bluuebunny/crossref_metadata_2025 huggingface dataset:
MO1023: Effects of Bortezomib on Complement Fixation and IGM Reactivity in Late Abmr — Results of A Randomized Controlled Trial (The Borteject Trial)
Authors: Doberer Konstantin , Eskandary Farsad , Wahrmann Markus , Haindl Susanne , A. Böhmig Georg , Bond Gregor
Published: May 2022

BACKGROUND AND AIMS

Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure. Currently, there is no proven effective treatment for this type of rejection. In a recent randomized controlled trial, we have reported no meaningful effect of plasma cell-directed treatment using the proteasome inhibitor bortezomib on the clinical course of late ABMR (BORTEJECT trial; ClinicalTrials.gov, NCT01873157; Eskandary et al. J Am Soc Nephrol, 2018; 29: 591). Treatment had also no significant effect on IgG type donor-specific antibody (DSA) patterns, possibly due to rapid reconstitution of the allospecific plasma cell repertoire. To further dissect the impact of bortezomib on donor-specific B cell alloimmunity, we here sought to investigate whether and to what extent bortezomib impacts the dynamics of specific alloreactivity patterns, in particular, the course of IgM type DSA and complement-activating capability of detected DSA.

METHOD

The BORTEJECT trial was a randomized, placebo-controlled parallel group trial designed to investigate whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8 and 11) were able to halt the progression of IgG-DSA-positive late ABMR. A total of 44 recipients were randomly assigned to receive bortezomib (n = 21) or placebo (n = 23). In the present re-analysis of biobanked serum samples obtained in the context of the trial, we applied modified single antigen bead assays to assess IgM-DSA and, in addition, complement (C1q) binding. To estimate antibody/complement binding, levels of mean fluorescence intensity (MFI) were recorded. IgM DSA was defined in relation to donor/recipient HLA typing, independently of IgG reactivity patterns.

RESULTS

At baseline, the complement-fixing capability of the immunodominant IgG DSA did not differ between groups. Thirty of 44 patients had detectable IgM DSA at baseline, and we observed a considerable overlap of IgG and IgM DSA specificities (22/30) without group differences. IgM DSA levels were also similar between groups.

Bortezomib treatment did not affect the complement-fixing capability of IgG DSA over time. Similarly, there was no effect on the course of IgM-DSA. There were also no significant differences between groups when analysing percentage changes.

CONCLUSION

A limited course of bortezomib as a sole treatment strategy may not be sufficient to impact on DSA levels, including the evolution of IgM type DSA and the complement-binding capability of detected alloreactivity patterns. Our study results, which may mirror the lack of clinical efficacy, reinforce the need for the development of innovative new strategies to effectively target plasma cells and halt the progression of ABMR.
MO1028: Vascular Access Type in Haemodialysis Paediatrics Patients—From Central Venous Catheter to Arteriovenous Fistula
Authors: Cohombo Josefa , Vilaça Joana , Costa Teresa , Do Sameiro Faria Maria , Conceição Mota Maria
Published: May 2022

BACKGROUND AND AIMS

Haemodialysis (HD) in children has become progressively more used, the efficiency of the treatment, as well as the technical improvements, are evident. Permanent access in the form of a fistula is the preferred type of vascular access (VA) for most paediatric patients on maintenance HD. However, age-related anatomical limitations, shorter waiting times for transplantation, or lack of paediatric/surgical expertise limit its use. Central venous catheter (CVC) remains the most used access in children. Here we present the results of the last 14 years of experience in paediatric HD vascular access from a reference centre in northern Portugal.

METHOD

A retrospective descriptive study of patients admitted to our paediatric HD Unit between January 2007 and December 2021. Clinical data were collected from medical records.

RESULTS

In total 46 patients were enrolled, mainly boys (n = 26, 56.5%), mean age at admission 10.8 + 5.3 years (1–17), 39.1% weighing ˂ 30 kg (n = 18) and 17.4% ˂15 kg (n = 8). More than half were incident patients starting on HD (n = 25, 54.3%), 45.7% (n = 21) were transferred from peritoneal dialysis (PD) and one patient had a previous kidney transplant (KT). Regarding CKD etiology, 52.2% (n = 24) were mainly due to congenital anomalies of the kidney and urinary tract; chronic glomerulonephritis was responsible for 19.6% of cases (n = 9). Most patients started HD with a CVC (n = 38, 82.6%), including two patients with an arteriovenous fistula (AVF) who required a temporary CVC until fistula maturation. At the end of follow-up, about 43.5% (n = 20) of the patients ended up with an AVF (compared with 17.4% at the beginning) and, not surprisingly, 90% (n = 18) of them weighed ˃ 30 kg and only one child ˂ 15 kg. The mean duration of dialysis was 1.1 + 0.5 years (1 month–8 years); 28 patients were submitted to KT (60.9%), 7 transferred to PD (15.2%) and 4 (8.7%) remain on HD. Average waiting times for KT are quite longer in patients with AVF (1.56 years), in comparison to CVC (0.584 years).

