bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO457: Diffusion-MRI Predicts Decline of Renal Function in Chronic Kidney Diseases and Kidney Allograft Patients
Authors: Berchtold Lena , Crowe Lindsey , Combescure Christophe , Kassai Miklos , Aslam Ibtisam , Legouis David , Moll Solange , Martin Pierre-Yves , de Seigneux Sophie , Vallée Jean-Paul 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Kidney cortical interstitial fibrosis is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted a diffusion-weighted imaging sequence, allowing for the discrimination between the kidney cortex and medulla. The cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated to histological interstitial fibrosis. The aim of this study was to assess whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of renal function decline and dialysis in chronic kidney diseases (CKD) and kidney allograft patients.

METHOD
We performed a prospective study including 197 patients. We measured ΔADC in 43 CKD patients [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73m2] and 154 kidney allograft patients (eGFR 53 ml/min/1.73m2). Patients underwent a renal biopsy and diffusion-weighted magnetic resonance imaging, within 1 week of biopsy. Follow-up was 2.2 years in median. During follow-up, laboratory parameters were measured. Primary outcome was defined as rapid decline of renal function (eGFR decline &gt; 30% or dialysis initiation) during follow-up.

RESULTS
Patients with low ΔADC (&lt;0 x10-6mm2/s) had 5.4 times more risk of rapid decline of renal function or dialysis [95% confidence interval (CI): 2.29–12.58; P &lt; 0.001]. After correction for renal function at baseline and proteinuria, low ADC still predict renal function loss with a hazard ratio (HR) of 4.62 (P &lt; 0.001, 95% CI 1.56–13.67).

CONCLUSION
We demonstrate in this study that low ΔADC is a predictor of renal function decline and dialysis initiation in CKD and kidney allograft patients, independent of baseline renal function and proteinuria.
MO458: Superb Micro-Vascular Imaging: An Innovative Ultrasound Technique for Early Detecting of Renal Damage
Authors: Armaly Zaher , Abu-Rahme Munai , Kinaneh Safa , Hijazi Basem , Habasshe Nayef , Abassi Zaid , Artul Suheil 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Novel ultrasound (US) methods are required to assess qualitative alterations in renal tissue. Superb microvascular imaging (SMI) is an innovative US technique designed for imaging and better visualization of micro-vascularization unseen with color Doppler US. We assume that SMI will provide sufficient information regarding the severity of chronic kidney disease (CKD) and reflect renal histological alterations. To assess the early detection of kidney dysfunction and renal fibrosis capabilities of SMI imaging in comparison to the reference standard renal biopsy, in order to determine the usefulness of this approach in the early diagnosis of kidney dysfunction and renal fibrosis.

METHOD
The SMI was performed in patients (n = 52) with CKD stage 2–5, where some of them underwent biopsy-proven chronic renal dysfunction and fibrosis as part of the diagnosis and therapeutic judgment as needed. In addition, biochemical tests were performed in order to determine kidney function (BUN, Serum Creatinine), a urine collection test for the assessment of proteinuria and estimation of GFR by MDRD formula in patients with CKD of various severity and healthy controls (n = 17). In addition, all subjects underwent SMI US imaging, where vascularity is expressed as SMI index (low index reflects low vascularity/fibrosis and vice versa).

RESULTS
As expected, SMI vascular index was significantly lower in CKD patients as compared with healthy control (72.2 ± 12.9 versus 49.9 ± 16.7 %, P &lt; 0.01). Interestingly, significant correlation between the SMI index and eGFR was found among the CKD patients (r = 0.56, P &lt; 0.001). Similarly, a keen correlation was found between the SCr and SMI index of the diseased subjects (r = −0.54, P &lt; 0.001). Among those who underwent renal biopsy, SMI index corresponds with the histological alterations such as fibrosis and CKD staging.

