bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1514 Elevated FGF23 increases systolic, and diastolic blood pressure, and pulse pressure in non-dialysis CKD patients
Authors: Rodelo-Haad Cristian , López Isabel López , Garcia-Saez Raquel , Jurado Daniel , Martin-Malo Alejandro , Rodriguez Mariano , de Mier M Victoria Pendon-Ruiz , Ojeda Raquel , Peregrín Cayetana Moyano , Soriano Sagrario , Santamaria Rafael , Muñoz-Castañeda Juan R 
Published: May 2024

Abstract

Background and Aims
Arterial stiffness is associated with high blood pressure. Elevated fibroblast growth factor 23 (FGF23) has been shown to produce changes in the phenotype of vascular smooth muscle cells that may cause an increase in arterial stiffness and an impairment of vascular function. Thus, we aimed to evaluate whether, in g5 non-dialysis CKD patients, higher concentration FGF23 is associated with elevated systolic (SBP), diastolic blood pressure (DBP), and pulse pressure (PP).

Method
We included 159 g5 non-dialysis CKD patients. Generalized additive models analyzed the association between intact FGF23, SBP, DBP, and PP. The body composition measurement was used to evaluate overhydration (OH). Given the potential non-linear relationship between iFGF23, with the other variables, iFGF23 was categorized into tertiles (T1 ≤ 389 pg/ml, T2 = 389—517 pg/ml, and T3 = &gt;517 pg/ml).

Results
The mean age was 65.2 ± 14.7 years. 46% (n = 73) were female. The mean values of SBP and DBP were 158.8 ± 21.3 mmHg, and 87.2 ± 12.3 mmHg respectively, and the PP was 76.6 ± 20 mmHg. The median concentration of iFGF23 was 468.3 (268.8—904.9) pg/ml. It was observed a positive correlation between iFGF23 tertiles and SBP (p &lt; 0.001), DBP (&lt;0.01), PP (p = 0.02), and OH (p &lt; 0.01) (Fig. 1). Multivariate generalized additive models showed an independent association of iFGF23 with SBP (Beta 5.16, CI 34-68), DBP (Beta 38.7, CI 24-53), and PP (Beta 36.3, CI 22.2-50.4). This association was not influenced by OH (%). Residual diuresis did not attenuate the association of iFGF23 with SBP, DBP, and PP.

Conclusion
Elevated FGF23 was associated with higher SBP, DBP, and PP in g5 non-dialysis CKD patients. This association was not modified by OH and residual diuresis.
#1725 Co-relation of bone mineral density (BMD) with static bone histomorphometric parameters in haemodialysis patients
Authors: Shukla Ravindra , Chaturvedy Manish , Das Tapabrata , Jhorawat Rajesh , Bajpai Nitin Kumar , Elhence Poonam , Mittal Madhukar , Banerjee Mithu , Goel Akhil Dhanesh 
Published: May 2024

Abstract

Background and Aims
A mineral bone disorder of CKD (CKD MBD) is a complication with abnormal bone turnover, mineralization, volume, vascular calcification, and a spectrum of biochemical abnormalities. This clinical study was designed to determine the correlation between BMD (DEXA parameter) and static bone histomorphometry in hemodialysis patients.

Method
This was a cross-sectional study in patients undergoing maintenance hemodialysis aged 18-60 years. Bone biopsy was done from the iliac crest, fixed in alcohol, processed, and stained by RGB trichrome stain. Histomorphometric analysis was done by using NIH software (image J) and Adobe Photoshop software for image masking into black and white for volume calculation. Determination of BMD was performed by DEXA SCAN (Model HORIZON A). The detection sections included the central skeleton's three areas- anteroposterior lumbar (L1-L4) spine, proximal femur (femoral neck), and distal radius.

Results
A total of 46 patients on maintenance hemodialysis were included. Thirty-one (67.39%) were male, and the mean age was 34.43 ± 12.5 years. Amongst the study population, 60.87% (28) patients had osteopenia, 19.57%(9) patients had osteoporosis, and 19.57%(9) patients had normal BMD. Out of 46, four biopsies were inconclusive, 50% (21) had adynamic bone disease, 19.05%(8) had high turnover bone disease, 19.05%(8) had high mixed uremic osteodystrophy and 11.9%(5) patients had normal parameters. Among biochemical parameters, serum iPTH, ALP, and calcium had a significant association with bone turnover. BMD was significantly associated with age. However, it had no significant association with dialysis vintage, sex, or the type of renal osteodystrophy. Static bone histomorphometric parameters were not significantly associated with the T score.