CONCLUSION

In children, choosing the best vascular access remains a challenge. CVCs continue to be the most used type of vascular access. This option can be justified by the limitations of smaller patients, the expectation of a short waiting time for KT and the need to cannulate every other day (with the pain and fear associated with it). CVCs were associated with less effective dialysis and higher complication rates. On the other hand, AVFs have shown excellent long-term patency in paediatric HD patients. In our group, no significant complications were reported and no thrombosis occurred.
MO1029: Is there a Relationship Between Fibroblast Growth Factor 23 and Blood Pressure in Children with Chronic Kidney Disease?
Authors: Balmukhanova Altynay , Kabulbayev Kairat , Alpay Harika , Balmukhanova Aigul , Kanatbayeva Assiya
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) is a complex medical and social problem worldwide due to high prevalence and mortality rates. According to the ESPN/ERA-EDTA, the prevalence of CKD stages 3–5 in children is about 55–60 pmarp [1]. Moreover, CKD usually causes different severe complications, including pathologic changes in the cardiovascular system, which significantly affect long-term survival. Unlike many complications of CKD, hypertension can be present in the earliest stages of the disease [2]. Nowadays, there has been a scientific and practical interest in Fibroblast growth factor 23 (FGF-23) which is mostly considered as a phosphate-regulating biomarker [3]. There are some speculations that FGF-23 affects blood pressure (BP) in adults due to the impact on the renin-angiotensin-aldosterone system (RAAS) by decreasing calcitriol [4] and the direct effect of FGF-23 on sodium reabsorption, which has been demonstrated in experimental models [5].

Therefore,  the aim of our study was to investigate the link between FGF-23 and BP in children with CKD. 

METHOD

There were 73 children with CKD stages 1–5, mean age was 9.79 ± 0.58 years. BP was determined by 3 times measurement and calculating the mean value. Received results were compared with percentile norms according to age and gender in order to divide patients into two groups: normotensive and hypertensive. FGF-23 was determined in serum by multimatrix ELISA kit (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was performed using SPSS version 26 (IBM, USA). 

RESULTS

In the group with normal BP the median of FGF-23 in serum was 1.8 [0.7–3.4] pmol/L. In comparison, in the group with a hypertensive level of BP median indicator of FGF-23 was 7.6 (1.98–18.5) pmol/L (P < .001). The prevalence of elevated FGF-23 in children with high BP predominates 1.6 times [95% confidence interval (95% CI): 1.2–2.1]. It is also noticed that pulse BP positively correlated with FGF-23 level in serum (r = 0.402, P < .001).

CONCLUSION

Our findings confirm that FGF-23 is linked to BP in children with CKD what makes us conclude that more careful attention to children with a high level of FGF-23 is needed in relation to hypertension and as a consequence cardiovascular complications. However, more investigations should be done in order to establish a causal relationship.
MO1046: The Selection of Renal Replacement Therapy for End-Stage Kidney Disease Patients by the Shared Decision-Making Method
Authors: Sakai Kentaro , Oota Osamu , Hisanaga Tetsuya , Yada Tomotaka , Matsui Rei , Higashi Harumichi
Published: May 2022

BACKGROUND AND AIMS

In Japan, > 97% of patients with end-stage kidney disease (ESKD) select hemodialysis as a renal replacement therapy (RRT). Hemodialysis (HD) and peritoneal dialysis (PD) have been provided at our hospital for many years, and kidney transplantation (KT) has been available here since 2015. In January 2018, we introduced the option of RRT for outpatients based on the shared decision-making (SDM) method, which was recently shown to be useful for patients.

METHOD

Patients receive ∼1-h explanation of the SDM method by a nurse in the outpatient department. If patients desire additional outpatient visits, they receive as many as they want; a decision about RRT is not required after a single visit and patients can change their decision at any time. We conducted a prospective observational study to investigate patients’ selection of RRT and the influence of the SDM method on the selection of RRT. The data were examined by Fisher's exact test and significance was accepted at P < 0.05.

RESULTS

During the period from January 2018 to December 2021, 116 patients visited our outpatient department and 69 patients underwent RRT. Only 53% of the patients initially requested hemodialysis (Figure 1), but > 80% of the patients eventually underwent hemodialysis (Figure 2). From 2018 to 2021, 156 patients started RRT; 58 of them (37%) had visited the outpatient department before starting RRT. The number of patients who visited the outpatient department has increased year by year. The emergency initiation of dialysis decreased significantly after the outpatient use of the SDM method began [odds ratio (OR) 0.44, P = 0.024].

CONCLUSION

There was a tendency for patients’ satisfaction regarding their own selection of RRT via the SDM method in the outpatient department. Patients can obtain the information they need and select a better treatment for themselves via an explanation of the SDM method. The SDM method is thus very effective for both patients and medical staff when considering RRT.
MO1049: An Intradialytic Exercise at Start versus End of HD Session to Improve Strength with Non-Immersive Virtual Reality: A Randomized Controlled Trial
Authors: José Martínez-Olmos Francisco , Garcia-Testal Alicia , Benavent Caballer Vicente , Valtueña-Gimeno Noemi , Toquero Correa Marina , Garcia-Maset Rafael , Rico-Salvador Inmaculada , Royo-Maicas Pilar , Vercher Narbona Verónica , Antonio Gil-Gómez José , Segura-Ortí Eva
Published: May 2022

BACKGROUND AND AIMS

Haemodialysis (HD) induces changes in addition to the kidney in other organs or systems so that patients usually present symptoms such as fatigue, generalized muscle weakness and low tolerance to exercise that result in functional impairment, decreased work capacity and dependence for activities of daily living. Intra-dialysis exercise programmes may help to partly reverse this situation. Exercise during the first 2-h of dialysis has proven to be safe. Our group showed that an acute session of virtual reality exercise during the last 30 min of HD was safe too. The aim of this study was to compare the impact of non-immersive virtual reality intra-dialysis during the first 2-h versus the last 2-h of dialysis on lower-limbs muscle strength.

