bluuebunny/crossref_metadata_2025 huggingface dataset:
#6883 PROTECTIVE ROLE OF THE PODOCYTE IL-15 / STAT5 PATHWAY IN EXPERIMENTAL FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS
Authors: Niasse Aissata , Louis Kevin , Lenoir Olivia , Mesnard Laurent , Hadchouel Juliette , Luque Yosu
Published: June 2023

Background and Aims

During glomerular diseases, podocyte-specific pathways can modulate the intensity of histological disease and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of kidney diseases. The Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently detailed in intrinsic kidney cells. We previously evidenced a protective role for a podocyte-expressed immune receptor such as the common gamma chain (ΓC) during glomerulonephritis (1). We also found that STAT5, a transcriptional factor classically described and activated downstream ΓC in T cells is upregulated in podocytes during glomerulonephritis.

Method

Using a mice model with a podocyte-specific deletion of Stat5, we analyzed the role of STAT5 in two experimental models of glomerular diseases.

Results

Here, we show, for the first time, that STAT5 is activated in human podocytes in focal and segmental glomerulosclerosis (FSGS). Additionally, podocyte-specific Stat5 inactivation aggravates the structural and functional alterations in a mouse model of FSGS (Figure 1). This could be due, at least in part, to an inhibition of autophagic flux and an alteration of mitochondrial function. Finally, Interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes and its administration alleviates glomerular injury in vivo by maintaining autophagic flux in podocytes.

Conclusion

In conclusion, activating podocyte STAT5 with commercially available IL-15 represents a potential new therapeutic avenue for FSGS.
#2496 ASSOCIATION OF ABNORMALITIES IN ELECTROCARDIOGRAPHY AND ECHOCARDIOGRAPHY WITH THE OCCURRENCE OF CARDIOVASCULAR DISEASE IN CHRONIC KIDNEY DISEASE
Authors: Hirabayashi Ken , Fujii Hideki , Kono Keiji , Yamatani Satoshi , Shimizu Mao , Watanabe Kentaro , Sakamoto Kazuo , Goto Shunsuke , Nishi Shinichi
Published: June 2023

Background and Aims

In chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) increases along with CKD progression. Although coronary artery disease (CAD) is one of the most critical CVDs, it is difficult to identify CAD because its symptom is usually atypical in CKD. Consequently, appropriate screening tests for CVD are important in this population. Electrocardiography (ECG) and transthoracic echocardiography (TTE) are commonly performed in daily clinical practice, and we researched whether these abnormalities are risk factors for CVD including CAD in patients with advanced CKD.

Method

This study included patients with CKD stage G4-5 who were admitted to our hospital from 2010 to 2019. Depending on the presence of ECG and/or TTE-indicated abnormalities, the study patients were divided into four groups: those without both ECG and TTE abnormalities (group A: ECG-, TTE-), those with only ECG abnormalities (group B: ECG+, TTE-), those with only TTE abnormalities (group C: ECG-, TTE+), and those with both ECG and TTE abnormalities (group D: ECG+, TTE+). The clinical characteristics, the occurrence of CVD events, their prognosis, and the prevalence of positive screening tests for CAD were compared among the four groups. CVD events were defined as CVD death and non-fatal CVD events.

Results

The number of study patients was 607, and they were divided into four groups as follows: 333 in group A, 106 in group B, 76 in group C, and 92 in group D, respectively. The median observational period was 21 months. The incidence of CVD events was highest in group D: 45 patients (13.5%) in group A, 25 patients (23.6%) in group B, 19 patients (25.0%) in group C, and 37 patients (40.2%) in group D, respectively. Multivariate analysis showed that the hazard ratios (HR) for CVD events was significantly higher in group C and D compared to group A as reference (HR: 1.620 in group B, p = 0.116; HR: 2.848 in group C, p = 0.001, and 4.111 in group D, p<0.001, respectively). Furthermore, group D had a higher positive rate of screening tests for CAD compared to the other three groups.

Conclusion

In patients with advanced CKD, ECG and TTE abnormalities were significantly associated with the occurrence of CVD events. Additionally, those with both ECG and TTE abnormalities may be at high risk for the presence of CAD.
#2524 RESOLVIN D1 ATTENUATES SEPSIS INDUCED ACUTE KIDNEY INJURY TARGETING MITOCHONDRIA AND NF-κB SIGNALING PATHWAY
Authors: Wang Liya , LI Jiameng , Su Baihai
Published: June 2023

Background and Aims

Acute kidney injury is a highly common and multifactorial renal disease resulting in significant morbidity and mortality, especially sepsis-induced acute kidney injury. There is no effective therapy available to treat or prevent sepsis-induced acute kidney injury. One of the specialized pro-resolving mediators, Resolvin D1 exhibits special anti-inflammatory effects in several inflammatory disease models, but there is little evidence about the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. To explore the renal protective role of RvD1 in SI-AKI and to further explore the inherent pathophysiological mechanism, especially the role of mitochondrial function and NF-κB signaling pathway, in vitro and in vivo experiments were conducted.

Method

We conducted experiments to explore the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. In vitro, human proximal tubular epithelial cells were used to test the apoptosis ratio, cell viability and reactive oxygen species level. In vivo, C57BL/6 mice were injected with lipopolysaccharide to establish a sepsis-induced acute kidney injury model. Renal function and structure, apoptosis ratio of kidney cells, mitochondrial structure and function and related protein and gene levels were assessed.