Conclusion
PTH, ALP, and serum calcium were significantly associated with bone turnover. Adynamic bone disease was the most common renal osteodystrophy. BMD was not significantly associated with static bone histomorphometric parameters in our study.
#2332 Systemic immune-inflammation index is associated with chronic kidney disease: evidence from NHANES 2009-2018
Authors: Li Jinxi , Chen Xinyun , Shi Fangyu , Gou Shenju , Fu Ping 
Published: May 2024

Abstract

Background and Aims
The systemic immune-inflammation index (SII), a novel inflammation index, reflects systemic inflammatory and immunologic conditions throughout the human body. However, the relationship between SII and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible relationship between SII and CKD.

Method
The cross-sectional study included participants with complete information on SII (platelet × neutrophil/lymphocyte count), serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear association between SII and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest.

Results
A total of 23 236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.01 (95% CI = 0.91-1.11, p &gt;0.05) for the Q2 group, 1.18 (95% CI = 1.08-1.30, p &lt; 0. 001) for the Q3 group, and 1.64 (95% CI = 1.50-1.80, p &lt; 0.001) for the Q4 group. In the association between SII and CKD, there was a significant interaction in age (p for interaction &lt; 0.05). And non-linear association between SII levels and CKD in the whole population (p for non-linear = 0.001). All sensitivity analyses supported the positive association between SII and CKD.

Conclusion
SII was positively correlated with increased risk of CKD. The SII may serve as a practical and cost-effective tool for identifying and intervening the individuals at risk for CKD.
#1003 Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of AZD2373, an antisense oligonucleotide targeting APOL1
Authors: Greasley Peter J , Agrawal Nikhil , Althage Magnus , Sanchez Jose , Kirk Sarah , Egeland Erlend Johannessen , Åstrand Magnus , Westergren Helena , Sherwood James , Mccarthy Michael , Patel Uptal , Macphee Iain 
Published: May 2024

Abstract

Background and Aims
APOL1 mediated kidney disease (AMKD) is associated with toxic gain of function variants in people of African ancestry carrying the high-risk APOL1 genotypes (G1 and G2). APOL1 protein is part of the innate immune system but not considered essential. AZD2373, an antisense oligonucleotide that targets APOL1 mRNA to reduce its protein synthesis, is in development for AMKD. In genomic APOL1-transgenic mice, AZD2373 reduced APOL1 expression in kidney and liver, reduced plasma APOL1 protein concentration, and prevented development of IFN-γ induced proteinuria in high-risk genotype mice. In a single ascending dose study (NCT04269031), AZD2373 was well tolerated. We assessed the safety and tolerability of AZD2373 in a multiple ascending dose study including pharmacokinetics, and pharmacodynamic effect on APOL1 plasma protein levels.

Method
In this phase 1, randomized, single-blind, placebo-controlled study (NCT05351047) in healthy male volunteers of West African ancestry, participants were enrolled after a pre-screening study where they were genotyped for APOL1 prospectively; 18 participants had either 1 copy or 2 copies of the G1/G2 APOL1 high-risk allele. Low, medium and high dose cohorts each with 8 participants each receiving six weekly subcutaneous injections of either AZD2373 (n = 6) or placebo (n = 2) and were subsequently followed up for 9-weeks post-last dose. The primary objective was safety and tolerability; secondary objectives included assessment of pharmacokinetics and pharmacodynamics of AZD2373.

Results
In total, 24 participants were randomized and completed the study. No major safety and tolerability concerns were reported up to the highest dose of AZD2373 administered. The most common adverse event was injection site reactions which were dose-dependent, mild to moderate in severity and did not lead to treatment discontinuation. After dosing, AZD2373 had a rapid distribution phase (hours) and prolonged elimination phase (days to weeks). Clearance was similar across dose levels after single and repeated dosing, and the renal contribution to overall clearance was minimal. Exposure generally increased in a dose proportional manner. Plasma APOL1 was knocked down in a dose dependent manner (Figure).