METHOD

This was a randomized controlled trial. Participants were randomized in two groups: group A performed the exercise during the first and second hour of the HD session and group B performed it during the third and fourth hour. Strength was measured bilaterally with a hand-held Lafayette dynamometer in three movements of the lower limbs (hip flexion, hip abduction and plantar flexion) during the HD session. The intradialytic exercise consisted of a non-immersive virtual reality video game adapted to the dialysis session, in which the patient must catch treasures while avoiding bombs by moving the lower extremities, with a progressive duration of 25–45 min, over a 12-week period.

RESULTS

A total of 33 subjects were included in the analysis, 17 subjects (median age 71.8 years; 10 men) in group A and 16 subjects (median age 73.3 years, 9 men) in group B. At baseline the period analysed, there were no significant differences between the two groups in any of the movements analysed. The force analysed in the different movements showed that there was a significant increase in all the movements analysed in both groups. There was an increase in force in the movements of the lower right limb of 3.31 N in hip flexion, 2.01 N in hip abduction and 1.10 N in plantar flexion, as well as an increase in the outside in the lower left limb of 3.82 N in hip flexion, 2.47 N in hip abduction and 4.63 N in plantar flexion. There were no significant differences in the increase in strength in the movements analysed between both groups in the movements analysed after the 12-week period analysed.

CONCLUSION

There are no differences in the application of an intradialytic exercise at the beginning versus at the end of the HD session to improve strength with non-immersive virtual reality. An intradialytic exercise with non-immersive virtual reality improves limb strength in HD patients.
MO1050: Covid-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study
Authors: Panizo Gonzalez Nayara , Fernanda Alvarado Maria , Garcia-Llana Helena , Gandia Lorena , Gimenez-Civera Elena , D'marco Luis , Jesãºs Puchades Montesa Maria , Sargsian Mari , Sanchis Irina , Juan-Garcia Isabel , Angel Solis Miguel , Maria Pérez-Baylach Carmen , Bonilla Begoña , Solano Rivera Camila , Moncho Francesc , Perez-Bernat Elisa , Luis Gorriz Teruel Jose
Published: May 2022

BACKGROUND AND AIMS

To our knowledge, the psychological impact of coronavirus disease (COVID-19) vaccination has not yet been evaluated for the general population nor for chronic kidney disease (CKD) patients.

The purpose of the study is to analyse the impact of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on anxiety and depression scores in patients with different modalities of CKD.

METHOD

A total of 117 renal patients (50 haemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants and 22 advanced CKD patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL) and perceived fears and resources with standardized (The Hospital Anxiety and Depression Scale; HADS) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination.

RESULTS

The main finding of the study is that there is a decrease in the global mean of normal scores for anxiety and depression symptoms in CKD patients, post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine and lack of information.

CONCLUSION

These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.
FC006: Sex Differences in the Recognition, Monitoring and Management of Chronic Kidney Disease in Health Care
Authors: Swartling Oskar , Yang Yuanhang , M. Clase Catherine , Fu Edouard , Hecking Manfred , Hödlmoser Sebastian , Trolle Lagerros Ylva , Evans Marie , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

Sex-specific differences exist in the population prevalence of chronic kidney disease (CKD), progression rates and health outcomes. Recognition, diagnosis and monitoring are central processes in the management of patients with CKD, but it is unknown whether these processes differ between men and women.

METHOD

This is an observational cohort study of all adult individuals (n = 227 847) with at least one eGFR (from serum creatinine) <60 mL/min/1.73 m2 during outpatient routine care in Stockholm, Sweden, 2009–2017. Through logistic regression, we evaluated differences by sex in carrying an ICD-10 code for CKD and provision of recommended medications (renin–angiotensin system inhibitors [RASi] and statins) at inclusion. Through Cox regression, we evaluated potential sex differences in receiving a CKD diagnosis, referral to nephrology care and performance of laboratory monitoring (creatinine and albuminuria) in the next 18 months from inclusion. We also explored time-trends, comparing the above-mentioned nephrology care indicators among 70–80 000 unique eligible individuals per calendar year (in total 695 632 observations), thus allowing participants to contribute to different calendar year-cohorts.

RESULTS

We identified more women (55%) than men (45%) with probable CKD (eGFR < 60 mL/min/1.73 m2). Women were generally older than men (median 77 versus 74 years), but eGFR was similar between sexes (51 mL/min/1.73 m2). More men than women had diabetes or myocardial infarction, but there was similar prevalence of hypertension. At inclusion and compared with men, women had lower risk of carrying an ICD-10 code for CKD (odds ratio [OR]: 0.47, 95% CI: 0.45–0.49) and were less likely to receive RASi (OR: 0.55; 0.50–0.61, among patient with albuminuria A3) or statins (OR: 0.64; 0.63–0.66, among patients ≥ 50 years), despite the presence of clear indications. In subsequent time-to-event analyses, women were less likely to receive a CKD diagnosis (hazard ratio [HR]: 0.43; 0.42–0.45) and visit a nephrologist (HR: 0.46; 0.43–0.48) regardless of CKD severity, presence of albuminuria or criteria for referral. Women were also less likely to undergo monitoring of creatinine or albuminuria, even among participants with diabetes (HR: 0.75; 0.74–0.76) or hypertension (HR: 0.76; 0.75–0.78). Multivariable adjustment including comorbidities, eGFR and indication for referral showed some attenuation of the effect, but a sex difference remained. Although in absolute terms there has been a gradual improvement in all nephrology care indicators over time, the observed sex gap persisted throughout.

