between 1998 and 2018, and performed long range PCR of all known HLA loci. Using these NGS results, we compiled a genomic HLA mismatch formula. We evaluated, if genomic HLA typing identifies more HLA mismatches compared to the results of previous HLA typing methods, that were recorded in the Eurotransplant database for our donor/recipient pairs.

Results

By genomic HLA typing, we were able to identify HLA mismatches in 10.2 % of donor/recipient pairs, that have been missed by previous methods. In our cohort, we recognized most mismatches in the DRB1 locus, that were missed with other HLA typing techniques.

Conclusion

Our results suggest, that genomic HLA typing can be more precise in detecting HLA mismatches in donor recipient/pairs. Especially in the course of living kidney transplantation, a higher accuracy in HLA typing might enhance donor selection. Furthermore, accurate HLA typing can influence graft management in the course of ABMR, as it may improve the detection of donor specific HLA directed antibodies.
P1779NOVEL ONCE-DAILY EXTENDED-RELEASE TACROLIMUS VERSUS TWICE -DAILY TACROLIMUS IN DE NOVO KIDNEY TRANSPLANT RECIPIENTS DURING THE EARLY POSTTRANSPLANT PERIOD
Authors: Polatkan Volkan , Ozdemir Ebru , Erturk Turker , Tatli Emel , Berber Ibrahim , Cakir Ulkem , Yilmaz Gulay
Published: June 2020

Background and Aims

Both under and over-dosing of tacrolimus may compromise clinical outcomes by exposing patients to either the risks of graft rejection or adverse events (AEs) associated with immunosuppressive therapy. This study is designed to compare the clinical follow-up of our kidney transplant recipients receiving once-daily, prolonged-release (PR-T; Advagraf) and twice-daily, immediate-release (IR-T; Prograf) tacrolimus in the early posttransplant period.

Method

This randomized study included 78 de novo, adult kidney transplant recipients to PR-T 0.15 mg/kg/day (Group I=39) and IR-T 0.15 mg/kg/day (Group II=39) for seven days in the posttransplant period. Demographic features and clinical parameters regarding levels of whole blood tacrolimus and serum creatinine were compared between the two groups. Presence of acute rejection and AEs were investigated. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations in all patients. SPSS 15 for Windows was used for statistical analysis.

Results

None of the patients suffered from acute rejection and there were no AEs in the early posttransplant period. However, Group II patients were found to have higher whole blood tacrolimus levels on the posttransplant 1st, 4th and 7th days (p=0.02, p=0.009 and p=0.013 respectively). Also serum creatinine levels were significantly increased in Group II patients on the posttransplant 7th day (p=0.02).

Conclusion

Prolonged release tacrolimus seems promising in preventing acute transplant rejection with adequate blood levels, as well as making it possible to avoid the interindividual variation in absorption and early calcineurin inhibitor toxicity.
P1780RENAL ALLOGRAFT TUBERCULOSIS - A CASE SERIES
Authors: BALAKRISHNAN SREEJESH , YADUR ANJANEY , NARAYANAN SAJITH , AZIZ FEROZ , N.A. ISMAIL , HAFEEQ BENIL , BHAT RAGHURAMCHANDRA , SASIDHARAN SOORAJ , GAFOOR ABDUL , SHAFEEQ SHYSIL
Published: June 2020

Background and Aims

Renal transplant recipients are at increased risk of tuberculosis (TB) than the general population especially in endemic areas. Post-transplant tuberculosis poses challenges to the physician both for diagnosis and treatment. There are no solid data regarding occurrence of renal allograft tuberculosis in this population. Here we report a case series of renal allograft recipients with occurrence of renal allograft tuberculosis.

Method

We analyzed data of 610 patients who underwent renal transplantation in our center between 2006 to 2019. Clinical details were retrospectively analyzed from Hospital Information System (HIS).

