bluuebunny/crossref_metadata_2025_split huggingface dataset:
#123 Impact of atacicept on hematuria in IGA nephropathy: post-hoc analysis of the phase 2b ORIGIN study
Authors: Floege Jürgen , Barratt Jonathan , Maes Bart , Cooper Kerry , Lin Celia , Wei Xuelian , Barbour Sean , Phoon Richard , Kim Sung Gyun , Tesar Vladimir , Jha Vivekanand , Wadhwani Shikha , Lafayette Richard 
Published: May 2024

Abstract

Background and Aims
Patients with IgA nephropathy (IgAN) and persistent hematuria during follow up have a greater decline in renal function than those with minimal or no hematuria, while hematuria resolution has been independently associated with less decline in renal function [1, 2]. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks for atacicept vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and robust reduction of galactose-deficient IgA1 vs placebo, with similar safety to placebo. This post-hoc analysis evaluates changes in hematuria during treatment with atacicept vs placebo over 36 weeks.

Method
The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24h urine protein &gt;0.75 g/day or UPCR &gt;0.75 g/g, and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Participants were randomized to atacicept 150, 75, or 25 mg vs placebo (2:2:1:2) self-administered by subcutaneous injection once weekly for up to 36 weeks. Microscopic hematuria was evaluated at weeks 2, 4, 12, 24, and 36 via urine dipstick at a centralized lab, and hematuria levels were graded negative/trace, 1+, 2+, or 3+. Hematuria improvement was defined as a decrease by ≥1 grade, and resolution was defined as a decrease to negative/trace.

Results
In the intent-to-treat population, 15 of 33 (45%) participants who received atacicept 150 mg and 19 of 34 (56%) who received placebo had hematuria (1+ or greater) at baseline. Of these, 87% (n = 13/15) on atacicept 150 mg had improved hematuria at 36 weeks vs 32% (n = 6/19) on placebo (p = 0.002), with 80% (n = 12/15) on atacicept 150 mg achieving resolution to negative/trace hematuria vs 5% (n = 1/19) on placebo (p &lt; 0.0001) (Figure). The atacicept 150 mg group steadily improved to lower hematuria grades over 36 weeks, with improvement occurring as early as 4 weeks, while the placebo group had no improvement in hematuria over time. The majority of participants without hematuria at baseline maintained negative or trace levels at 36 weeks.

Conclusion
In a post-hoc analysis, atacicept treatment was associated with hematuria resolution at 36 weeks in a substantially greater percentage of participants as compared with placebo, with improvements seen as early as 4 weeks. These results add to the growing body of evidence supporting atacicept as a potential disease-modifying treatment for IgAN. Atacicept 150 mg is currently being evaluated in a global Phase 3 randomized placebo-controlled trial.
#2640 Hyperuricemia in Gitelman syndrome 132 patients
Authors: Lyu Ning , Zhang Lei , Ji Peili , Xu Lubin , Chen Limeng 
Published: May 2024

Abstract

Background and Aims
Thiazide diuretics, the most common prescription for hypertension, were partly restricted by the hyperuricemia induced by the impairment of uric acid clearance serum uric acid. Gitelman syndrome (GS, OMIM263800), caused by mutations of the SLC12A3 gene encodes the thiazide-sensitive human Na–Cl co-transporter (hNCC), might shed light on the precision mechanism of hyperuricemia induced by Thiazide diuretics.

Method
We retrospectively reviewed 132 GS patients and pertinent articles and analyzed their clinical and genetic characteristics with or without hyperuricemia. Our study also employed Illumina Human Asian Screening Array-24 + v1.0 (ASA) gene chips to screen available samples from 87 patients with Gitelman Syndrome, which included a subgroup of 17 individuals exhibiting elevated uric acid levels characteristic of GS.

Results
The average uric acid level of 132 genetic-confirmed GS patients was 351.4 ± 95.1 µmol/l, with 21.2% hyperuricemia (mean 482.1 µmol/l) and 2 cases of gout. The GS patients with hyperuricemia had higher BMI (24.3 ± 3.9 vs. 21.6 ± 3.5 kg/m2, P = 0.001), lower FEUA (4.6 ± 1.0 vs. 7.0 ± 2.7%, P &lt; 0.001), urinary calcium/creatinine (0.05 vs. 0.11 mmol/mmol, P = 0.01), and△FECl (0.6 ± 0.4% vs 1.2 ± 1.1%, P = 0.02) of the HCT test, indicating more severe NCC function injury. Fisher's exact test yielded non-significant associations of the ten uric acid-predicting SNPs between the patients with or without hyperuricemia at the conventional P-value cut-off of 0.05.