Results

In vitro, the resolvin D1-treated group showed higher cell viability and lower reactive oxygen species levels and apoptosis ratios than the LPS group. In vivo, Resolvin D1 can not only improve renal function and mitochondrial function but also reduce the apoptosis ratio, while mediating mitochondrial dynamics and inhibiting NF-κB pathway.

Conclusion

Resolvin D1 has a good renoprotective effect by maintaining mitochondrial dynamics and inhibiting the NF-κB pathway. This provides an important basis for us to further develop the clinical therapeutic value of RvD1 in acute renal injury in sepsis.
#2556 BIOLOGICAL EFFECTS OF A SHORT PERIOD OF NORMOTHERMIC MACHINE PERFUSION IN MARGINAL KIDNEYS: RESULTS OF A PROTEOMICS ANALYSIS
Authors: Neri Flavia , Bruschi Maurizio , Candiano Giovanni , Granata Simona , Furian Lucrezia , Zaza Gianluigi
Published: June 2023

Background and Aims

Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37°C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, the biological effects of this technique on the marginal kidneys are uncertain. We consequently used mass spectrometry to define the proteomic profile of kidney tissue and urine from eight organs, considered unsuitable for transplantation, reconditioned for 120 min using a Kidney Assist device.

Method

Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine was collected at T0, T30, T60, and T120. Multiple algorithms, support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) were used to select the most discriminative proteins during NMP.

Results

Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 in kidney tissue during NMP. Machine learning algorithms recognized the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1, and F9) in the kidney and urine after NMP. Functional analysis showed that the most upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins were involved in the complement system and coagulation cascade. Results were, then, validated by classical and highly conservative biomolecular lab techniques.

Conclusion

Our proteomic analysis revealed that even brief periods of NMP induce substantial metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.
#2589 TIMING OF ATRIAL FIBRILLATION OCCURRENCE IN HEMODIALYSIS PATIENTS WITH CARDIAC IMPLANTABLE ELECTRICAL DEVICES
Authors: Kida Hirota , Kikuchi Yoshitaka , Sato Nobuhiroo , Kawasaki Masato , Watanabe Tetsuya , Yamada Takahisa
Published: June 2023

Background and Aims

Hemodialysis (HD) patients has the high prevalence of atrial fibrillation (AF), and the procedure of HD itself might be related to risk factors for the onset of AF. On the other hand, cardiac implantable electronic devices (CIEDs), such as pacemaker, implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) have the function for arrhythmia detection. However, in HD patients with CIEDs, there are no studies that observe AF over long periods of time. The aim of this study is to investigate AF onset and duration of HD patients with AF, using the AF detection and memory function of CIEDs.

Method

Consecutive HD patients who were newly implanted with CIEDs between January 2008 and December 2021 were retrospectively analyzed in this study. Patients with chronic AF, with leadless pacemaker and without post-implantation follow-up were excluded from this study. Subclinical AF was defined from previous studies as atrial tachyarrhythmia lasting more than 6 minutes in memories of devices. The primary endpoint of this study was the subclinical AF within one year after CIESDs implantation. HD week was defined as follows according to HD schedule, HD1: Monday or Tuesday; HD1+1: Tuesday or Wednesday; HD2 Wednesday or Thursday; HD2+1 Thursday or Friday; HD3 Friday or Saturday; HD3+1 as Saturday or Sunday; and HD3+2 Sunday or Monday. We examined the association between onset and duration of AF and HD.

Results

Fifty-four HD patients who had been implanted with CIEDs (pacemaker: 37, ICD: 6, CRT: 11) were enrolled in the study. During a mean follow-up period of 352 ± 36 days, in 26 of 54 (48.1%) patients, 124 subclinical AF events (1-8 events / patient) were detected with CIEDs. History of clinical AF (46.2% vs 7.1%, p = 0.003) and sick sinus syndrome (53.8% vs 10.7%, p = 0.005) were significantly higher in HD patients with than without subclinical AF. The frequency of subclinical AF onset on HD day was approximately twice higher than on non-HD day (83 episodes [27.7 episodes/day] vs 41 episodes [10.3 episodes/day]), and subclinical AF onset on HD1 day was most frequent among a week (Figure 1a). Limited to HD day, subclinical AF events were observed more frequently especially during HD (30/86 events: 34.9%) and five hours after HD (28/86 events: 32.6%) (Fig. 1-b). Subclinical AF duration was significantly longer during HD compared to non-HD time (216 [90, 1066] min vs 96 [30, 418] min, p = 0.008).

Conclusion

In HD patients, subclinical AF occurred more frequently on HD day, especially during HD and several hours after HD. Careful observation during and after HD might help early diagnosis of clinical AF.
#2622 COST-EFFECTIVENESS OF SGLT2 INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES AND ITS COMPLICATIONS
Authors: Igarashi Ataru , Tachimori Hisateru , Maruyama-Sakurai Keiko , Kubota Anna , Segawa Yasumasa , Akiyama Hiroki , Imai Naohiko , Kohsaka Shun , Miyata Hiroaki
Published: June 2023

Background and Aims

Diabetes and its complications (e.g. chronic kidney disease [CKD] and cardiovascular disease [CVD]) impose significant clinical and financial burden. Recent large-scale randomized controlled trials have demonstrated cardiorenal benefit of the anti-diabetic drug sodium glucose co-transporter 2 (SGLT2) inhibitors, and they are approved for the treatment of CKD and/or heart failure (HF) in many countries. In the present study, we assessed the economic effectiveness of SGLT2 inhibitors for patients with type 2 diabetes (T2DM) using a cost-analysis model that adopts CKD-dependent increases in the risk of developing CVD.

