bluuebunny/crossref_metadata_2025_split huggingface dataset:
SO086SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY
Authors: Raggi Paolo , Bellasi Antonio , Bushinsky David , Bover Jordi , Rodriguez Mariano , Ketteler Markus , Sinha Smeeta , Garg Rekha , Padgett Claire , Perelló Joan , Gold Alex , Chertow Glenn 
Published: June 2020

Abstract

Background and Aims
In the CaLIPSO study, SNF472 significantly attenuated progression of coronary artery calcium (CAC) volume score compared with placebo. This pre-specified analysis examined the effect of SNF472 on CAC progression in key subgroups of patients in CaLIPSO.

Method
Patients with a CAC Agatston score of 100 to 3500 at baseline were randomized to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91), infused during hemodialysis (HD) thrice weekly for 52 weeks. Patients received standard of care therapy, including phosphate binders and calcimimetics as determined by investigator. The primary endpoint (change in log CAC volume score from baseline to week 52 in the combined dose groups vs placebo) was analyzed for patients who received SNF472 or placebo and had an evaluable CT scan post-randomization (modified ITT population). Sensitivity analysis was also performed for the per protocol population of patients that met entry criteria, received 80% of scheduled treatment, completed the study procedures, and had both a baseline and week 52 evaluable CT scan. The analysis plan pre-specified key subgroups: age, sex, diabetes, dialysis vintage, and arteriosclerotic cardiovascular disease (ASCVD), as well as baseline use of non-calcium phosphate binders, calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, or statins.

Results
Demographics and disease characteristics were similar across the treatment groups. Age (mean±SD) at baseline was 63.6±8.9 years and 39% of the patients were female; 62% had diabetes and 41% had prior ASCVD. Median dialysis vintage was 42.4 months; 33% had received hemodialysis for ≥5 years. Concomitant medications at baseline were: non-calcium phosphate binders, 62%; calcium-based phosphate binders, 28%; calcimimetics, 31%; activated vitamin D, 51%; warfarin, 8%; and statins, 64%. CAC volume progression was 11% for the combined dose groups and 20% for placebo (p=0.016). Treatment differences for CAC volume score progression from baseline to week 52 were similar across the subgroups (FIGURE). All interaction p-values were non-significant, and comparisons favored SNF472 vs placebo in each subgroup for both the modified ITT and per protocol population.

Conclusion
SNF472 treatment for 52 weeks attenuated CAC progression compared with placebo in all subgroups of the CaLIPSO study. These results support the potential benefit of SNF472 across a broad population of patients with cardiovascular calcification. Future studies are needed to determine the effects of SNF472 on cardiovascular events in patients receiving HD.
SO087RISK OF INTRADIALYTIC HYPOTENSION BY DAY OF THE WEEK IN MAINTENANCE HEMODIALYSIS
Authors: Correa Simon , Guerra-Torres Xavier E , Waikar Sushrut S , Mc Causland Finnian R 
Published: June 2020

Abstract

Background and Aims
Intradialytic hypotension (IDH) affects up to 50% of maintenance hemodialysis (HD) patients and is associated with a higher risk of cardiovascular (CV) events and mortality. CV events are more common on the days of dialysis and are most pronounced following the longer interdialytic interval. We wished to investigate if the rates of IDH differed according to dialysis day.

Method
We examined data from adult patients undergoing in-center thrice-weekly maintenance HD (N= 975 patients/n=59,004 sessions from a large dialysis organization [LDO] and N=1,838 patients/n=64,407 sessions from the Hemodialysis [HEMO] Study). We fit random effects logistic regression models to determine the association of day of HD (Mon/Tue [HD1]; Wed/Thu [HD2]; Fri/Sat [HD3]) with various definitions of IDH. Models were adjusted for age, sex, race, Kt/V, membrane flux, heart failure, peripheral vascular disease, diabetes, access type (catheter vs. fistula vs. graft), pre-dialysis blood urea nitrogen, ultrafiltration rate, pre-HD systolic blood pressure (SBP). IDH definitions included Nadir90 (nadir intra-HD SBP &lt;90mmHg), Nadir90/100 (nadir intra-HD SBP &lt;90mmHg if pre-HD SBP &lt;160mmHg or &lt;100mmHg if pre-HD SBP ≥160mmHg), Fall20 (pre-SBP minus nadir SBP ≥20mmHg) and Fall30 (pre-SBP minus nadir SBP ≥30mmHg).

