bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5438 SERUM TUMOUR NECROSIS FACTOR RECEPTOR 1 PROTEIN ACCURATELY PREDICTS RAPID DISEASE PROGRESSION IN DIABETIC KIDNEY DISEASE
Authors: Bidin Mohammad Zulkarnain , Shah Anim MD , Stanslas Johnson , Ghani Fauzah Binti Abd , Goh Bak Leong , Lim Christopher Thiam Seong 
Published: June 2023

Abstract

Background and Aims
Diabetic kidney disease (DKD) has an enormous disease burden globally. In the area of personalised medicine, biomarker is set to play an important role in the management of DKD. Prior studies have reported the possible association of Tumour Necrosis Factor Receptor 1 (TNFR1), Dickkopf-3 (DKK3) and B cell lymphoma 3 (BCL-3) with the pathogenesis of DKD. However, there had been no prior studies that investigate the association of these biomarkers as prognostic markers for DKD disease progression. Hence, we aim to investigate the correlation of these biomarkers with renal progression among the diabetic population with and without kidney disease.

Method
A total of 156 subjects were recruited, which consisted of 64 control vs 92 patients with DKD. The principal outcomes of this study were rapid renal decline (doubling of serum creatinine, renal decline &gt; 5ml/min/year and &gt; 10 ml/min/year) and their association with serum TNFR1, BCL-3 and urine DKK3. A bivariate analysis was used to test the association of rapid renal decline, and sensitivity and specificity were used to test the validity of the level of the biomarkers with outcomes.

Results
The baseline parameters for both case and control: age 50.19±9.22 vs 60.35±13.73, serum albumin 38.97±2.07 vs 33.01±8.98g/l (p&lt; 0.001), eGFR 117.96±31.94 vs 38.00±22.04 ml/min/ 1.73 m2 (p&lt;0.001), serum creatinine 77.34±14.15 vs 247.45±148.09 µmol/L (p&lt; 0.00), uPCI g/day 0.001±0.0 vs 4.268±5.29 (p&lt; 0.001), HbA1c 7.83±1.88 vs 7.86±1.78 mmol/L (p = 0.942), sTNFR 11781.91±337.46 vs 4394.03±1960.06 pg/mL (p&lt;0.001), uDKK3/creatinine 132.84±37.61 and 1243.63±495.27 pg/mg (p&lt; 0.001), and sBCL3 194.60±32.81 vs 490.17±259.02 pg/mL(p&lt;0.001). During the follow-up, there was a significant association of sTNFR1 with rapid renal decline &gt; 5ml/min/year, &gt; 10 ml/min/year and doubling of serum creatinine [p &lt; 0.003 [IQR = 2891.50-4885.75], p&lt; 0.009 [2891.50-4885.75], p&lt; 0.001 [2891.50-4885.75] but not with uDKK3 and sBCL-3 (Table 1). Specificity and sensitivity analyses on the performance of the biomarkers versus outcomes were highly significant (Figure 1).

Conclusion
Despite TNFR1, BCL-3 and urine DKK3 were all elevated in our DKD patients, there was a strong association between incident serum TNFR1 level and the subsequent deterioration of renal function which has not been reported in the literature before. In addition, TNFR1 level had consistently picked up cases of DKD that would experience rapid renal progression, be it &gt; 5ml/min/year, &gt; 10 ml/min/year or doubling of serum creatinine. The correlation studies have shown TNFR1 level high sensitivity, and specificity of TNFR1 on the rapid renal function decline. Thus, we believe in our DKD population, targeting TNFR1 pathway could be a promising tool in monitoring and treating our DKD population.
#5439 HOME DIALYSIS DOES NOT HAVE THE MONOPOLY ON LOW COST
Authors: Laruelle Eric , Huré Fabrice , Dolley-Hitze Thibault , Vega Isabella Vanorio , Bayat Sahar , Couchoud Cécile 
Published: June 2023

Abstract

Background and Aims
End-stage kidney disease (ESKD) is a major challenge for health-care systems around the world because of its ever-rising rates and the ensuing rise in health-care costs. The objective of this study was to compare the cost of four dialysis modalities that enable patients to play a substantial role in their own care and have social and professional lives.

Method
We identified all patients in the national French ESKD REIN registry aged 18–65 years who received any dialysis treatment in 2015-2019, used stepwise indirect linkage with the national health database to analyse exhaustive hospital stays and outpatient health-care utilisation. Four treatment groups were defined: non-assisted haemodialysis in self-care units (scHD), non-assisted automated peritoneal dialysis (naAPD), daily home HD (dhHD), and non-hospital-based nocturnal extended hours HD (neHD).Total costs by categories and subcategories were aggregated monthly and by patient. Costs are expressed as their medians and interquartile ranges (Q1-Q3).