CONCLUSION

We found profound sex differences in the detection, recognition, monitoring and management (including referrals) of CKD in healthcare, also across high-risk groups and indications.
FC024: Renal Proximal Tubules CB1 Receptor Modulates MTORC1 Signalling in Health and Disease
Authors: Hinden Liad , Ahmad Majdoleen , Hamad Sharleen , Nemirovski Alina , Glasmacher Sandra , Kogot-Levin Aviram , Gertsch Jürg , Leibowitz Gil , Tam Joseph
Published: May 2022

BACKGROUND AND AIMS

Diabetic kidney disease (DKD), the renal manifestation of diabetes, contributes to increased morbidity and mortality of patients with diabetes. Activation of the cannabinoid-1 receptor (CB1R) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of DKD. However, whether these two signalling molecules interact with each other to regulate kidney function during health and disease has not been described yet.

METHOD

By using a multidisciplinary approach that includes pharmacological and genetic manipulations of CB1R and mTORC1, we assessed the effect of CB1R activation/inhibition on mTORC1 activity under conditions of acute and chronic hyperglycaemia or normoglycaemia in RPTCs and mice.

RESULTS

We showed hyperglycaemia-induced endocannabinoid/CB1R stimulation. This stimulation increased mTORC1 activity and resulted in enhancing the expression of sterol regulatory element-binding protein 1c (SREBP1c) and its nuclear translocation, which in turn, induced the transcription of the facilitative glucose transporter 2 (GLUT2), thus leading to the development of DKD in mice. This effect was ameliorated by CB1R or mTORC1 nullification specifically in RPTCs. However, in non-diabetic conditions, CB1R maintained normal activation of mTORC1 by preventing the cellular excess of various amino acids via regulating their transporters, megalin, SLC6A19 and SLC7A5.

CONCLUSION

Our findings highlight two novel molecular mechanisms by which the activation of mTORC1 in RPTCs is tightly controlled by CB1R, either by enhancing the reabsorption of glucose and inducing renal dysfunction in diabetes or by preventing amino acid uptake and maintaining normal kidney function in healthy conditions. Moreover, this work highlights the therapeutic potential of targeting peripheral CB1Rs for the treatment of DKD, and on the other hand, avoiding its use in non-diabetic patients due to their possible effect on enhancing mTORC1 signalling.
FC029: A Multivariate Model Identifies Genotype, Hypertension and Kidney Length as Independent Baseline Predictors of Disease Progression in a Longitudinal Autosomal Dominant Polycystic Kidney Disease Patient Cohort
Authors: Cong Eugene Chen Wen , Ong Albert , Han Chong Jie
Published: May 2022

BACKGROUND AND AIMS

Patients with autosomal dominant polycystic kidney disease (ADPKD) and evidence of rapid kidney function decline (∆eGFR > 2.5 mL/min/year) are eligible for disease modifying therapy. Predictors of ∆eGFR are important to identify rapid progressors at an early stage before significant loss of kidney function. Genotype and baseline total kidney volume (TKV) are considered the most accurate individual prognostic factors though neither is widely performed in clinical practice. The major objective of this study was to assess what baseline clinical factors could most accurately predict ∆eGFR in an unselected ADPKD cohort (n = 625) followed-up through a specialist PKD clinic between 2010 and 2021.

METHOD

A cross-sectional retrospective analysis was performed in all ADPKD patients with sufficient data. The mean follow-up duration was 11 (±11.2) years. The rate of estimated glomerular filtration rate (eGFR) decline was determined by linear regression, based on a minimum of 5 years of renal function prior to the study or renal replacement therapy. Patients who were genotyped (n = 390) were classified into those with PKD1 (T, truncating or NT, non-truncating), PKD2, other genes (non-PKD1 or PKD2) or NMD (no mutation detected). Genotype combined with baseline imaging (ultrasound) was available in a subset of patients (n = 138). There was insufficient TKV information in this cohort to include it as an independent variable.

RESULTS

Kaplan–Meier plots (probability of eGFR > 60 mL/min/1.73 m2 v age, n = 368) showed a significant genotype–phenotype correlation with a median age of 54, 61, 69 and 73 years for PKD1-T, PKD1-NT, PKD2, NMD/other genes, respectively. Dividing the cohort into 3 ∆eGFR groups (<2.5, 2.5–5, >5 mL/min/year,  n = 316) confirmed significant differences in genotype (PKD1-T), baseline hypertension, mean kidney length and proteinuria (PCR > 50 mg/mmol) between patients in the low (<2.5) and very rapid (>5) decline groups. A multivariate linear regression model was developed with all potential baseline factors significant on univariate analysis. We found that a PKD1 truncating mutation (PKD1-T), mean kidney length and baseline hypertension were significant independent predictors for ∆eGFR. This model accounted for 27% of the variability in ∆eGFR (r2 = 0.2668; P < 0.05).