Method

We constructed a natural history model for T2DM patients incorporating CKD, end-stage renal disease, and CVD including myocardial infarction, HF, and stroke as diabetic complications. All diseases except for CKD were considered independent (i.e., the development of CKD increases the risk of CVD manifestation but a patient who develops one disease does not present with another disease). By using a population-based microsimulation, we estimated the 10-year medical costs in Japanese Yen (JPY) and outcomes (development of complications and quality-adjusted life years [QALY]) for patients who initiated antidiabetic therapy with SGLT2 inhibitors or conventional therapy. Probabilistic sensitivity analysis (PSA) was performed with 1,000,000 iterations.

Results

The total medical costs per person were JPY 1,193,000 versus JPY 1,160,000 and the QALYs were 8.13 versus 8.02 years for the SGLT2 inhibitor strategy versus the conventional strategy, respectively. As a result, the incremental cost-effectiveness ratio (ICER) was 302,000 JPY/QALY, well below the threshold value of JPY 5,000,000/QALY. The PSA revealed that the probability of ICER being below the threshold was 97.7%.

Conclusion

We demonstrated that the use of SGLT2 inhibitors was cost-effective compared to the conventional strategy for treating patients with T2DM, and these results suggest clinical and financial benefit of SGLT2 inhibitors that can holistically approach T2DM and its renal and cardiovascular complications.
#2629 ROS-SCAVENGING BLOCKS GLUCOSE INDUCED OXIDATIVE PERITONEAL CELL DAMAGE IN VITRO
Authors: Oberacker Tina , Schricker Severin , Schanz Moritz , Ketteler Markus , Latus Jörg
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as RRT is limited due to adverse effects of high glucose-based PD fluids (PDFs) to the structure and function of the peritoneal membrane. Our group recently elucidated one pathological mechanism showing that glucose-based PDFs enhance oxidative DNA-damage in PD patients due to reduced thioredoxin (TRX) activity trigged by thioredoxin-interacting-protein (TXNIP) upregulation (Oberacker et al., 2022). Therefore, the aim of this in vitro study was to investigate drug treatments to mitigate oxidative stress and oxidative DNA-damage due to glucose-dependent induction of TXNIP expression.

Method

Using a mesotheliomal cell line (NCl-H28, ATCC) we performed in vitro studies mitigating reactive oxygen species (ROS) production and oxidative DNA damage as well. Cells were treated for three and eight hours with high-glucose media (1.5%, 2.3% and 4.25% glucose; glucose concentrations were adapted to PDFs from Fresenius Medical Care) compared to control media (normal glucose concentration). mRNA expression of TXNIP, TRX and further redox-related genes like superoxide dismutases (SODs) or catalase were analyzed by qPCR. Since TRX is negatively regulated by TXNIP, we investigated TRX activity in cell lysates. ROS production was monitored using a bioluminescent assay and immunofluorescence using the redox dye CellRoxGreen as well. The content of oxidative DNA-damage was investigated by immunofluorescence. Furthermore, we have preliminary analysis using primary human peritoneal mesothelial cells derived from PD effluent (PDF).

Results

We demonstrated a dose-dependent upregulation of round 1.5 fold TXNIP expression on mRNA level. However, no change in the expression of TRX, SODs and catalase could be observed. Interestingly, we observed a 20% reduction in TRX activity upon glucose stimulation compared to cells treated with control media. These findings are consistent with the previously published data on human peritoneal biopsies. Beyond, we demonstrated a dose-dependent increase in ROS production and increase in oxidative DNA-damage. However, ROS production and oxidative DNA damage could be prevented upon pre-incubation with the ROS-scavenger N-acetylcysteine (NAC).

Conclusion

Here, we show that enhanced levels of ROS and oxidative DNA damage due to glucose induced TXNIP expression could be diminished using ROS scavengers. These findings show that further antioxidative substances may be potential drugs, which could also be potential drug candidates for use in clinical practice to treat PD patients.
#2633 ROLE OF INTRAVENOUS ASCORBIC ACID IN THE MANAGEMENT OF ANEMIA IN HEMODIALYSIS PATIENTS
Authors: El Shinnawy Howayda , Alghitany Ahmed , Ishak Marina , Khedr Abdelrahman , Attallaha Aber
Published: June 2023

Background and Aims

Patients with end-stage kidney disease (ESKD) suffer from functional iron deficiency where despite the presence of sufficient iron stores in the body, adequate iron is unavailable for heme synthesis. This study hypothesis was that in patients undergoing hemodialysis (HD), administration of intravenous (IV) ascorbic acid (AA) exerts a good effect on the management of anemia, either by increasing the mobilization of iron from tissue stores or acting as an antioxidant to overcome the inflammatory block and increase the erythropoietin sensitivity.

Method

Fifty patients with ESRD who were on regular HD were included in the study. Patients’ ferritin levels ranged from 500 to 1200 ng/mL with transferrin saturation of 30% or more. However, all patients were anemic and received erythropoietin therapy. Iron therapy was discontinued in the first group, whereas it was continued in the second group that received IV AA.

Results

A significant increase in the levels of Hb was observed in the second group after 6 months despite the decrease in ferritin levels in both the groups. Transferrin saturation decreased in both groups, the decrease being more in the first group. The levels of C-reactive protein (CRP) decreased in the second group, whereas these increased in the first group.

