bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2421 Kidney injury in scleroderma: serum level of fibroblast growth factor-23, klotho and neutrophil gelatinase-associated lipocalin after iloprost infusion
Authors: De Marco Oriana , Rosato Edoardo , Gigante Antonietta , Pellicano Chiara , Colalillo Amalia , Cianci Rosario 
Published: May 2024

Abstract

Background and Aims
Systemic sclerosis (SSc) is characterized by progressive derangement of the microcirculation leading to a state of chronic tissue hypoxia with release of several inflammatory cytokines such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho.
Renal scleroderma associated-vasculopathy is characterized by vascular damage with normal renal function and increased intrarenal stiffness, assessed by renal resistive index (RRI) Aim of this study was to evaluate at baseline serum levels of FGF-23, Klotho and NGAL in SSc patients and healthy controls (HC) and to correlate the serum levels of these markers with microvascular damage of skin and kidney. Secondary aim was to evaluate the serum levels of FGF-23, Klotho and NGAL after Iloprost infusion.

Method
Twenty-one SSc patients and 20 HC were enrolled. All patients had a 2-months wash-out of Iloprost infusion before of clinical, laboratory and instrumental assessment. Peripheral venous blood was collected at three different time points for SSc patients: t0 immediately before the first Iloprost infusion (after 2-months wash-out period), t1 immediately after the first Iloprost infusion and t2 the day of the next Iloprost infusion (about 14 days from the last infusion).

Results
SSc patients had higher serum level of FGF-23 [18.7 pg/mL (± 6.4) vs 3.6 pg/mL (± 2.2), p &lt; 0.001], Klotho [5.1 pg/mL (±0.8) vs 2.3 pg/mL (±0.6), p &lt; 0.001] and NGAL [20.9 pg/mL (±2.6) vs 14.5 pg/mL (±1.7), p &lt; 0.001] compared to HC. The one-way repeated-measures ANOVA showed that mean FGF-23 [F (2,40) = 71.255, p &lt; 0.001], Klotho [F (1.405, 28.103) = 195.095, p &lt; 0.001] and NGAL [F (2,40) = 48.024, p &lt; 0.001] differed significantly between time points.

Conclusion
SSc patients had higher FGF-23, Klotho and NGAL than HC. Our present data demonstrate that microvascular damage is associated to chronic hypoperfusion with increased circulating markers such as FGF-23, Klotho and NGAL. For the first time, we demonstrated that Iloprost infusion reduces significantly serum level of FGF-23, Klotho and NGAL and it has showed to be a key role in renal vasculopathy in SSc patients. In literature, there are no data about the modification of these serum markers before and after vasoactive treatment, especially of Iloprost infusion.
#2897 Urinary CD44 levels in chronic kidney disease: a validation study
Authors: Gaipov Abduzhappar , Suleimenova Yerke , Makhammajanov Zhalaliddin , Kuspanov Abuali 
Published: May 2024

Abstract

Background and Aims
Proteinuria is the one of the main cause of kidney failure progression. There is inadequate data about protein components in urine and CKD severity. Our recent urinary proteomics study demonstrated the higher expression of CD44 in the urine proteome of healthy participants compared to CKD patients, arguing the protective role of CD44 in kidney health. However, the validation study needed to proof those differences in CD44 levels by ELISA tests in healthy participants and CKD patients. Therefore, we aimed to investigate urinary CD44 levels in our previously studied cohort of healthy controls and CKD patients using ELISA test.

Method
This study included 49 healthy participants and 88 early-stage CKD patients. Along with routine laboratory tests, 24 h collected urine samples were investigated using liquid chromatography-mass spectrometry (HPLC-MS) for proteomic analysis. Exponentially Modified Protein Abundance Index (emPAI) was used to estimate peptide count of proteins. Additionally, urinary CD44 levels were measured using ELISA kit to validate findings from proteomic study.

Results
A brief baseline characteristics of study population presented in Table 1. CKD group represented with lower eGFR, increased creatinine and higher proteinuria compared to healthy controls. Urinary CD44 levels were significantly higher in CKD group compared to healthy controls. Both CD44 levels measured by HPLC-MS and ELISA methods significantly positively correlated with eGFR levels (Table 2).

Conclusion
In this validation study, we compared the levels of CD44 measured by HPLC-MS and ELISA in healthy controls and CKD patients. We demonstrated that CD44 is overexpressed in urine samples of healthy people compared to CKD patients and may play a protective role in the kidney health. Further investigations needed to explain this finding in a different cohort and large number of CKD patients.
#228 APOL1 variants and chronic kidney disease in Morocco: case control study
Authors: Bahadi Abdelaali , Elkabbaj Driss 
Published: May 2024

Abstract

Background and Aims
APOL1 genetic variants account for much of the excess risk of chronic and end stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. These genetic variants were never tested in north African patients and this is the first study aimed to search the existence of this variants in general Moroccan people and patients with chronic kidney disease.