Results

Out of 610 transplant recipients, four (0.65%) were found to have renal allograft TB. One of the donors had a history of pulmonary tuberculosis which was treated. Among the recipients, one had history of disseminated TB 2 years prior to transplantation. Only one patient received induction immunosuppression with lymphocyte depleting agent. All of them received triple immunosuppression with tacrolimus, mycophenolate and prednisolone. None of them received isoniazid/rifampicin prophylaxis. The shortest time interval to the occurrence of allograft tuberculosis was 2 months (donor had history of tuberculosis). The longest was 78 months. All patients presented with fever and allograft dysfunction. Three out of 4 patients had biopsy showing granulomatous interstitial nephritis with urine culture for Mycobacterium tuberculosis positive. One of them had PUJ obstruction due to tuberculosis for which Boari flap vesicocalicostomy was done. One patient had perigraft collection, drainage of which showed Acid Fast Bacilli (AFB) and culture positivity for mycobacterium tuberculosis. The immunosuppression was not reduced for any of them and all were treated with non Rifampicin containing anti-tuberculosis treatment (ATT) regime for 9 months to 1 year. All patients had good response and complete remission. There was no mortality related to allograft tuberculosis. All the patients had their renal function back to baseline at the end of treatment.

Conclusion

Graft tuberculosis may present as fever as allograft dysfunction. The treatment with Anti tuberculosis drugs is effective in achieving complete cure and restoring the graft function.
P1784CARDIOVASCULAR RISK ASSESSMENT PRIOR TO KIDNEY TRANSPLANTATION
Authors: Matej Vnuäã¡k , Graňák Karol , Skálová Petra , Dedinska Ivana
Published: June 2020

Background and Aims

Cardiovascular diseases (CVD) are the most frequent cause of death in dialysed patients. Patients in the risk group of CVD examined prior to kidney transplantation (KTx) are indicated for coronarography (SCG). The aim of our analysis was to identify risk factors (RF) for positive finding of patients undergoing SCG before KTx.

Method

Our analysis consisted of 55 dialysed patients (46 males, 9 females, P<0.0001), undergoing SCG before inclusion on waiting list (WL). We identified patient’s information (age in the time of SCG, gender, ethiology of kidney failure, comorbidities - arterial hypertension, ischemic heart disease /IHD/, diabetes mellitus /DM/), biochemical parameters in the time of SCG (serum level of lipids, haemoglobin, calcium-phosphate metabolism). We divided patients, according to SCG results (negative finding; n=40 v.s positive finding; n=15).

Results

Patients without percutaneous coronary intervention (PCI) (negative finding) we confirmed significantly lower incidence of diabetic nephropathy (P=0.0484) IHD (P=0.0174) and coronary artery disease (P=0.0001). We confirmed, haemodynamically significant coronary stenosis correlate with the occurrence of stroke or transient ischemic attack in patient’s history (P=0.0104). Consequently, we identified predictors for realization PCI (positive result): type 2 DM [OR 2,3492 (P=0.0472)], HDL ≤ 1,03 mmol/l [OR 4.3276 (P=0.0359)], total calcium level ≤ 2mmol/l [OR 2.4935 (P=0.0309)], phosphate level ≥ 1.45 mmol/l [OR 0.2034 (P=0.0351)]. In our analysis, patients non-listed on WL had significantly higher incidence of type 2 DM (P=0.0087), smoking (P=0.0079) and were treated more often with statins (P=0.0025).

Conclusion

In our analysis, patients with DM and poorly managed chronic kidney disease - mineral bone disease are the most at risk group in the group of patients with CVD with positive SCG finding. Patients with high cardiovascular risk, without DM or other RF can profit from non-invasive imaging methods following faster listing on WL.
P1785KIDNEY TRANSPLANTATION ACROSS VERY HIGH DONOR SPECIFIC ANTIBODIES(DSA) - A SINGLE CENTER EXPERIENCE OF A TERTIARY LEVEL HOSPITAL FROM INDIA
Authors: Hota Jayanta Kumar
Published: June 2020

Background and Aims

Kidney Transplantation across very high donor specific antibodies (DSA) poses a significant challenge even today . With our current understanding and precise desensitization techniques, we are now able to do kidney transplantation across such high DSA . Here we are reporting ten such cases where baseline DSA were more than 10,000 mean fluroscent intensity (MFI) on Single Antigen Bead (SBA) Luminex.

