bluuebunny/crossref_metadata_2025_split huggingface dataset:
FC 117TIME TRENDS IN PROBABILITY OF STARTING HOME DIALYSIS OVER A 20 YEAR PERIOD: A DUTCH REGISTRY STUDY
Authors: Bonenkamp Anna , Hoekstra Tiny , Hemmelder Marc , Van Eck van der Sluijs Anita , Abrahams Alferso C , Van Ittersum Frans J , Van Jaarsveld Brigit 
Published: May 2021

Abstract

Background and Aims
A growing number of patients suffers from End Stage Kidney Disease(ESKD), causing a logistical and economic burden to the healthcare system. Utilization of home dialysis is low in many countries worldwide, although home dialysis has several advantages including higher quality of life and possibly lower costs. The aim of this study is to explore time trends in the use of home dialysis in the Netherlands.

Method
Anonymized registry data from the Dutch Renal Registry (RENINE) were used for this study. All dialysis episodes of adult patients who started dialysis treatment between 1997 through 2016 in the Netherlands were included, including those who previously underwent kidney transplantation. Dialysis episodes shorter than 90 days were excluded. The probability of starting home dialysis between 1997 through 2016 was evaluated in time periods of 5 years, using logistic regression analysis. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years after dialysis start. A logistic multilevel model was used to adjust for clustering at patient level. The cumulative incidence function of start of home dialysis in incident patients was estimated with a competing risk model with recovery of kidney function, kidney transplantations, and all-cause mortality as competing events. All analyses were stratified for age categories at dialysis start: 20-44 years, 45-64 years, 65-74 years and ≥75 years.

Results
A total of 33,340 dialysis episodes in 31,569 patients were evaluated. Between 1997 and 2016, mean age at start of dialysis treatment increased from 62.5±14.0 to 65.5±14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9±15.1 to 62.5±14.6 years in home dialysis patients. In patients &lt; 65 years, the probability of starting home dialysis was significantly lower during each 5-year period compared to the previous period, and kidney transplantation occurred more often. In patients ≥ 65 years, incidence of home dialysis remained constant, whereas mortality decreased.

Conclusion
In patients &lt; 65 years, the overall probability of starting home dialysis declined consistently over the past 20 years. The age of home dialysis patients increased more rapidly than that of in-centre dialysis patients, implying that pre-dialysis education and organization of home dialysis must be adapted to the needs of the elderly patient. These developments have a significant impact on the organisation of home dialysis for patients with ESKD.
FC 118DIALYSIS WITHDRAWAL IN THE NETHERLANDS BETWEEN 2000-2020: TIME TRENDS AND CENTRE VARIATION
Authors: Van Oevelen Mathijs , Abrahams Alferso C , Bos Willem Jan W , Hoekstra Tiny , Van Buren Marjolijn 
Published: May 2021

Abstract

Background and Aims
Treatment withdrawal is an important cause of death among dialysis-dependent patients. Widely variable withdrawal rates were reported in studies using varying designs and definitions in culturally different regions of the world, limiting comparability of individual studies. Cessation of life-prolonging treatment is a well-accepted option in the Netherlands, however it is unclear if these premises result in higher dialysis withdrawal rates and if this effect is generalisable. This study aims to describe dialysis withdrawal practice in the Netherlands, focussing on time trends and practice variation between centres.

Method
Patient data was retrieved from RENINE, the Dutch national registration which includes nearly all patients requiring dialysis for at least 28 days. All patients who initiated maintenance dialysis from January 1, 2000, to December 31, 2020, and died within this period were included for analysis. Since the primary aim of this study concerned cause of death on dialysis, data of patients in whom dialysis was stopped due to kidney transplantation or recovery of kidney function, were excluded. Main outcome was death by dialysis withdrawal, as registered by the treating physician using ERA-EDTA codes. Other causes of death were used as comparison. Time trends for dialysis withdrawal were first analysed as unadjusted data (proportion per year). Univariable logistic regression analyses were then used to identify factors associated with dialysis withdrawal, including year of death in five-year strata. A multivariable model was subsequently used to determine risks, adjusting for factors associated with dialysis withdrawal. Centre variation was compared visually by using funnel plots.