Conclusion

Intravenous AA as an adjuvant therapy with iron exerts a favorable and significant effect on the Hb, serum ferritin, and CRP levels in patients with ESKD having anemia. The discontinuation of iron therapy only decreases the serum ferritin levels and does not improve the Hb or CRP levels.
#2634 ROLE OF LIGHT CHAIN CLEARANCE IN THE RECOVERY OF RENAL FUNCTION IN MULTIPLE MYELOMA: ANOTHER POINT OF VIEW
Authors: Liébana Marc Patricio , Senin Alicia , Azancot Maria , Gironella Mercedes , Gaibor Néstor Toapanta , Garcia Sheila Bermejo , Martin Lucia , Caravaca-Fontán Fernando , Pérez-Ávila Clara Cuéllar , Martínez-López Joaquin , Rodríguez-Garcia Eva , Matamoros Oriol Bestard , Romeo Maria José Soler , Terrades Natàlia Ramos
Published: June 2023

Background and Aims

Acute Kidney Injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in a MM patient population: standard dialysis procedure versus IHD with either PMMA or hemodiafiltration with endogenous reinfusion (HFR).

Method

Multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary of MM requiring RRT were included. Patients that underwent IHD received 6 dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at six months follow-up.

Results

A total of 25 patients were included. Seventeen patients received IHD and 8 standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, fourteen (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared to those who remained in HD (92.9% vs 36.4%, p:0.007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared to standard dialysis group (p = 0.024).

Conclusion

Early reduction of FLC with IHD as an adjuvant treatment along with MM targeted therapy may exert a positive impact on renal recovery.
#2635 ASSOCIATION BETWEEN PLASMA LYSO-GB3 LEVELS AND BONE MINERAL DENSITY IN PATIENTS WITH FABRY DISEASE
Authors: Nose Yuma , Fujii Hideki , Goto Shunsuke , Kono Keiji , Okamoto Hayaki , Watanabe Kentaro , Nishi Shinichi
Published: June 2023

Background and Aims

Fabry disease is a rare X-linked genetic disorder that contributes to various clinical manifestations including cardiac hypertrophy, renal dysfunction, cerebrovascular disease, angiokeratoma, and anhidrosis. Several previous reports showed that male patients with Fabry disease had decreased bone mineral density (BMD). However, the association of BMD with clinical characteristics and biomarkers of organ damage in patients with Fabry disease has not been sufficiently studied. Therefore, we aimed to investigate their associations in patients with Fabry disease.

Method

Patients with Fabry disease who attended our hospital from January 2008 to June 2021 were included in this study. Patients without enough clinical and laboratory data were excluded from the present study. The remaining fifteen patients were assessed in this study. We examined clinical characteristics, biomarkers including blood globotriaosylsphingosine (lyso-Gb3) levels, and BMD, and compared them between male and female patients. We measured the lumbar spine and femoral BMD by dual-energy bone X-ray absorptiometry and calculated the Z-score. Furthermore, we also examined ΔBMD, defined as the two-year change in the Z-score, for ten patients who underwent BMD measurement before and after starting ERT. Because two patients already had received ERT, two did not undergo BMD measurement, and one took an anti-osteoporotic agent, they were excluded from the analysis.

Results

Both lumbar spine BMD and femoral BMD decreased in male patients, while they were preserved in female patients (lumbar spine Z-score: -1.9 ± 2.0 versus 0.8 ± 0.8, p < 0.05; femoral Z-score: -1.0 ± 1.4 versus 0.6 ± 0.6, p < 0.05) among all the study patients. Lumbar spine and femoral BMD showed a significantly negative correlation with blood lyso-Gb3 levels. Moreover, blood lyso-Gb3 levels were significantly correlated with the lumbar spine BMD (r = -0.92; p < 0.01) and femoral BMD (r = -0.91; p < 0.01) in male patients. On the other hand, there was no significant correlation of blood lyso-Gb3 levels with the lumbar spine BMD (r = 0.66, p = 0.18) and femoral BMD (r = 0.11; p = 0.99) in female patients. After starting ERT, blood lyso-Gb3 levels were significantly reduced in both male and female patients. The lumbar spine ΔBMD in male patients improved whereas that in female patients remained unchanged despite no changes in kidney function and serum calcium and phosphate levels.

Conclusion

Our findings suggested that lumbar spine BMD and femoral BMD decreased in male patients with Fabry disease possibly due to the deposition of lyso-Gb3 in bone tissue and ERT could improve BMD in these patients.
#2648 IMPACT OF ACUTE AND CHRONIC KIDNEY FUNCTION ON THE SIZE AND PROGNOSIS OF ISCHEMIC STROKE AFTER THROMBECTOMY
Authors: Bobot Mickaël , Hak Jean-François , Burtey Stephane , Doche Emilie , Suissa Laurent
Published: June 2023

Background and Aims

Patients with Chronic Kidney Disease (CKD) have an increased risk of ischemic and haemorrhagic stroke and CKD seem associated with worse outcome after a stroke. Few studies specifically investigated the impact of mechanical thrombectomy on outcomes after an ischemic stroke. The main objectives of our study RISOTTO were to evaluate the influence of CKD (eGFR < 60 mL/min/1.73m²) and Acute Kidney Injury (AKI) on the size of cerebral ischemic lesions and their outcome.

Method

Multicenter cohort study. Patients with at the acute phase of ischemic stroke following a large artery occlusion managed with mechanical thrombectomy were included. CKD was defined as eGFR < 60 mL/min/1.73m² for more than 3 months, AKI by 2012 KDIGO score, infarcted volume by ASPECTS and functional prognosis at 3 month by modified Rankin Scale (mRS).