Method:

It is a retrospective analiysis of ten kidney transplant patients from January 2017 to March 2019 . Patients with MFI more than 10,000 to class II HLA antigens at baseline with negative CDC and flow cytometry cross match were included in this study. All patients were treated with 1 dose of Rituximab (375mg/M? before plasma exchanges (PLEX) were started . Each session of PLEX was followed by 10 grams of intravenous human immunoglobulin (IVIg). Solid based SBA Luminex for both class I and II antigens was repeated after the third exchange and fifth exchange and seventh exchange depending on the level of MFI .

Results

Ten patients ( seven males three females ) of age 37± 7 years were included in this study . History of blood transfusion with 5±2 units was present in 7 patients . All females were multiparous ( 3±1children). Mean solid based SBA Luminex for class I HLA antigens was 12000 ± 1500 and for II HLA antigens with MFI 16500 ± 3500 (Chart 1). Mean number of PLEX needed was 5 ± 2 . All patients had solid based SBA MFI was 1500±300 and for class II antigens 2500 ± 1500 before transplantation(Chart 2).There was no incidence of acute antibody mediated rejection . Baseline serum creatinine at discharge was1.35±0.35mg%. There were 3 (30%) biopsy proven cases of acute cellular rejection . There was evidence of BK viremia in 3(30%) patients, CMV infection in 1 (10%) patient, Klebsiella pneumonia in 1(10%) patient and cryptosporium infection in 1 (10%) patient each . There was no mortality and mean serum creatinine at 6 months follow-up was 1.55±1.05mg%. All 3 patients of BK Viremia were treated with modification of immunosupression with substitution of leflunamide for mycophenolate and all are doing well with good graft function with a mean serum creatinine of 1.75±0.55mg% . Other infections were treated accordingly.

Conclusion:

Transplantation across very high donor specific antibodies is possible with excellent immediate and short term graft function with judicious de-sensitization techniques . There was increase in infection rate but none was life threatening and can be managed with proper care.
P1796FACTORS PREDICTING SUBCUTANEOUS INSULIN REQUIREMENT AFTER KIDNEY TRANSPLANT
Authors: Bansal Beena , Bansal Shyam
Published: June 2020

Background and Aims

Diabetes is the most common cause for end stage renal disease leading to kidney transplant. Post transplant glycemic management has significant impact on long term outcomes, but is challenging, especially while transitioning patients from intravenous to subcutaneous insulin dose. This study was therefore planned to assess factors which influence subcutaneous insulin dose after kidney transplant.

Method

Data was prospectively collected from 98 consecutive kidney transplant patients with type 2 diabetes at a tertiary care hospital in India, with regards to age, gender, height, weight, duration of diabetes, pre transplant insulin dose, pre transplant use of oral antidiabetics. First two days after transplant patients are nil by mouth and are on insulin infusion (column based method). On third day, patients are transitioned to multiple subcutaneous insulin. We assessed and recorded the subcutaneous insulin dose requirement by 4th and 5th day.

Results

Mean (SD) for patients’ age was 52.28 (6.32) years, height 167.83 (5.64) cm, weight 70.55 (14.32) kg, body mass index 25.39 (4.72) kg/m2 and duration of diabetes 13.3 (7.02) years. All 98 transplant recipients were male. Mean insulin requirement before transplant was 15.37 (20.24) units/day. Mean post transplant intravenous insulin infusion rate for 4 hours before transitioning to subcutaneous insulin was 2.07 (0.987) units/hour. Mean subcutaneous insulin requirement after transplant was 73.18 (25.45) units/day or 1.12 (0.61) units/kgbw. Mean basal insulin dose was 25.32 (10.91) units. Mean bolus dose before breakfast was 10.75 (4.37) units, before lunch was 20.12 (7.4)) units, before evening snack was 6.65 (3.43) units and before dinner was 10.75 (4.11) units. In terms of proportion of total daily dose (TDD), mean basal insulin was 0.34 (0.08) of TDD, bolus dose before breakfast was 0.15 (0.03) of TDD, before lunch was 0.28 (0.05) of TDD, before evening snack was 0.09 (0.04) of TDD and before dinner was 0.15 (0.04) of TDD.

