bluuebunny/crossref_metadata_2025 huggingface dataset:
#2967 CALCULATION OF THE RISK OF CONSTRAST-INDUCED ACUTE KIDNEY DAMAGE IN THE CUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH DIABETES MELLITUS
Authors: Nigmonov Baxodir , Muminov Shavkat , Saipova Durdona
Published: June 2023

Background and Aims

Analysis of the pathogenetic mechanisms of the development of contrast nephropathy in patients with coronary artery disease on the background of type 2 diabetes mellitus and the effectiveness of the proposed preventive measures.

Method

The study took place in two stages. The study included 56 patients with type 2 diabetes, the average age of the patients was 58 years, the CG consisted of 20 healthy persons. In most patients, the reason for which the endovascular radiopaque procedure (EVRCP) was performed was associated with atherosclerotic lesions: coronary artery disease, chronic lower limb ischemia (CLLI), atherosclerosis of the brachiocephalic arteries (BCA). EVRCP was performed on the vessels of the coronary basin, BCA, abdominal aorta and its branches, lower extremities. A retrospective analysis included a comparative analysis of two groups of patients with type 2 diabetes who underwent (EVRCP): 29 patients who developed CI-AKI (CI-AKI+ group) and 27 patients in whom the post-procedure period was uneventful. CI-AKI was defined as an increase in venous creatinine concentration of more than 25% by the end of 48 hours after EVRCP. During this phase of the study, the patient's medical history was analyzed - their anamnestic data, glycemic status, general urinalysis, kidneys, estimated glomerular filtration rate (eGFR) initially, 2,4,6,8 and 10 days after the procedure. The first stage, a retrospective one, included a comparative analysis of two groups of diabetic patients who underwent an endovascular radiopaque procedure (EVRCP): 29 patients who developed CI-AKI (CI-AKI+ group) and 27 patients in whom the post-procedure period was uneventful. CI-AKI was defined as an increase in venous creatinine concentration of more than 25% by the end of 48 hours after EVRD.

Results

Based on the analysis, we developed a risk scale for the development of CI-AKI in patients with DM. In the process of compiling the scale, the value of RR for the development of CI-AKI in the presence of the corresponding factor, rounded to the nearest whole number, was used as risk coefficients. According to the developed scale, in the presence of a risk factor, the patient is assigned a certain score. The score determines the risk of CI-AKI.

Conclusion

Thus, the present study showed that in patients with DM, compared with healthy volunteers, there is a change in kidney function, which is more pronounced in individuals prone to the development of CI-AKI. Changes in the cellular and biochemical blood composition in patients with DM are characteristic of diabetic nephropathy and are also more pronounced in patients at risk of CI-AKI.
#2993 INCIDENCE AND TYPES OF GASTROINTESTINAL BLEEDING EPISODES IN DIALYSIS
Authors: Larkin John , Jiao Yue , Lama Suman , Chaudhuri Sheetal , Willetts Joanna , Winter Anke , Stauss-Grabo Manuela , Usvayt Len , Hymes Jeffrey , Maddux Franklin , Wheeler David C , Stenvinkel Peter , Floege Jürgen
Published: June 2023

Background and Aims

Gastrointestinal bleeding (GIB) has been suggested to be the most frequent cause of bleeding events in the dialysis population [1]. Despite this, there are scarce reports showing GIB incidence in large cohorts and the occurrence of specific GIB types is unknown. We used data on a nationally representative sample of dialysis patients treated at an integrated kidney care provider to characterize the incidence of GIB episodes by the type of bleed and location of diagnosis.

Method

We used data from dialysis patients treated in the United States during 01-Jan-2018 to 31-Mar-2021. GIB episodes were identified from international classification of diseases (ICD) diagnosis codes recorded as a comorbid condition during dialysis care, or as the primary, secondary, or tertiary discharge reason for hospitalization. ICD clusters for GIB episodes/types were based on the United States Healthcare Cost and Utilization Project [2]. GIB incidence rates were calculated per 1000 patient-years (p1000py).

Results

Among a population of 405,530 dialysis patients, 6.7% (n = 27,087) of patients experienced ≥1 GIB episode. There was a total of 56,454 GIB observations, of which 17,602 were recorded as a comorbid condition (n = 12,350 patients), 38,852 were recorded as the hospitalization cause (n = 25,315 patients). Overall, 26.4% (n = 5289) of dialysis patients were diagnosed with a GIB comorbidity and had a GIB hospitalization. The GIB incidence rate was 13.4 p1000py for a GIB comorbidity and 29.5 p1000py for a GIB hospitalization. The highest incidence rates among GIB types were found for unspecified GIBs (6.9 p1000py GIB comorbidity & 19.3 p1000py GIB hospitalization), followed by upper GIBs (5.5 p1000py GIB comorbidity & 6.2 p1000py GIB hospitalization), and then lower GIBs (1.0 p1000py GIB comorbidity & 4.0 p1000py GIB hospitalization). Considering upper GIB subtypes, ulcers/perforation below the esophagus were the most common comorbidity and hospitalization cause (Table 1). For lower GIB subtypes, a hemorrhage of the rectum and anus were the most common comorbidity and hospitalization cause.

Conclusion

The GIB incidence rate is about 7-fold higher in the dialysis population compared to the general population [3]. GIB appears to commonly be diagnosed during a hospitalization without any known comorbid condition, emphasizing a potential need for improved detection in the provision of outpatient dialysis care. Most GIB episodes were classified as an unspecified type, which shows a possible need for improved evaluation and/or coding. Further investigations are needed to understand the mortality rate after a GIB episode and should consider adjustments for age and sex.
#3004 INCIDENCE, RISK FACTORS, AND OUTCOMES OF ACUTE LIVER INJURY IN HOSPITALIZED ADULTS WITH ACUTE KIDNEY INJURY: A LARGE MULTICENTER STUDY
Authors: Yuxin Lin , Liu Jiao , Nie Sheng , Xin Xu
Published: June 2023

Background and Aims

Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) was still remains unknown. The current study was aimed to describe the incidences, risk factors, and outcomes of AKI-ALI.