Conclusion
The prevalence of hyperuricemia in GS patients exceeds that observed in the general population. GS patients with hyperuricemia might be because of a high body mass index (BMI) and more severe impairment of NCC function, which suggested the crosstalk between NCC and Uric acid transporter.
#2644 Clinical impact of proteinuria and hematuria remission criteria in IgA nephropathy patients defined by the Japanese Society of Nephrology
Authors: Yasuda Yoshinari , Kaihan Ahmad Baseer , Kaihan Ahmad Naseer , Tanaka Akihito , Imaizumi Takahiro , Maeda Kayaho , Kato Noritoshi , Kosugi Tomoki , Maruyama Shoichi 
Published: May 2024

Abstract

Background and Aims
IgA nephropathy (IgAN) is one of the most common glomerulonephritis worldwide, especially in the Pacific Rim and Mediterranean countries. Hematuria is almost inevitable clinical findings and massive proteinuria is well established risk factor in IgAN. However, a few studies reported hematuria and proteinuria remission in IgAN, and their definition varies in clinical studies. The Japanese Society of Nephrology (JSN) defined new criteria for hematuria and proteinuria remission and relapse for IgAN patients. The objective of the present study was to analyze the utility of JSN criteria to predict renal prognosis among IgAN patients after immunosuppressive treatment.

Method
One hundred IgAN patients were recruited between 2003 and 2014 at Nagoya University Hospital and followed up until December 2017. According to JSN criteria, hematuria remission (HR) and proteinuria remission (PR) are defined as &lt; 5 RBC/HPF, and &lt; 0.3 g/g Cr, in three consecutive urine exams over six months of observation, respectively. Clinical remission (CR) is defined as both HR and PR in 3 consecutive urinalysis over six months. HR, PR and CR were analysed with 30% eGFR decline as a renal outcome.

Results
Baseline proteinuria, serum creatinine, and eGFR were 1.3g/day, 0.8 mg/dL, and 80 mL/min/1.73 m2. The mean age was 34.7 ± 12.5 years old, and 61% of the study population was female. Seventy-two percent of patients received intensive methylprednisolone pulse therapy (mPSL), and the incidence of HR, PR and CR were 76, 50 and 46%, 50%, respectively. Kaplan-Meier curves analyses showed a significant difference between HR and non-HR, PR and non-PR, and CR and non-CR groups (Fig.). In univariate analyses, hypertension, eGFR, HR, PR, CR, and T-score in the Oxford classification of IgAN were significantly associated with renal outcome. In multivariate Model-A, HR, and PR were significant factors for renal outcome after adjusting with sex, hypertension, eGFR and T-score. While in multivariate model-B, CR was also significantly associated with renal outcome after adjustment (Table). However, 36% and 46% of patients demonstrated hematuria and proteinuria relapses after remission.

Conclusion
JSN novel criteria for HR and PR predict renal outcomes in IgAN patients. Further studies are required to verify their clinical utility of JSN criteria in a larger sample size with different ethnicities.
#972 A Novel Single Compound from Chinese Herbs as a Potential Candidate for Reducing obesity induced diabetic nephropathy via ATF3-RARRES1 axis pathway
Authors: Wu Yueh-Lin , Chen Hsi-Hsien , Lin Heng 
Published: May 2024

Abstract

Background and Aims
Billions of people have obesity induced diabetic nephropathy. Promoting the browning of white adipose tissue has been suggested as a potential strategy for, but a drug still needs to be identified.

Method
First, WT and ATF3 knockout mice fed a high-fat diet were treated with STZ to determine that ATF3 plays an important role in obesity-induced diabetic nephropathy. Second, DBA mice fed a high-fat diet were infused with STZ, and db/db KO mice were fed a high-fat diet, and the two mouse models were injected intraperitoneally with or without the ATF3 inducer ST32da (the structure is a single drug designed based on the traditional Chinese medicine Salvia miltiorrhiza). After about one and a half months, all related kidneys function values were measured.

Results
After analysis the relationship between ATF3 and diabetic nephropathy in human GEO DataSet Browser indicated that the gene expression of ATF3 was lower in patients groups. Genetic deletion of activating transcription factor 3 (ATF3−/−) in mice under a high-fat diet (HFD) and STZ treatment resulted in more aggravated nephropathy phenomenon syndrome including higher urine albumin, lower creatinine clearance and high risk in death. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate inflammatory genes and ameliorated foot process effacement resulting in reduced diabetic nephropathy by suppressing the podocyte apoptosis via interleukin (IL)-6 and retinoic acid receptor responder protein 1 (RARRES1) axis.