Subcutaneous insulin dose after transplant correlated with insulin dose of the recipient before transplant (Pearson’s coefficient 0.43; p value 0.003) and weight of the patient (Pearson’s coefficient 0.32; p value 0.001). It did not correlate with age of the recipient, duration of diabetes, intravenous insulin infusion rate or tac level.

On multivariate linear regression analysis to assess the factors predicting subcutaneous insulin dose after transplant, only pre-transplant insulin dose was significant (p value 0.046). Age of the recipient, duration of diabetes, weight of the patient, intravenous insulin infusion rate or preoperative use of oral anti diabetic were not significant

Conclusion

In kidney transplant patients with type 2 diabetes, only pre transplant insulin dose predicted the subcutaneous insulin dose post transplant.
P1797ACUTE RENAL GRAFT FAILURE ASSOCIATED WITH AT1 RECEPTOR ANTIBODIES : 2 CASES IN SKMC
Authors: Bashir Nihal , AlSeiari Mohamed
Published: June 2020

Background and Aims

Some kidney transplantation recipients with negative donor specific antibodies can develop acute rejection episodes which are difficult to treat, associated with non-HLA antibodies like angiotensin 2 type 1 receptor antibodies (AT1R Ab). The mechanism of rejection by AT1R ab involves vascular injury. Our cases are unique as the first patient got mineralocorticoid deficiency like picture unexpectedly. For the second case, hyperacute rejection cause in the first allograft was not identified and but hyperacute rejection episodes involving antibodies against endothelial cells are reported in literature.

Method

2 patients received renal transplantation from life related donors in out institute developed acute rejection episodes. As part of investigations, we did non -HLA antibodies testing which came positive .

Results

Case 1 30 years old male, with end stage renal disease on hemodialysis . The patient had a live related renal transplant with Mismatch 1-1-1 and negative DSA. Induction with Basiliximab was initiated but changed to ATG due to delayed graft function.

Kidney biopsy on day 6 post operatively showed diffuse moderate to severe acute tubular injury (up to necrosis) with glomerular intracapillary fibrin microthrombi, focal minimal peritubular capillaritis and mild glomerulitis and focal weak C4d positivity, highly suspicious for active antibody mediated rejection.

The patient was treated with pulse steroids, ATG total of 7.5mg/kg, 3 sessions of Plasma exchange and IVIG 2 g/kg and 2 doses of Rituximab for his hyperacute rejection. AT1R antibodies titer was 11U/ml. MICA was negative. Losartan was initiated as a maintenance therapy.
P1808INHIBITION OF MIR-155 IMPROVES PROGNOSIS IN AN EXPERIMENTAL FSGS MOUSE MODEL BY REGULATING AUTOPHAGY
Authors: Zhang Yu , Wang Jie , Zhou Jianhua
Published: June 2020

Background and Aims

Focal segmental glomerulosclerosis (FSGS), a podocytopathy, is one of the most common primary glomerular diseases causing end-stage renal disease in children. Its mechanisms remain unclear and the effective treatment lacks. MiR-155 is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. The present study aimed to investigate the role of miR-155 in the pathogenesis of FSGS.

Method

A FSGS model was establishe by injection of adriamycin in miR-155 knockout mice. Renal pathological changes were observed by Periodic Schiff-Methenamine Silver staining and Masson trichrome staining. Podocyte morphology and autophagosomes were examined with electron microscopy. Podocyte density was estimated by the Weibel-Gomez method. Expression of autophagy markers and apoptosis-associated proteins were analyzed by Western blotting analysis.

Results

Silencing of miR-155 significantly decreased urinary protein excretion and ameliorated glomerulosclerosis in adriamycin-induced FSGS mice. We found that adriamycin treatment led to fusion of podocyte foot processes, swelling of the podocyte body, dilated mitochondria, and podocyte loss. Inhibition of miR-155 improved podocyte depletion and the above cytopathies induced by adriamycin. In addition, the results also demonstrated that in miR-155 KO mice, the expression of LC3 and ATG5 was increased and the expression of P62 was decreased.