Method

The study population included AKI patients aged 18–99 years with enough serum creatinine testing and liver function testing (LFT) hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. The Cox proportional hazards model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazards regression model was used to estimate the association between AKI-ALI and in-hospital mortality.

Results

Among the 18461 patients with AKI (median [Interquartile Range, IQR] age, 65.71 [52.78, 76.36] years, 9725 (52.7%) males), ALI occurred in 1689 (9.1%) patients. Patients with AKI who were male, have used drugs including antibiotics, diabetes agents, diuretics, glucocorticoids, immunosuppressants, nonsteroidal anti-inflammatory drugs or vasopressors, with heart failure, respiratory failure, malignant tumor or shock, have lower platelets levels, higher aspartate aminotransferase levels or higher glutamyl transpeptidase levels at baseline, have received general surgery or thoracic surgery were associated with higher risk of AKI-ALI. Patients with AKI-ALI had longer length of hospital stay and were associated with a higher risk of in-hospitalized mortality (Hazard ratio [95% Confidence Interval] 1.51, [1.33, 1.72]) compared with patients with AKI but without ALI. In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (P for interaction = 0.036).

Conclusion

ALI was common among patients with AKI and AKI-ALI was associated with an increased risk of in-hospital mortality. This study suggests interventions for liver function early to improve in-hospital prognosis of patients with AKI.
#3118 ERECTILE DYSFUNCTION IS A HARBINGER OF CHRONIC KIDNEY DISEASE
Authors: Jansz Thijs , Wood Andrew , Tyrrell Jessica , Oram Richard
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) shares similar cardiovascular risk factors with erectile dysfunction (ED). ED is an early warning sign for future cardiovascular events, however it is not yet known whether it also behaves as a harbinger of future CKD.

Method

We identified cases of ED and CKD using diagnostic codes from primary care records, hospital episode statistics, Death Register records, and self-reported diagnoses in a prospective cohort of 94,955 male participants of UK Biobank who had linkage to primary care records, from 01/01/2000 until 01/09/2017. We excluded participants with CKD diagnosed prior to this period as well as before the age of 35. We compared risk of CKD using cause-specific Cox proportional hazards models with competing risk of death, using age as time scale and adjusted for time-fixed covariates (birth cohort, ethnicity, body mass index [BMI], Townsend deprivation index [TDI], and smoking status) and time-dependent covariates (hypertension, diabetes mellitus, ischaemic heart disease, and ischaemic stroke/transient ischaemic attack). We imputed missing values for BMI, TDI, and smoking status (percentage missing ranging between 0.16-0.71%) using multiple imputation with predictive mean matching. As a sensitivity analysis, we repeated the analyses in a propensity score-matched cohort.

Results

Among 15,848 men diagnosed with ED, 830 developed CKD (71.9/10,000 person-years) median 5.9 years later (IQR 2.8-10.4), compared with 3,452 among 79,107 men without ED (39.6/10,000 person-years). Men with a diagnosis of ED had higher BMIs than men without (28.7 vs 27.7 kg/m2) and were more likely to have other diagnoses such as hypertension (38% at time of diagnosis of ED/56% at any time vs 40% at any time) and diabetes mellitus (21% at time of diagnosis of ED/30% at any time vs 12% at any time). A diagnosis of ED (without hypertension or diabetes mellitus) carried an increased risk of subsequent CKD (Figure 1), with an adjusted cause-specific hazard ratio of 1.53 (95% CI 1.33-1.77). There was significant interaction with hypertension (p<0.001), i.e. the increase in hazard of CKD by ED was smaller (adjusted hazard ratio 1.10, 95% CI 1.00-1.20), whereas there was no significant interaction with diabetes mellitus; i.e. men with a diagnosis of ED had a similar hazard ratio for CKD regardless of presence of diabetes mellitus (p = 0.33 for interaction). These results were numerically similar in a propensity score matched analysis.

Conclusion

Men who are diagnosed with ED are at a higher risk of developing CKD, independent of comorbidities such as diabetes mellitus. A diagnosis of ED should therefore prompt screening for CKD and its risk factors.
#3204 CASE-BASED ONLINE MEDICAL EDUCATION ENHANCES PHYSICIANS’ KNOWLEDGE AND COMPETENCE IN THE MANAGEMENT OF PATIENTS WITH DIABETES WITH CARDIORENAL DISEASE
Authors: Trier Joachim , Groop Per-Henrik , Da Silva Rita Moreira
Published: June 2023

Background and Aims

Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) have a substantially impaired cardio-renal health prognosis and a reduced life expectancy highlighting the urgent need for early detection and comprehensive vascular risk control. The goal of this activity for primary care physicians (PCP) and diabetologists/endocrinologists (D/E) was to improve their understanding of and competence in managing patients with diabetes with cardiorenal disease in clinical practice.

Method

An interactive educational program including one detailed patient case challenges clinicians to apply most recent evidence-based guideline recommendations. Detailed scenarios prompt learners to determine the correct treatment and follow-up for the patient with expert commentaries providing in-depth advice at each stage and a conclusion at the end of the program. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge/competence, 1 question rated on a Likert-type scale assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, a McNemar's test was conducted at the question level (5% significance level). Cohen's d with correction for paired samples estimated the effect size of the education on number of correct responses. Data collection from 5/25/22 to 9/13/22.