Results
A total of 34.692 patients commenced maintenance dialysis of which 20.389 died. After applying exclusion criteria, a cohort of 18.412 patients was used for analysis. Dialysis withdrawal was an increasingly common cause of death, increasing from 13.5% in 2000 to 31.2% in 2019 (22.1% overall). In multivariable analysis, increasing age, female sex, increasing dialysis vintage, haemodialysis as treatment modality, and year of death were independent factors associated with death by dialysis withdrawal. Centre variation was large, even after correction for confounding factors (36.6% outside 95% control limits).

Conclusion
Treatment withdrawal has become the main cause of death in the Netherlands among dialysis-dependent patients during 2000-2020. Large practice variations were observed between centres, even after correction for confounding factors. These findings emphasize the need for timely advance care planning and urge treating health care professionals to better inform their patients when choosing to start dialysis or not.
FC 020SINGLE CELL SEQUENCING REVEALS TRANSCRIPTIONAL SIGNATURES AND CELL CROSSTALK IN PATIENTS WITH HYPERTENSIVE NEPHROPATHY
Authors: Tang Rong , Meng Ting , Lin Wei , Zhong Yong 
Published: May 2021

Abstract

Background and Aims
Hypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease (ESRD). HTN is characterized by injury to the glomerulus, arterioles and tubulointerstitium, yet the precise mechanisms and cell-specific gene expression changes are still unknown. This study used single-cell RNA sequencing (scRNA-seq) to explore novel molecular mechanisms and the gene targets for HTN.

Method
The gene expression profiles of human renal biospsy samples obtained from subjects with HTN and pre-transplant healthy living controls were determined by scRNA-seq technology. Then the differentially expressed genes (DEGs) and their functions were identified. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted, and the ligand-receptor interaction among different cell populations were anlyzed.

Results
18 distinct cell clusters were identified in kidney from HTN patients. Endothelial cells overexpressed LRG1, a pleiotropic factor linked to apoptosis and inflammation, which was validated at proteome level in kidney from HTN, providing a potential novel molecular target. In HTN patients, mesangial cells highly expressed proliferation related signatures (MGST1, TMSB10, EPS8 and IER2) not detected in renal diseases before. The upregualted genes in tubules of HTN were mainly participating in inflammatory signatures including IFN-γ signature, IL-17 signaling and TLR signaling. Specific gene expression of kidney-resident immune cells including dendritic cells and CD8+ T cells revealed abnormal regulation associated with cell adhesion and inflammation. Furthermore, the receptor-ligand interactions analysis indicated cell-cell crosstalks in kidney contribute to recruitment and infiltration of inflammatory cells into kidneys, and fibrotic process in hypertensive renal injury.

Conclusion
In brief, our data identifies distinct cell-specific gene expression profile, pathogenic signaling pathways and potential cell-cell communication in pathogenesis of HTN. These findings will provide a promising novel landscape for mechanisms and treatment of HTN.
FC 133HEMODIAFILTRATION IS ASSOCIATED WITH REDUCED INFLAMMATION AND INCREASED BONE TURNOVER COMPARED TO CONVENTIONAL HEMODIALYSIS IN CHILDREN - THE HDF, HEART AND HEIGHT (3H) STUDY
Authors: Fischer Dagmar-Christiane , Smith Colette , De Zan Francesca , Askiti Varvara , Bayazit Aysun Karabay , Canpolat Nur , Litwin Mieczyslaw , Paglialonga Fabio , Schaefer Franz , Schmitt Claus , Shroff Rukshana 
Published: May 2021

Abstract

Background and Aims
Children on dialysis have a high burden of bone related comorbidities and fractures. We report a post-hoc analysis of the HDF-Hearts-Height study to determine the prevalence and risk factors for mineral bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD).