Conclusion
Our study identified the ATF3 inducer ST32da and Salvia miltiorrhiza extraction, may as a promising therapeutic drug for treating diet-induced obesity induced diabetic nephropathy.
#1802 Treatment with potassium binders in central Sweden—an observational study based on the DEMONSTRATE database
Authors: Eriksson Svensson Maria K , Furuland Hans , Larsson Anders , Uhde Milica , Almstedt Matilda , Cars Thomas 
Published: May 2024

Abstract

Background and Aims
Hyperkalemia (HK), defined as a plasma potassium level (&gt; 5.0 mmol/L), is associated with adverse outcomes, including cardiac arrhythmias and mortality. Until recently, HK was managed mainly with sodium polystyrene sulfonate (SPS) (first generation potassium binders) but concerns regarding the safety profile warranted new alternatives. The second-generation potassium binders, patiromer and sodium zirconium cyclosilicate (SZC) were introduced in Sweden in 2018 and 2019 respectively. The aim of this observational study was to understand the current use of new potassium binders, the related potassium values triggering treatment and to describe the clinical characteristics of patients treated with first- and second-generation potassium binders (SPS and patiromer/SZC respectively) in Sweden.

Method
An observational study based on laboratory data from six regions in central Sweden (18% of the Swedish population), linked to national health registry data, comprising information on clinical events and pharmacy drug dispensations. All treatment episodes of potassium binders between 01 July 2005 and 31 December 2022 were selected and restricted to patients with information on potassium values. A new treatment episode was defined as a gap of at least 120 days to the prior pharmacy dispensations of potassium binders. We analyzed potassium values (up to 60 days prior to initiation of potassium binders), demographics, comorbidities and treatments. Results are mainly presented by treatment episodes and strata of; (a) all, (b) first- and (c) second-generation potassium binders.

Results
In total, we identified 13 441 treatment episodes of which 13 218 episodes (n = 7086 individuals), were attributed to first generation potassium binders (throughout the study period) and 223 episodes (n = 151 individuals) to second-generation potassium binders (from 2018-2022) (Table 1). Baseline characteristics are presented by treatment episodes. Baseline potassium value prior to treatment was 5.6 (0.8) mmol/L for first and 5.6 (0.7) for second generation potassium binders. Mean eGFR prior to treatment was 22.3 (16.3) ml/min/1.73 m2 for first and 18.7 (16.0) for second-generation potassium binders. Compared to first generation, second-generation potassium binders were prescribed to patients with more comorbidities (41.7% vs 32.1% for heart failure, 88.3% vs 81.7% for hypertension, and 39.5% vs 28.9% for dialysis) and more frequently from cardiology/internal medicine units (41.7% vs 30.0%). Distribution of potassium levels at baseline is shown in Fig. 1.

Conclusion
Compared to first- generation potassium binder, we observed fewer treatment episodes with second generation potassium binders, of which majority had a more severe comorbidity profile. There was no difference in potassium values prior to treatment between first- and second-generation potassium-binders.
#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD
Authors: Zou Yutong , Liu Fang 
Published: May 2024

Abstract

Background and Aims
Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels.

Method
Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality.

Results
Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C &lt;1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders.

Conclusion
This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.
#950 Conservative care management in chronic kidney disease: a value for the money?
Authors: Farinha Ana , Barata Pedro 
Published: May 2024

Abstract

Background and Aims
In Portugal, in 2021 the Directorate General of Health proposed the implementation of conservative care management (or kidney palliative care) as an option to handle frail Chronic Kidney Disease (CKD) patients or those who opt not to proceed to Kidney Replacement Therapy Options (KRT). A guideline regulated the clinical framework for this proposal but its socioeconomic evaluation and subsequent reimbursement has not been established. This has become a barrier to its application by public and private providers. This work intends to evaluate the limitations of costs and outcomes analysis in context of end-of-life care in CKD patients and propose indicators to compare cost effectiveness in dialysis and conservative care management.

Method
A narrative review from the literature have been made to evaluate epidemiological, social, individual and economic burden of ESKD and its treatment modalities. A reflection has been made on the benefits of Conservative Care (CC) and the limitations to evaluate cost effectiveness for this option compared to dialysis.

Results
Cost-effectiveness analysis is a method of comparing costs and effects of two or more alternatives in health or social care interventions to an outcome. Conceptual models of cost-effectiveness analysis evaluate outcomes compared to costs. Quality-adjusted life-years (QALYs) is a popular measure of outcome, but its use is problematic in ESKD. Costs of care are mostly elevated at the end of life and the way they are calculated is also debatable (Fig. 1). Some indicators may be used to compare CC and dialysis (Fig. 2).