Results

74% of PCP (n = 74) improved their knowledge regarding the need for comprehensive vascular risk control in patients with T2D and CKD and their competence related to the practical implementation of the latest diabetes guidelines for the individualized management of these patients (p<.001; d = 0.56)

• 56% of D/E (n = 32) advanced their knowledge regarding the need for comprehensive vascular risk control in patients with T2D and CKD (P<.01, d = 0.35)

• 39% of PCP and 41% of D/E increased their confidence (p<.001 and p<.01 respectively) in proactively monitoring their patients with T2D for kidney disease

Conclusion

Participation of PCP and D/E in an interactive online case-based education program improved their understanding of the need for comprehensive vascular risk control and the competence of PCPs in managing patients with T2D and cardiorenal disease in clinical practice.
#3220 Z-DNA BINDING PROTEIN 1 AGGRAVATED THE SEPSIS-INDUCED ACUTE KIDNEY INJURY VIA PANOPTOSIS
Authors: You Ruilian , Xu Jiatong , MA Yixin , Shi Xiaoxiao , Huadong Zhu , Chen Limeng
Published: June 2023

Background and Aims

Sepsis-induced acute kidney injury (SI-AKI) is a severe complication of critical patients with high morbidity and mortality. Apoptosis, pyroptosis, and necroptosis, regulated by a common pathway - PANoptosis, play essential roles in SI-AKI without the clarified mechanisms.

Method

We first established the SI-AKI model by intraperitoneal injection of the lipopolysaccharide (LPS) (O111:B4) in the C57B/L6J mice with increased Serum creatinine (Scr), blood urea nitrogen (BUN), and kidney injury biomarkers (NGAL, KIM-1) in renal tissue. The expression of crucial molecules in PANoptosis were examined by quantitative real-time PCR (qPCR) and Western blotting. RIPK1 inhibitor-necrostatin-1(Nec-1) (1.65mg/kg) and pan-caspase inhibitor- Emricasan (10mg/kg) were further employed to mice with LPS. Potential interacting proteins of panoptosome were detected by co-immunoprecipitation. We also analyzed the methylation level of ZBP1 in cell-free DNA among sepsis-non-AKI and SI-AKI patients.

Results

The expression of crucial molecules in PANoptosis, including IL-1β(0.82 vs. 0.35, P = 0.003), mixed lineage kinase domain-like (MLKL) (0.67 vs. 0.41, P = 0.014), protein kinase 1 (RIPK1) (1.07 vs. 0.72, P = 0.002), cleaved-caspase 3 (1.13 vs. 0.59, P < 0.001), and FAS-associated death domain protein (FADD) (0.78 vs. 0.43 P < 0.001) elevated in the SI-AKI group. Z-DNA binding protein 1 (ZBP1), a typical sensor of PANoptosis, is dramatically activated in the SI-AKI mice. Co-immunoprecipitation showed that caspase 8, ZBP1, peptidoglycan recognition protein 1 (pglyrp1), and RIPK1 are potential components of PANoptosome. Nec-1 and Emricasan could attenuate the LPS-induced increases in the concentrations of BUN and inflammatory cytokine (TNF-a and IL-6), as well as the methylation level of ZBP1 in cell-free DNA decreased in SI-AKI patients verse sepsis-none-AKI (P = 1.60E-06).

Conclusion

ZBP1 exacerbated SI-AKI via activating PANoptosis with the potencial PANoptosome of ZBP1, caspase 8, pglyrp1, and RIPK1.
#3278 HUMAN PHARMACOKINETICS OF MULTIPLE, STEADY-STATE DOSING OF IPTACOPAN
Authors: Schmouder Robert , Junge Guido , Nidamarthy Prasanna , Kulmatycki Kenneth
Published: June 2023

Background and Aims

Iptacopan (LNP023) is a first-in-class, oral, proximal complement inhibitor that specifically binds to Factor B and inhibits the alternative complement pathway (AP). Current Phase III studies of iptacopan focus on diseases associated with AP activation, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, IgA nephropathy, and atypical hemolytic uremic syndrome. Early modeling efforts suggested that an iptacopan concentration of ∼1000 ng/mL would provide near-maximal AP inhibition. The aim of this study was to evaluate the PK of oral iptacopan in healthy subjects to determine the dose that results in a ∼1000-ng/mL mean steady-state concentration over the entire 12-h dosing interval.

Method

In this blinded, controlled, randomized study, a total of 32 healthy subjects were enrolled into 5 cohorts receiving twice-daily dosing for 14 days: placebo (n = 8) or iptacopan 25, 50, 100, or 200 mg (n = 6 per group). Plasma iptacopan concentration was intensively measured for 72 hours post day 14 dose using a validated LC-MS/MS assay (LLOQ = 1 ng/mL).

Results

Iptacopan treatment was safe and well tolerated at all dose levels. Iptacopan steady-state concentration-time curves are shown below. Iptacopan was rapidly absorbed, with a median Tmax of approximately 2 hours (Figure 1). The mean half-life was moderately long at 18 to 25 hours. The inter-subject variability (CV%) of iptacopan Cmax and AUCinf was low at approximately 12% to 27%, and both parameters were under-dose proportional with increasing dose. At all time points from 0 to 12 hours, mean iptacopan concentration for the 200-mg dose cohort was >1000 ng/mL.

Conclusion

Iptacopan was rapidly absorbed, had low inter-subject variability, and a moderately long half-life. Only the 200-mg b.i.d dose produced mean iptacopan concentrations of ≥1000 ng/mL over the dosing interval, and thus is expected to result in near-complete, continuous AP inhibition. These results support the rationale for use of iptacopan 200 mg twice daily as the therapeutic dose in ongoing clinical trials and provide evidence of durable AP inhibition in patients administered oral iptacopan therapy.
#3317 THE EFFECT OF HEMOPERFUSION ON SURVIVAL AMONG COVID-19 CRITICALLY ILL PATIENTS IN A TERTIARY HOSPITAL IN DAVAO CITY, PHILIPPINES
Authors: Lacang Joy Blossom Anne , Tom Mark Anthony
Published: June 2023

Background and Aims

Cytokine storm in COVID-19 is an excessive immune response through the overproduction of inflammatory cytokines which significantly increases mortality. Hemoperfusion has been granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in an effort to eliminate circulating inflammatory mediators among COVID-19 critical patients to improve clinical outcomes and survival. This study aims to determine the 8 – day survival of critical COVID-19 patients who received hemoperfusion.