Method
This is a case control multi center study including Moroccan adult with GFR less than 60 ml per min secondary to unknown etiology or nephroangiosclerosis. Patients with known nephropathy or diabetes were excluded. Between July 2014 and June 2017, patients and 100 controls were enrolled for testing APOL1 variants. ADN extraction was done by isolate II Blood DNA kit and nucleic acid concentration by spectrophotometry. The allele frequency was calculated by PCR TaqMan.

Results
During the inclusion period 117 patients with chronic kidney disease from unknown etiology and 8 patients with nephroangiosclerosis were included from all the twelve Moroccan regions. There mean age was 49 years and more than 60% were males. The age of end stage renal disease was 42 years. Testing APOL1 variants did not find G1 or G2 classic mutations but we find a G2 deletion and a new mutation GAT to AAT in two patients. We find also a silent mutation AGA to AGG that we are exploring in a family investigation.

Conclusion
APOL1 genetic variants as described in the literature are not significantly present in Moroccan patient with chronic kidney disease and cannot be yet used as a risk factor in our context. However we find a new mutation needing a wide exploration in a bigger cohort
#1265 Circulating neutrophils in diabetic kidney disease—the relationship with long-term cardiovascular outcomes
Authors: Xie Ruiyan , Zhang Danting , Jason Sher Ka Ho , Yap Desmond 
Published: May 2024

Abstract

Background and Aims
Neutrophils play important roles in the pathogenesis of cardiovascular inflammation and affects cardiovascular disease (CVD) outcomes. The relationship of circulating neutrophil counts with cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) remains unclear.

Method
We retrieved data from 44,494 participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020, and investigated the associations between circulating neutrophil counts, kidney functions and CVD mortality in T2DM and DKD patients. Clinical predictive models and risk scores for long-term mortality were constructed.

Results
Among the cohort of 44,332 patients (18% with T2DM and 82% without T2DM), a total of 2,220 patients were diagnosed with diabetic kidney disease (DKD) and 775 of them experienced mortality (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94-6.42) years. The weighted mean of peripheral neutrophil count level (×109 /L) in DKD participants was 4.98. DKD patients in the highest quintile of neutrophil count exhibited a positive correlation with urine albumin-creatinine ratio (uACR) and a negative association with estimated glomerular filtration rate (eGFR), when compared to those in the lowest quintile. In the multivariate logistic regression analysis with RCS, circulating neutrophil counts showed a U-shaped association with CVD mortality. Neutrophil counts of 3.68 × 109 /L and 3.69 × 109 /L were associated with the lowest risk of CVD mortality and all-cause mortality respectively in DKD patients. Clinical predictive models showed good diagnostic performance for 5- and 10-year CVD mortality-free survival (all ROC AUC values &gt;0.75).

Conclusion
In this study, higher peripheral neutrophil count was associated with an increased risk of cardiovascular mortality in DKD individuals. Our clinical predictive models may help identify at-risk patients for more aggressive CVD risk factors control.
#2404 Predictors of mortality in patients with chronic kidney disease stages 3-4 without heart disease
Authors: Ostlund Ylva , Guron Gregor , Saeed Aso 
Published: May 2024

Abstract

Background and Aims
Cardiovascular disease is common in patients with chronic kidney disease (CKD). This may, at least in part, explain the high risk of mortality in this patient group. The aim of the present study was to identify factors associated with mortality in patients with CKD stages 3 and 4 without a diagnosis of heart disease.

Method
Study subjects were derived from a cohort of patients with CKD stages 3 and 4 who were recruited from our Nephrology Outpatient Clinic between February 2009 and December 2011. Ninety-one patients without a diagnosis of heart disease were included in this cross-sectional study. Mortality data were collected in April 2023.

