bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4088 IMPACT OF DYSMAGNESEMIA ON ATRIAL FIBRILLATION IN MAINTENANCE HAEMODIALYSIS PATIENTS: A NATIONWIDE STUDY
Authors: Toida Tatsunori , Kurita Noriaki , Masanori Abe , Hanafusa Norio , Joki Nobuhiko 
Published: June 2023

Abstract

Background and Aims
The dose-response relationship between serum magnesium (sMg) and atrial fibrillation (AF) and the contribution of dysmagnesemia to AF remain unknown among haemodialysis patients.

Method
This was a nationwide cross-sectional study on the Japanese Society for Dialysis Therapy registry as of the end of 2019. Eligible participants were adult patients undergoing haemodialysis thrice a week. The main exposure was sMg, categorised into seven categories (≤1.5, &gt;1.5-≤2, &gt;2-≤2.5, &gt;2.5-≤3, &gt;3-≤3.5, &gt;3.5-≤4, and ≥4.0 mg/dL). The outcome was AF reported by dialysis facilities. The independent contribution to AF was assessed via logistic regression to generate population-attributable fractions, assuming a causal relationship between sMg and AF.

Results
A total of 165,926 patients from 2,549 facilities were analyzed. The prevalence of AF was 7.9%. Compared with the reference (&gt;2.5-≤3 mg/dL), lower sMg was associated with increased AF (adjusted ORs [95%CI] of 1.49 [1.19-1.85], 1.24 [1.17-1.32], and 1.11 [1.06-1.16] for sMg of ≤1.5, &gt;1.5-≤2.0, and &gt;2.0-≤2.5 mg/dl categories, respectively). The slightly high sMg was associated with fewer AF (adjusted OR 0.87 [95%CI 0.79-0.96] for sMg of &gt;3.0-≤3.5 mg/dl). The adjusted population-attributable fraction of lower sMg and higher and lower sMg for AF was 7.4% and 6.9%, respectively.

Conclusion
An association does indeed exist between lower sMg and AF, with the fewest percentages of AF at sMg levels above the reference range for the general population. Dysmagnesemia may be an important contributor to AF among adult haemodialysis patients. Further longitudinal studies are warranted to determine whether correction of sMg reduces the incidence of AF.
#4110 BIO-CONDUCTIVITY MEASUREMENTS ENABLE PORTABLE AND SELF-ADMINISTRATED CHRONIC KIDNEY DISEASE SCREENING AND MONITORING
Authors: Cheung Pak To , Zouari Fedi , Touboul Adrien , Ho Cheuk Man , Sin Venice , Wong Eddie C , Zhou Iris , Yap Desmond , Chan Russell 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is an escalating health concern. The identification of CKD during mass public screening by laboratory tests constitutes important resource implications. Home-based and self-administrated approach to screen and monitor disease severity in both healthy and CKD subjects are eagerly awaited. Frequency-difference electrical impedance tomography (fdEIT) reconstructs the interior of a body by measuring the electrical responses to a small alternating current applied at the surface of the subject at various frequencies. Kidney fibrosis is a cardinal feature of CKD, which is associated with alterations in renal molecular composition and hence electrical conductivity. Therefore, this study aims to investigate the feasibility of a portable, self-administrated approach to assess CKD severity using fdEIT in the kidney region.

Method
Clinical subjects are recruited at Queen Mary Hospital, Hong Kong. EIT data was collected via a PVC belt acting as an electrode holder placed circumferentially on the upper abdominal region of the subject. The belt was connected to a portable console to collect EIT data. 24 frequencies ranging from 10KHz to 300KHz are used to stimulate electrical responses in the body. (Figure 1A) Paired blood and urine samples were collected for measured of eGFR. Group source separation was implemented to extract the kidney region of interest (ROI) and extract conductivity features (Figure 1A); these features, together with the age of the subject, are then input into a regression model to estimate the eGFR and the CKD stage of the subject according to the following classification scheme: stage 1 CKD (eGFR &gt; 90) as healthy subjects, stages 3, 4, 5 CKD (eGFR &lt; 60) as unhealthy subjects, stage 2 CKD (60 &lt; eGFR &lt; 90) as borderline cases.

Results
75 subjects were recruited (54 with CKD and 21 were healthy volunteers). We obtained an eGFR estimation model with R2 score of 0.40. We also obtained a CKD stage classifier with sensitivity of 87.5% and specificity of more than 99.9%. (Figure 1C) The mean conductivity in the extracted kidney signal comprises 40% weighting in the regression model (Figure 1B), showing comparable importance as the age in predicting the eGFR.