Method

This is a descriptive study conducted among critically ill COVID-19 patients who completed hemoperfusion treatment admitted from October 2020 to October 2021 in a tertiary hospital in Davao City, Philippines. The inclusion criteria were adult patients greater than 18 years of age with RT-PCR confirmed SARS-CoV-2 infection who underwent and completed hemoperfusion during hospitalization for COVID-19. While those patients who did not complete the hemoperfusion treatment because of hemodynamic instability or death were excluded. All of the patients classified as COVID-19 critical received the standard treatment for COVID-19 such as steroids (dexamethasone) and antiviral (Remdesevir). Among the 1,037 COVID-19 adult patients admitted from October 2020 to October 2021, 28 of them were classified as critical and received hemoperfusion, but only 19 patients completed the treatment.

Results

Majority of patients in the study were males (14/19, 73.68%) with a mean age of 59 years (SD 12.90). Hypertension (n = 15, 78.95%) and Diabetes Mellitus (n = 14, 73.68%) were the most common comorbid illnesses. Cough (n = 15, 78.95%), fever (n = 11, 57.90%), and dyspnea (n = 7, 36.84%) were the frequent symptoms. The laboratory parameters (median hemoglobin, leukocytes, thrombocytes, creatinine, and ALT were within normal range except for an elevated median AST (54 U/L). Forty-two percent (8/19) of patients survived at day 8 (Figure 1). Survivors had higher baseline oxygen saturation compared to non-survivors (89% vs 78%), but in both groups, the oxygen saturation increased after hemoperfusion (Figure 2). All inflammatory markers (CRP, ferritin, LDH, and procalcitonin) decreased among survivors

post-hemoperfusion. However, the ferritin, LDH, and procalcitonin remained elevated among non-survivors (Figure 3A, B, C D). The median time from symptoms onset to hemoperfusion initiation was longer in non-survivors compared to survivors (10 days vs 8 days) (Figure 4).

Conclusion

Close to half (42.11%) of the critical COVID-19 patients who underwent hemoperfusion survived at day 8. Therefore, hemoperfusion remains to be a beneficial adjunct treatment for critical COVID-19 patients especially if initiated early.
#3348 NATIONAL PREVALENCE OF CHRONIC KIDNEY DISEASE AMONG KOREAN ADULTS, 2007–2020, INCLUDING THE COVID-19 PANDEMIC: A KOREAN REPRESENTATIVE SERIAL STUDY
Authors: Yoon Soo-Young , Lee Hyo Jin , Kim Dae Kyu , Kim Jong Ho , Lim So Jin , Kim Jin Sug , Hwang Hyeon Seok , Jeong Kyunghwan
Published: June 2023

Background and Aims

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the pandemics’ impact on CKD diagnosis. We aimed to investigate the long-term trends in CKD prevalence throughout the pre- and early pandemic periods in adults using a nationwide serial survey from South Korea.

Method

We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was <60 mL/min/1.73 m2, one-time spot proteinuria was ≥1+ on a urinary dipstick test according to recent guidelines, or previous diagnosis of CKD. We examined the overall trends in the prevalence of CKD during the study period and the impact of the early pandemic on the prevalence of CKD.

Results

Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007–2010, 5.1% [95% confidence interval (CI), 4.7–5.5]; 2017–2019, 7.1% [95% CI, 6.6–7.6]; pandemic period, 6.5% [95% CI, 5.7–7.3]; and βdiff, -0.19; 95% CI, -0.24–-0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic.

Conclusion

This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Our results improve the understanding of outpatient health service utilization during the COVID-19 pandemic and suggest the need for governmental support to prevent the aggravation of CKD in society. Consequently, the nephrology community has a potential role in pertinent policies to reduce the public health burden of CKD by properly allocating limited medical resources.
#3357 MORPHOMETRIC AND FUNCTIONAL EVALUATION OF A NON-RENAL VASCULATURE IN FEMALE AND MALE PKD/MHM (CY/+) RATS
Authors: Liu Baoer , Mayer Tobias , Kraft Patricia , Heigwer Jana , Clanget Tilmann , Brune Maik , Sayour Alex , Schaefer Franz , Karck Matthias , Szabó Gábor , Korkmaz-Icöz Sevil
Published: June 2023

Background and Aims

Polycystic kidney disease (PKD) is a cystic genetic disorder of the kidneys. Vascular abnormalities are the most important non-cystic complications in PKD. In the present study, we evaluated aortic morphometry and vascular function in female and male PKD/Mhm (Cy/+) rats, an animal model of autosomal dominant PKD.

Method

Thoracic aortic rings from six month-old heterozygous PKD/Mhm (Cy/+) female (n = 10; 307±4g) and male (n = 10; 470±24g) and age-matched non-affected homozygous (+/+) Control-female (n = 9; 312±6g) and Control-male (n = 13; 460±14g) rats were used a) to evaluate both contractile/relaxation responses ex vivo using organ bath experiments and b) to study aortic morphometry assessed by hematoxylin&eosin staining. Furthermore, immunohistochemistry for cleaved poly (ADP-ribose) polymerase (PARP)-1 was performed.