Results
Our study included 1932 patients with 39 966 patient treatment-months. The median monthly cost for one patient was €6154 (IQR €5088 – €7566) and varied from €5700 for naAPD to €7903 € for dhHD. Analysis by cost subcategories showed that the main cost came from dialysis fee payments —60% of the monthly cost. Hospitalization costs came next (11%). The costs of the different subcategories varied between dialysis modalities. During the study period, the hospitalization rate was 33 per 100 months at risk: 14 for inpatient admissions and 19 for day hospitalization. Day hospitalization was more frequent for patients with home treatment. Various compensatory allowances were paid to 49% of the patients.

Conclusion
Most of the cost difference variability related to payment methods for the different dialysis techniques. Our study shows that different care strategies could be offered to French dialysis patients. Underused techniques such as neHD might usefully be promoted as they do not involve any excess costs, at least compared with dhHD. Real cost analyses are however needed because some reimbursements are not adapted and deserve to be revised upwards.
#5476 SEX DIFFERENCES IN INCIDENT KIDNEY FAILURE AND THE IMPACT OF RISK FACTORS IN A POPULATION STUDY
Authors: Sullivan Michael , Mata Nicole De La , Rosales Brenda , Wyld Melanie , Mark Patrick , Webster Angela , Lees Jennifer 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) has different effects on women and men. Women are more likely to have CKD, but men are more likely to develop kidney failure requiring treatment (KFRT: dialysis or transplantation). Recent studies have highlighted sex differences in CKD progression and there is a need to determine if this relates to differential effects of risk factors.

Method
We used primary care data stored within the electronic health records repository Secure Anonymised Information Linkage Databank (SAIL) for adults with CKD stages G3/4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) living in Wales, UK. We studied the relationship between sex and the development of kidney failure (KFRT or incident eGFR&lt;15 mL/min/1.73 m2 for ≥3 months). Sex-specific rates of kidney failure were compared using an event plot with patients censored on the date of death. Cox proportional hazards models tested associations between sex and kidney failure, before and after adjustment for other known risk factors (age, baseline eGFR, smoking, social deprivation, diabetes mellitus and hypertension). Interactions between sex and risk factors were sought and interaction terms were retained if these were statistically significant (p-value&lt;0.05). Models were then stratified by sex to compare the impact of risk factors in men and women.

Results
135,635 patients (median age 78 years, 57% female, median baseline eGFR 50 mL/min/1.73 m2) were followed up for a median of 6.8 years, representing a total of 782,237 patient years. 1.1% of women and 2.3% of men developed kidney failure. An unadjusted Cox model including both sexes showed a hazard ratio of 2.06 (95% confidence interval 1.89-2.24) for men. After adjustment for all risk factors and inclusion of interaction terms (between sex and baseline eGFR and sex and age), men were not more likely to develop kidney failure (aHR 0.91, 0.60-1.38) (Figure 1A). In sex-stratified models, kidney failure was most likely to develop in those with low baseline eGFR, younger age, current and ex-smokers, patients with diabetes mellitus and patients with hypertension (Figure 1B). Diabetes was a more important risk factor for kidney failure in women (aHR in women 1.73 (1.51-1.98) compared with men (aHR 1.56, 1.39-1.74). Hazard ratios for other risk factors were similar in men and women.

Conclusion
We found that sex differences in rates of kidney failure are related to a differential impact of risk factors – in particular diabetes – on CKD progression. These results warrant further investigation with a need to determine whether risk reduction strategies should be different in men and women with CKD, or whether current diagnosis, monitoring and treatment strategies are either applied differentially or have different benefit and harms by sex.
#5534 HIFS AND BUTS: A NETWORK META-ANALYSIS OF HIF-PH INHIBITORS AND ESAS IN NDD-CKD PATIENTS WITH ANEMIA COMPARING THEIR SAFETY AND EFFICACY
Authors: Warudkar Sandesh , Jain Amit B , Sharma Jay , Dave Nilanj , Chaturvedi Alok 
Published: June 2023

Abstract

Background and Aims
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines for the management of anemia in CKD patients. These agents are found to be efficacious in the management of renal anemia, however safety is still under scrutiny. While, ESAs (Erythropoietin stimulating agents) are available since long with a well-established clinical profile. This network meta-analysis aimed to compare
the safety and efficacy of HIF-PHI vs ESA in CKD patients with anemia not undergoing dialysis.