CONCLUSION
These findings show that SMI technique could be used due to its diagnostic capacity as a simple and practical method for evaluation of chronic renal histological changes and for the differentiation between CKD grades.
MO461: A Novel Chronic Kidney Disease to HFpEF Connection: Inflammatory Signaling, Micro-RNAs, and NF-KB
Authors: Chade Alejandro , Mohamed Tamer , Miller Jessica , Aboulesia Riham , Ouand Qinghui , Tang Hui , Saadiq Ishran , Eirin Alfonso 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) is an independent risk factor for heart failure with preserved ejection fraction (HFpEF), a progressive condition that affects ˃50% of patients in dialysis. We developed a swine model of CKD-HFpEF and showed that renal inflammatory signaling plays a key role in HFpEF pathophysiology via cardiac activation of nuclear factor-kappa B (NF-kB). However, the mechanisms of CKD-induced cardiac NF-κB activation remain unclear. We hypothesized that micro-RNA (miRNA)-mediated processes contribute to cardiac NF-kB activation in CKD-HFpEF.

METHOD
Using an in-silico approach (miRWalk3.0 and TargetScan 7.2), we identified all miRNAs capable of targeting the NFKB Inhibitor Alpha (NFKBIA) gene. We then identified those expressed in swine myocardium and measured their levels in normal and CKD pigs by qPCR. In a biomimetic heart culture system that mimics the cardiac CKD-HFpEF microenvironment, pig heart slices were exposed to plasma from normal or CKD pigs, and cardiac kinetics, NF-kB signaling, and miRNA expression levels were investigated in vitro.

RESULTS
We identified 5 miRNAs expressed in swine hearts capable of targeting NFKBIA, of which only miR-1271–3p showed higher expression in the myocardium of CKD-HFpEF pigs compared to normal pigs. miR-1271–3p upregulation was mirrored in pig heart slices exposed to plasma from CKD pigs, associated with blunted cardiac contraction/relaxation kinetics, downregulation of NFKBIA, and increased protein expression of NF-κB (Figure).

CONCLUSION
Our data support a novel pathophysiological mechanism for cardiac activation of NF-κB in CKD via post-transcriptional modulation of NFKBIA partly through miR-1271–3p. This miRNA might represent a novel therapeutic target to ameliorate the deleterious effects that renal inflammatory signaling in CKD imposes on the heart and may lead to HFpEF.
MO467: Time to Improvement of Itch Intensity in Patients With Chronic Kidney Disease-Associated Pruritus Treated With Difelikefalin
Authors: Csiky Botond , Walpen Sebastian , Schaufler Thilo , Morin Isabelle , Wen Warren , Menzaghi Frederique 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease-associated pruritus (CKD-aP) is frequently reported by patients with CKD undergoing haemodialysis (HD), impacting sleep quality, quality of life and depression. Difelikefalin is a selective kappa-opioid receptor agonist approved in the United States for the treatment of moderate-to-severe pruritus in adults undergoing HD. In the Phase 3 KALM-1 and KALM-2 multicentre, placebo-controlled trials, difelikefalin significantly reduced itch intensity in HD patients with CKD-aP. The KALM trials used the Worst-Itching Numerical Rating Scale (WI-NRS) to assess itch intensity [range from 0 (no itching) to 10 (worst itching imaginable)], for which a ≥ 3-point improvement has been validated as a clinically relevant reduction in itch in this patient population. The aim of this post hoc analysis was to determine the time to clinically relevant improvement in WI-NRS score in patients with CKD-aP treated with difelikefalin.

METHOD
The KALM-1 and KALM-2 studies enrolled maintenance HD patients with moderate-to-severe CKD-aP [mean baseline 24-h WI-NRS score &gt; 4 (KALM-1) or ≥ 5 (KALM-2)]. Patients were randomized 1:1 to intravenous difelikefalin 0.5 mcg/kg or placebo 3 times/week for 12 weeks. Patients completed the WI-NRS questionnaire daily. A post hoc analysis was performed to assess the cumulative proportion of patients achieving a ≥ 3-point improvement in WI-NRS score each week.