Results

Although there was no significant difference in body weight, serum creatinine levels were increased in the PKD-female and PKD-male rats compared with the respective controls (PKD-female 50.0±1.7 vs. Control-female 43.9±2.1 µmol/L; PKD-male 178.7±21.0 vs. Control-male 40.4± 1.3 µmol/L, p<0.05) and were found to be higher in PKD-male rats than in the PKD-females (p<0.0001). Compared to Control-male, PKD-male rats showed decreased maximum relaxation to acetylcholine (55±2% vs. 77±1%, p<0.05), indicating impaired endothelial function. Contractile responses to phenylephrine (3.0±0.1g vs. 3.4±0.1g, p<0.05) and high potassium (3.3±0.1g vs. 3.7±0.1g, p<0.05) were reduced in the PKD-male compared to Control-male. Additionally, in PKD-male aortas, the concentration-response curve to sodium nitroprusside, an endothelium-independent vasodilator, was shifted to the right compared to Control-male. Morphometrical analysis revealed that wall thickness and wall cross-sectional area normalized to body weight, and the wall:lumen area ratio were significantly higher in PKD-male aortas compared to Control-male. Additionally, PKD-male showed increased cleaved PARP-1 immunoreactivity confined to endothelial level compared to Control-male. All these parameters were unchanged in PKD-female rats compared to Control-female.

Conclusion

Six month-old PKD-male, not female, rats show endothelial dysfunction, impaired smooth muscle contraction and relaxation, pathological changes in aortic morphometry, and apoptosis in a non-renal vasculature. The rat model of autosomal dominant PKD in males can be used to identify novel targets for the treatment of this disease.
#3474 ROLE OF INTEGRIN, FIBRONECTIN, AND UPAR IN PODOCYTE-GLOMERULAR BASEMENT MEMBRANE INTERACTION UNDER FLUID SHEAR STRESS
Authors: Kim Jae Seok , Kim Ji-Hee , Kim Junyoung , Eom Minseob , Yang Jae Won , Han Byoung Geun , Choi Seong Ok , Cha Seung-Kuy
Published: June 2023

Background and Aims

Podocyte-glomerular basement membrane (GBM) interaction is the main component to maintain glomerular filtration barrier. Interestingly, the podocyte-GBM interaction is not static, but dynamic according to various podocyte conditions. Thus, we hypothesized that the podocyte-GBM interaction would be changed under stress conditions such as fluid shear stress (FSS). Here, we aim to explore the change of specific integrin (Itg αVβ3), fibronectin, and uPAR in the podocyte-GBM interaction under fluid shear stress (FSS).

Method

We used conditionally immortalized human podocyte cells which were differentiated only under specific (non-permissive) temperature (37°C). We exposed the podocytes to 200 rpm of FSS and applied various dish coating agents. We observed cell morphology and documented the protein and mRNA expressions of Itg β3, fibronectin, and uPAR under FSS.

Results

Podocyte morphology became more elongated with actin rearrangement under FSS. Protein expression of Itg β3 did not change under FSS, while activated Itg β3 increased from early phase (30 min after exposure to FSS) (Figure 1). Fibronectin (Figure 2) and uPAR (Figure 3) gradually increased under FSS. mRNA expressions of Itg β3, fibronectin, and uPAR did not change under FSS. Cell viability increased in collagen-1 coated dish compared to non-coated under FSS.

Conclusion

This study demonstrates that Itg αVβ3 is activated, fibronectin and uPAR increase under FSS. In addition, it is shown that extracellula matrix contributes to podocyte stability. The results suggest that Itg αVβ3, fibronectin and uPAR may have specific roles to maintain podocyte's stability through the modulation of the podocyte-GBM interaction.
#3478 THE EFFECT ON NET ULTRAFILTRATION WHEN TRANSFERRING PATIENTS FROM NOCTURNAL INTERMITTENT (NIPD) TO CONTINUOUS CYCLING PERITONEAL DIALYSIS (CCPD)
Authors: Theodoridis Marios , Panagoutsos Stylianos , Margaritis Nikos , Bounta Triantafyllia , Mourvati Efthimia , Tsalikidis Christos , Charitaki Evaggelia , Thodis Elias
Published: June 2023

Background and Aims

Peritoneal Dialysis (P.D.) Adequacy includes a variety of targets such as the sufficient uremic toxins removal (Κt/V), patients’ euvolemia, acid-base and electrolyte balance etc.. Based on incremental PD prescription NIPD is often a reasonable modality choice when there is adequate Residual Renal Function (RRF). Eventually due to RRF decrease patients need to increase their PD adequacy by adding a solution during the day i.e Icodextrin (CCPD). The aim of this study was to evaluate the alteration of Cyclers’ ultrafiltration(UF) as well as Total Ultrafiltration (sum of Cycler ultrafiltration and the UF of the initial drainage) when transferring patients from NIPD to CCPD

Method

This is a single center retroprospective study of 16 patients (m = 9,f = 7). These patients were transferred from NIPD to CCPD due to inadequate PD adequacy. The patients’ mean age was 53.4±19 years, their mean PD duration was 74.3±25.7 months and their mean Peritoneal Solute Transfer Rate (PSTR-D/Pcr) was 0.69±0.12. We evaluated small solute clearance targets (Kt/V – t:total,p:peritoneal,r:renal), RRF (eGFR, Vurine), Cycler’ ultrafiltration, the UF of the initial drainage and the sum of them (Total UF) on three consecutive days before the initiation of CCPD and three consecutive days after the initiation. The patients’ cycler treatment program remain constant and all of them received an initial day volume of 1000 ml with Icodextrin.

Results

We compared the alterations with Paired t-Test (normal distripution)

We found a statistically significant improvement of the peritoneal fraction of Kt/V when applying CCPD (p = 0.01), on the other hand we found a statistically significant decrease from Cycler's UF (p<0.05) as well as from Total UF (p<0.05) without any statistically significant increase in urine's volume. Additionally, from the regression analysis there was statistically significant correlation between PSTR and ΔUF(UFNIPD-UFCCPDtotal) showing that the faster the transporter the greater the ultrafiltration loss (p = 0.035, R = 0.58).

