bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5630 SCREENING AND DIAGNOSIS STRATEGY FOR FABRY DISEASE IN TAIWANESE PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Wu Mlng-Ju , Wu Chih-Jen , Lin Cheng-Jui , Yang Feng-Jung , Wu Mai-Szu 
Published: June 2023

Abstract

Background and Aims
Fabry disease (FD) is not uncommon in patients with chronic kidney disease (CKD) who are on dialysis or have stroke at a young age, left ventricular hypertrophy (LVH) or hypertrophic obstructive cardiomyopathy (HOCM). However, FD is easily overlooked by physicians due to the heterogeneity of clinical manifestations. Therefore, an expert consensus meeting was held to establish a screening algorithm for FD in patients with CKD.

Method
The first meeting was held in Taiwan in August 2022. The screening criteria for FD with respect to age, sex, family history, cardiac involvement and signs and symptoms were discussed. The findings of meeting and the consensus opinion of the expert group were summarized.

Results
The screening algorithm was shown in Figure 1. It is recommended to screen for FD regardless of age. Screening for FD is recommended for CKD patients with family history of FD, stroke at young age (&lt;55 years) or typical signs and symptoms including angiokeratoma, hypohidrosis, neuropathic pain, heat/cold and exercise intolerance, hearing loss and cornea verticillata. If CKD patients have one of the cardiac symptoms including dyspnea, palpitation and chest pain, it is recommended to check the cardiac-related red flags including LVH and HOCM using echocardiogram, short PQ interval, atrioventricular block and prolonged QRS interval using electrocardiogram, and low native T1 and posterolateral late gadolinium enhancement using magnetic resonance imaging. If cardiac-related red flags are present, screening for FD is recommended. Screening can also be performed in patients with CKD who do not have any typical symptoms but have a high suspicion of FD. In males, screening can be performed by measuring α-galactosidase A enzyme activity. If the enzyme activity is reduced or absent, assessment of globotriaosylsphingosine (lyso-Gb3) levels in plasma and genetic analysis are recommended. In female, assessment of lyso-Gb3 levels in plasma and genetic analysis are recommended.

Conclusion
FD is an underrecognized and not so rare disease. Physicians should maintain a skeptical attitude in clinical practice in order to make diagnosis in time and help patients and their entire families avoid life-threatening diseases at a young age. There are still more issues to be addressed, including whether to inform patients of the screening results, how to interact and communicate with patients, etc.
#5632 THE CLINICAL AND ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE IN GREECE
Authors: Stafylas Panos , Sarafidis Pantelis , Tychala Christiana , Pella Eva , Karaiskou Marianthi , Valsami Renata , Stergiou George , Boletis Ioannis 
Published: June 2023

Abstract

Background and Aims
Chronic Kidney Disease (CKD) is a progressive disorder with a substantial clinical and economic burden. This burden is expected to grow, mainly because of the ageing population, and the increasing incidence of diabetes mellitus and arterial hypertension. The objective of this study is to provide insights into the clinical and economic burden of CKD in Greece.

Method
A cost of illness (COI) study has been performed to approximate the burden of CKD in Greece from the perspective of EOPYY (National Organization for Health Care Services Provision), with reference year 2022. The COI model employs a prevalence-based approach using national and international sources and approximates the annual direct cost of CKD. The direct costs included in this analysis are categorized into primary care, medication, hospitalization and renal replacement therapy (RRT) costs.

Results
It has been estimated that there about 1,115,991 patients with CKD (stages 1–5) in Greece, most of them in stage 3 (about 534,694), and about 15,337 receiving RRT or having received a kidney transplant. In 2032 this population is expected to increase to approximately 1,249,475 patients. The total annual direct cost of CKD was estimated at €845,936,094. The main cost driver was RRT, which accounted for roughly 49% (417 millions) of total cost of care, followed by hospitalizations 29% (246 millions) and medications 17% (143 millions). The progression of the disease is strongly correlated with an increase in the annual management cost. About 1.4% of the CKD population (RRT group) spent about half of the total CKD budget or more than 4% of the total public health expenditure, higher than other European countries.