Method
144 children were included in baseline cross-sectional analysis, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23 (FGF23) and klotho were measured.

Results
Inflammatory markers interleukin-6 [IL-6], tumor necrosis factor-alfa [TNF-α], and high-sensitivity CRP [hsCRP] were lower in the HDF compared to HD cohorts at baseline and 12 months (p&lt;0.001). Concentrations of bone formation (bone-specific alkaline phosphatase, BAP) and resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) markers were comparable between cohorts at baseline, but after 12-months the BAP/TRAP5b ratio increased in HDF (p=0.004) and was unchanged in HD (p=0.44). On adjusted analysis the BAP/TRAP5b ratio was 2.66-fold lower (95%CI -3.91, -1.41; p&lt;0.0001) in HD compared to HDF. FGF23 was comparable between groups at baseline (p=0.52) but increased in HD (p&lt;0.0001) and remained static in HDF (p=0.34) at 12-months. Klotho levels were similar between groups and unchanged during follow-up. The FGF23/klotho ratio was 3.86-fold higher (95% CI 2.15, 6.93; p&lt;0.0001) in HD compared to HDF.

Conclusion
We conclude that children on HDF have increased bone turnover, an attenuated inflammatory profile and lower FGF23/klotho ratios compared to those on HD. Long-term studies are required to determine the effect, if any, of an improved bone biomarker profile on fracture risk and growth.
FC 062OBESITY AS A CAUSE OF KIDNEY DISEASE - INSIGHTS FROM MENDELIAN RANDOMISATION STUDIES
Authors: Xu Xiaoguang , Eales James , Jiang Xiao , Sanderson Eleanor , Scannali David , Morris Andrew , Guzik Tomasz , Charchar Fadi , Holmes Michael , Tomaszewski Maciej 
Published: May 2021

Abstract

Background and Aims
Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. We aim to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different measures of kidney health and disease.

Method
We performed conventional observational and Mendelian randomisation (MR) study to examine if modifiable anthropometric indices of obesity exert putatively causal effects on different kidney health and disease-related phenotypes. These analyses were conducted using approximately 300,000 participants of white-British ancestry from UK Biobank and up to 480,000 participants of predominantly European ancestry from genome-wide association studies.

Results
The Mendelian randomisation analysis indicated that increasing values of genetically predicted BMI and waist circumference were causally linked to changes in renal function indices including reduced estimated glomerular filtration (PeGFRcystatineC=5.96 × 10-59 for BMI and PeGFRcystatineC=1.72 × 10-69 for waist circumference) and increased blood urea nitrogen (PBUN=2.01 × 10-10 for BMI and PBUN=4.54 × 10-12 for waist circumference) in UK Biobank individuals. These associations were replicated using data from CKDGen Consortium individuals (PeGFRcystatineC=1.47 × 10-5 for BMI and PeGFRcystatineC=7.63 × 10-5 for waist circumference; PBUN=1.96 × 10-4 for BMI and PBUN=3.10 × 10-3 for waist circumference). One standard deviation increase in genetically-predicted BMI and waist circumference decreased the relative odds of kidney health index by 14% and 18% (OR=0.86; 95%CI: 0.82-0.92; P=9.18 × 10-6 for BMI and OR=0.82; 95%CI: 0.75-0.90; P=2.12 × 10-5 for waist circumference). Approximately 13-16% of the causal effect of obesity indices on kidney health was mediated by blood pressure. Obesity increased the risk of both acute and chronic kidney disease of several aetiologies including hypertensive renal disease (OR=1.79; 95%CI: 1.14-2.82; P=1.15 × 10-2 for BMI and OR=2.41; 95%CI: 1.30-4.45; P=5.03 × 10-3 for waist circumference), renal failure (OR=1.51; 95%CI: 1.25-1.83; P=2.60 × 10-5 for BMI and OR=1.86; 95%CI: 1.43-2.42; P=4.16 × 10-6 for waist circumference) and CKD (OR=1.50; 95%CI: 1.16-1.96; P=2.44 × 10-3 for BMI and OR=1.83; 95%CI: 1.28-2.63; P=9.49 × 10-4 for waist circumference) and diabetic nephropathy (OR=1.92; 95%CI: 1.44-2.54; P=6.86 × 10-6 for BMI).