Conclusion

Transferring patients with adequacy problems from NIPD to CCPD improves small solute clearances but in some cases the risk for total ultrafiltration decrease is important and may lead to overhydration. It is necessary to contact perspective studies with hydration status evaluation ie Bioimpedance Spectroscopy.
#3484 A NETWORK META-ANALYSIS COMPARING INTENSIVE GLYCEMIC CONTROL AND SGLT-2 INHIBITORS IN PREVENTING RENAL OUTCOMES
Authors: Ghosal Samit
Published: June 2023

Background and Aims

Type 2 diabetes (T2D) is one of the prominent causes for chronic kidney disease (CKD) leading to end-stage renal failure. Traditionally, prevention and retardation of CKD was attempted with effective glycemic and blood pressure control. In recent times sodium glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP1-RA), and non-steroidal mineralocorticoid receptor (MRA) inhibitors have proved to be excellent agents in preventing cardio-renal outcomes in patients with T2D, independent of baseline glucose control. SGLT-2is rank the highest in recent network meta-analysis-based scoring. We conducted this network meta-analysis to explore the ranking of intensive glucose therapy in comparison to SGLT-2is, to better understand the present position of the traditional approach and its relevance.

Method

A database search was conducted using the Cochrane library to identify relevant citations. Analysis was conducted using RStudio (2022.07.1, Build 554). Using progression of macroalbuminuria and end-stage kidney disease (ESKD) as the outcomes of interest, scoring was performed comparing intensive glycemic control (IGC) and SGLT-2is. Using a frequentist approach P-score was conducted and corroborated using the Surface Under the Cumulative Ranking (SUCRA) using Bayesian network meta-analysis.

Results

A pooled population of 62,742 patients from twelve citations were included for analysis. The Cochrane risk of bias was used to assess quality of the studies. IGC scored higher than SGLT-2is as far as retardation of progression of macroalbuminuria was concerned while using both the P-score (0.99 Vs 0.50) as well as the SUCRA (0.97 Vs 0.52). A similar trend was also observed with ESRD as the end point with both the P-score (0.84 Vs 0.65) and the SUCRA (0.81 Vs 0.68) rankings favoring IGC (Fig. 1).

Conclusion

The importance of achieving glycemic targets should be emphasized in recommendations in the same footing as the choice of individual reno-protective agents.
#3485 IMPROVING THE DIAGNOSIS OF MYOCARDIAL INFARCTION IN CHRONIC KIDNEY DISEASE
Authors: Mcdonald-Coley Marrica , Wright Marilyn Lawrence-
Published: June 2023

Background and Aims

Chronic Kidney Disease has significant morbidity and mortality owing to the increased prevalence in cardiovascular disease. This increase in morbidity and mortality is seen more so as glomerular filtration rate (GFR) declines, that is, advanced kidney failure with GFR equal to or less than 30ml/min/1.73m2. Hence, it is important to control risk factors and accurately diagnose myocardial infarction in this cohort of patients.

Secondary objectives showed that social isolation was significantly associated with confirmed myocardial infarction. Additionally, ST changes, and T- QRS discordance on electrocardiogram were found more commonly in the myocardial infarction group. Other diagnostic tools such as angiography proved to be an underutilized investigation with a prevalence of 13% in the kidney disease cohort at the University of the West Indies during the years 2018 to 2020.

Method

In this retrospective cross-sectional study, data was collected from the online records system at the University of the West Indies. Patients with an admission diagnosis of acute coronary syndrome, unstable angina, non-ST elevation myocardial infarction, ST elevation myocardial infarction and chronic kidney disease were included in the study population. Cases were assigned based on whether or not myocardial infarction was confirmed on echocardiogram.

Results

Of the total number of 102 cases, 58 were chosen based on fulfillment of our inclusion criteria. 13 (22.4%) had echocardiographic evidence of a new myocardial infarction while 44 (75.9%) had no echocardiographic evidence of new myocardial infarction. Receiver Operator Characteristic Curves (ROC) used to evaluate the diagnostic performance of high sensitivity cardiac troponin T and interval/ delta changes showed an ideal value 141.50ng/L on first troponin T and 100.75ng/L on serial troponin T with delta change of 20.5%, (sensitivities of 61.5%, 72.7% and 72.7% respectively). Area under the Receiver-Operating Characteristic Curve (AUC) used to determine the diagnostic accuracy of the highly sensitivity cardiac troponin T and interval delta change demonstrated high accuracy of 0.708 for the first troponin T, 0.750 for the second troponin T and 0.767 for the interval or delta change.

Conclusion

Overall, we showed that serial troponin measurements in kidney disease patients increase sensitivity for predicting myocardial infarction and that the values are nearly 10 times that used for the general population. An interval change of 20.5% was also predictive of myocardial infarction.
#3486 CELL-FREE CIRCULATING DNA IN ANCA-ASSOCIATED VASCULITIS – A COMPARISON OF PATIENTS DURING ACTIVE DISEASE AND REMISSION
Authors: Karlsson Julia , Weiner Maria , Appelgren Daniel , Bruchfeld Annette
Published: June 2023

Background and Aims

Patients with ANCA-associated vasculitis (AAV) undergo immunosuppressive treatment to thwart organ failure and avoid relapse. However, the treatment is associated with risk of infections and malignancy. There are currently no reliable biomarkers which can be used in the clinic to assess disease activity. Neutrophil extracellular traps containing nuclear (n) and/or mitochondrial (mt) DNA have been implied in the pathogenesis of AAV. The aim of this study was to explore whether there is a difference in levels of circulating cell-free DNA (cfDNA) amongst AAV patients during active disease and in remission.