Results

296 patients were included. Sixty-three patients (22.8%) had CKD. In univariate analysis, patients with CKD had more white matter vascular lesions (Fazekas 1.7±0.8 vs. 1.0±0.8, p<0.0001), had lower initial infarcted volume (ASPECTS 7.6±1.7 vs. 6.7±1.8, p = 0.003), for equivalent severity (NIHSS: 9.2±7.0 vs. 10.1±7.7, p = 0.404), had more thrombectomy failure (12.7% vs. 3.8%, p = 0.008) compared to non-CKD patients. At 3 months, CKD was associated with equivalent functional prognosis (mRS 3–6: 51.6% vs. 42.2%, p = 0.193) but higher mortality: 24.2% vs. 9.5%, p = 0.004. Forty-eight patients (19.6%) developed an AKI. AKI was associated with increased initial gravity (NIHSS 18.8±5.2 vs. 16.7±5.7, p = 0.014, equivalent stroke volume (ASPECTS 7.3±1.9 vs. 6.8±1.8, p = 0.254. At 3 months, CKD was associated with poorer functional prognosis (mRS 3–6: 64.6% vs. 39.4%, p = 0,002) and mortality: 25.0% vs. 8.4%, p = 0.003. In multivariate analysis, AKI appeared as a independent risk factor of poor neurological outcome (OR 2.16 [1.05-4.46], p = 0,036 and mortality: OR 2.47 [0.96-6.35], p = 0.059 at 3 month, as CKD was not.

Conclusion

CKD was associated with smaller initial ischemic lesions for equivalent neurological severity, and more recanalization failures. CKD was not an independent risk factor for mortality or poor functional prognosis at 3 months. CKD patients seem to benefit from thrombectomy and should not be contraindicated to this technique. AKI is associated with greater initial neurological severity, poorer functional prognosis and increased mortality at 3 months and is an independent risk factor for poor prognosis.
#2652 ANTIPROTEINURIC EFFECT OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN GLOMERULAR AND SYSTEMIC DISEASES: A REAL-WORLD CLINICAL STUDY
Authors: Caravaca-Fontán Fernando , Stevens Kate , Kronbichler Andreas , Anders Hans Joachim , Floege Jürgen , Juarez Gema Maria Fernandez , Praga Manuel
Published: June 2023

Background and Aims

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently begun to be used in glomerular/systemic autoimmune diseases with glomerular involvement for the treatment of proteinuria, although the information on real-world clinical settings is very scarce.

Method

Retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-hour proteinuria from SGLT2i initiation to 3, 6, 9, 12 months. Secondary outcomes included percentage proteinuria reduction by type of disease and a reduction of proteinuria ≥30% from SGLT2i initiation.

Results

The study group consisted of 493 patients with a median age of 55 years. All patients were on renin-angiotensin system blockade. Geometric mean percentage change of proteinuria from baseline was –35%, –41%, –45% and –48% at 3, 6, 9 and 12 months after SGLT2i initiation, respectively. Geometric mean percentage change of eGFR was –6%, –3%, –8%, –10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. However, a significant correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up (R = –0.11; p = 0.02). By mixed-effects binomial logistic regression model, serum albumin at the onset of SGLT2i emerged as the main predictor of a ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dl: 0.53; 95% CI 0.30–0.91; p = 0.02). Finally, a slower eGFR decline over time was observed in patients achieving a ≥30% proteinuria reduction: –3.7 versus –5.3 ml/min/1.73m2/year (p = 0.001).

Conclusion

The use of SGLT2i was associated with a significant reduction of proteinuria, irrespective of the underlying glomerular/systemic disease. This percentage change was higher in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
#2685 SLC34A2 EXACERBATES TUBULAR INTERSTITIAL FIBROSIS VIA INDUCTION OF APOPTOSIS AND CELL CYCLE ARREST IN S PHASE
Authors: Hu Liang-Shuan , Chang Sheng-Cheng , Tsai Chia-Hui , Wu Chun-Ching , Nguyen Phuong Thao Hoang , Chang Wei-Che , Chang Wei-Ya , Yang Ya-Chien , Jao Tzu-Ming
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is an urgent public health issue in the world. However, effective treatments for intervention of CKD remain undefined. Phosphate (Pi) is an essential element for synthesis of DNA, RNA, ATP, phospholipid membranes, and for regulation of phosphorylation/dephosphorylation, cellular signaling and metabolic pathways. Solute carrier family 34 (SLC34) is responsible for Pi absorption in the small intestine. However, the role of SLC34 in progression of CKD is still unknown.

Method

A membrane protein, solute carrier family 34 member 2 (SLC34A2), was discovered by using big data mining from the National Center for Biotechnology Information (NCBI). SLC34A2 was overexpressed in human proximal tubular cells, HK-2, by Lipofectamine 3000. RNA sequencing was carried out to uncover SLC34A2-mediated signaling pathways by using Illumina platform. Apoptosis was evaluated by Annexin V-PI staining and TEUNEL assay in cells and mouse kidneys, respectively. Cell cycle was measured by flow cytometry. Unilateral ureteral obstruction (UUO) and bilateral renal ischemia-reperfusion injury (bIRI) were employed to generate CKD mouse models.