Conclusion
The results demonstrate that measuring bio-conductivity anomalies through fdEIT is highly accurate and non-invasive, and can be developed into a portable and self-administrable device to screen and monitor CKD
#4534 FINERENONE ADDED TO RAS/SGLT2 BLOCKADE FOR NON-DIABETIC CHRONIC KIDNEY DISEASE: RESULTS OF A PRECLINICAL DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL
Authors: Zhu Zhihui , Kusunoki Yoshihiro , Rosenkranz Karoline , LI Chenyu , Klaus Martin , Gross Oliver , Angelotti Maria Lucia , Cirillo Luigi , Romagnani Paola , Bülow Roman David , Boor Peter , Anders Hans-Joachim 
Published: June 2023

Abstract

Background and Aims
Inhibitors of the renin-angiotensin system (RAS), sodium-glucose transporter (SGLT)-2, and the mineralocorticoid receptor (MR) have all demonstrated renoprotective effects in large clinical trials of diabetes-related CKD. Furthermore, dual RAS/SGLT2 blockade showed additive renoprotective effects also in non-diabetic CKD. We hypothesized that triple RAS/SGLT2/MR blockade would be even superior to dual RAS/SGLT2 blockade in non-diabetic CKD.

Method
We performed a “no touch” preclinical randomized controlled trial in Col4a3-deficient mice with spontaneous and progressive CKD (registry ID: PCTE0000266). Treatments were administered as food admix from 6-14 weeks of age at the following estimated doses: 10 mg/kg ramipril, 30 mg/kg empagliflozin, 10 mg/kg finerenone. The prespecified primary endpoint was total lifespan up to uremic death. Ancillary studies addressed baseline histology, and mechanistic studies on a subset of mice after 2.5 weeks of treatment.

Results
At the time of randomization, Col4a3-/- mice had albuminuria, elevated serum creatinine, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Total lifespan was 63.7 ± 9.99 days (vehicle), 77.25 ± 5.34 days (ramipril), 80.3 ± 10.98 days (ramipril+empagliflozin), and 103.05 ± 20.28 days (triple therapy), respectively. Artificial intelligence-based histopathology and RNA sequencing analysis documented a potent anti-sclerotic, -inflammation and -fibrotic effect of the triple combination.

Conclusion
Adding finereone to dual RAS/SGLT2 blockade significantly prolongs uremia-free lifespan even when started at an advanced stage of Alport nephropathy. Triple RAS/SGLT2/MR blockade could be a potent treatment strategy to prolong uremia-free lifespan in patients with CKD related to Alport syndrome and possibly other progressive kidney disorders.
#5127 COMBINED ACTIVITY AND CHRONICITY SCORE FOR PROGNOSTIC ASSESSMENT IN ANCA-ASSOCIATED VASCULITIS WITH GLOMERULONEPHRITIS
Authors: Moura Marta Casal , Fervenza Fernando Custodio , Warrington Kenneth , Specks Ulrich , Sethi Sanjeev 
Published: June 2023

Abstract

Background and Aims
Previous studies have shown that chronic changes on kidney biopsy are useful for stratifying the risk of kidney failure in patients with AAV-GN. We aimed to evaluate the impact of inflammatory activity for the prediction of renal outcomes.

Method
A retrospective cohort study of MPO- or PR3-ANCA positive patients with AAV and active renal disease. Inflammatory activity was assessed by the Activity Index (AI): a ratio between the number of crescents and/or necrosis and the total number of glomeruli (in percent). We calculated the AI score: 0-5 = 0; 6-10 = 1; 11-15 = 2; 16-20 = 3; 21-25 = 4; 26-37.5 = 5; 37.6-50 = 6; 51-65 = 7; 66-80 = 8; 80-90 = 9; 90-100 = 10. Chronicity was evaluated with the Mayo Clinic Chronicity Score (MCCS). For the combined score, we summed the MCCS and the AI.