Conclusion
CKD is creating a high and growing clinical and economic burden, largely driven by the RRT cost. There is an urgent need for public health strategies aiming at early detection and management of CKD.
#5649 HEPARANASE OVEREXPRESSION MODIFIES PODOCYTE MOTILITY
Authors: Lensky Aviya , Suleiman Hanan Abu-Tayeh , Vlodavsky Israel , Ilan Neta , Assady Suheir 
Published: June 2023

Abstract

Background and Aims
Heparanase is an endo-β-d-glucuronidase that degrades heparan sulfate side chains, which are essential components of extracellular matrices and cell surfaces, including in the kidney filtration apparatus, the glomerulus. Upregulation of heparanase in glomerular diseases (GDs) was demonstrated in experimental models of GDs and in humans. Using transgenic mice overexpressing the human heparanase gene, we recently showed that heparanase reduced proteinuria and preserved the glomerular filtration barrier (GFB) after Adriamycin-induced injury. Furthermore, heparanase improved survival of key GFB cells, the podocytes and enhanced their autophagic flux both in vitro and in vivo. Here, we aimed to study the potential role of heparanase on podocyte locomotion and adhesion.

Methods
We utilized immortalized human podocyte cell line AB8/13 (a kind gift of Prof. Moin Saleem, Bristol, UK) as an experimental platform. Cells were infected with pLenti6/V5-DEST carrying the heparanase gene construct (H) or control empty vector (V) and were allowed to differentiate for 14 days. To induce injury, differentiated podocytes were treated with Adriamycin (0.5 μg/mL), mimicking Adriamycin nephropathy, an established experimental model for progressive proteinuric GDs. For readouts, we used scratch assay, RT-qPCR, Western blot (WB) and immunofluorescence (IF) analyses.

Results
The in vitro scratch assay showed that differentiated (H) podocytes migrated at a slower rate compared with control (V) podocytes, both at baseline and after a 12-hour treatment with Adriamycin. Hence, we hypothesized that heparanase may alter podocyte adhesion properties. Indeed, IF staining of differentiated (H) podocytes exhibited an increase in focal contacts containing vinculin compared with control (V) cells treated with Adriamycin. Of note, we observed no differences in vinculin abundance by WB, suggesting that heparanase mediates the active form of vinculin. Moreover, among the integrins, we noticed temporal upregulation of ITGB1 transcription, as early as two hours after Adriamycin treatment, in (H) compared with control (V) podocytes (P = 0.032).

Conclusions
Collectively, our results suggest that in response to Adriamycin injury, constitutive heparanase overexpression could stabilize podocyte focal adhesions and control motility. Although further research is needed, improving the anchoring of podocytes over the basement membrane may provide an additional cellular mechanism by which heparanase conferred protection against Adriamycin toxicity.
#5666 FATTY ACID BINDING PROTEINS (FABPS) INHIBITION IMPAIRS METABOLIC HOMEOSTASIS IN RENAL TUBULAR CELLS
Authors: García-Giménez Jorge , David Gina Marcela Córdoba , Ortiz Alberto , Cortassa Adrián Mario Ramos 
Published: June 2023

Abstract

Background and Aims
The fatty acid binding proteins family of lipid chaperones (FABPs) mediate lipid trafficking and lipid-mediated metabolic pathways. Despite inhibition of induced FABPs may be beneficial in kidney damage, their enrolment in renal metabolic homeostasis remains elusive. Therefore, we approached this issue in cultured renal tubular cells.

Method
FABP mRNA and protein expression were evaluated in C57/BL6 mice subjected to folic-acid kidney injury. Mitochondrial redox status, proliferation, death rate, and fatty acid oxidation (FAO) were studied in renal tubular cells in conditions of overall FABP inhibition with BMS309403. In these conditions, lipid trafficking was addressed by oil red content and pulse-chase assays using the fluorescent lipid RedC12. Delivery of RedC12 within LD or mitochondria was followed with BODIPY493/503 and Mitotracker and confocal microscopy. Free and esterified RedC12 species were assessed by thin-layer chromatography (TLC). The impact of ATGL lipase activity on cellular behaviour and bioenergetics were assessed by diethylumbelliferyl phosphate (DEUP)-mediated inhibition.

Results
Kidneys from mice with AKI exhibited early lowered FABPs tubular expression. In serum-depleted murine tubular cells, pharmacological FABPs inhibition with BM309403 (BMS) led to sudden necrosis, whereas, in non-depleted cells, BMS eventually leads to apoptosis, increased the mRNA expression of proinflammatory cytokines and oxidative stress-responsive genes, and restrained proliferation. BMS also rapidly decreased ATP levels consistent with FAO inhibition and induced adaptive AMPK phosphorylation/activation and FAO gene program (but not glycolytic gene expression). BMS also mediates mitochondrial depolarization, mitochondrial oxidative stress and decrease of mitochondria number. Serum-depleted cells revealed lipid droplet (LD) voiding and RedC12 delivery to mitochondria. By contrast, in BMS-treated cells growing in serum, despite the lowered ATP content and transcriptional FAO upregulation, RedC12 neither localized with LDs nor with mitochondria, suggesting a low-energy state by impairment of both lipid transit and FAO. Accordingly, TLC assessment did not show lipid breakdown-derived products, which otherwise did appear in serum-depleted cells doing FAO. Mechanistically, ATGL inhibition protects from general ROS production, LD voiding and apoptosis.