Results

By using big data mining from the NCBI, we identified a membrane protein, SLC34A2, was upregulated in various types of nephropathies including diabetic nephropathy, focal segmental glomerulosclerosis, minimal change disease, ANCA-associated vasculitis. Overexpression of SLC34A2 suppressed viability of HK-2 cells. RNA sequencing revealed that apoptosis and cell cycle are high scored pathways modulated by SLC34A2. The results were further verified in HK-2 cells. Ectopic SLC34A2 promoted apoptosis via downregulation of BCL-2. Moreover, SLC34A2 induced cell cycle arrest in S phase via downregulation of CDK2. CKD mouse models of UUO and bIRI were carried out to confirm in vitro findings. In mice kidneys, the expression of Slc34a2 in UUO and bIRI groups was superior to that in sham groups. Enriched Bax and TUNEL-positive cells were observed in the fibrotic kidneys of mice. Moreover, increased expression of p21 and downregulated Cyclin A2 in the fibrotic kidneys further confirmed that Slc34a2 induced cell cycle arrest in S phase.

Conclusion

Slc34a2 induced apoptosis and halted cell cycle in S phase, resulting in subsequent tubulointerstitial fibrosis in mice. Our results suggest that targeting SLC34A2 might be a promising strategy for intervention of CKD.
#2686 15-YEAR TEMPORAL CHANGES IN RATES OF ACUTE KIDNEY INJURY AMONG CHILDREN: A POPULATION-BASED COHORT STUDY
Authors: Høyer Sidse , Heide-Jørgensen Uffe , Jensen Simon Kok , Nørgaard Mette , Christiansen Christian and Fynbo
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is defined as a sudden decrease in kidney function and is associated with increased morbidity and mortality. The reported prevalence of AKI among hospitalized children is approximately 30% but varies widely depending on population characteristics and method used to define AKI. Little is known about the incidence of community-acquired AKI and potential temporal changes in AKI incidence among children. Such information is important for AKI prevention, resource allocation and future research. In this study, we aimed to examine overall temporal changes in the rate of hospital- and community-acquired pediatric AKI and to describe associated changes in potential underlying risk markers.

Method

In this population-based cohort study, we included children aged 0-17 years from 1 January 2007 to 31 December 2021 in Denmark. In 2021, the Danish population consisted of 1,168,222 children. We obtained clinical plasma creatinine measurements from the Danish laboratory databases to identify all KDIGO-defined AKI episodes within the study period. For each child, only the first AKI episode per year was included and we defined an AKI episode as a period of 30 days. AKI was defined as community-acquired if the plasma creatinine at time of AKI was taken in the outpatient clinic or the first day of admission/acute setting. We estimated the annual AKI rate as first AKI episodes in a year among children residing in an area covered by the laboratory databases divided by the number of children residing in this area in the same year. Unadjusted rates as well as sex- and age-standardized rates was reported. Using Danish medical databases, we identified potential risk markers for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors including low birth weight and preterm birth.

Results

In total, 14,262 children contributed with 16,492 AKI episodes. The average annual rate of AKI was 149 per 100,000 children and was stable throughout the study period (figure). Of the AKI episodes, 10,921 (66.2%) were community-acquired and 12,714 (77.1 %) were stage 1 AKI. No major changes were seen in the prevalence of risk makers among AKI episodes.

Conclusion

The rate of AKI among Danish children was stable from year 2007 to 2021 and potential risk markers were largely similar over time.
#2694 URAEMIC CARDIOMYOPATHY AS PREMATURE PRESBYCARDIA
Authors: Chinnappa Shanmugakumar , Mooney Andrew
Published: June 2023

Background and Aims

Presbycardia, the age-related decline in cardiac function, has been shown in the general population by demonstrating gradual decline in peak cardiac performance with advancing age [1]. Chronic kidney disease (CKD) has shown phenotypic similarities with premature aging. Studies have shown accelerated vascular aging and skeletal muscle wasting in CKD. However, it is not known whether CKD patients show age related decline in cardiac function and whether the impairment is more pronounced for the given age (premature presbycardia). In the present study, we set out to test the hypothesis that CKD patients have premature presbycardia by measuring peak cardiac power (CPOpeak) non-invasively across different age groups.

Method

A cross sectional study (n = 170) of healthy male volunteers (n = 100) and male CKD patients (n = 70) spanning ages 19 to 75 years. CKD patients were grouped into early (CKD 2–3, n = 29) and late CKD (CKD 4–5, n = 41). Patients with diabetes or any known cardiovascular diseases were excluded. CPOpeak was measured using a specialised cardiopulmonary exercise test (CPX) using CO2 rebreathing method [2]. The association between age and CPOpeak was evaluated. The regression lines of CKD patients and healthy volunteers were compared using ANCOVA. P<0.05 is considered significant.

Results

The mean eGFR of early CKD and late CKD were 57.8±17.2 ml/min and 16.8±5.8 ml/min respectively. The mean CPOpeak of the study groups were 5.35±0.94 W (Control), 4.93±0.71 W (early CKD) and 4.26±0.69 W (late CKD). Fig. 1 shows the association between CPOpeak and age along with the regression equations for the individual study groups. Comparison of the regression lines using ANCOVA did not show any difference in slopes between the groups (P = NS). There was a diminution in CPOpeak of 0.2W per 10 years of advancing age. However, for any given age, the CPOpeak was diminished by 0.38 W in early CKD (P = 0.023) and 0.93 W in late CKD (P<10−3) compared to control. In other words, the cardiac age was older by 19 years in early CKD and by 46.5 years in late CKD compared to healthy volunteers.