CONCLUSION

Our multivariate linear regression model confirms the importance of genotype, phenotype and imaging factors as independent prognostic variables determining ∆eGFR over a minimum period of 5 years follow-up in a longitudinal ADPKD cohort. Since the current model accounts for 27% of variability, it will be important to identify other relevant clinical, genetic or epigenetic factors that determine ∆eGFR.
FC031: Validation of a Prediction System for Risk of Allograft Loss (IBOX) in Pediatric Kidney Transplant Recipients
Authors: Hogan Julien , Divard Gillian , Garro Rouba , Boyer Olivia , Seifert Michael , Smith Jodi , Tönshoff Burkhard , Twombley Katherine , Warady Bradley , Weng Patricia , Zhar Rima , Patzer Rachel , Loupy Alexandre
Published: May 2022

BACKGROUND AND AIMS

Kidney allograft loss is a common cause of end-stage renal disease but accurate prediction models of kidney allograft loss are lacking in children. The iBOX system has been broadly validated among adults. We aimed to validate the iBOX system in a large international cohort of pediatric kTx recipients.

METHOD

In this observational study, we used data from pediatric (<21) patients transplanted between 2005 and 2017 from 20 institutions in Europe and the USA. Patients with functional parameters (eGFR and UPCR), donor specific antibody and biopsy results (Banff scores g, ptc, cg, i, t and IFTA) were included. Individual predictions of allograft loss were obtained by applying the iBOX score on our data. The prediction performances of the model in our population were assessed via discrimination (c-statistics) and calibration.

RESULTS

A total of 573 kTx recipients were included. Median time from transplantation to evaluation was 1.0 (0.5–2.0) year with a mean age at evaluation at 12.1 (5.5) years and mean follow-up after transplantation 5.1 (2.8) years. Five-year death-censored graft survival from evaluation was 95%. At the time of evaluation, mean eGFR and uPCR were 65.5 (29.6) mL/min/1.73 m2 and 0.25 (1.2) g/g, respectively. A total of 118 (20.6%) of the patients had DSA. The iBOX system showed good discrimination with a c-statistic of 0.81 and good calibration (Figure 1).

CONCLUSION

The iBOX system demonstrated high accuracy in predicting kidney allograft loss in children with performances similar to those reported in adults.
FC048: New Tool to Predict the Clinical Course and Renal Failure in Patients with Immunoglobulin a Nephropathy
Authors: Paolo Schena Francesco , Walter Anelli Vto , Cornacchia Giandomenico , DI Noia Tommaso , Stangou Maria , Papagianni Aikaterina , Coppo Rosanna
Published: May 2022

BACKGROUND AND AIMS

Idiopathic Immunoglobulin A nephropathy (IgAN) is the most common biopsy-proven glomerulonephritis in the world. Approximately 40% of IgAN patients reach renal failure (RF) 20 years after their kidney biopsy. The high prevalence of RF shows that IgAN has a significant economic impact in the countries because renal replacement therapy is costly. Moreover, the disease's onset in the second and third decades of life represents a social challenge because patients are typically very active and highly productive in the workplace. This challenge is one more reason to move on the prediction of the clinical course and RF in IgAN patients at the time of the kidney biopsy and during the follow-up. We developed an artificial neural network (ANN) tool (DialCheck 1.0) based on seven variables and the histological score of the kidney biopsy to predict RF in IgAN patients at the time of kidney biopsy [1].

METHOD

We have recently developed a new tool which consists of a set of ANN-powered models that combine temporally accurate observations for fine-grained features and leverage state-of-the-art deep neural network techniques to forecast the patient's clinical evolution.

RESULTS

A cohort of 948 IgAN patients, of whom the clinical course of the disease was known, was used to develop the new tool that predicts the dynamics of age and disease laboratory parameters (serum creatinine, daily proteinuria), blood pressure, histological score of the kidney biopsy and the RF. The system was designed to help the physicians give a broader spectrum of information regarding the patient and the potential clinical development of IgAN and outcomes.

In detail, the model computes a latent dynamic representation of the patient and predicts a prospective clinical picture of the patient and the probability of RF. The tool with an accuracy of >80% will be tested in an independent retrospective cohort of 454 IgAN patients and in a prospective multicenter randomized clinical study in which 426 IgAN patients will be enrolled in two different groups based on the type of kidney lesions (active and chronic renal lesions).

CONCLUSION

We have a new tool (DialCheck 2.0), based on ANN, that may predict the outcome and the RF in IgAN patients. Moreover, it may help the physician to analyze the long-term response to therapy.
FC051: Atacicept Reduces Serum ANTI-GD-IGA1 Levels in IgAN Patients
Authors: Barratt Jonathan , Lin Celia , Nawaz Nadia , Molyneux Karen , A. Tumlin James , Suzuki Yusuke
Published: May 2022

BACKGROUND AND AIMS

Gd-IgA1 plays a central role in IgAN pathogenesis. In IgAN patients, antibodies develop against Gd-IgA1, which then form immune complexes that deposit in the kidney. Increased circulatory levels of autoantigen (Gd-IgA1) or autoantibody (anti-Gd-IgA1) levels correlate with increased risk of progression and worse clinical outcomes. The Ph2a JANUS trial was the first to show substantial serum Gd-IgA1 reduction with atacicept in a randomized clinical trial with IgAN patients. This analysis investigates whether atacicept can also reduce serum anti-Gd-IgA1.

METHOD

JANUS patients were evaluated for serum anti-Gd-IgA1 at baseline, weeks 4, 12, 24, 48, and 72. An ELISA was developed using as the capture antigen an intact IgA1 paraprotein, which displayed high HPA lectin binding measured Gd-IgA1-specific IgG. Serum samples were normalized using three standard serum samples included on all plates.