Conclusion
In brief, FABP inhibition disrupts tubular energetic status and favours cell stress. Thus, protecting FABP activity could help to preserve tubular metabolic homeostasis during early kidney damage.
#5667 PULMONARY CONGESTION IN HEMODIALYSIS: PREVALENCE, DYNAMICS AND ASSOCIATED FACTORS
Authors: Saleh Kaysi , Pacha Bakhtar , Antoine Marie Hélène , De Prez Eric , Collart Frederic E , Nortier Joelle 
Published: June 2023

Abstract

Background and Aims
Lung ultrasound (LUS) helps detecting pulmonary congestion (PC) among haemodialysis (HD) patients. This study investigated the relation between PC, cardiac function parameters, volume status and ultrafiltration, as well as chronic inflammation in two consecutive HD sessions with different inter-dialytic intervals.

Method
Prospective observational study, where 18 HD patients underwent LUS to calculate the B Lines Score (BLS) using the 8 zone method, inferior vena cava (IVC) dimensions measurement, and echocardiography before and after their regular first (S1) and second (S2) HD sessions of the week. The cut-off for BLS was fixed as 0.54 line per zone. Total body volume using Bio-electrical Impedance Analysis (BIA) was measured before both HD sessions besides serum NT-pro BNP (N-Terminal Pro-Brain Natriuretic Peptide Type B) levels. Moreover, circulating markers of inflammation (soluble urokinase Plasminogen Activator Receptor [suPAR] and soluble Suppression of Tumorigenicity 2 [sST2]) were measured before each session.

Results
Interdialytic interval did not impact BLS, which was high before and after both sessions. There was no significant difference in BLS before and after S1, whereas the difference was significant in S2 (P: 0.03, ES: 0.54). BIA was correlated to PC only before S2 (R² = 0.374, P = 0.007). BLS and the systolic cardiac function represented by the ejection fraction were correlated only after S2. Nt-ProBNP levels and BLS were correlated before both sessions (R²: 0.421, P: 0.004; R² = 0.505, P = 0.001), respectively. Cardiac diastolic function was correlated with BLS before S1 (R² = 0.476, P = 0.002) and after S2 (R² = 0.193, P = 0.034). Mean levels (± SD, ng/ml) of suPAR (7.88 ± 3.07), (7.78 ± 3.02) remained significantly above the normal range (&lt; 4 ng/ml), while sST2 levels reached 2-fold the upper normal value in some patients (27.4 ± 17.8).

Conclusion
PC is common in HD patients even after reaching their dry weight at the end of their two consecutive sessions. It is not only correlated to volume status and cardiac function. Chronic inflammation may be involved in PC pathophysiology. A better management strategy is thus needed to better reduce PC in HD patients.
#5680 FIRST REPORT OF AN EVOLOCUMAB INDUCED NEPHROTIC SYNDROME
Authors: Saleh Kaysi , Badawaki Hanaa , Baz Mahmoud , Farah Ibrahim 
Published: June 2023

Abstract

Background and Aims
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) reduce LDL-C and short-term risk of cardiovascular events by acting on the proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme produced in the liver. This article highlights the case of a 69 year-old man who developed nephrotic syndrome (NS) secondary to EVOLOCUMAB injection. To our knowledge, this is the first time that minimal change disease is described as associated with EVOLOCUMAB.

Method
Case Report describing a 69-year-old male with coronary artery disease who started EVOLOCUMAB injection every two weeks. Six weeks later, after the third dose of Evolocumab, he developed edema, and high blood pressure 180/90 mmHg. Laboratory tests showed a creatinine of 88 µmol/l and a GFR of 77 ml/min/m² associated with severe proteinuria of 9g/24H, normal level of anti-PLA2R, negative ANA (&lt;1/80) and ANCA (&lt;1/80), and negative hepatitis B and C serology.

Results
Kidney biopsy was obtained to investigate this nephrotic syndrome and showed minimal change disease. There was a mild focal mesangial prominence not exceeding three or four cells per segment by light microscopy (LM). Immunofluorescence was negative. EVOLOCUMAB was stopped and proteinuria dropped from 9g to 6g/25H, and stabilized at that level, so treatment with prednisone 1mg/kg was initiated, reducing proteinuria to 3g/24H one month later with clinical improvement.