Conclusion
Repeated doses of AZD2373 were safe and well tolerated, reducing plasma APOL1 concentrations in a dose- and time-dependent manner in healthy males of West African ancestry.
#150 Effect of dapagliflozin in patients with CKD depending on primary kidney disease
Authors: Abdullaev Sherzod , Daminov Botir , Sharapov Olimkhon 
Published: May 2024

Abstract

Background and Aims
Multiple trials have reported that SGLT2 inhibitors reduce the risk of its primary composite outcome of kidney disease progression or cardiovascular death in a wide range of patients with CKD. Our aim was to compare effects on kidney outcomes among the different types of kidney diseases.

Method
Eligible patients with eGFRs ≥30-45, or ≥45-90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio of ≥300 mg/g, and receiving renin angiotensin system inhibitor, where indicated and tolerated were randomized to dapagliflozin 10 mg once daily vs placebo. Kidney disease progression was defined as a sustained ≥30% eGFR decline from randomization or to &lt;10 mL/min/1.73 m2, start of maintenance dialysis or receipt of a kidney transplant, or renal death, and the effects of dapagliflozin were analyzed using a pre-specified Cox model. Testing for heterogeneity of effect between pre-specified kidney disease subgroups was performed, including exploratory analyses by specific glomerular disease etiologies.

Results
362 participants were followed for a median of 2.0 years. 90 (24.8%) had diabetic kidney disease, 126 (34.8%) had glomerular disease, 94 (26%) had hypertensive or renovascular disease, and 52 (14.4%) had other or unknown causes. Overall, dapagliflozin reduced the risk of kidney disease progression by 34% (dapagliflozin 29/178 vs placebo 48/184; hazard ratio 0.62, 95% CI 0.51-0.78). This relative risk reduction appeared broadly similar in subgroup analyses by primary cause of kidney disease and by different types of glomerular disease.

Conclusion
Our study with a few numbers of patients with diabetic and non-diabetic causes of CKD showed that dapagliflozin reduced risk of kidney disease progression with relative risk reductions that were broadly similar across the different CKD etiologies.
#1277 Comparing advanced glycation end products removal in super high-flux hemodialysis versus high-volume hemodiafiltration: a randomized, crossover study
Authors: Thanaprirax Ployrawee , Nongnuch Arkom , Boongird Sarinya , Assanatham Montira 
Published: May 2024

Abstract

Background and Aims
Expanded hemodialysis using super high-flux membrane, is a promising therapy for effectively clearing middle molecule uremic toxins. However, its impact on advanced glycation end products (AGEs), which is related to an increase in cardiovascular mortality [1], remains inconclusive. Previous studies demonstrated that AGEs increased over time in patients treated with high-flux hemodialysis (HD) [2, 3] while remaining stabilized in online hemodiafiltration (ol-HDF) [3]. This study aims to compare the longitudinal tissue AGEs measured by skin autofluorescence (SAF) between super high-flux hemodialysis (SHF-HD) and high-volume post-dilution ol-HDF.

Method
In this open-label prospective cross-over 24-week trial, twenty-two prevalent HD patients were randomly assigned to undergone two sequences of 24-week treatment periods: SHF-HD followed by high-volume postdilution ol-HDF or vice versa, with a 4-week wash-out period with high-flux HD between. SAF was measured at baseline and 24 weeks. Midweek pre-HD measurements of beta-2 microglobulin (B2M), serum albumin, normalized protein catabolic rate (NPCR) and Kt/V were obtained every 8 weeks. The amount of dialysate albumin was collected by continuous sampling of spent dialysate method and determined by immunoturbidimetric assay