Results
Mean age was 60 years, 44% were female and 38% were black in the LDO cohort, while mean age was 58 years, 56% were female and 63% were black in HEMO. Nadir90 occurred in 15% of LDO and 11% of HEMO sessions; Nadir90/100 occurred in 18% of LDO and 14% of HEMO sessions; Fall20 occurred in 76% of LDO and 68% of HEMO sessions; Fall30 occurred in 60% of LDO and 50% of HEMO sessions. Overall, a monotonic increase in the risk of IDH was observed for HD2 and HD3 compared with HD1 for all IDH definitions in both cohorts (see Table and Figure).

Conclusion
We observed a consistent monotonic increase in the risk of IDH for HD2 and HD3, compared with HD1 in two separate cohorts of maintenance HD patients. Potential explanations may relate to progressive reduction in post-HD weight during the dialytic week, or perhaps more aggressive ultrafiltration in advance of the longer interval. Further research to determine the underling mechanisms is necessary to guide practicing nephrologists when individualizing the HD prescription.
SO088BURDEN OF VALVULAR HEART DISEASE IN HAEMODIALYSIS RECIPIENTS
Authors: Elewa Mohamed , Jayanti Anu 
Published: June 2020

Abstract

Background and Aims
Valvular heart disease (VHD) is highly prevalent in maintenance haemodialysis patients. This high prevalence is associated with poor outcomes and higher mortality [Samad et al., Journal of the American Heart Association, 6 (10), (2017)]. Previous large studies found VHD prevalence between 14% and 16% among prevalent haemodialysis patients [2018 USRDS Annual Data Report | Vol 2] [Hickson et al., Journal of the American College of Cardiology, 67(10), (2016)]. KDIGO consensus group identified several evidence gaps where research is necessary in order to improve our understanding of diagnosis and management of VHD in this population [Marwick et al., Kidney international, 96 (4), (2019)]. The aim of our study is to assess the burden of VHD in a large cohort of haemodialysis recipients in one center in the United Kingdom (UK).

Method
This is a retrospective cross-sectional evaluation of valvular heart disease in prevalent haemodialysis patients. Prevalent haemodialysis recipients were defined as patients established on haemodialysis for ≥ 3 months. Echocardiographic data was collected for all patients. Patients were considered to have VHD if they had significant aortic (AVD) or mitral valve disease (MVD) based on standard echocardiographic criteria. These valvular diseases are classified as mild, moderate or severe. Here, we report some descriptive statistics from our data.

Results
The study group includes 544 prevalent haemodialysis patients. Mean age was 62 years (SD 15.28), 40% females and 60% were males. Median dialysis vintage was 1.9 years (IQR 1, 3.2) [Range: 0.2, 10.2]. 14 % of patients received home-based hemodialysis and 86% received in-center dialysis. 30% of patients were actively awaiting a transplant. A total of 1155 echocardiography studies were reviewed. Of the 425 patients who had an echocardiogram; 34% (n=143) had evidence of VHD as defined above. Significant AVD was identified in 18% of patients (n=78). The dominant lesion was aortic regurgitation in 11%, and aortic stenosis in 7% of patients. 20% of patients (n=85) had significant MVD with mitral valve stenosis in 0.7% of patients (n=3) and mitral regurgitation in 18% of patients. 5% of patients had cardiothoracic intervention (n=21) for valvular heart disease, which included aortic valve replacement (n=9), transcatheter aortic valve implantation (TAVI) (n=9), and mitral valve replacement (n=3).