Conclusion
The occurrence of reversible glomerular lesions reported here should be considered as a potential adverse effect when administrating a prolonged treatment of Evolocumab. We suggest performing urine test at least once a week, to detect early proteinuria in patients receiving this medication.
#5690 COMBINED USE OF SOLUBLE ST2 AND NT-PROBNP FOR PREDICTING MAJOR ADVERSE CARDIOVASCULAR EVENTS IN TYPE 2 DIABETES AND DIVERSE RENAL FUNCTION
Authors: Olloquiegui Xabier Irazusta , Gutierrez Jose Maria Mora , Castañeda-Infante Laura Juliana , Andueza Saioa Echeverria , Izco Marina Pascual , Ravassa Susanna , Diaz-Dorronsoro Agnes , Fernandez-Seara Maria A , Escalada Francisco Javier , Garcia-Fernandez Nuria 
Published: June 2023

Abstract

Background and Aims
Plasma levels of soluble ST2 protein (sST2), a biomarker associated with fibrosis and inflammation, have been related with an increased risk of adverse events in patients with heart failure (HF) [1,2]; however, data is limited on the prognostic value of sST2 in patients with type 2 diabetes mellitus (T2DM) [3], particularly in association with chronic kidney disease (CKD)4. We aimed to evaluate the impact on cardiovascular (CV) prognosis of sST2 in a population of T2DM with diverse renal function.

Method
A prospective observational study was conducted in patients with T2DM. Demographic, clinical and analytical data were collected. The main objective was to analyze a composite of combined CV events (major adverse cardiovascular events; MACE) including: CV death, acute myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, atrial fibrillation, significant valvular heart disease, and hospitalization for any other CV cause). The levels of sST2 and NT-proBNP were analyzed in association with the primary endpoint, as well as with each event separately by survival analysis (log-rank test).

Results
Ninety-three patients were included with a mean follow-up of 3.5 (3.4-4.2) years. Median sST2 concentrations were 29.8 ng/mL. Table 1 shows the baseline characteristics of patients according to sST2 levels. Univariate analysis showed that higher sST2 levels independently predicted the occurrence of MACE (HR = 2.92; 95% CI: 1.35-6.33) (Figure 1). These results persisted after adjusting for age, sex, and glomerular filtration rate. In addition, a significant interaction was found between sST2 and NT-proBNP, showing a significant relationship between the combination of both biomarkers and the main event (Figure 1).

Conclusion
Elevated sST2 levels are associated with the occurrence of long-term major cardiovascular events in patients with T2DM, independently of renal function. These findings could allow stratification of patients with T2DM according to their cardiovascular risk in order to develop therapeutic strategies based on precision medicine.
#5729 HIGHER DAILY PROTEIN INTAKE CAN IMPROVE THE GRAFT FUNCTION OF KIDNEY TRANSPLANT RECIPIENTS IN THE EARLY POSTTRANSPLANT PERIOD
Authors: Yang Binqi , Liu Yuan , Tao Ye , Shi Yunying 
Published: June 2023

Abstract

Background and Aims
Protein-energy wasting (PEW) is commonly seen among uremic patients, which may still exist after they received kidney transplantation,[1,2] and it is a determining factor in the progression of chronic kidney disease (CKD).[3] The use of immunosuppressants and glucocorticoids after transplantation will also affect the patients' metabolism and aggravate their malnutrition.[4,5] Adequate daily protein intake (DPI) in the early posttransplant period facilitates the rapid recovery of surgical wounds.[6] However, few studies focused on the impact of DPI on the early recovery of graft function. This study aimed to explore the relationship between DPI and graft function at month 3 posttransplant, which may provide a basis for clinical nutritional regimen of kidney transplant recipients.

Method
This is a retrospective observational study. 176 kidney transplant recipients (KTRs) who underwent kidney transplant in West China Hospital from December 2021 to June 2022 were included and followed up regularly. 24-hour urine urea data were collected at month 3 posttransplant to calculate their DPI. These KTRs were further divided into two groups according to the recommended DPI for KTRs by the 2021 Practice Guidelines for the Nutritional Management of Chronic Kidney Disease,[7] namely high intake group (Group 1, with DPI ≥ 1.4g/kg·d, n = 66) and low intake group (Group 2, with DPI &lt; 1.4g/kg·d, n = 110). Laboratory data and posttransplant adverse events within 3 months were recorded. Multiple logistic regression was used to analyze the relationship between DPI and early posttransplant graft function.