Method
An electronic database search was carried out in EBM (Evidence Based Medicine) Reviews, Cochrane Library and PubMed from inception to July 2022 for phase III clinical trials comparing six different HIF-PHIs and ESA for treating anemia in non-dialysis-dependent (NDD) CKD patients. The outcomes included the serious adverse events (SAEs) and change in hemoglobin (Hb) levels.

Results
Total 163 records were identified out of which 6 studies involving a total of 6847 patients were eligible for analysis. Compared to ESA, all HIF-PHIs increased risk for SAEs (daprodustat of RR, 1.21[95% CI, 0.825–1.77]; desidustat, 1.38[95% CI, 0.695–2.76]; enarodustat, 1.29[95% CI, 0.568–3.02]; molidustat, 1.02[95% CI, 0.585–1.74]; roxadustat, 1.29[95% CI, 0.674–2.57] and vadadustat, 1.01[95% CI, 0.693–1.47]) although these differences were statistically non-significant. When change in Hb was analyzed, there was no statistically significant difference between the two groups. The mean difference in change in HB with various HIFs as compared to ESA were: daprodustat (MD: 0.0796, 95% CI −0.676–0.838), desidustat (MD: 0.120, 95% CI: −0.626–0.883), enarodustat (MD: -0.600, 95% CI: −1.36–0.157), molidustat (MD: -0.309, 95% CI: −1.07–0.449), roxadustat (MD: -0.0702, 95% CI: −0.831–0.692) and vadadustat (MD: -0.0402, 95% CI: −0.802–0.720).

Conclusion
In terms of safety, HIF PHIs were associated with more SAEs compared to ESA although these differences are not statistically significant. Comparing efficacy, HIF-PHIs and ESA both effectively increase Hb level in NDD-CKD patients without any significant difference. Results of our network meta-analysis suggest the need for larger and long-term studies comparing HIF-PHIs with ESAs to have better understanding of their comparative efficacy and safety profiles.
#5559 BONE SPECIFIC ALKALINE PHOSPHATASE AS A POTENTIAL BIOMARKER OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PROGRESSION
Authors: Jankowska Magdalena , Qureshi Abdul Rashid Tony , Haarhaus Mathias Loberg , Debska-Slizien Alicja , Stenvinkel Peter , Evenepoel Pieter , Lindholm Bengt 
Published: June 2023

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disease, resulting in a dysfunction of the primary cilium, a sensory organelle ubiquitously present in human cells. Ciliopathies are characterized by disorders of seemingly unrelated organs and functions, which depend on integrity of the primary cilium, among them the skeleton and the kidneys. A distinct bone phenotype has been reported in ADPKD patients in several cohort studies. Findings, however, were heterogenous. Present study aimed to measure bone turnover biomarkers in patients with ADPKD across disease severity measured by eGFR and height-adjusted total kidney volume (HtTKV).

Method
In this cross-sectional study, we included 80 ADPKD patients with different chronic kidney disease (CKD) stages (G1 and G2 (n = 39), and G3 and G4 (n = 41)) with median age 44.0 (33.5-50.5) years, 62.5% men, and BMI 25.1 (23.3-28.7) kg/m2. HtTKV was measured with magnetic resonance imaging. We measured biochemical parameters of mineral metabolism, including bone specific alkaline phosphatase (BALP) and total ALP, calcium (Ca), parathyroid hormone (PTH), and 25(OH) vitamin D (25(OH)D) and bone strength index (BSi) with microindentation, using an OsteoProbe® (Active Life Scientific, USA). Microindentation is minimally invasive technique assessing bone quality. The cortical bone at the mid-shaft of the tibia is penetrated with the indenter to measure bone resistance.

Results
Bone biomarkers expressed as median and interquartile range were as follow: Ca 9.6 (9.3-9.9) mg/dL, BALP 9.0 (7.0-12.5) ug/L, ALP 59.0 (46.0-72.0) U/L, PTH 43.5 (26.6-72.0) pg/mL and 25(OH)D 25.4 (16.6-33.5) ng/mL. Median BSi was 79.1(73.5-82.1) in men and 68.5 (62.1-78.6) in women (lower than the average score in healthy caucasians). Among analyzed bone markers only BALP significantly associated with severity of ADPKD. BALP - but not eGFR - associated with HtTKV and was different across HtTKV tertiles. BALP was also higher in the highest BSi group, but BSi did not associate with HtTKV (Figure 1).