Results
All-cause mortality was 28.6% (26 patients) during a mean follow-up of 11.2 ± 2.7 years.
Comparison of baseline data between non-survivors and survivors showed that non-survivors were significantly older, had lower glomerular filtration rate (GFR), higher ambulatory systolic blood pressure (ASBP), less nocturnal dipping of ASBP, higher carotid–femoral pulse wave velocity (cfPWV) and higher serum levels of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [Tables 1 and 2]. In addition, the proportion of patients with diabetes and on treatment with beta-blockers was elevated in non-survivors [Tables 1 and 2]. There were no statistically significant differences between groups in smoking history, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, alpha-blockers, statins, active vitamin D analogs, calcium-based or non-calcium-based phosphate binders.
In a binary logistic regression analysis, to identify independent predictors of mortality, we included age, gender, baseline GFR, serum NT-proBNP, TnT, cfPWV, percent of nocturnal dipping of ASBP, diagnosis of diabetes, and treatment with beta-blockers. Only less nocturnal dipping of ASBP (Exp [β] value of 0.86, 95% CI 0.77–0.97, p = 0.016) and advancing age (Exp [β] value of 0.91, 95% CI 0.84–0.99, p = 0.024) significantly predicted all-cause mortality.

Conclusion
In patients with CKD stage 3 and 4 without a diagnosis of heart disease only older age and less nocturnal dipping of ASBP were independently associated with mortality. Although baseline levels of serum NT-proBNP and TnT were elevated in non-survivors, neither serum NT-proBNP nor TnT showed independent associations with mortality in this cohort.
#1137 Association between cognitive function, depressive symptoms and quality of life in older patients with severely reduced GFR and kidney failure
Authors: Demirhan Imre , Van Oevelen Mathijs , Voorend Carlijn , Mooijaart Simon , van Buren Marjolijn , Bos Willem Jan W , Abrahams Alferso 
Published: May 2024

Abstract

Background and Aims
Impaired cognitive function and reduced health-related quality of life (HRQoL) are common in older patients with chronic kidney disease (CKD) with severely reduced GFR and kidney failure. Older patients with CKD often regard HRQoL as a health priority, but it is unknown whether cognitive function associates with HRQoL and whether depressive symptoms mediate this association. We therefore aim to examine the association between cognitive function and HRQoL, and explore the mediating role of depressive symptoms.

Method
Patients aged 65 years and older with an eGFR between 20 and 10 mL/min/1.73 m2 participating in the ongoing DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study were included. Cognitive function, depressive symptoms and HRQoL were assessed using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15) and Twelve-Item Short Form Health Survey (SF-12) questionnaire, respectively. The SF-12 yields a Mental Component Summary (MCS) score and Physical Component Summary score (PCS). We created a diagram of the hypothesized direct and indirect pathways between cognition and HRQoL, with depressive symptoms as the purported mediator (Fig. 1). We used cross-sectional multivariable linear regression analyses to examine the association between cognitive function and both mental and physical HRQoL, and multivariable mediation analyses to explore the role of depressive symptoms.

Results
In total, 403 patients were included with a mean age of 76.5 years, with a standard deviation (SD) of 5.8 and a mean eGFR of 14.5 mL/min/1.73 m2 (SD 3.0). A majority of patients were male (71.5%). Cognitive function associated significantly with mental HRQoL (adjusted β 0.30, 95% confidence interval (CI) 0.05; 0.55, p 0.021), but not with physical HRQoL (adjusted β 0.18, 95% CI −0.09; 0.44, p 0.20). The mediation effect of depressive symptoms between cognitive function and MCS remained significant after adjustment (indirect effect 0.15, 95% CI 0.04; 0.26). Thus, lower cognitive function was associated with lower mental HRQoL, which was partly mediated by corresponding increases in depressive symptoms.

Conclusion
Cognitive function is associated with mental HRQoL, but not with physical HRQoL in older patients with severely reduced GFR and kidney failure. This association is partially mediated by depressive symptoms. These findings underline the importance of screening for cognitive impairment and depressive symptoms in this population and may increase the understanding of what potentially affects HRQoL. As HRQoL is seen as a health priority, further research should explore whether cognitive interventions or treatment of depressive symptoms result in improvement of HRQoL in this population.
#2283 Vitamin D metabolism in end stage kidney failure: people receiving haemodialysis can still synthesise 1,25-dihydroxyvitamin D
Authors: Huish Sharon , Hewison Martin 
Published: May 2024

Abstract

Background and Aims
A large proportion of haemodialysed patients remain vitamin D deficient, contributing to the development, and severity, of chronic kidney disease-mineral bone disorder (CKD-MBD). This study aimed to investigate the effect of vitamin D (cholecalciferol) supplementation on serum levels of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in a group of people receiving haemodialysis.

Method
Eighty-one haemodialysis patients (dialysis vintage ≥1 month) with low serum total 25(OH)D consented to participate. 40,000IU cholecalciferol was given weekly for 12-weeks followed by a maintenance dose of 20,000IU fortnightly (administered by dialysis nursing staff as part of routine care). Patients remained on active vitamin D (1,25(OH)2D3 and analogues) as part of routine care (clinician prescribed for management of calcium and PTH). Baseline and 12-month data were compared using related-samples Wilcoxon signed rank test (Table 1). NHS research ethics committee approval was received.