Conclusion

These suggest that modulated miR-155 can prevent podocyte damage, by regulating the level of autophagy. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of podocytopathy.
P1817DOES EPIGENETIC FACTORS LIKE HDAC2 PLAYS ROLE IN STEROID RESISTANCE VIA REGULATION OF P-GP AND MRP-1 IN CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME?
Authors: SINGH HARSHIT , Prasad Narayan , Agarwal Vikas , Jaiswal Akhilesh Kumar
Published: June 2020

Background and Aims

The action of glucocorticoids is to switch off activated inflammatory genes. The activated glucocorticoid receptors (GR) interact with co-repressor molecules to impair NFκB-associated co-activator activity, reducing histone acetylation, chromatin remodelling. Reduction in histone acetylation occurs via recruitment of histone deacetylase (HDAC) 2 to the activated inflammatory gene complex by activated GR, resulting in efficacious suppression of activated inflammatory genes within the nucleus.

To evaluate the effect HDAC 2 on P-gp and MRP-1 expression and function.

Method

Total of 78 subjects were considered in the study out of which 50 were steroid sensitive nephrotic syndrome (SSNS), and 28 were steroid resistant nephrotic syndrome (SRNS) patients. mRNA expression was analyzed on peripheral blood mononuclear cells (PBMCs) in SRNS patients (mean age 8.43±3.8 years), SSNS patients (mean age 7.54±3.5 years). PBMCs were treated with 1µM of Theophylline (HDAC2 stimulator) and 0.8µM of Trichostatin A (HDAC2 inhibitor) for a period of 48 hours. Quantitative PCR was performed using light cycler LC480 using SYBR green PCR technology with SYBR premix relative gene expression levels were calculated and normalized to the corresponding levels of the housekeeping gene (GAPDH).

Results

Expression of P-gp (4.79±0.970 v/s 2.13±0.72, p<0.0001) and MRP-1 (3.99 ±0.8 v/s 1.99 ±0.91, p<0.0001) on PBMCs was increased in SRNS as compared to that of SSNS. HDAC2 mRNA levels were significantly decreased in SRNS patients as compared to that of SSNS patients (2.97 ± 0.95 v/s 6.02 ± 1.13, p<0.0001).

Theophylline(HDAC stimulator) for a period of 48 hours decreased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 1µM (fold change 2.65 and 2.21, *p<0.0001) However HDAC2 mRNA expression increased significantly (fold change5.67, *p<0.0001). In SSNS patients P-gp and MRP-1 mRNA expression decreased at1µM (fold change 1.25, 1.24, *p<0.0001) while the mRNA expression was increased (fold change 6.93, *p<0.0001).

TSA(HDAC inhibitor) for a period of 48 hours increased mRNA levels of P-gp and MRP-1 in PBMCs of SRNS with maximal induction at 0.8µM (fold change 7.51, 7.31, *p<0.0001) and significantly decreased the level of HDAC2 (fold change1.50, *p<0.0001) similarly in SSNS patients P-gp and MRP-1 mRNA expression increased at 0.8µM (fold change 3.49, 3.35, *p<0.0001) and HDAC2 decreased (fold change2.53, *p<0.0001) at 0.8µM.

The functional activity of P-gp and MRP-1 was significantly higher in SRNS group as compared to SSNS group (p<0.001), whereas enzymatic activity of HDAC2 was increased in SSNS group as compared to SRNS group (p<0.001)

Conclusion

As we observed that HDAC2 regulates P-gp and MRP-1 efflux pumps, Inducer of HDAC2 may be a probable treatment stratergy for patients of Idiopathic Nephrotic Syndrome.
P1818CLINICAL AND MOLECULAR CHARACTERISTICS OF CHILDREN WITH WT-1-ASSOCIATED STEROID-RESISTANT NEPHROTIC SYNDROME
Authors: Prikhodina Larisa , Bashirova Zilya , Lepaeva Tatjana , Povolotskaya Inna , Sherbakova Natalia
Published: June 2020

Background and Aims

The Wilms tumor suppressor gene 1 (WT1) (MIM 607102) has an important role in renal and gonadal development. WT1 mutations was found to be associated with a large spectrum of phenotypes with autosomal-dominant inheritance, including Wilms tumor, Denys-Drash syndrome (DDS), Frasier syndrome (FS), and isolated steroid-resistant nephrotic syndrome (SRNS). The aim of the study was to investigate clinical and molecular characteristics in children with WT1-associated SRNS.