Results
Seventeen out of twenty-two patients completed the study. At baseline, SAF levels (3.88 ± 0.14 vs 3.99 ± 0.14 AU, p = 0.463) and pre-HD B2M (22.66 ± 1.41 vs 21.09 ± 1.41 mg/L, p = 0.228) were similar between the SHF-HD and ol-HDF groups. After 24 weeks, SAF levels showed no significant change in SHF-HD (from 3.88 ± 0.14 to 3.91 ± 0.14 AU, p = 0.846) and ol-HDF (from 3.99 ± 0.14 to 3.95 ± 0.14 AU, p = 0.796), with a mean difference of change 0.06 (95% CI −0.34, 0.47, p = 0.75). Similarly, mid-week pre-HD serum B2M at 24 weeks exhibited no significant change in the SHF-HD group (22.66 ± 1.41 to 22.18 ± 1.47 mg/L, p = 0.722) and the ol-HDF group (21.09 ± 1.41 to 21.83 ± 1.45 mg/L, p = 0.577), with a mean difference of change −1.22 (95% CI −4.94, 2.49, p = 0.519). The spKt/V urea did not exhibit any notable differences. Furthermore, pre-HD levels of all small uremic toxins after the 24-week periods did not differ between both groups. Nutritional status measured by serum albumin and NPCR were comparable despite higher dialysate albumin loss in postdilution ol-HDF group (0.82 ± 0.04 vs 1.92 ± 0.12 g, p &lt; 0.001 in SHF-HD and ol-HDF, respectively)

Conclusion
After 24 weeks of treatment, SHF-HD demonstrated levels of AGEs, pre-HD serum B2M, and serum albumin comparable to high-volume ol-HDF. If high-volume postdilution ol-HDF is not feasible, SHF-HD may serve as a valuable alternative treatment for stabilizing AGEs in chronic hemodialysis patients.
#1813 Safety and efficacy of reducing hemodialysis fluid flow rate—contribution to planetary health
Authors: Woitas Rainer , Haarhaus Mathias , Pfab Thiemo , Nedess Martin , Krupsack Helma , Macário Fernando 
Published: May 2024

Abstract

Background and Aims
Historically, increasing dialysate flow rates (Qd) have been recommended to improve hemodialysis (HD) efficiency. For decades, Qd has routinely been set to a fixed rate of 500 ml/min. A standard HD treatment uses on average around 500 L of water [1], resulting in a consumption of 78 000 L per patient and year with an additional estimated 10 000 L for post-dilution hemodiafiltration. This corresponds to the annual water consumption of 1.5 persons in developed countries and considerably more in developing countries. We investigated the effect of reducing dialysate flow rates on HD safety and efficacy.

Method
This is a prospective single-center non-blinded observational study. We investigated the effect of a 1:1 adjustment of online Qd to blood flow rate by adjusting autoflow (AF) settings of the dialysis monitor to a calculation factor of 1.0 with a lower Qd limit of 350 ml/min (AF 1.0 mode). We examined the effect on dialysis efficacy, metabolic markers, and anemia in routine biochemical analyses, and calculated energy, water, and waste savings in 116 stable chronic HD patients. Data were compared with previous turnover in energy, waste, and water, as well as with clinical results prior to the mentioned modifications.

Results
After 12 months of HD treatment with AF 1.0 mode we observed reductions of 10% in electricity consumption, 19% in raw water consumption, and 24% in dialysate concentrate consumption. Conversely, we did not observe deteriorations in treatment quality or dialysis dose (Table 1), nor phosphate or hemoglobin.

Conclusion
Long-term HD treatment with reduced dialysate fluid flow rates led to substantially improved water and carbon footprints with potential effects on planetary health and economic savings, while dialysis quality remained unchanged.
#50 The relationship between pre-dialysis plasma endothelin-1 and the intradialytic decline in blood pressure
Authors: Pstras Leszek , Correa Simon , MC Causland Finnian R 
Published: May 2024

Abstract

Background and Aims
Endothelin-1 (ET-1), a potent vasoconstrictor, may play an important role in the blood pressure (BP) response to hemodialysis (HD). Patients receiving maintenance HD have higher concentrations of plasma endothelin-1 than non-HD patients with advanced chronic kidney disease or patients receiving peritoneal dialysis. We wished to examine the association between the pre-HD level of ET-1 and the magnitude of intradialytic systolic BP decline.