RESULTS

Decrease in serum anti-Gd-IgA1 levels was observed in both atacicept 25- and 75-mg groups over time. At 24 weeks, mean % change from baseline was 24% decrease for atacicept 25 mg and 29% decrease for atacicept 75 mg. At 72 weeks, 28% decrease for atacicept 25 mg and 39% decrease for atacicept 75 mg was observed. Plot of mean % change in serum anti-Gd-IgA1 levels over time is presented in the Figure 1.

CONCLUSION

Atacicept is the first therapeutic to show a reduction in anti-Gd-IgA1 in IgAN patients. Atacicept’s ability to decrease both circulatory Gd-IgA1 and IgG autoantibodies to this protein, which are central to the pathogenesis and progression of IgAN, supports its potential as a disease modifying therapy for IgAN patients.
FC062: Baseline Soluble Immune Checkpoints Predict Relapse Risk in PR3-Anca Vasculitis Following Rituximab Induction Therapy
Authors: Kronbichler Andreas , Gamerith Gabriele , Mildner Finn
Published: May 2022

BACKGROUND AND AIMS

We investigated whether soluble immune checkpoints (sICPs) predict treatment-resistance, relapse risk and risk of infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).

METHOD

Plasma levels of sICPs were measured by enzyme-linked immunosorbent assay from samples obtained at baseline and during follow-up from patients with AAV in the RAVE trial and were correlated with selected clinical outcomes. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J.

RESULTS

Among 95 patients receiving rituximab as induction therapy, lower soluble (s)Lag-3 (<90 pg/mL) and higher sCD27 (>3000 pg/mL) were predictive of not achieving remission. Among patients with remission, 32.9% relapsed with a median relapse free survival of 5.64 months. Low baseline values of sTim-3 (<1200 pg/mL), sCD27 (<1250 pg/mL) and sBTLA (<1000 pg/mL) were associated with disease relapse. In addition, patients with high levels of at least one of these markers were prone to infectious complications. These findings were restricted to patients with proteinase 3 (PR3)-ANCA vasculitis and not observed in patients with myeloperoxidase (MPO)-ANCA vasculitis. Moreover, these relationships do not hold for the group of patients randomized to receive cyclophosphamide/azathioprine.

CONCLUSION

Rituximab-treated patients achieved remission less frequently when sLag-3 was low and sCD27 was high. Higher expression of sTim-3, sCD27 and sBTLA at baseline was associated with a lower risk of relapse in PR3-ANCA vasculitis following rituximab. These results will require confirmation in future studies, but may contribute to personalized medicine in AAV.
FC081: Cholinesterase Inhibitors and Kidney Function Decline in Patients with Alzheimer's Dementia
Authors: Xu Hong , Garcia-Ptacek Sara , Bruchfeld Annette , Fu Edouard , Darreh Shori Taher , Lindholm Bengt , Eriksdotter Maria , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. This study explores a plausible effect of ChEIs on slowing kidney function decline.

METHOD

Observational study with a landmark design of patients with incident AD from the Swedish Dementia Registry (SveDem) 2007–2018 with complete extraction of routine serum creatinine tests from the Stockholm CREAtinine Measurements (SCREAM) registry to evaluate estimated glomerular filtration rate (eGFR) over time. Patients starting on ChEI within 90 days of an AD diagnosis were compared to patients with AD not receiving ChEI. The primary study outcome was CKD progression, defined as the composite of a sustained eGFR decline of >30% from baseline, initiation of kidney replacement therapy or death attributed to kidney disease. Secondary outcome was death. Inverse probability of treatment weighting Cox models were used to estimate hazard ratios, balancing 45 confounders.

RESULTS

We included 11 898 incident patients, of whom 6803 started on ChEI and 5095 did not. Mean age was 80 years, 64% were women and mean baseline eGFR was 68 mL/min/1.73 m2. After weighting, and during median follow-up time of 3.0 (IQR 1.3–4.5) years, 1231 events of CKD progression occurred, along with 5691 deaths. Compared to noninitiators, ChEI use was associated with a 18% lower risk of CKD progression [adjusted hazards ratio (aHR) 0.82; 95% confidence interval (95% CI) 0.70–0.96] and a 21% lower risk of death (aHR 0.79; 0.72–0.86). Results were consistent across subgroups of age, sex, and across ChEI subclasses and after accounting for competing risks.

CONCLUSION

In routinely cared patients with incident AD diagnosis, use of ChEI (versus no-use) was associated with lower risk of CKD progression and death, lending support to the role of CAP activation on preservation of kidney function.
FC085: Cerebral Oxygenation During Exercise Across Different Stages of Chronic Kidney Disease
Authors: Theodorakopoulou Marieta , Zafeiridis Andreas , Dipla Konstantina , Faitatzidou Danai , Koutlas Aggelos , Eleni Alexandrou Maria , Polychronidou Georgia , Chalkidis Georgios , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2022

BACKGROUND AND AIMS

Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Proper brain function relies on sufficient blood flow and oxygen supply by the cerebral vasculature. A reduction in cerebral oxygenation of more than 10% may deteriorate brain function and influence the decision to continue exercise. This study aims to examine the cerebral oxygenation and blood volume during a mild physical stress as an index of brain activation in patients at different stages of CKD and controls without CKD.

METHOD

This is a preliminary analysis of an observational study enrolling patients with CKD stage 2–4 (matched for age and sex within the different stages) and controls without CKD. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in prefrontal oxygenation (oxyhaemoglobin—O2Hb) and deoxyhaemoglobin—HHb) and total blood volume (total hemoglobin—tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS).