Conclusion
In patients with ADPKD and different stages of CKD, BALP associates with bone strength and kidney volume, suggesting that it may be a sensitive marker of systemic ADPKD manifestations. Further studies should elucidate whether BALP may be a more sensitive marker for ADPKD progression than GFR.
#5566 DIETARY MAGNESIUM SUPPLEMENTATION REDUCES RENAL AND CARDIAC FIBROSIS IN AN EXPERIMENTAL MODEL OF TYPE 4 CARDIORENAL SYNDROME
Authors: Muñoz-Castañeda Juan R , Muñoz Andrés Carmona , Martinez-Moreno Julio Manuel , Obrero Teresa , Lopez-Baltanas Rodrigo , Guerrero Fatima , Romero Ana Torralbo , Membrives Cristina , Ortiz Maria Encarnacion Rodriguez , Haad Cristian Rodelo , Peregrín Cayetana Moyano , de Mier M Victoria Pendon-Ruiz , Rodriguez Mariano 
Published: June 2023

Abstract

Background and Aims
In chronic kidney disease (CKD) patients, high serum phosphate (HP) levels are associated with the development of a cardiorenal renal syndrome type 4 (CRS4). In this syndrome, the heart is damaged by oxidative stress, inflammation, and fibrosis in renal tissue. In this study we have evaluated if dietary Mg supplementation could reduce CRS4.

Method
The in vivo studies were performed in 5/6Nx rats fed a high (0.9%) phosphate diet with high or low dietary content of Mg to evaluate: 1) The effect of dietary Mg supplementation (0.3%) on oxidative stress, inflammation and fibrosis of kidney and heart. 2) The contribution of hypomagnesemia (using a low Mg diet (0,03%) to the progression of CRS4 in Nx rats and normal rats as controls. 3) Whether dietary Mg supplementation (8 weeks) reduces renal and cardiac fibrosis in Nx rats with established CRS4. In vitro, we evaluated the effects of Mg (Mg2Cl) on mesangial and tubular cells and also cardiomyocytes cells expose to TGF-β.

Results
Dietary Mg supplementation (0,3%) improved renal function, decreased oxidative stress, FGF23 levels, hypertension, renal and cardiac fibrosis and recovered renal expression of Klotho. A low Mg diet increased FGF23 and renal fibrosis but a subsequent switch to dietary Mg supplementation did not significantly improve CRS4 parameters although it reduced the values of blood pressure. In HK2 and rat mesangial cells treated with TGFβ (100 ng/ml), high Mg levels (1,4- and 2,8-times basal levels in the medium) reduced the amount of pro-fibrotic proteins such as α-smooth muscle actin, fibronectin, or renin, recovering Klotho expression and decreasing Smad3 phosphorylation.

Conclusion
Dietary Mg supplementation is a useful tool to improve renal function and prevent CRS4, by reduction the progression of renal and cardiac fibrosis.
#5658 TUBULE-SPECIFIC CYCLIN-DEPENDENT KINASE 12 KNOCKDOWN POTENTIATES KIDNEY INJURY THROUGH TRANSCRIPTIONAL ELONGATION DEFECTS
Authors: Zhang Yilin , Wang Bin , Liu Bicheng 
Published: June 2023

Abstract

Background and Aims
Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood.

Method
Here, we established a cisplatin-induced AKI mouse model with CDK12 knockdown mice and created stable in vitro models with CDK12 knockdown tubular epithelial cells. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg). After 2 days following cisplatin treatment, blood and kidney tissues were harvested. Renal function and histology were evaluated. DDR, tubular apoptosis, cell proliferation were evaluated by immunofluorescence assays, real-time PCR, flow cytometer and western blot analysis. Notably, we performed single-molecule real-time sequencing (SMRT), a long-read sequencing platform, to identify the formation of novel transcripts involved in the above events.

Results
We found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/− mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis.

Conclusion
These data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.
#5665 C3 GLOMERULOPATHY CURRENT THERAPY AND REAL-WORLD MANAGEMENT - INTERIM RESULTS FROM A MULTI-COUNTRY STUDY
Authors: Proudfoot Clare , Pannagl Katharina , Ndife Briana , King Andrea , Murphy Kathleen , Libby Susanna , Lafayette Richard 
Published: June 2023

Abstract

Background and Aims
C3 glomerulopathy (C3G) is a rare form of glomerulonephritis, with an estimated incidence of 1 – 2 per million per year. C3G is associated with a high risk of disease progression with approximately 50% of patients reaching kidney failure within 10 years of diagnosis. No treatments have been proven effective through randomized controlled trials. KDIGO glomerular disease guidelines recommend treating with renin-angiotensin-aldosterone system inhibitors (RAASi) to reduce blood pressure and proteinuria, and, in select patients, utilization of immunosuppressants such as mycophenolate mofetil and corticosteroids. Newer agents, such as eculizumab, are also sometimes used off-label. The aim of this analysis was to better understand the current management of C3G in the US, Europe, and Asia.