Conclusion
These findings indicate that obesity is causally linked to indices of renal health and the risk of different kidney diseases. This evidence substantiates the value of weight loss as a strategy of preventing and/or counteracting a decline in kidney health as well as decreasing the risk of renal disease.
FC 063DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE 2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL
Authors: Jong Niels , Chertow Glenn , Hou Fan Fan , McMurray John , Correa-Rotter Ricardo , Rossing Peter , Sjöström David , Stefansson Bergur , Toto Robert , Langkilde Anna Maria , Wheeler David C , Lambers Heerspink Hiddo 
Published: May 2021

Abstract

Background and Aims
Reductions in albuminuria are consistently associated with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes. Whether this effect persist in patients with chronic kidney disease (CKD) with and without diabetes is unknown. We therefore assessed and compared the effects of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes from the DAPA-CKD trial.

Method
We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified exploratory outcome. We used regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to micro- or normoalbuminuria (&lt;300 mg/g), and progression in UACR stage, defined as a transition from non-nephrotic (&lt;3000 mg/g) to nephrotic range albuminuria (≥3000 mg/g), as additional endpoints. Subgroup analyses were performed according to baseline type 2 diabetes status.

Results
Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3% (95% confidence interval [CI] 25.2, 33.1; p&lt;0.001), with a 35.1% (95%CI 30.6, 39.4) reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in patients without type 2 diabetes (p for interaction &lt;0.001). Among 3860 patients with UACR ≥300 mg/g at baseline, dapagliflozin significantly increased the likelihood of regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among 3820 patients with UACR &lt;3000 mg/g at baseline, dapagliflozin significantly decreased the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401).

Conclusion
In patients with CKD with and without type 2 diabetes dapagliflozin significantly reduced albuminuria, with a larger reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR suggest that part of dapagliflozin’s protective effect in patients without diabetes is mediated through pathways unrelated to UACR reduction.
FC 064A RENAL-CARDIO INFLAMMATORY AXIS MEDIATES CARDIAC DYSFUNCTION IN CKD VIA IL-33-ST2: A NOVEL MECHANISM
Authors: Chade Alejandro , Hall Michael , Fortenberry Deandra , Bossier Drew , Bidwell Gene 
Published: May 2021

Abstract

Background and Aims
We developed a swine model of chronic kidney disease (CKD) that also display cardiac abnormalities associated with heart failure (HF). Inflammation contributes to progressive renal dysfunction and increases cardiovascular mortality of patients with CKD. Interleukin (IL)-33 is a tissue-derived nuclear cytokine from the IL family. IL-33 constitutively expressed but upregulated and released after cellular damage or necrotic cell death, acting as a pro-inflammatory cytokine. We hypothesize that IL-33 plays a prominent mechanistic role in renal-cardio pathophysiology in CKD.

Method
We induced CKD in 10 pigs via bilateral renovascular disease and dyslipidemia. We developed a renally-targeted biopolymer-fused peptide inhibitor of nuclear-factor kappa (NF-k)B (ELP-p50i) and show it blocks NFkB activity in vitro and in vivo. NF-kB is a key pro-inflammatory transcription factor upregulated in CKD and closely interacts with IL-33. Pigs were observed for 6 weeks, renal (multi-detector CT) and cardiac structure and function (echo) were quantified, then randomized to single intra-renal ELP-p50i or placebo (n=5 each), and studies repeated 8 weeks later. Blood was collected to measure circulating TNF-α, IL-33 and its specific decoy receptor soluble (s) ST2 (ELISA). Heart weights were measured after euthanasia, and renal and cardiac expression of ST2 and morphometric analyses were performed.