Method

Paired samples from 7 male and 9 female patients with AAV, of which 10 were diagnosed with GPA, were obtained during both active disease and clinical remission as part of an ongoing observational prospective study. Participants’ ages ranged from 21.8 to 80.0 years (median = 64.9), and 11 participants had a history of kidney engagement. After DNA-extraction digital droplet PCR was performed to obtain levels of mtDNA and nDNA. Clinical diagnosis (GPA or MPA), ANCA-positivity, kidney involvement, and Birmingham vasculitis activity score (BVAS) were also assessed.

Results

There were no significant differences in levels of mtDNA or nDNA in patients with active disease compared to remission; mtDNA (median = 14 520 and 11 985 copies/µL respectively, p = .379) and nDNA (median = 4.45 and 4.70 copies/µL, p = .569). The ratio between mtDNA and nDNA did not differ either (median 2100 and 2400, p = .679). A strong correlation between mtDNA- and nDNA levels (r = .920, p < .001) was found, whereas no correlations were found between cfDNA and age, sex, clinical phenotype, ANCA positivity, kidney engagement or BVAS (Tables 1 and 2).

Conclusion

This study provides additional information regarding levels of mtDNA and nDNA comparing AAV patients during active disease and in clinical remission. The lack of association with disease activity and the correlation between nDNA and mtDNA may indicate cell damage as a source of cfDNA. To further delineate the contribution of NETs to the levels of cfDNA, and the mechanisms behind cellular injury and inflammation, studies with larger samples with longitudinal follow-up and healthy controls are needed.
#3496 HOURGLASS APPEARANCE ON FACE IN SAGLIKER SYNDROME IN CKD WITH SH.FACE MAP'S IMAGE PROCESSING LIKE FROM SATELLITES IN SKY AND FROM DRONES IN FUTURE
Authors: Sagliker Yahya , Sagliker Hasan Sabİt , Ozkaynak Piril Sagliker , Paylar Nuray , Sagliker Cemal
Published: June 2023

Background and Aims

Image processing is critical component in science and technology (Doughert, 2009). Soil surveyors use image process methods to classify differentiation of soils by using satellite images. Marine scientists use image process methods for monitoring marine pollution. Astronomers and space scientists use image processing techniques to classify objects in galaxy (Sararu, 2009). Image processing is process of modifying or interpreting existing pictures, such as photographs. (Hearn & Baker, 1997). SS patients have uglifying human face appearances, extremely severe maxillary and mandibulary changes, soft tissue in mouth, teeth/dental abnormalities, skull deformities, (Sagliker, 2004–12).

Method

SS patients have two kinds of photographs in literatures, before SS nondeformed and after SS deformed. We studied to create face map in SS by using technic in soil survey.10 face images (5 before SS and 5 after SS) were used. Unsupervised Classification (UC) system of Erdas 8.4 software was used to classify images. Methodology had 3 phases in this research In first phase, we got the images at same scale by cutting them around faces images. In final phase, we applied coloring on 10 classes of images. We used same color for same class number both CIbSS and ClaSS images. If color classes are in same structure of face (on cheek, forehead, etc), they may be combined.

Results

We have very important results on deformed faces photos in SS (CIaSS). First finding is all CIaSS have specific “hourglass”shapes [figure4]. “Hourglass” is enclosing red area for sample A and B Figure 3, Column 1: photos of patients before SS (raw images), column 2: classified photos of column 1, column 3: classified photos of patients after SS, Figure 5. “Hourglass” is Comformity of “Hourglass” form for all CIaSS curved face.

Conclusion

Image processing plays very important role in clinical practices and biomedical researches. SS is a kidney disease and derived from inside of the body but its effects are appearance outside of human body, such as head, face, skull deformations. These symptoms can be put forward by using Image Classification for SS. Moreover, shape of “hourglass” can be an index for SS and this is very specific for SS.“Hourglass” can be an indicator for grading SS. Finally, “hourglass” should be carefully evaluated in SS.
#3534 ASSOCIATION OF STOPPING RENIN–ANGIOTENSIN SYSTEM INHIBITORS DURING AN ACUTE KIDNEY INJURY EPISODE WITH CARDIOVASCULAR AND ALL-CAUSE MORTALITY
Authors: LI Yanqin , Nie Sheng , Xin Xu , Hou Fan Fan
Published: June 2023

Background and Aims

The management of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with ongoing acute kidney injury (AKI) during hospitalization is debated. This study is aimed to explore whether the use of ACEI or ARB (ACEI/ARB) during an AKI episode is associated with adverse clinical outcomes.

Method

This nationwide, retrospective cohort study included 10,559 patients aged 18–100 years who had a hospital-acquired AKI (HA-AKI) episode and who were using ACEI/ARB at the time of AKI detection during the hospitalization between January 1, 2000 and May 26, 2021 from 19 medical centers across China. The primary exposure was stopping or continuing the use of ACEI/ARB after HA-AKI detection during hospitalization. The primary outcome was all-cause mortality (30-day, 180-day, and in-hospital mortality) after HA-AKI. Secondary outcomes included cardiovascular death and new-onset chronic kidney disease (CKD). Propensity scores were used to construct a matched-pairs cohort of patients who stopped or continued the use of ACEI/ARB during the HA-AKI episode.