Method
An analysis was conducted using interim data from the Adelphi C3G Disease Specific Programme (DSP), a cross-sectional survey of C3G-treating nephrologists in US, EU5 (France, Germany, Italy, Spain, UK), China and Japan (study ongoing since August 2022; interim analysis based on data until November). Nephrologists completed structured forms administered via online links for consecutive patients presenting with C3G. Forms included information on current and most recent therapy.

Results
In this interim analysis, 88 nephrologists had completed records for 277 patients, including 95 in US, 120 in EU5, 39 in China and 23 in Japan. Median patient age at time of the survey was 44, and 60% were male. 80% had C3 glomerulonephritis (C3GN) and 19% had dense deposit disease (DDD). At the time of the survey, 82% out of 277 patients were receiving treatment. The majority (69%) of 228 treated patients were receiving RAASi, 27% were receiving mycophenolate mofetil/ mycophenolate sodium, 48% corticosteroids, and biologics were used in almost a third of patients. At the time of the survey, mean proteinuria was 2.1 g/day, with 60% of patients having proteinuria ≥1 g/day (Table 1).

Conclusion
C3G is a rapidly progressing glomerulonephritis for which there is no approved therapy. Most patients in this real-world study were receiving treatment, with both conventional immunosuppressants and biologics frequently added to RAASi. Despite this, proteinuria remained high, with the majority of patients having proteinuria ≥1 g/day. This highlights the need for novel therapies to actively treat C3G.
#5672 CORTICAL IRON DEPOSITION ASSESSED BY MAGNETIC RESONANCE IMAGE IS ASSOCIATED WITH KIDNEY FIBROSIS
Authors: Couceiro Carlos , Codina Sergi , Sandoval Diego , Oliveras Laia , Puig Isabel , De Lama Eugenia , Sola Anna , Manonelles Anna , Melilli Edoardo , Montero Nuria , Coloma Ana , Favà Alexandre , Maus Mate , Serrano Manuel , Cruzado Josep 
Published: June 2023

Abstract

Background and Aims
Fibrosis is responsible for the loss of kidney function as a result of several insults, such as ischemia-reperfusion injury or hyperfiltration. This process can continue even after cessation of the primary insult, as documented in acute kidney injury to chronic kidney disease. Recently, we discovered that iron accumulation is a hallmark of fibrotic diseases [1]. We found that in mouse models, iron deposition in the kidney accompanies the progression of the disease. Based on these results, we propose that chronic-low grade hemolysis produced in situation like ischemia-reperfusion injury may be one of the drivers of fibrosis through the damage that the filtrated hemolytic iron cause to the kidneys. Early detection of this iron could help the detection of ongoing fibrogenesis and improve the outcomes by prompt intervention. The challenge of this approach is the lack of non-invasive markers of fibrosis. We evaluated if magnetic resonance image (MRI)-based detection of iron levels in the kidney are correlated to fibrosis in biopsies from kidney transplant recipients.

Method
After approval from the Institutional Revision Board, we carried out a transversal study in our center between 2020 and 2021. We evaluated iron deposits through MRI in patients who underwent a kidney biopsy (per protocol or by clinical indication) and its association with histological parameters. MRI was performed at the same period the biopsy was done. Iron deposits were estimated by using the R2* sequence considering the Grassedonio protocol [2].

Results
We collected data from 15 kidney transplant recipients. Mean age was 58.3 years old. Mean time from kidney transplant to the biopsy was 4.3 years and mean eGFR was 44.4 ml/min/1.73 m2.We analyzed by MRI the R2* signal in the kidney cortex, and their level of fibrosis measured on the biopsies (IFTA score, interstitial fibrosis and tubular atrophy). We found that patients with high IFTA score (2 and 3) presented with significantly higher R2* signal (p = 0.005), than patients with low IFTA score (0 and 1). We also found positive and significant correlation between IFTA (0-3) and iron deposits (Spearman correlation index: r = 0.7537, p = 0.0012).

Conclusion
Iron deposits in the kidney are higher in patients with more fibrosis, and its detection through MRI could be considered a non-invasive marker.