Methods
Data was collected in a prospective study of 50 patients receiving maintenance HD admitted to Brigham and Women's Hospital in Boston, MA, USA. BP was measured before and every 15 min during a single HD session using an automated BP cuff. The systolic BP decline was calculated as the pre-HD minus the lowest intradialytic systolic BP. Blood samples were collected pre-HD. Patients with missing data, HD &lt;3 h, or pre-dialysis BP &lt;85/55 mmHg were excluded from the analysis (n = 8). Spearman's rho (ρ) was used to assess the correlation between pre-HD ET-1 and intradialytic systolic BP decline.

Results
Of the 42 included patients, 17 were females, median age 62 [25th, 75th percentile: 50, 70] years. The median HD duration was 232 [210, 242] min and median ultrafiltration was 2.1 [2, 3] L. Before HD, the median ET-1 was 2.4 [1.9, 3.0] pg/mL, the median systolic BP was 141 [119, 167] mmHg, and the median diastolic BP was 68 [63, 84] mmHg. A moderate negative correlation was observed between the baseline ET-1 and the intradialytic decline in systolic BP (ρ = –0.34, P = 0.03). This correlation was stronger in patients with baseline systolic BP &gt;120 mmHg (ρ = –0.51, P = 0.004, n = 30) and much stronger in patients with baseline systolic BP &gt;140 mmHg (ρ = –0.66, P = 0.001, n = 21). Almost all cases (8 out of 9) with an intradialytic decline in systolic BP of &gt;50 mmHg occurred in patients with baseline ET-1 below the pre-HD median level.

Conclusions
Our results suggest that hospitalized patients with pre-HD systolic BP &gt;140 mmHg and lower baseline ET-1 may be more likely to experience larger intradialytic declines in systolic BP. Whether measurement of pre-HD ET-1 could help identify hypotensive-prone patients requires further investigation in larger studies.
#1956 Effect of hemodialysis modalities on infection-related mortality
Authors: Zhang Yan , Alejos Belen , Winter Anke , Carioni Paola , Arkossy Otto , Usvyat Len , Maddux Franklin 
Published: May 2024

Abstract

Background and Aims
A growing body of evidence have suggested hemodiafiltration (HDF) provide survival benefit for dialysis patients. HDF may improve immune modulation with enhanced clearance of azotemic toxins, compared to high-flux hemodialysis (HD). We therefore assess the effect of dialysis modalities on infection-related mortality in patients treated in real-world settings.

Method
We conducted a retrospective cohort-study based on 85,117 adult haemodialysis (HD) patients who were treated in EMEA NephroCare Clinics between January 1, 2019 and December 31, 2022. All patients’ data were extracted from the European Clinical Database (EuCliD®), including mortality from any infection, viral infection, and COVID-19 infection. The definition of mortality cause is based on ICD-10 codes. Any infection related mortality includes a broad range of infection disease types, such as viral, bacterial, parasitic, and fungal infections. The associations between dialysis modality and infection-related mortality were analyzed by multivariable Cox regression models, with both dialysis modality and COVID-19 infection as time-dependent covariates. To account for potential impact of difference in patients’ characteristics, we adjusted for multiple confounding factors. Competing risk analyses with death from non-infection as the competing event were performed by cause-specific and Fine-Gray subdistribution hazard models.

Results
At baseline 45.0% patients were treated with HDF, which changed to 52.6% by the end of follow-up. Of all HDF treatments in post-dilution mode (account for 98.4% HDF treatments) during follow-up, the average convection volume was 25.7 liters (median [interquartile range], 25.8 [23.9–28.0]). Patients treated with HDF at baseline were younger, with less comorbidities and longer dialysis vintage, compared to patients with HD (Table 1). During a median follow-up of 22.6 months, death from any infection occurred among 6.9% patients, of which 40.1% died from COVID-19 infection. Compared to HD, HDF was associated with a reduced risk of dying from any infection (hazard ratio [HR], 0.89 [95% CI, 0.82–0.97]), which however disappeared if excluding death from COVID-19 infection (Table 2). Similar pattern was also observed for death from viral infection. Association of HDF with death from COVID-19 infection persisted after controlling for multiple confounders (HR, 0.81 [95% CI, 0.71–0.93]). Similar results yielded from competing risk analyses.

Conclusion
In this large, unselected patient population, the beneficial effect of HDF for infection-related mortality was confined to mortality from COVID-19 infection. Further studies are needed to unravel the relation between dialysis modalities and death from different types of infection.