Method

Retrospective analysis of phenotype and genotype of six children (3M/3F) with SRNS and heterozygous WT1 mutations was performed. Karyotypes were available in all patients. Data on renal histology had three subjects with FS. The median follow-up period was 35.5 (IQR: 20.0; 57.5) months. WT1 mutations identified by direct Sanger sequencing (n=3) and next generation sequencing (n=3).

Results

The median age at onset of WT1-associated SRNS was 10.0 (IQR: 5.5; 22.5) months. 4/6 (66.7%) patients presented with infantile nephrotic syndrome and 2/6 (33.3%) with SRNS. Arterial hypertension was determined in 4/6 (66.7%) of individuals. Among children with WT1-associated SRNS 3/6 (50%) patients had DDS (2M/1F) and 3/6 (50%) subjects had FS (1M/2F). Children with DDS had Wilms tumor in 2/3 (66.7%) of cases and gonadal dysgenesis with hypospadias in 1/3 (33.3%) of children. Causative mutations were identified in all three patients with DDS, including 2 earlier described c.1384C>T in exon 9 and c.1098 + 1G>A in intron 6 in WT1 gene, and one novel mutation с.1378Т>G in exon 9. All DDS children had decreased eGFR to CKD stage 2-3 in two patients aged 7 and 11 years and ESKD in one child at the age of 2 years. All 3 patients with FS had focal segmental glomerulosclerosis on biopsy. Two phenotypic girls with FS had karyotype 46, XY and presented with pseudohermaphroditism. The same earlier described splice site mutation c.1432 + 5G>A in intron 9 in WT1 gene was identified in both cases. One boy with FS had typical male chromosome pattern (46, XY) and gonadal dysgenesis. Splice site mutation c.1432 + 4C>T in intron 9 in WT1 gene was found in the child. Nobody of patients with FS developed gonadoblastoma. Progression to CKD was found in all three cases with FS, including CKD stage 2-3 in two subjects aged 5 and 15 years and ESKD in one phenotypically girl with sex reversal developed at the age of 8 years.

Conclusion

We found that children with WT1-associated SRNS had a wide spectrum of renal and extrarenal phenotypes concerning the development of urogenital system and Wilms tumor with high risk of progression to CKD during childhood. Their phenotypes are clearly associated with the type and location of WT1 mutations led to DDS or FS. Genetic WT1 diagnostics is important in all children with SRNS for early detection, optimal treatment, tumor prevention and prognosis.
P1825ANALYSIS OF LATE RENAL COMPLICATIONS AND RISK FACTORS IN CHILDREN WITH HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Gurbanov Anar , Gülhan Bora , Kuşkonmaz Barış , Okur Fatma Visal , Uçkan Çetinkaya Duygu , Ozdemir Gulsah , Taş Nesrin , Çelegen Kübra , Ozaltin Fatih , Duzova Ali , Topaloglu Rezan
Published: June 2020

Background and Aims

The aim of the study is to investigate the incidence and risk factors of hypertension (HT) and chronic kidney disease (CKD) in patients who had hematopoietic stem cell transplantation (HSCT) during their childhood.

Method

Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding renal complications were collected from the medical records of the patients. Guidelines of European Society of Hypertension (ESH) and American Academy of Pediatrics (APA) were used for the evaluation of hypertension. 24-hr ambulatory blood pressure monitoring (ABPM) was performed in children older than 5 years of age (68 patients). Ambulatory hypertension is diagnosed when systolic and/or diastolic blood pressure (BP) load is higher than 25%. Ambulatory prehypertension is diagnosed when mean systolic and/or diastolic BP is less than 95th percentile with systolic and/or diastolic BP load higher than 25%.