RESULTS
Two-thirds of patients treated with difelikefalin who reported a response did so within 4 weeks. A further 4 weeks of treatment resulted in over 90% of difelikefalin responders reporting a clinically relevant improvement (Figure 1). Fewer patients receiving placebo reported a reduction in itch at any time during treatment (44% versus 57% of difelikefalin-treated patients) and any improvements in pruritus were reported later than for difelikefalin-treated patients.

CONCLUSION
A clinically relevant response to difelikefalin is likely to be reported by most patients within 4 weeks and almost all patients benefit from improvement after a further 4 weeks of treatment. Compared with patients receiving a placebo, those treated with difelikefalin are more likely to experience clinically-relevant reductions in itch, as well as an earlier improvement in pruritus.
MO479: CKD Coding Across Hertfordshire and West Essex. Are We Missing the Chance for Early Intervention?
Authors: Findlay Andrew , Sivaramakrishnan Ramanarayanan , Hanna Antonious 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Coding of chronic kidney disease (CKD) is associated with better outcomes through addressing the risk factors, and CKD-coded cases were found to have fewer unplanned hospital admission rates.
We aim to compare the CKD coding across Hertfordshire and West Essex to the published CKD prevalence by Quality and Outcomes Framework (QOF) and New Opportunities for Early Renal Intervention by Computerised Assessment (NEOERICA), and to demonstrate variation in coding across primary care practices within the region.

METHOD
In August 2020, we reviewed data for Clinical Commissioning Groups (CCG), Primary Care Networks (PCN), practice code and practice name. Data were obtained from 136/144 practices, including the numbers of adult patients, number of CKD-coded patients, and percentage as a total of the adult population by practice, PCN and CCG were derived. Then we compared the actual obtained data with predicted numbers and percentages of CKD patients estimated from practice-registered adult populations using QOF (2009–10) that demonstrated a 4.3% prevalence [1] and NEOERICA (2003) that demonstrated an 8.5% prevalence [2].

RESULTS
Across the adult population of 1.2 million, 38 645 patients had a CKD code, giving a 3.2% CKD prevalence. Assuming a QOF of 4.3% prevalence, then 13 316 CKD patients are uncoded. While considering a NEOERICA 8.5% prevalence, this would yield the assumption of 64 160 CKD uncoded patients. East & North Hertfordshire NHS Trust had the lowest coded CKD percentage at 2.7% of the served adult population. All three CCG areas had considerable percentage variations in CKD coding across the 135 practices.

CONCLUSION
Across Hertfordshire and West Essex, CKD coding is below the published CKD prevalence from QOF and NEOERICA, suggesting significant numbers of patients are uncoded. There are variations in coding percentage between primary care practices within the PCN and CCG groups. Suboptimal coding may decrease the ability to offer early intervention to decrease CKD progression and would be associated with poor outcomes, including cardiovascular disease. This demonstrates the current unmet need for improved coding through community nephrology surveillance between primary and secondary care.
MO481: Novel Predictors of CKD in Metabolic Fatty Liver Disease Patients: Steatosis Vs Fibrosis. A Prospective Study Using Transient Elastography With Controlled Attenuation Parameter
Authors: Marc Luciana , Mihaescu Adelina , Lupusoru Raluca , Bob Flaviu , Chisavu Lazar , Timar Bogdan , Timar Romulus , Schiller Adalbert 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Recent data have proven that NAFLD (nonalcoholic fatty liver disease) and NASH (nonalcoholic steatohepatitis) increase the risk of CKD. Changing the concept of NAFLD to MAFLD (metabolic dysfunction associated fatty liver disease) changes the data of inclusion of patients in the new category and also the relationship with CKD. Our study aimed to explore this relation using liver steatosis and liver fibrosis assessments by transient elastography (TE) with controlled attenuation parameter (CAP).