Results
Complete data were available and analysed for 55 patients. 1,25(OH)2D3 levels were low at baseline (48.3pmol/L, IQR 35.9-57.9pmol/L) despite 44 of 55 patients (80%) being prescribed an active vitamin D analogue (normal range 60-120pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D3 and 1,25(OH)2D3 and significantly increased 24,25(OH)2D3 (Table 1).

Conclusion
Synthesis of 1,25(OH)2D3 is maintained (in kidney failure) but is substrate dependent, and low serum 25(OH)D was evident at baseline. 1,25(OH)2D3 deficiency is therefore partly a consequence of 25(OH)D deficiency, rather than solely due to elevated FGF23 and reduced renal 1α-hydroxylase activity (which is shown to be present in kidney failure). Cholecalciferol supplementation increases the inactive substrate 25(OH)D3 rather than directly increasing 1,25(OH)2D3. Increases in 25(OH)D3 and 24,25(OH)2D3 are disproportionate to 1,25(OH)2D3 increases, demonstrating the known tight regulation of 1,25(OH)2D3 synthesis and secretion (in response to calcium and parathyroid hormone). Conventional oral vitamin D supplementation may provide a cheap and safe strategy for the management of vitamin D homeostasis in chronic kidney disease.
#1086 Blood-brain barrier permeability in patients with end-stage kidney disease: results from the BREIN study
Authors: Bobot Mickaël , Guedj Eric , Resseguier Noémie , Faraut Julien , Garrigue Philippe , Jourde-Chiche Noemie , Hache Guillaume , Vial Romain , Bouchouareb Dammar , Gonzalez Sandra , Guillet Benjamin , Burtey Stephane 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD.

Method
The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants.

Results
15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p &lt; 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels.

Conclusion
This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.
#1923 Anticoagulation and risk of stroke in patients with incident atrial fibrillation and CKD stages 4-5—results from the nationwide FinACAF study
Authors: Jyrkilä Heini , Kaartinen Kati , Martola Leena , Halminen Olli , Haukka Jari , Linna Miika , Mustonen Pirjo , Putaala Jukka , Teppo Konsta , Hartikainen Juha , Airaksinen Juhani , Lehto Mika 
Published: May 2024

Abstract

Background and Aims
Atrial fibrillation (AF) is common in patients with chronic kidney disease (CKD). It is well known that CKD in AF patients increases the risk of thromboembolic complications, and also bleeding. However, there is lack of safety and efficacy data of oral anticoagulation (OAC) in patients with advanced CKD.

Method
The FinACAF study includes data from 411 000 patients covering all Finnish AF patients from 2004 to 2018. Using national unique personal identification numbers, individual patients’ data from several registries and laboratory databases were linked together. The inclusion criteria of this study were all patients 20 years or older with a new-onset, non-valvular AF between 2010 and 2018 and a measured estimated glomerular filtration rate (eGFR) within the proximity of the AF diagnosis. Risk of stroke in patients with CKD stages 4-5 (eGFR &lt; 30 ml/min/1.73 m2) was evaluated. Patients on dialysis and those with functioning graft were excluded. Participants were followed for the occurrence of ischemic stroke (IS) until December 31st 2018 or until death or until the OAC exposure reached a maximum duration of 730 days, whichever came first. The follow-up period was capped at 730 days due to the limited number of patients with direct oral anticoagulation (DOAC) exposure exceeding 730 days. Hazard ratios [95% confidence intervals (CI)] comparing different OACs or no OAC were derived from the Cox regression model.

Results
The study cohort included 4148 patients. The mean (SD) eGFR was 21.5 (6.7) ml/min/1.73 m2. 1940 patients had no OAC, 1658 patients had warfarin and 550 patients had any DOAC (396 apixaban, 121 rivaroxaban, 17 dabigatran and 16 edoxaban). During the follow-up 146 patients (3.5%) had ischemic stroke. Compared to patients with no OAC (reference) HRs were 0.42 [95% CI 0.30-0.59)] for the patients with warfarin and 0.28 [95% CI 0.01-0.52)] for the patients with DOACs. Cumulative hazards for ischemic stroke are shown in the Figure.

Conclusion
Among patients with incident AF and advanced CKD, the risk of stroke was lowest in patients with DOACs and the worst in patients with no OAC. Warfarin users were positioned in between these two groups. Further analysis is needed to evaluate also the safety of different OACs in our cohort.