Results
Results. We analyzed 326 patients with kidney biopsies available to score. The biopsies had in median (IQR), 13 glomeruli (9-20), 4 crescents (2-6) and an AI of 28.6% (15.3-47.6). The population was classified according with the risk of progression to kidney failure (KF) in 3 classes as (i) low (0-6) – 114 (35.0%), (ii) intermediate (7-11) – 152 (46.6%), and (iii) high (≥12) – 60 (18.4%). Median eGFR at baseline correlated with the overall risk categories: 42.2 vs. 22.1 vs. 13.4 mL/min/1.73 m2, p&lt;0.0001. The proportion of patients with eGFR&lt; 30 mL/min/1.73 m2 was increased in patients classified as high: 88.3% vs. 66.4% vs. 36.0%, p&lt;0.0001. Renal recovery was more frequent in patients at low risk of progression: 87.7% vs. 64.6% vs. 36.6%, p&lt;0.0001, whereas kidney failure at 12 months and dialysis were more frequent in patients at higher risk (36.7% vs. 12.4% vs. 3.8%, p&lt;0.0001; 35.6% vs. 13.0% vs. 2.9%, p&lt;0.0001, respectively). The combination of AI with MCCS independently predicted the risk of KF at 12 months (HR 1.916, 95%CI 1.210 - 3.033, p = 0.006), particularly increased in patients classified as high risk (HR 3.124, 95%CI 1.224 – 7.970, p = 0.017) and in patients with PR3-ANCA (HR 1.896, 95%CI 1.012 - 3.551, p = 0.046) independently of eGFR at AAV-GN diagnosis and adjusted for severity of renal involvement and age.

Conclusion
The combined assessment of acute inflammatory activity and chronic changes on kidney histology independently predicted renal outcomes in patients with AAV-GN. The impact of the inflammatory activity is cumulative to the chronic changes.
#5319 ACCURACY OF PLATELET INDICES AS PREDICTOR OF IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE KIDNEY INJURY REQUIRING RENAL REPLACEMENT THERAPY
Authors: Balasa Melvy June 
Published: June 2023

Abstract

Background and Aims
Acute kidney injury (AKI) is a major medical complication associated with a markedly increased risk of death, particularly in patients admitted to the ICU where in-hospital mortality exceeds 50%1. This study aimed to determine the accuracy of MPV, platelet count, and PDW as predictors of adverse outcomes in patients with AKI who received initiation renal replacement therapy (RRT).

Method
A retrospective cohort single-center study was done in a local private tertiary hospital in Cebu. Four hundred ninety-one patients with AKI who underwent RRT between January 2018 and December 2021 were enrolled. A retrieval of data on demographic and clinical parameters during the initiation of RRT was done. The impact of mortality-related factors were identified using univariate and multivariate logistic regression analysis. Determination of optimal cut-off values of platelet indices for in-hospital mortality was done.

Results
This study showed that the in-hospital mortality of patients was 58.45%, with a mean age of 68.6 ± 16.28 years among non-survivors. Among the platelet indices, platelet count and PDW were good predictors of in-hospital mortality in patients who received initiation renal replacement therapy. The optimal cut-off value of platelet count was 173 × 103/uL (sensitivity 56.45%, specificity 62.25%, PPV 67.78%, NPV 50.40%, AUC 0.604). The optimal cut-off value of PDW was 16.45% (sensitivity 50.87%, specificity 71.57%, PPV 71.57%, NPV 50.87%, AUC 0.611).

Conclusion
Platelet indices are feasible parameters that can be used as prognostic markers for mortality in patients with AKI requiring RRT. The in-hospital mortality of patients with AKI requiring initiation RRT is high (58.45%). Low platelet counts, high MPV values, and high PDW values are associated with poorer outcomes and higher mortality risk as compared to patients with normal indices.
#5393 INFLUENCE OF CELLULAR INFLAMMATION ON THE OUTCOME OF KIDNEY TRANSPLANTATION AFTER RECURRENCE OF IGA NEPHROPATHY
Authors: Vázquez Teresa , Rodrigo Emilio , Porras Luis Fernando Quintana , Fructuoso Ana Sanchez , Gomez-Ortega Jose María , Buxeda Anna , Gavela Eva , Castello Maria Isabel Beneyto , Oliva Maria Ovidia Lopez , Hernández Domingo 
Published: June 2023

Abstract

Background and Aims
The recurrence of IgA nephropathy (rIgAN) worsens the prognosis of renal transplantation, representing the third cause of loss in these recipients. Several variables at the time of recurrence, such as worse renal function, greater proteinuria, previous steroid withdrawal, and MEST-C histological findings have been associated with a higher risk of graft loss after recurrence. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with rIgAN.

Method
A multicenter retrospective study was carried out including renal transplant recipients with biopsy-proven IgA nephropathy as the underlying disease in which the recurrence of the primary disease had been verified by means of graft biopsy and in which the Banff criteria were available or could be reviewed. Cellular inflammation was defined according to Banff scores as “t” or “i” ≥2. The main endpoint was progression to CKD stage 5 or death censored-graft loss (DCGL).