METHOD
We prospectively evaluated 402 diabetic patients with MAFLD and high CKD risk using TE with CAP (FibroScan®). CKD was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines. Inclusion criteria: patients &gt;18 years old and the presence of MALFD. Exclusion criteria: pregnancy, ascites, outliers, known chronic liver disease, decompensated liver disease, cardiac pacemaker, end-stage renal disease, heart failure, unreliable or invalid TE and CAP measurements, AST and ALT levels &gt;5 times the upper limit of normal. Transient elastography was performed with the FibroScan® device. To discriminate between fibrosis and steatosis stages, we used the TE and CAP cut-off values from a published multicentric trial compared with biopsy. Logistic regression and stepwise multiple logistic regression were used to evaluate the factors associated with CKD. In addition, ROC analysis was used to assess the performance of CAP and TE in predicting CKD. The study was conducted &gt;1 year period.

RESULTS
The prevalence of CKD in our group was 60.8%. Patients with CKD had higher mean LSM and CAP values than those without CKD (LSM 8.64 ± 4.30 versus 8.03 ± 6.57; P = .04 and CAP 320.09 ± 57.12 versus 306.29 ± 61.21; P = .04). We found that hepatic steatosis was a better predictor of CKD than fibrosis. Univariate regression showed that CAP values &gt; 353 dB/m were predictive of CKD, and multivariate regression analysis (after adjustment according to sex, BMI, LDLc, HDLc and fasting glucose) showed that CAP values &gt;353 dB/m were more strongly associated with the presence of CKD compared with LSM (fibrosis) values.

CONCLUSION
In patients with MAFLD, CAP-assessed steatosis appears to be a better predictor of CKD compared with LSM-assessed hepatic fibrosis.
MO490: Fast and High Phosphate Reduction With Lanthanum Dioxycarbonate Versus Selevamer In In-Vivo Study
Authors: Khare Atul , Pramod Gupta 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Over 7 million patients suffer from end-stage kidney disease (ESKD) worldwide [1]. Due to low kidney function, patients often become hyperphosphatemic, which leads to an increased risk of death [2]. Patients usually rely on dietary restrictions and phosphate (P) binders to address hyperphosphatemia. Current P binders often do not achieve desired levels of P3 and have a high pill burden due to the high quantity of large pills [4, 5]. A therapeutic option with a potentially smaller dose volume (i.e. fewer pills and smaller pill size) and efficacy similar to or possibly better than current products would enhance patient quality of life (QoL). Lanthanum dioxycarbonate, RENAZORB(LDC), is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity versus other P binders [6], with a potentially smaller pill size that is swallowed rather than chewed. We present the results of an in-vivo study evaluating the reduction of urine P levels by LDC and sevelamer (SVH).

METHOD
An in-vivo study evaluated the reduction of urine P levels by LDC and SVH in healthy mice. For 7 days, 1 group of 6 mice received 0.394 g LDC/day, and another group of 6 mice received 0.412 g SVH/day, which represent comparable doses.

RESULTS
On day 1, LDC decreased urine phosphate excretion by 93% versus 42% with SVH. LDC decreased urine phosphate excretion throughout the treatment. However, SVH decreased urine phosphate excretion only in the first 3 days. The health of surviving animals did not appear to be affected. The incidence of animals that did not survive the study duration was similar across groups.

CONCLUSION
LDC effectively decreased urinary phosphate excretion on day 1 and maintained effectiveness throughout the treatment period. LDC appeared to have at least similar if not improved efficacy compared with SVH in this animal model. LDC may be a welcome choice for patients as it is effective and is targeted to be available in a small, easy-to-swallow pill.
MO507: Prediction of CKD Progression and Cardiovascular Events Using Pulse Wave Velocity and Albuminuria
Authors: Carlsen Rasmus , Sherzad Khatir Dinah , Jensen Danny , Birn Henrik , Henrik Buus Niels 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD) and death. Albuminuria has been identified as a risk factor, however, additional biomarkers predicting CKD progression and CVD are needed. Arterial stiffness is an easily measurable candidate that has been associated with CVD and mortality. We compared the ability of carotid-femoral pulse wave velocity (PWV) and urine albumin-creatinine (UAC) ratios to predict CKD progression, cardiovascular events (myocardial infarction or stroke) and mortality in a cohort of CKD patients.