Results
Mean DPI levels at month 3 posttransplant were 1.75±0.56 g/kg·d in Group 1 and 0.98±0.24 g/kg·d in Group 2, respectively. There was no significant difference in age, gender, pretransplant body mass index (BMI), dialysis type and time, donor type, or the ratio of delayed graft function (DGF) between the two groups. The levels of estimated glomerular filtration rate (eGFR), body mass index(BMI), hemoglobin (Hb), high-density lipid-cholesterol (HDL), and urinary protein at month 3 posttransplant in Group 1 were significantly higher than those in Group 2 (P &lt; 0.005, Fig. 1). No statistical difference was found in the incidence of adverse events between the two groups at month 3 posttransplant. The results of multiple logistic regression analysis showed that higher DPI in the early posttransplant period was a protective factor for graft function after kidney transplantation.

Conclusion
In the early posttransplant period, higher dietary protein intake (DPI ≥ 1.4 g/kg·d) may improve graft kidney function, lipid metabolism, and renal anemia.
#5734 RENAL AUTOLOGOUS CELL THERAPY (REACT™) FOR DIABETIC CHRONIC KIDNEY DISEASE: PHASE II TRIAL WITH BILATERAL CORTEX INJECTIONS AND RE-DOSING TRIGGERS
Authors: Stavas Joseph , Silva Arnold , Aqeel Ahmed , Prakash Rachita , Yanover Melissa , Wooldridge Tom , Cooper Kerry 
Published: June 2023

Abstract

Background and Aims
Well-based therapies may repair diseased nephrons and stabilize and enhance kidney function to delay the onset of end-stage kidney disease and improve co-morbidities. REACT™ is a novel product formed of cryopreserved autologous homologous selected renal cells, undergoing phase III clinical trials for diabetic kidney disease (DKD). We describe an open label phase II study to evaluate how patients respond to REACT™ injections in both kidneys and a redosing trigger, as being evaluated in a Phase III blinded data trial (proact 1 & 2 trials).

Method
REGEN 007 is a multi-center Phase II, open label 1:1 randomized controlled trial enrolling up to 50 patients ages 30-80 years with DKD, who have an eGFR of 20 - 50 mL/min/1.73 m2. Each patient undergoes a percutaneous kidney biopsy and ex vivo culture expansion of their selected renal cells. Patients are then randomized to an arm where they receive two REACT™ injections, one in each kidney, three months apart if they meet inclusion criteria, or an arm with an initial single REACT™ dose in one kidney and a 2nd REACT™ dose in the contralateral kidney &gt; 90 days apart, based on a sustained eGFR decline of ≥ 20%, and/or an increase in the urine albumin to creatinine ratio (UACR) from baseline of ≥ 30% and ≥ 30 mg/g. CT-guided bilateral percutaneous renal cortex injections of REACT™ are performed under conscious sedation. Trial design, inclusion and exclusion criteria can be found at the National Clinical Trial Registry (Trial number 05018416).

Results
Thirty-one of the targeted 50 participants have been enrolled with the following characteristics at screening: 64.0% males, 97.0% Non-Hispanic/Latino. Mean age 62.9 years, serum creatinine (sCr) 2.0 mg/dL ±0.50, Cystatin C 2.0 mg/L ±0.40, eGFR (sCr + Cystatin C) 31.2 ml/min/1.72m2 ±7.88, HgbA1C 7.4% ± 1.14, Hgb 12.9 g/dL ± 1.78, K+ 4.6 mEq/L ± 0.44, Bicarbonate 20.3 mEq/L ± 3.0, and a median UACR 662 mg/g [SD 705.8]. Percent baseline medications are: Angiotensin Converting Enzyme inhibitors 25.8, Angiotensin Converting Enzyme receptor Blockers 48.4, beta blockers 64.5, diuretics 64.4, glucose lowering agents 100, Sodium glucose Cotransporter 2 inhibitors 32.3, and platelet inhibitors 67.7. Efficacy endpoint is an eGFR slope improvement from first injection to 18 months after last injection. REACT™ and procedure related serious adverse events are expected to be commensurate with ongoing trials and standard of care

Conclusion
REACT™ cell-based therapy has the potential to effect nephron structure and function by stabilizing or improving DKD progression and its comorbidities. Current phase II and III trials are underway to determine efficacy, safety, renal function-dependent dosing, and time to treatment with bilateral kidney injections of REACT™.