Results
118 kidney transplant recipients were included with an age of 47 ± 14 years at recurrence, 80% male, with a mean time to biopsy of 65 ± 69 months and a post-transplant follow-up of 118 ± 70 months. After recurrence, 34 (28.8%) transplants were lost after 35 ± 28 months, excluding death. Using univariate Cox regression, the factors related to CKD stage 5 or graft loss were systolic blood pressure (HR 1.039, 95%CI 1.016-1.064, p = 0.001), glomerular filtration rate (HR 0.948, 95%CI 0.922-0.974, p &lt;0.001), the logarithm of proteinuria (HR 15.836, 95% CI 5.504-45.565, p &lt; 0.001), Oxford-C score (HR 3.490, 95% CI 2.137-5.699, p &lt;0.001), interstitial fibrosis (HR 2.173, 95% CI 1.362-3.468, p = 0.001) and cellular inflammation (HR 2.458, 95% CI 1.237-4.884, p = 0.010). After multivariate analysis, cellular inflammation remained significantly related to CKD stage 5 or DCGL (HR 2.338, 95% CI 1.077-5.075, p = 0.032). independently of systolic blood pressure, glomerular filtration rate, the logarithm of proteinuria and Oxford-C score.

Conclusion
In addition to the previously described factors usually related to worse evolution of IgA nephropathy in the native kidney and after post-transplant recurrence, we observed that cellular inflammation influences worse evolution after rIgAN. We suggest to considering the Banff criteria for acute cellular inflammation to better understand the subsequent evolution of patients with rIgAN.
#5504 EXTENDED VALIDATION OF THE IBOX IN REAL LIFE SETTING, DIFFERENT TRANSPLANT SYSTEMS AND CLINICAL TRIALS: THE IBOX EXTENDED TRIAL
Authors: Naser Sofia , Divard Gillian , Raynaud Marc , Naesens Maarten , Segev Dorry , Stegall Mark , Lefaucheur Carmen , Aubert Olivier , Loupy Alexandre 
Published: June 2023

Abstract

Background and Aims
The iBox is a validated prognostication system predicting long-term kidney allograft failure. Recently, it received regulatory endorsement by EMA, for surrogate endpoint for clinical trials. As the iBox system was primarily built using a deep phenotyped cohort, there is a need for proof of validity in extended clinical scenarios, geographic distinct medico-economic cohorts and transplant allocation systems.

Method
10,851 transplant recipients were included from 17 academic medical centers from France, Belgium, Spain, Germany, Finland, United States, Brazil and Argentina. We applied to these cohorts the iBox algorithm that integrates eight independent prognostic factors including the time from transplantation to risk evaluation, functional parameters (eGFR, proteinuria), allograft histological lesions (IFTA, g+ptc, i+t, cg Banff scores), and circulating anti-HLA DSA. We stratified the performances of the iBox according to several real-life scenarios, including: 1) iBox + different eGFR formulas (MDRD186, MDRD175, CKD-Epi); 2) iBox + urinary dipstick; 3) iBox Functional + Structural (absence of DSA measurements); 4) iBox functional + Immunological (absence of histology); 5) iBox in response to treatment in T-cell mediated rejection (TCMR); 6) iBox for in response to treatment antibody mediated rejection (ABMR) clinical trials. The performances of the iBox system were assessed with the discrimination (C-index) and calibration.

Results
The derivation cohort included 4,000 recipients from France, and the international external validation cohort included 6,851 recipients from Europe (France, Belgium, Spain, Germany, Finland n = 4,643), the United States (n = 1,537) and South America (Brazil, Argentina n = 671). The mean recipient age was 50.26 years (14.05) with a median follow-up after evaluations of 5.41 years [IQR: 3.26 to 7]. 1336 patients (12.31%) lost their graft during the study follow-up. The performances of the iBox were confirmed in the different real-life setting with the following C-Index: 1) iBox + different eGFR formulas (MDRD186, MDRD175, CKD-Epi) 0.81; 2) iBox + urinary dipstick 0.80; 3) iBox Functional + Structural (histology) 0.80 (derivation) and 0.84 (validation); 4) iBox functional + Immunological 0.80 (derivation) and 0.83 (validation); 5) iBox in response to treatment in T-cell mediated rejection 0.81; 6) iBox for in response to treatment antibody mediated rejection trials 0.81. The score showed an accurate calibration in every scenario.