METHOD
In stage, CKD stage 3–4 patients PWV and UAC were measured at baseline. The endpoint of CKD progression was defined as a 50% decline in estimated glomerular filtration rate (eGFR), the initiation of dialysis or renal transplantation. The composite endpoint was defined as the CKD progression endpoint, myocardial infarction, stroke or death. Endpoints were analyzed in a Cox regression analysis adjusted for age, gender, blood pressure, baseline eGFR, BMI and including both PWV and UAC. Data were collected from individual patient biochemistry files, the Danish National Nephrology Registry and the Danish Health Data Registry.

RESULTS
We included 182 patients [median age 69 (interquartile range 60–75) years, 68% males] with a mean eGFR 37 ± 12 mL/min/1.73 m2 and a UAC of 52 (5–453) mg/g. The mean PWV was 10.6 m/s. The median follow-up until the first event was 4 (3–6) years, with 44 and 89 patients reaching the CKD progression and the composite endpoints, respectively. UAC (mg/g) significantly predicted both the CKD endpoint [HR: 1.0005 (1.0002–1.0008)] and the composite endpoint [HR 1.0004 (1.0001–1.0007)] in adjusted cox regression. In contrast, PWV (m/s) was not associated with the CKD endpoint [HR: 0.99 (0.84–1.18)] nor the composite endpoint (HR: 1.03 (0.92–1.15)].

CONCLUSION
In an ageing CKD population, UAC predicted both CKD progression and a composite endpoint of CKD progression, cardiovascular events, or death, while PWV at baseline did not.
MO511: Epidemiology of Idiopathic Nephrotic Syndrome in Children Before and During Covid-19 Pandemic in Paris Area
Authors: Thenot Victoire , Parmentier Cyrielle , Boyer Olivia , Mahdi Fouad , Nathanson Sylvie , Zenkhri Ferielle , Blanc Philippe , Mendli Nasser , Galerne Aurelien , Mandelcwajg Alexis , Hogan Julien , Dossier Claire 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The aetiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been reported to be associated with INS onset and relapse. The COVID-19 pandemic led to several national lockdowns aimed at limiting virus transmission. In France, schools were closed during the first lockdown (15 March–11 May 2020). Circulation of other respiratory viruses was lower due to restrictive lockdown measures. We hypothesized that these lockdown measures would be associated with a decrease in the incidence of idiopathic nephrotic syndrome in children. The aim of this study was to describe the incidence of INS over the last 4 years and during the lockdown measures and to compare this incidence with the 2007–10 period (NEPHROVIR-1 cohort).

METHOD
A written questionnaire was sent to corresponding the paediatricians of all 37 hospitals in the Paris area. Children aged 1–15 years with INS onset between January 2017 and December 2020 and living in the Paris area were included. Clinical data were collected from medical charts. To estimate incidence, population-based denominators were obtained from the National Institute for Statistics and Economic Studies (INSEE). For analyses, we separated the study period into two periods: during lockdown measures (2 months) and the rest of the time (46 months).

RESULTS
A total of 95% of centres responded to the questionnaire. On the whole, 248 cases of INS were reported, 94% of whom were steroid sensitive. The median age at diagnosis was 5.6 years. Male/female ratio was 2.1: 1. Annual incidences of INS were 2.66, 2.49, 2.91 and 2.40/100 000 children under age 15 years in 2017, 2018, 2019 and 2020, respectively, with no significant difference between years. There was also no difference between annual incidence of the 2017–20 period and the NEPHROVIR-1 cohort period (2007–10) (P = .6). The incidence of INS during the lockdown measures was 0.51 versus 2.71 for the rest of the study period (P = .03). During week 15 (6–12 April 2020), with the highest number of hospital admissions for COVID-19, no case were reported.

CONCLUSION
Over the last decade, the incidence of childhood INS was stable in the Paris area. In 2020, no peak of incidence occurred concomitantly with the COVID pandemic. In addition, during lockdown measures, the incidence of INS was significantly lower. Interestingly, incidence of other respiratory viral infections was reported decreased during lockdown measures. Together, these results argue again for a link between INS onset and viral infections, while COVID-19 does not appear to be a significative trigger for nephrotic syndrome onset in children.