Results

A total of 72 patients (41 males and 31 females) were included in the study. The mean age of the patients at last visit was 10.8±4 years. ABPM revealed ambulatory HT in 6 patients (8.8%) and ambulatory prehypertension in 12 patients (17.6%). Office BP revealed HT in 3 patients (4.2%) and increased BP in four patients (5.6%) according to APA guideline (2017). In cohort, 12 patients with normal office BP (according to APA guideline) had ambulatory prehypertension or hypertension with ABPM. Office BP revealed HT in 1 patient (1.4%) and high-normal BP in 3 patients (4.2%) according to ESH guideline. In cohort, 15 patients with normal office BP (according to ESH guideline) had ambulatory prehypertension or hypertension with ABPM (Table 1). After a mean follow-up period of 4.4±2.5 years, CKD developed in 8 patients (11.1%). Patients with chronic graft-versus-host disease, with HLA-mismatched HSCT and/or transplantation of peripheric or cord blood hematopoietic stem cells had increased risk of CKD (p=0.041, p=0.033 and p=0.002, respectively).

Conclusion

Patients with HSCT should be regularly followed for the development of HT and ABPM should be used on regular basis. Patients with risk factors should be closely monitored for the development of CKD.
P1831ABPM DIFFERENCE BETWEEN OBESE AND NON OVERWEIGHT HYPERTENSIVE CHILDREN
Authors: Corcione Adele , Apuzzo Diletta , Pedoto Deianira , Barra Giuseppina , Annicchiarico Petruzzelli Luigi , Pecoraro Carmine , Malgieri Gabriele , Ascione Serena , Barra Pasquale , Pagano Annamaria , Lepore Lorenza
Published: June 2020

Background and Aims

The goal of our study was to analyze the difference in ABPM pattern in overweight and non overweight hypertensive children

Method

The ABPM were performed using Spacelab 90207 and recorded over 24h.Readings were taken every 15 minutes while awake,and every 20 minutes while asleep. In both groups were evaluated the 24h MAP,daytime MAP,nocturnal MAP, systolic and diastolic load,mean 24h SBP and DBP.

A total of 108 pts were enrolled. Pts were divided in two groups.In the first group 54 pts non overweight with primary hypertension:33 male and 21 female with mean age of 10.4 y. In the second group the obese hypertensive children, with mean age of 10.5 y, were divided into two subgroups according to BMI Z-scores:subgroup 1 BMI Z-score >2<3 n 40 pts (17 f;21m); subgroup 2 BMI Z-score >3 n (4f;10m).

Results

Systolic load was significantly higher in obese group (p 0,0409).In obese group n.12 were dipper (22,2%).Obese with BMI zscore >3 was all non dipper (n14 ;100%). In the lean group n 26 was dipper (48.1%),and 28 (51.8%) non dipper. 24 h MAP, Systolic and Diastolic load were significantly higher (p 0,0001) in the obese with BMI z score >3 compared to the lean group.

Conclusion

The statistically significant pathological pattern among obese is the increase inmean PAS and systolic load, as well as the absence of night dipping in severe obese. The increase in systolic load is already evident in obese mild.This gives a significant predictive value of cardiovascular damage to ABPM which increases with the severity of obesity worse.
P1842THE HISTORY OF VETERINARY RENAL PHYSIOLOGY AND NOSOLOGY IN ANCIENT AND MIDDLE AGES GREEK TEXTS
Authors: Diamandopoulos Athanasios
Published: June 2020

ackground and Aims

Background and Aims: To present the ideas of Ancient and Byzantine Greek authors about the renal anatomy, physiology and nosology of mammals, birds, insects and fishes.

Method

Method: We searched for the appropriate passages in the works of Aristotle, Aristophanes Byzantius, Galen, Cladius Aelianus, Alexander Aphrodisiensis, Basilius Caesariensis, Gregorius Nyssensus, Nemesius Emesenus, Hippiatrica Berolinensia, Hippiatrica Parisiana, Hippiatrica Cantabergiensia, Michael Ephesius and Michael Glycas. These texts extended from the 4th cent. BC until the 12th cent. AD.