Conclusion
The iBoxEXTENDED trial confirms in various medico-economic settings the performances transportability and surrogacy of the iBox system, further reinforcing its use as a surrogate end point for clinical trials including TCMR and ABMR.
#5699 IS GFR DECLINE INDUCED BY SGLT-2 INHIBITOR OF CLINICAL IMPORTANCE?
Authors: Guenes-Altan Merve , Bosch Agnes , Striepe Kristina , Schiffer Mario , Bramlage Peter , Schmieder Roland E , Kannenkeril Dennis 
Published: June 2023

Abstract

Background and Aims
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcome and with nephroprotection independent of diabetes status. However, the use of SGLT2i often cause an initial decline in estimated glomerular filtration rate (eGFR). This study addresses the question whether there is a relationship between vascular improvement and GFR dipping.

Method
We measured GFR (mGFR) and calculated GFR (eGFR) in 65 patients with T2D at baseline and after 12 weeks of treatment with either a combination of Empagliflozin (E) + Linagliptin (L) (n = 34) or Metformin (M) + Insulin (I) (n = 31). mGFR was measured using the gold standard clearance technique by infusion of inulin. In addition, pulse wave velocity (PWV) was obtained at office and under ambulatory conditions. We splitted the study cohort according to the median change of mGFR after 12 weeks and compared the baseline characteristics.

Results
mGFR and eGFR decreased significantly with E+L and with M+I (Ott C et. al. Cardiovasc Diabetol. 2021). However, no correlation was noticed between the change of mGFR and change of eGFR for either treatment cohorts (E+L: p = 0.404; M+I: p = 0.460). We found a significant decrease in office PWV in the E+L group only (8.2±1.6 to 7.8±1.5, p = 0.028) without any change in 24-h PWV. The change of office PWV correlated with the change of mGFR (p = 0.009) in E+L group only and remained significant after adjustment for the change of office systolic BP (p = 0.018). In addition, we observed a correlation between the change of high sensitive C reactive protein (hsCRP) and change in mGFR (p = 0.031).
We identified patients with higher albumin excretion (p = 0.044), higher fasting plasma glucose (p = 0.014) and high hsCRP (p = 0.057) to have a greater decline in mGFR with E+L.

Conclusion
First, eGFR may not be an appropriate parameter to assess the true change in renal function after receiving E+L in a single patient. Second, after E+L medication a high decrease in mGFR goes in parallel with vascular improvement and less inflammation thereby reflecting the pleiotropic pharmacologic effects of SGLT 2 inhibitors.
#5721 HEPATITIS B VIRUS REACTIVATION IN KIDNEY TRANSPLANT RECIPIENTS TREATED WITH BELATACEPT
Authors: Schwarz Chloe , Morel Antoine , Matignon Marie , Grimbert Philippe , Rondeau Eric , Ouali Nacera , Francois Helene , Mesnard Laurent , Petit-Hoang Camille , Rafat Cédric , Dahan Karine , Luque Yosu 
Published: June 2023

Abstract

Background and Aims
Hepatitis B virus (HBV) reactivation in kidney transplant recipients may be associated with liver failure and graft loss, especially in anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients. Belatacept, a selective costimulation blocker, has been used in kidney transplantation for some time and has been associated with reactivation of other viruses as BK or CMV. However, there are few data on HBV reactivation among kidney recipients treated with belatacept.

Method
We performed a retrospective study in two French kidney transplantation centres including all transplant recipients receiving belatacept. Among HBcAb-positive patients, we analyzed HBV reactivation rate, outcomes and risks factors.

Results
135 patients treated with belatacept were included, and 32 were HBcAb-positive. Seven patients reactivated HBV (21.9% of HBcAb-positive patients), including 5 HBsAg-negative patients (16.7%); reactivation occurred 54.8 (± 70.9) months after transplantation. There was no significant difference in survival between patients that reactivated HBV and patients that did not: 5-year patient survival of 100% (28.6; 100) and 83.4% (67.6; 100), respectively (p = 0.363) and 5-year graft survival of 100% (28.6; 100) and 79.8% (61.7; 100), respectively (p = 0.335). No factor, including HBsAb positivity and antiviral prophylaxis, was statistically associated with the risk of HBV reactivation.

Conclusion
Compared to the few studies that exist in this area, the HBV reactivation rate was high in patients treated with belatacept in our study. Our findings suggest that systematic antiviral prophylaxis for anti-HBc antibody (HBcAb)-positive HBs antigen (HBsAg)-negative patients should be considered and that there should be close monitoring of HBV serology and viral load in these patients to detect early HBV reactivation.