RESULTS

A total of 59 participants are included in this preliminary analyses (n = 11 controls, n = 15 stage 2 CKD, n = 18 stage 3 CKD and n = 15 stage 4 CKD patients). During HG-exercise, O2Hb significantly increased (P < 0.001) and HHb remained relatively unchanged in all groups compared to pre-exercise values. However, this O2Hb increase was progressively lower with advancing CKD Stages (controls: 2.58 ± 1.43;  stage 2: 1.51 ± 1.31;  stage 3: 1.29 ± 0.97;  stage 4: 0.95 ± 0.92;  P = 0.006) (Figure). During HG, tHb (an index of microvascular blood volume) increased significantly in controls, stage 2 and stage 3 CKD patients (P < 0.05) but not in stage 4 CKD patients (P = 0.100). As before this tHb increase was progressively lower with advancing CKD stages (P = 0.030). Controlling for age differences between groups did not alter the above observations.

CONCLUSION

Brain activation/response during a mild physical task appears to decrease with advancing CKD as suggested by the smaller rise in cerebral oxygenation and blood volume. This may contribute both impaired cognitive function and reduced exercise tolerance with advancing CKD.
FC 105: Multidimensional Prognostication Tool for Kidney Transplant Patient Survival: The Mortality Mbox
Authors: Debiais-Deschamps Charlotte , Aubert Olivier , Yoo Daniel , Divard Gillian , Legendre Christophe , Loupy Alexandre
Published: May 2022

BACKGROUND AND AIMS

Predicting kidney transplant patient mortality has been hampered by registry-based studies and low-level phenotyped cohorts without specific design towards mortality prediction. This represents a limitation for decision making and ultimately patient care. We aimed to build a robust patient mortality prognostication system.

METHOD

We enrolled 1446 patients transplanted in France between 2004 and 2014 in whom a protocol-based collection including more than 160 parameters from the recipient (past medical history, risk factors) donor and graft, biological and imaging data, was performed on the day of transplantation (TX) and during the first year of transplantation. Multivariable Cox model was used to develop an individual predictive score of mortality, further improved by a Lasso regression in order to retain the strongest predictors of mortality.

RESULTS

Among the 1446 kidney transplant recipients included, 309 patients died after a median post-TX follow-up time of 7.6 years (IQR 5.40–10.78).

Among the 120 parameters, 19 predictors were selected using lasso regression. The strongest predictors of patient survival were (1) baseline recipient factors (age, history of cancer, diabetes mellitus, chronic obstructive pulmonary disease, cardiovascular events: myocardial infarction, stroke or arteritis, supraventricular cardiac rhythm disorder, psychiatric history and VHC status); (2) post-TX parameters (need for dialysis, cardiovascular complications and cancer in the first year of TX); and (3) seven biological variables (HbA1c, C-reactive protein, albumin, gamma-glutamyl transferase, uric acid, neutrophils and urinary protein). The mortality score showed accurate calibration and discrimination at 10 years [C-statistic = 0.81; 95% confidence interval (95% CI) 0.78–0.83].

CONCLUSION

We generate the first integrative patient survival score that shows a superior prediction performance when compared to previous prognostic systems, reaching 81% prediction accuracy at 10 years. A reliable survival prediction tool will enable improved patient monitoring and therapeutic decision making to alter the course of an unfavorable patient survival outcome and may provide a surrogate endpoint in clinical trials.
FC 110: Survival Benefit of Preemptive Simultaneous Pancreas-Kidney Transplantation
Authors: Montagud-Marrahi Enrique , Cuadrado Elena , Hermida Evelyn , Cucchiari David , Revuelta Ignacio , Del Risco Zevallos Jimena , Esforzado Nuria , Cofan Pujol Federico , Oppenheimer Federico , Torregrosa Jose-Vicente , Ferrer Joana , Amor Antonio J , Esmatjes Enric , Jose Ramirez Maria , Musquera Mireia , Enriqueta Bayes Genis Beatriu , Maria Campistol Plana Josep , Diekmann Fritz , Ventura Aguiar Pedro
Published: May 2022

BACKGROUND AND AIMS

The evidence regarding the benefits of performing preemptive SPK (pSPK) is controversial. The aim of the present study was to evaluate the impact of pSPK on long-term patient and grafts outcomes when compared with npSPK and pKTA through a national registry study with recipients reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) registry, and to analyse the potential benefits associated with pSPK not only in patients with T1D but also in patients with T2D.

METHOD

To explore the survival advantage of performing a pSPK, we compared the outcomes in pSPK with nonpreemptive SPK (npSPK) recipients between 2000 and 2017 from the OPTN/UNOS registry. To account for the potential benefit provided solely by the kidney transplant, we further compared to recipients of preemptive Kidney Transplantation Alone (pKTA) with diabetes. A propensity score analysis was applied.

RESULTS

A total of 1522 patients received a pSPK, 7894 an npSPK and 3343 a pKTA. Overall recipient survival was superior for the pSPK group when compared with the pKTA (97.7%, and 80.9% versus 97.7% and 72.9% at 1 and 10 years, respectively, P < 0.001), with pKTA being associated with an increased risk of patient death [HR 1.34, 95% confidence interval (95% CI) 1.10–1.63; P = 0.003]. Estimated kidney graft survival was similar in both groups. After IPTW adjustment, pKTA was significantly associated with an increased risk of death-censored kidney graft failure (HR 1.31, 95% CI 1.09–1.56; P = 0.002). The npSPK patients presented both worse patient and kidney graft survival when compared with pSPK.