Results

Aristotle elaborates on the varied number of kidneys in several animals and on the abundance of perirenal fat. The last tissue is essential for protecting and warming the animal but, in excess, it may be lethal, as in the case of sheep. He then describes the multilubular kidneys of some animals and the supposed lack of a bladder in birds and marine animals, with the exception of the sea turtle. Aristophanes adds the issue of the deer’s ectopic kidneys and their number in canines. Basilius and Gregorius elaborate on the minute details of some animals’ organs, like the kidneys and feathers of flying ants and the moral rationale of all these. Nemesius discusses the possibility of some animals surviving without kidneys. The monumental work “Hippiatrica” deals exclusively with horse health and refers, inter alia, to kidney afflictions. It describes the clinical signs of what it calls “nephritis”, with oedema and predominating neurological symptoms. For treatment it recommends several methods of causing renal hyperaemia, like massaging, ointments, warm rooms, heated irons, but also bloodletting. Michael Ephesius returns on the absence of proper kidneys in birds and their substitution with kidney-like organs called “nephroids”. Glycas “justifies” the lack of bladder and kidneys in birds as useless because they secrete their excess water via the feathers, a long flying time and watery stools.

Conclusion

The Ancient and Byzantine Greek authors had understood well several topics of the anatomy, physiology and nosology of the veterinary renal system but they also made some very great mistakes. We will present the above conclusions in length.
P1856KIDNEY CRISES: USING IN SITU SIMULATION TEACHING TO FACILITATE MULTIDISCIPLINARY TEAM WORKING IN RENAL EMERGENCIES
Authors: Nimmo Ailish , Adams Katie
Published: June 2020

Background and Aims

The haemodialysis unit is a unique clinical environment. Specialist nursing staff look after patients, frequently without on-site medical cover, and need to manage medical issues until help arrives. Junior doctors often have limited experience managing renal patients and may not be aware of specialty-specific issues when dealing with medical emergencies. The different skill sets in these groups creates an opportunity for shared learning. Simulation teaching provides a safe environment for individuals to develop communication, team working and clinical skills and helps facilitate discussion and reflection on clinical scenarios. We describe a programme of renal in situ simulation sessions for nurses and junior doctors to allow them to practise their roles in an emergency and evaluate feedback on their perception of the programme.

Method

Seventeen hour-long simulation sessions were delivered between June 2017 and January 2020 within the renal ward in 2 hospitals and in a satellite outpatient dialysis unit. They utilised a high-fidelity SimMan® mannequin. Scenarios were based on common or rare-but-serious medical emergencies (hyperkalaemic cardiac arrest, arrhythmia on dialysis, air embolism, major haemorrhage post-renal biopsy, line sepsis, hypertensive seizure, pulmonary oedema and drug-induced anaphylaxis). Sessions comprised an orientation to the mannequin, a clinical scenario and a debrief discussion. Doctors and nurses completed post-tutorial feedback exploring their thoughts on the programme.

Results

59 healthcare professionals (40 doctors and 19 nurses) participated and completed post-event feedback. All attendees felt that sessions improved their knowledge and increased their confidence in managing similar scenarios in the future. They all felt they would be able to apply their learning to their day job. 86% of participants strongly agreed that the programme helped them develop stronger relationships with colleagues. In white-space boxes, individuals described the sessions as being helpful in developing communication, teamwork, leadership and delegation skills in addition to specific learning points for the individual scenarios. Sessions also identified practical issues, such as where to source medications or monitoring equipment, and led to the creation of an updated protocol folder and distribution of Advanced Life Support algorithms throughout the ward.

Conclusion

Nurses and junior doctors report increased confidence in managing medical emergencies in renal patients and improved relationships with colleagues following a simulation training programme. The programme promotes a learning culture within the unit. It provides an opportunity to discuss potentially serious situations and allows reflection on similar scenarios encountered within the ward and dialysis unit. Further work is needed to determine if in situ simulation teaching has an impact on patient outcome measures.