Conclusion

The results demonstrate that CKD is associated with premature presbycardia. This phenomenon may offer explanation for the high prevalence of heart failure in advanced CKD. Further studies exploring the underlying mechanisms of premature aging in CKD may be worthwhile in the future.
#2697 ASSOCIATION OF CARDIOMETABOLIC PROTEINS WITH EGFR DECLINE IN OLDER ADULTS WITH ADVANCED CHRONIC KIDNEY DISEASE
Authors: Aylward Ryan , Hayward Samantha , Chesnaye Nicholas , Evans Marie , Drechsler Christiane , Wanner Christoph , Dekker Friedo W , Torino Claudia , Szymczak Maciej , Jager Kitty J , Ben-Shlomo Yoav , Tiffin Nicki , Rayner Brian , Birnie Kate , Caskey Fergus
Published: June 2023

Background and Aims

Cardiovascular disease and advanced chronic kidney disease often coexist and share risk factors in older individuals. We investigated the association of cardiometabolic and cardiovascular proteins and pathways with decline in estimated glomerular filtration rate (eGFR).

Method

Two plasma protein panels (Olink® cardiometabolic T96 and cardiovascular II T96, Uppsala, Sweden) were analysed at the baseline visit of individuals enrolled in the prospective observational European QUALity (EQUAL) study of older people > 65 years with advanced CKD (incident eGFR < 20 ml/min/1.73m2). Generalised linear mixed effects models with a log link and random intercept and slope were used to determine annualised eGFR slope (CKD-EPI 2009 equation) using a complete case model. The model was executed in a “discovery” sample (Germany, United Kingdom and Poland) and positive results (< false discovery rate [FDR] of 5%) were tested in a Swedish “validation” sample using the same FDR criterion. The primary analysis was adjusted for baseline age, sex, country, diabetes mellitus status, primary renal disease, systolic blood pressure, urine albumin to creatinine ratio (ACR), and the use of renin-angiotensin aldosterone inhibitors and β-blockers. A sensitivity analysis was conducted to determine the effect of informative censoring on eGFR slope using a joint model.

Results

The discovery and validation samples had 254 subjects (median age 67 years, 41% female, median baseline eGFR 18 ml/min/1.73m2) and 247 (median age 75 years, 28% female and median baseline eGFR 18 ml/min/1.73m2) respectively with longer follow-up time for the validation sample (median 3.6 versus 2.6 years) primarily due to less kidney replacement therapy initiation (33% versus 37%) and fewer losses to follow up (5% versus 12%). Two of the 175 proteins showed more rapid eGFR annual decline per doubling in protein levels (Figure 1): Receptor-type tyrosine-protein phosphatase S [PTPRS] (-15%; 95% confidence interval [CI] –24 to –7%, pFDR = 0.01) and Insulin-like growth factor-binding protein 6 [IGFBP6] (–8%; 95% CI –12 to –3%, pFDR = 0.03) (Figure 2). Predicted slopes were similar across both samples and for the sensitivity analyses.

Conclusion

Receptor-type tyrosine-protein phosphatase S and Insulin-like growth factor-binding protein 6 were associated with more rapid CKD progression. Further research is needed to determine if these proteins are pathophysiologically linked to accelerated progression of CKD in older people or a secondary consequence of disturbances in protein sequestration or excretion.
#2728 THROMBOINFLAMMATORY BIOMARKERS AND THEIR RELATIONSHIP WITH CIRCULATING GLYCOSAMINOGLYCANS IN END-STAGE RENAL DISEASE PATIENTS
Authors: Bansal Vinod , Allen Madeline , Siddiqui Fakiha , Hoppensteadt Debra , Krupa Emily , Kantarcioglu Bulent , Fareed Jawed
Published: June 2023

Background and Aims

End stage renal disease (ESRD) is a complex progressive medical condition that affects multiple organ systems. Given the high risk of morbidity and mortality of ESRD as well as its rising incidence, it is critical to understand the relevance of thromboinflammatory biomarkers in disease development and progression of kidney dysfunction. The purpose of this study is to profile the levels of thromboinflammatory biomarkers in ESRD patients including D-Dimer, C-reactive protein (CRP), von Willebrand factor (vWF), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI). In addition, the levels of anti-PF4 IgG and endogenous circulating glycosaminoglycans (GAGs) were measured.

Method

Citrated plasma samples were collected from seventy-three ESRD patients. Control plasma samples (NHP) from healthy, non-smoking adults aged 19 to 53 were obtained commercially. Validated ELISA methods have been used to profile each of the biomarkers. The levels of endogenous GAGs were determined (Redprobes UG, Germany). To compare the levels of thromboinflammatory biomarkers, anti-PF4 IgG, and endogenous GAGs in different groups, appropriate statistical methods included Mann-Whitney U, t-tests, Kruskal-Wallis ANOVA and experiment correlation analysis methods were performed.

Results

All of the biomarkers and GAGs were significantly elevated, with the exception of TAFI, in ESRD patients. The ESRD patients exhibited varying levels of increase in the D-Dimer, CRP, vWF, PAI-1, anti-PF4 IgG, and GAGs as shown in Figure 1 (p < 0.05). D-Dimer showed the most pronounced increase (1075%) followed by PAI-1 (361.31%), anti-PF4 IgG (209.78%), CRP (101.77%) and endogenous GAGs (17.29%). The correlation analysis revealed varying degrees of association among these biomarkers (Figure 2).