CONCLUSION

In conclusion, the observed survival benefit of performing an SPK preemptively reinforces the need for early referral for transplantation in patients with insulin-dependent diabetes and advanced chronic kidney disease.
FC 120: Lipid Changes as Early Indicator for Diabetes Induced Renal Pathology
Authors: Rietjens Rosalie , Wang Gangqi , Sol Wendy , Heijs Bram , van den Berg Bernard , Rabelink Ton
Published: May 2022

BACKGROUND AND AIMS

Diabetic nephropathy (DN), chronic loss of kidney function due to diabetes mellitus, is a common complication in diabetes which currently lacks effective long-term treatment. Microalbuminuria is now the earliest marker for DN, thereby disregarding renal changes that occur before this first indication of decreased kidney function. For better diagnosis and treatment strategies, it is important to study diabetes induced early renal changes. Renal-specific changes of the lipid metabolism could serve as an indicator for early kidney damage. Mass spectrometry imaging (MSI) allows to study the lipid metabolism in the context of tissue histology without the need for labeling (i.e. antibody or radioactive). Existing literature applying this technique focuses on later stages of diabetic kidney disease, thereby overlooking its potential to serve in an earlier stage of diagnosis. The aim of this project is to identify renal cell-specific lipid changes using MSI which could serve as damage markers for early diabetes induced renal pathology.

METHOD

To study diabetic renal changes, apolipoprotein E-knockout mice were treated with streptozotocin (STZ) and put on an enriched cholesterol diet to induce diabetes. After 12 weeks, both control (n = 4) and diabetic (n = 4) mice were sacrificed and kidneys were harvested for immunohistochemical and matrix assisted laser desorption/ionization (MALDI) MSI. Post-MSI immunofluorescent staining in combination with tissue morphology was used to identify different renal cell types. Analysis of MALDI-MSI data allows us to spatially segment the results per cell type for further statistical analysis of the metabolic MSI data (Figure 1A).

RESULTS

Two weeks after STZ induction, blood glucose levels of the diabetic mice were significantly elevated compared to control. Spatial segmentation analysis of the MSI data revealed that in both groups different renal cell types could clearly be distinguished based on their metabolic profile. Using the immunofluorescence-based cell type annotation, we zoomed in on various morphological regions of the kidney to specifically test for changes in lipid profiles. Here, the proximal tubular cells in the cortex and the outer stripe of outer medulla had the highest number of significantly changed lipids (Figure 1B). Focusing the analysis on these two groups of cells revealed specific molecular signatures to be discriminative between diabetes and control (Figure 1C).

CONCLUSION

Using MSI, we were able to identify renal cell type-specific differentially expressed lipids in diabetic mice compared to the healthy control group. The proximal tubular cells in the cortex and outer stripe of the outer medulla had the most altered lipid composition. These molecular signatures might serve as an early indicator of diabetes induced renal changes, thereby opening up a potential window for treatment before the kidney is damaged beyond repair.
FC 121: The Combination of Empagliflozin and Atrasentan on Top of RAS Blockade Ameliorates Cardiorenal Injury in a Type 2 Diabetic Mouse Model
Authors: Vergara Arana Ander , Jacobs Cachá Conxita , Molina Mireia , Llorens Cebrià Carmen , Dominguez Pamela , Bermejo Sheila , Paul Pieper Michael , Benito Begoña , Jose Soler Romeo Maria
Published: May 2022

BACKGROUND AND AIMS

sodium-glucose 2 cotransporter inhibitors (SGLT2i) prevent cardiovascular events in diabetic patients. Moreover, their diuretic effect could attenuate the adverse events of endothelin receptor antagonists (ERA), which have also shown kidney protective effects in diabetes. The present study aimed to evaluate the beneficial cardiorenal impact of the combination of SGLT2i, ERA and ramipril versus treatment with ramipril alone in experimental diabetes.

METHOD

Twelve-week-old db/db mice were treated for 8 weeks with different combinations of an SGLT2i (empagliflozin, 10 mg/Kg/day), an ERA (atrasentan, 7 mg/Kg/day) and an RAS blocker (ramipril, 8 mg/Kg/day). Vehicle-treated diabetic and nondiabetic mice were included as controls. During the experiment, blood pressure (BP), glomerular filtration rate (GFR) and echocardiographic parameters were measured. Kidney and heart were collected at the end for histological studies.

RESULTS

The triple therapy with empagliflozin, atrasentan and ramipril was superior to ramipril alone in reducing BP (mean BP 61.0 mmHg versus 67.10 mmHg in the ramipril group), preventing diabetic hyperfiltration (214.3 μL/100 g/min GFR decrease versus 34.7 μL/100 g/min decrease in the ramipril group) (Figure 1), and improving echocardiographic parameters of diastolic dysfunction, including left atrium diameter and isovolumetric relaxation time. Moreover, the combined therapy offered protection against diabetic injury in kidney and heart by a reduction of mesangial matrix expansion (46.0% of glomerular mesangial matrix versus 46.9% in the ramipril group), as well as left ventricle cardiomyocyte hypertrophy (mean cardiomyocyte area 125 μm2 versus 131 μm2 in the ramipril group) and heart collagen deposition (Figure 1).

CONCLUSION

In experimental diabetes, combined therapy of ramipril, empagliflozin and atrasentan promotes both heart and kidney protective effects that outweigh the beneficial effects of ramipril alone.