bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2749 QUANTIFICATION OF URINE PROTEINS FOR DISCOVERY OF BIOMARKERS FOR KIDNEY INJURIES BY DIA-PROTEOMICS
Authors: Yamamoto Keiko , Yamamoto Tadashi 
Published: June 2023

Abstract

Background and Aims
Recent advances in proteomics have enabled to quantify proteins comprehensively. We aimed to establish a platform of urine quantitative proteomics for selection of the biomarkers and assessment of health conditions. Since plasma proteins of varying amounts of were present in urine especially from proteinuric patients, we subtracted the plasma protein conteents from total urine proteomes after the quantitative proteomics for discovery of biomarkers for kidney injuries. On the other hand, urine proteins excreted from plasma may be indicators of pathophysiological conditions in the body, suggesting that the urine proteome profiles figure out health conditions and early discovery of any diseases in the future.

Method
More than 120,000 urine samples (∼10 ml each) have been collected from ∼15,000 patients with various diseases and healthy volunteers (HV) and stored in -20C freezers. In this study, urine samples were selected from HV, diabetic patients (DM) with or without microalbuminuria and other CKD patients. Proteins were precipitated by a methanol/chloroform precipitation method from 1 ml urine. The protein fractions were digested with trypsin and the tryptic peptides were purified by C18 column chromatography. The tryptic peptides of 200 ng each were analyzed by LC-MS (tims-TOFpro, Bruker) by quantitative Data-independent acquisition (DIA) proteomics and proteins were quantified by the DIA-nn tool. Major top 30 plasma proteins were removed from the quantitative proteomics data and kidney- and other urinary tract organ-derived proteins were normalized to compare their proportions in urine.

Results
Approximately 2,500 proteins were quantified by the DIA analysis. In urine from HV, proportions of plasma proteins were small, however, in urine from DM patients with microalbuminuria or CKD patients, the plasma protein contents were increased, resulting in relative decreases of urine proportions of other proteins derived from the kidney or other urinary tract organs. By subtraction of the plasma proteins from total urine proteins, protein proportions were comparable to select candidates of biomarkers for kidney injuries. Comparison of total urine protein profiles between HV and DM elucidated their differences, which might indicate changes of pathophysiological conditions.

Conclusion
By recent quantitative proteomics urine proteins were quantified comprehensively, facilitating discovery of biomarkers for kidney injuries and also evaluation of health conditions in the body.
#2846 DEVELOPMENT OF THE JAPANESE VERSION OF THE BASEL ASSESSMENT OF ADHERENCE TO IMMUNOSUPPRESSIVE MEDICATIONS SCALE
Authors: Kosoku Akihiro , Iwai Tamoaki , Masuda Hiroo , Kabei Kazuya , Nishide Shunji , Maeda Keiko , Yoshikawa Yuki , Nakamura Yasutaka , De Geest Sabina , Uchida Junji 
Published: June 2023

Abstract

Background and Aims
One of the major barriers for long-term transplant outcomes in kidney transplant recipients is medication non-adherence, which is a risk factor for de novo donor-specific antibody development leading to antibody-mediated rejection and graft loss. Identifying non-adherent patients is the first step in minimizing the risk of complications of medication non-adherence. However, to date, there is no validated Japanese self-report instrument to evaluate the MA for transplant patients. This study aimed to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (J-BAASIS).

Method
We conducted a single-center cross-sectional study for kidney transplant recipients who visited our hospital. The eligible and willing participants were randomly assigned to two groups, the J-BAASIS group and the J-BAASIS+MEMS group, with random numbers generated by computer. All participants filled out a questionnaire including the J-BAASIS (the first survey). They filled out a questionnaire again including the J-BAASIS in similar conditions during their following outpatient visit 4-6 weeks later (the second survey). The participants in the J-BAASIS+MEMS group took the methylprednisolone tablets daily using the MEMS until the second survey. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system (MEMS) and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias tool.

Results
A total of 106 kidney transplant recipients (the J-BAASIS group, 56; the J-BAASIS+MEMS group, 50) were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the MEMS, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the “medication compliance” subscale was 0.38 (p&lt;0.001).

Conclusion
The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate medication adherence may help clinicians to identify non-adherent transplant patients and institute appropriate corrective measures to improve transplant outcomes. Moreover, this study, which demonstrated the concurrent validity with the MEMS, the gold standard for measuring medication adherence, further strengthens the evidence for the psychometric properties of the original BAASIS.
#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

Abstract

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

Abstract

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

Abstract

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

Abstract

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&lt;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

Abstract

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&lt;.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&lt;.01, d = 0.35)
• 39% of PCP and 41% of D/E increased their confidence (p&lt;.001 and p&lt;.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

Abstract

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 &lt; 0.001), and FAS-associated death domain protein (FADD) (0.78 vs. 0.43 P &lt; 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

Abstract

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 &gt;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.