Results
Loss of renal function in CKD was accompanied by increased heart weight, left ventricular (LV) hypertrophy, diastolic dysfunction, abnormal LV strain, renal/cardiac fibrosis, circulating TNF-α, IL-33 but unchanged sST2, and increased renal/cardiac ST2 expression. Most of these changes were improved after intra-renal ELP-p50i and accompanied by augmented sST2, suggesting that inhibition of renal inflammation can attenuate cardiac abnormalities via augmented clearance of IL-33 (Figure).

Conclusion
Our study supports a prominent role for renal inflammation as a driving force for precursors of HF in CKD, proposing a renal-cardio inflammatory axis possibly mediated by NF-kB-TNF-α-IL-33/ST2 interactions. TNF-α can stimulate IL-33 as IL33 can activate NF-kB and TNF-α, extending this inflammatory loop in both the kidney and heart. We show that a translational renal anti-inflammatory strategy via targeted inhibition of renal NFkB inhibits this axis and improves renal and cardiac function, which may guide to new treatments targeting renal inflammation in CKD.
FC 134WATER SAVING COMPARISON AT DIFFERENT DIALYSATE FLOWS IN EXPANDED HEMODIALYSIS
Authors: Molano-Triviño Alejandra , Vesga Jasmin , Romero Gregorio , Ronco Claudio 
Published: May 2021

Abstract

Background and Aims
Expanded hemodialysis (HDx) improves clearance of middle molecules as a target for uremia treatment. According to previously published results, high cut off filters have high enough clearance to allow diminishing of dialysate flow (Qd) without detrimental in HD adequacy outcomes with less water waste.
According to World Health Organization (WHO), globally, almost 800 million people lack access to safe water and 2.5 billion lack access to optimal sanitation. Is our duty to search for ways to avoid water waste.
Our aim is to describe the differences in water use between HDX patients receiving Qd 400 mL/min (Group 1) vs 500 ml/min (group 2) in HD patients from 10 renal clinics in Colombia as an alternative to reduce water waste in chronic HD as a strategy from Blue Planet Dialysis initiatives.

Method
We performed a Sub-analysis of CORHEX Study: We calculated water use at different Qd from our database: prospective, multicentre, observational cohort study of 992 adult patients undergoing chronic HD from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. All patients were prescribed with HDX three times a week for a minimum of 4 hours.
We analysed patients with weight lower than 70 Kg at different Qd prescriptions to calculate water use at different Qd prescriptions and performed a prediction analysis, adjusting to Qd 400 mL/min, the whole potential population with weight lower than 70 Kg.

Results
462 patients with weight lower than 70 Kg were analysed, 127 patients received Qd 400 mL/min.
When diminishing Qd from 500 to 400 mL/min, 24 litres were saved per session per patient without detriment of middle molecule clearance. There were no differences in adequacy HD parameters between Qd prescriptions (Table 1 and 2).

Conclusion
HDX allows lowering of Qd to 400 mL/min without harm for patients and with remarkable savings of potable water: 24 Litres were saved in each session per patient that can be translated in almost 3500 Litres of water each year by patient which is enough for one year for 47 adults. (Based on the WHO minimum for basic health protection of at least 20 L per person/day) (2).
We consider our results especially relevant since the World Health Organization estimates that within the next 5 years, over 50% of world population could reside in geographies lacking sufficient access to water.
We hope that our results from the Blue Planet dialysis research group, alongside with Dr. Agar`s and Dr. Barraclough`s green nephrology initiatives, can help educate the nephrology community on the ecological impact of dialysis and can present an innovative solution to offer HD therapy even in countries suffering from limited access to potable water.