Conclusion
The health policies should guarantee access to the health care, with quality, effectiveness and safety in the provision of services with efficiency but at the same time to assure financial sustainability and patients’ satisfaction. For some patients CC may embody an option that represents value for the money. To prove this reality, a cost-effectiveness evaluation must be implemented based on pre-specified indicators that override the limitations of this analysis in this specific context.
#2605 Evaluation of cardiac fetal gene program in experimental uremia
Authors: Chinnappa Shanmugakumar , Maqbool Azhar , Viswambharan Hema , Mooney Andrew , Denby Laura , Drinkhill Mark 
Published: May 2024

Abstract

Background and Aims
Heart failure (HF) and uremia share several potent cardiac hypertrophic stimuli such as wall stress, sympathetic activation, renin angiotensin system activation and oxidative stress. In heart failure, induction of fetal gene program is one of the major processes through which such stimuli lead to progressive pathological hypertrophy and myocardial dysfunction. The fetal genes are activated by the transcription factor, myocyte enhance factor 2 (MEF2) which is a downstream target of the Ca++- Calmodulin Dependent Kinase II (CAMKII) pathway. The CAMKII pathway has been shown to be the major transduction pathway of the hypertrophic stimuli in HF [1, 2]. We hosphorzed that such mechanisms are also at play in uremic cardiomyopathy and tested the hypothesis in a rodent model of experimental uremia.

Method
Wistar rats (n = 18) had subtotal nephrectomy (STNx) or sham surgery (sham) and were followed up for 10 weeks. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted, and protein expression of CAMKII and hosphor-CAMKII were quantified using immunoblotting. Protein expression of MEF2 and its target fetal genes were also studied. Histological analyses were performed to quantify myocardial fibrosis. Data was analysed using an independent sample t-test with Welch's correction and expressed as mean± SEM.

Results
STNx resulted in higher echocardiographic left ventricular mass, heart weight to tibia length ratio and myocardial fibrosis in the STNx group (Fig. 1) demonstrating cardiac pathological hypertrophy. CaMKII signalling was activated and the expression of MEF2 was also increased following STNx (Fig. 1). There was trend towards increased expression of fetal genes (Fig. 1). However, the difference did not reach statistical significance.

Conclusion
The study shows that experimental uremia induces cardiac pathological hypertrophy along with activation of intracellular pathways involved in fetal gene induction. Further studies evaluating fetal genes at an earlier time course in the evolution of pathological hypertrophy will be worthwhile.
#2387 Case study of a patient with gouty nephropathy treated with immunosorbent therapy
Authors: Xu Xuecheng , Lei Yu 
Published: May 2024

Abstract

Background and Aims
Gouty nephropathy is a kidney disease caused by chronic hyperuricemia, in which uric acid crystals are deposited in the kidneys leading to tubular and glomerular damage, which in turn affects kidney function.

Patient
female, 68 years old, 7 years ago, no obvious cause of the first toe joint of the right foot, the right ankle joint redness, swelling and pain, the local skin temperature increases, serious limitation of activities, had checked the high uric acid (specific unknown), diagnosed as “gout”, simple treatment after the symptoms are relieved, but did not have systematic treatment, and gradually appeared in the left foot, the first toe joint, the left ankle joint, double knee joint redness, swelling and pain, oral pain medication treatment, pain disappears after still no systematic treatment. After that, redness, swelling and pain appeared gradually in the first toe joint of the left foot, left ankle joint and both knee joints, and the pain disappeared without systematic treatment after taking pain-relieving medicines. He was admitted to our hospital as an outpatient with the diagnosis of “gout”.

Method
Immunosorbent therapy was given once/day on days 1-3, along with Jinshuibao and urotoxin clearing granules. Immunosorbent therapy was given again three times on the 8th-10th day of admission.

Results
Before admission, uric acid: 899.3 µmol/L; creatinine: 586.1 µmol/L, both seriously out of the normal range. 3 days later, uric acid: 770.4 µmol/L, creatinine: 468.7 µmol/L. At the time of discharge, serum uric acid: 298.5 µmol/L and creatinine: 182.6 µmol/L were detected and restored to the normal range.

Conclusion
The case demonstrated the presence of gout with arthritic symptoms, vascular damage, anemia, and hepatic and renal impairment. The patient's gout progressively worsened due to prolonged absence of systemic treatment. After admission, the levels of uric acid and creatinine were effectively controlled and restored by immunosorbent therapy. This indicates that immunosorbent therapy plays a positive role in removing uric acid from the body and improving renal function. Meanwhile, the management and control of gout was further strengthened by combining the comprehensive treatment with Jinshuibao and uremic acid granules.