Results

This study included 10,559 adults (mean [standard deviation] age, 67.4 [14.4] years; 6,606 [62.6%] male). A total of 2,015 (19.1%) participants stopped the usage of ACEI/ARB within 1 day after AKI detection. Among 1,915 matched-pairs, compared with those continued the using of ACEI/ARB, stopping the use of ACEI/ARB was associated with lower risks of 30 day all-cause mortality (adjusted hazard ratio (aHR), 0.67; 95% confidence interval [CI], 0.51-0.87), 180 day all-cause mortality (aHR, 0.77; 95%CI, 0.63-0.94) and in-hospital all-cause mortality (aHR, 0.64; 95%CI, 0.46-0.87). Similar results were found between stopping the use of ACEI/ARB and the risks of 30-day cardiovascular death (aHR, 0.58; 95%CI, 0.49-0.69), 180-day cardiovascular death (aHR, 0.57; 95%CI, 0.36-0.90), in-hospital cardiovascular death (aHR, 0.41; 95%CI, 0.19-0.86), and new-onset CKD after discharge (aHR, 0.76; 95%CI, 0.61-0.96). These protective effects were consistent in multiple sensitivity analyses.

Conclusion

Our study for the first time demonstrates that stopping the use of ACEI/ARB during an AKI episode is associated with lower risks of mortality and new-onset CKD. These findings provide strong evidence for the recommendation of avoiding renin-angiotensin system inhibitors during AKI from clinical guidelines.
#3571 GROWTH PATTERNS IN PEDIATRIC KIDNEY TRANSPLANT RECIPIENTS: A RETROSPECTIVE SINGLE CENTER STUDY
Authors: Askiti Varvara , Malakasioti Georgia , Gole Evangelia , Mitsioni Andromachi
Published: June 2023

Background and Aims

Attainment of a normal adult height remains a great challenge in the care of children with end stage kidney disease. Moreover, the incidence of overweight and obesity increases post kidney transplantation (KT). We aimed to describe growth parameters and predictive factors in children post KT.

Method

We retrospectively reviewed the records of 28 children who underwent KT in our center between 2002-2022. Height (hSDS) and body mass index (BMISDS) z-scores at various time points and possible predictors were assessed.

Results

Median age at KT was 11.2 years (5.3-14), 20 were male, mean time on dialysis was 5.95 years. KT from a living donor (LRD) was performed in 18 patients. Mean follow-up time was 4.88 (1-10) years. rhGH was administered pre-KT in 15/28 patients and in 3 post KT. Following the first year post KT, steroid free, alternate day and daily steroid regimes were adopted for 9, 11 and 8 patients, respectively. Mean hSDS at the time of KT, one year after and at last visit were -1.76, -1.87, and -1.77 (p>0.05). Mean BMISDS at the respective time points were 0.13, 0.65 and 0.05 respectively (p>0.05). At last visit, 29% and 17% of children showed moderate and severe height deficit. hSDS at last visit was associated with preoperative hSDS, whereas difference between hSDS pre and last visit post KT (ΔhSDS) was associated with the type of KT [mean ΔhSDS for LRD and DDT -1.45 (95%CI -1.87, -1.03) and -2.66 (95%CI -3.4, -1.93) respectively, p = 0.002] and steroid regime [mean ΔhSDS for daily and alternate day steroid treatment -0.39 (95%CI -0.77, -0.003) and 0.55 (95%CI -0.07, 1.17) respectively, p = 0.037]. Τhere was no association between ΔhSDS and rejection episodes or rhGH administration pre-KT. At the time of KT and at last visit 25% and 10.7% were overweight, respectively, whereas only 1 patient was obese preoperatively but none at last visit. The overall incidence of overweight and obesity had reduced at last visit compared to pre-KT (p = 0.01).

Conclusion

Linear growth post KT remained limited, resulting in short stature in nearly half of children. Strategies to improve height post pediatric KT could include height optimization pre-KT, steroid withdrawal/avoidance protocols, and LRD KT.
#3581 ACSS2-INDUCED FATTY ACID SYNTHESIS PROMOTES NLRP3 INFLAMMASOME AND PYROPTOSIS OF RENAL TUBULAR CELLS IN SEPSIS-INDUCED ACUTE KIDNEY INJURY
Authors: Lu Jian , Jiang Chun-Ming
Published: June 2023

Background and Aims

Cellular fatty acid metabolism was supposed to be tightly associated with immune responses. Pyroptosis is a form of programmed cell death dependent on the NLRP3 inflammasome activation. Previous studies have revealed that acyl-CoA synthetase 2 (ACSS2) promoted fatty acid synthesis under metabolic stress. However, whether ACSS2-mediated fatty acid metabolism can regulate pyroptosis and inflammatory responses of renal tubular cells in AKI remain unclear.

Method

lipopolysaccharide (LPS) was intraperitoneally injected to establish the sepsis mouse model, and in vitro HK-2 cell culture model was achieved by LPS stimulation. HE and PAS staining were carried out to evaluate pathological injury of kidneys in mice. The renal tissue immunostaining was conducted to detect IL-1β expression and macrophage distribution in kidney tissues of mice. Gene expression of inflammatory factors was evaluated by real-time PCR. Western Blot was conducted to the activation of the NLRP3 pathway and pyroptosis in vivo and in vitro.

Results

Here, we demonstrated that the expression of ACSS2 was significantly increased in the renal epithelial cells of mice with Lipopolysaccharide (LPS)-induced AKI when compared to wild-type mice. ACSS2 regulates NLRP3-mediated caspase-1 activation and IL-1β production through the stimulation of fatty acid synthase (FASN) in renal epithelial cells. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model. Consistently, ACSS2-deficient mice displayed impaired FASN-mediated lipid synthesis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and decreased fatty acid synthesis through the downregulation of FASN. The treatment with the chemical inhibitor C75 suppressed NLRP3-mediated caspase-1 activation and pyroptosis of HK-2 cells under LPS treatment in renal tubular cells.

Conclusion

Our results suggested that ACSS2 regulated the NLRP3 inflammasome activation and pyroptosis by inducing the FASN-mediated fatty acid synthesis pathway in renal epithelial cells. These results identified ACSS2 as a potential therapeutic target in AKI.