Conclusion

These results suggest that thromboinflammatory biomarkers offer the potential utility of identifying inflammation in end-stage renal disease. Marked increase in thromboinflammatory mediators due to endothelial damage may result in the upregulation of glycosaminoglycans and anti-PF4 IgG antibodies in the ESRD patients.
#2758 AMBIENT HEAT EXPOSURE AND ESTIMATED GLOMERULAR FILTRATION RATE TRAJECTORY: A POST-HOC ANALYSIS OF THE DAPA-CKD TRIAL
Authors: Zhang Zhiyan , Heerspink Hiddo Lambers , Chertow Glenn , Correa-Rotter Ricardo , Gasparrini Antonio , Jong Niels , Langkilde Anna Maria , Mistry Malcolm , Mcmurray John , Rossing Peter , Toto Robert , Vart Priya , Nitsch Dorothea , Wheeler David C , Caplin Ben
Published: June 2023

Background and Aims

Higher ambient temperatures have been associated with higher rates of admission for kidney stones and acute kidney injury. Occupational heat stress is also a risk factor for impaired kidney function in several rural resource-poor settings. It is unclear if higher ambient heat exposure is associated with a faster loss of kidney function in patients with established, all-cause, chronic kidney disease (CKD). We therefore undertook a post-hoc analysis of the DAPA-CKD trial linking participant data to publicly available climate measurements.

Method

The DAPA-CKD trial randomized 4304 patients with proteinuric CKD (estimated glomerular filtration rate, eGFR, 25-75 mL/min/1.73 m2; urine albumin-to-creatinine ratio, ACR, 23-566 mg/mmol) to dapaglifozin or placebo in addition to standard of care. We examined the association between daily study centre-level ambient heat exposure (defined as a mean heat index, HI, >30; European Centre for Medium-Range Weather Forecasts ERA5 reanalysis dataset) and individual-level change in eGFR using both a linear-mixed effects model and a case-time series approach to address potential unmeasured individual- and centre-level confounding.

Results

Climate and eGFR data were available on 3915 (91%) participants across 361 centres in 21 countries. Over a median of 28 months, participants (mean age: 62 years; mean eGFR: 43mL/min/1.73 m2) were followed-up at centres where there was a median of 1 day (interquartile range: 0 to 64 days) with an HI>30. Each 30-day period of HI>30 over the study period was associated with a change in eGFR of -0.7% (95% CI: -1.0% to -0.3%), equivalent to an additional eGFR loss of between 1.2 and 4.0mL/min/1.73 m2 per year in a patient with an eGFR of 45mL/min/1.73 m2 located in a very hot versus temperate environment. Similar estimates were obtained using the case time series approach. This association persisted after adjustment for potential haemoconcentration effects on the day of testing and further analyses provided no evidence that these findings varied with baseline eGFR, albuminuria or randomised treatment arm (Figure 1), or by high- versus middle-income country study centre location.

Conclusion

Higher ambient heat exposure is associated with a more rapid decline in kidney function among patients with CKD. Efforts to mitigate heat exposure should be prospectively tested as part of a comprehensive strategy to slow the progression of kidney disease.
#2787 HOSPITAL MANAGEMENT OF AN INTEGRATED CLINICAL PRACTICE UNIT OF VASCULAR ACCESS FOR HEMODIALYSIS: A CHALLENGE FOR IMPROVING HEALTHCARE QUALITY?
Authors: Simó Vicent Esteve , Lao Elisabeth González , Allué Angels Esquerda , González Irati Tapia , Pallares Sara Ibañez , Rubio Sandra , Serna Manel Ramírez de Arellano
Published: June 2023

Background and Aims

Vascular access (VA) for haemodialysis (HD) is essential for renal patients due to its high morbimortality and economic cost. Integrated Clinical Practice Units (ICPU) allows health organizations to establish comprehensive care, improve the quality and safety of care processes, as well as favor the accessibility of health care. The VA multidisciplinary teams for HD are crucial in the proper management of VA, although their implementation in daily clinical practice is not fully consolidated. The aim of this study was to analyze the effectiveness of the healthcare processess in patients with VA for HD after the creation of our ICPU focused in the multidisciplinary management of the VA (FUVA) through quality of care indicators.

Method

12 years retrospective unicentric study analyzed in two periods: first period (2010-2015) and second period (2016-22) after FUVA creation. The indicators include sociodemographic data, processes activities (first and successive visits, endovascular procedures, type and number of surgical interventions, delayed time for interventions, mean hospitalitation stay, and results oriented to the patient's quality of life (VA initial assessment and dysfunction, inpatient and outpatient VA interventions).

Results

551 VA for HD hospital admissions r were performed (53.2% in charge of nephrology, with 893 total days of stay and mean stay of 3.6 days), 670 surgical interventions (69.7% native fistulas, 47.3% admitted, 37±9.7 days of surgical delay) and 320 endovascular procedures (28.1% admitted, 11 ± 1.2 days delay). After the creation of the ICPU (FUVA), a total of 631 visits (96% first visit) were made in 451 patients with mean age 65.7 ± 17.5 years (66% men), 495 VA Doppler ultrasounds, 287 HD catheter placements (54.1% permanent, 29.2% left) and 84 withdrawals. Similarly, in this period there was a decrease in the number (160 vs 130) and percentage (92.4 vs 34.3%) of VA for HD admissions, a shorter surgical delay time (39 ± 9.3 vs 32 ± 9.1 days) and a reduction in the mean hospital stay (3.7 vs 2.9 days), respectively. Similarly, outpatient management of all endovascular procedures performed (187) was achieved without repercussion on the waiting time for the procedure (11 ± 0.9).

Conclusion

In our study, the hospital management of VA for HD through the creation of an UPCI, allowed a more efficient management of the available care resources through the continuity of care of the process, favoring the integral and integrated care of the patient as well as contributing to the improvement in the management and survival of VA for HD. Similarly, elaboration and analysis of helathcare indicators have been useful tools in the evaluation of the quality of healthcare of our vascular access unit.