Conclusion
We found that at least one third (34%) of patients in this cohort had significant VHD- higher than the previously published figures. The numbers are likely to be higher, if echocardiogram information was available for all patients in the study. Timely echocardiographic studies and follow-up imaging for those with established disease are essential to identify patients with significant VHD, in order to establish impact of disease on both dialysis delivery and patient symptoms.
SO089THE EVOLUTION OF THE RENAL FUNCTION IN A COHORT OF ITALIAN PATIENTS WITH ADPKD: AN ANALYSIS BY THE JOINT MODEL
Authors: Galliani Marco , Vitaliano Elio , Chicca Silvana , Paone Antonio , Di Lullo Luca , Tosti Maria Elena , Mele Alfonso , Calvaruso Luca , D'Arrigo Graziella , Tripepi Giovanni Luigi , Zoccali Carmine 
Published: June 2020

Abstract

Background and Aims
The natural history of ADPKD has been defined in numerous studies in various countries and in various genetic and environmental contexts but the problem has not yet been studied in sufficiently large studies in the Italian population. We have studied the evolution of ADPKD in a cohort of 445 incident patients enrolled in a time span between 2012 and 2016 in 28 nephrological centers in 3 regions of central Italy. The main demographic and clinical characteristics of this cohort are reported below.
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Method
The analysis was carried out on a sample of 296 patients with at least 2 creatinine measurements prior to ESKD and with eGFR at onset ≥45 ml/min/1.73m2. The median follow-up was 15 years (range 1-42 years). The analysis of the data was carried out with the Joint model, an approach that allows the simultaneous modeling of longitudinal (repeated over time) and time to event ESKD or GFR&lt;45 ml/min/1.73m2 data. This approach produces two sub-models: a longitudinal model (mixed linear model, sub-model A in the table) and a time to event model (Cox model, survival sub-model B in the Table). The two models are mutually associated through an analytical structure that quantifies the relationship between the variables of interest.
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Results
The average eGFR decline in the entire population was -2.13 ml/min/1.73m2/year. In males the decline in GFR was significantly higher than in females (M: -2.63 ml/min/1.73m2; in F -1.74 ml/min/1.73m2/year, p &lt;0.005) while it was not significant differences are observed for the different age groups considered separately in the two sexes (p = 0.158 in the M; p = 0.625 in the F).
In the longitudinal model the age at diagnosis &gt;30 years and the presence of hypertension were significantly associated with an accelerated decline in GFR and patients older than 50 years exhibited a reduction by 35 ml/min/1.73m2 greater than those younger than 30 years. In the survival model the GFR trend and sex were associated with the risk of renal survival. For each incremental baseline unit of GFR the risk for ESKD decreased by 16% (HR: 0.84) and in females the risk was about one third compared to males (HR: 0.31).

Conclusion
This study, the first to apply the joint model in the analysis of the evolution of renal function in ADPKD and the first in a sizeable cohort in Italy, provides important information on the progression of polycystic kidney disease in an incident series of Italian patients with ADPKD.
SO092REDUCED QUALITY OF LIFE IN ADPKD PATIENTS WITH CKD STAGE 1-3: THE CYSTIC I QUALITY OF LIFE STUDY
Authors: Winterbottom Jean , Simms Roslyn , Ong Albert 
Published: June 2020

Abstract

Background and Aims
ADPKD is the most common inherited kidney disease in man, a major cause of end-stage renal disease and is a significant medical and economic burden across Europe. However the impact of this major disease on the quality of life of patients with preserved kidney function has not been systematically explored.

Method
The CYSTic 1 study was an academic prospective study designed to study the natural history of ADPKD, the impact of the disease on individual patients and the health economic costs on care systems across Europe in adult patients with preserved kidney function (eGFR ≥30 mls/min). Around 400 patients were recruited from 6 expert centres across Europe (Belgium, France, Italy, Netherlands, Spain, UK) with baseline clinical data recorded including HR-QOL (Health-Related Quality of Life) incorporating a Kidney Disease QOL short form (KDQOL-SF v1.3 questionnaire), renal MRI for TKV (Total Kidney Volume) and DNA for genotyping. Here we report initial results based on baseline HR-QOL data in the UK patients.

Results
Detailed analysis was conducted on 76 patients recruited from a single centre (UK) whose mean age was 43 years, 53.9% were female with a mean eGFR-EPI of 69ml/min/1.73m2 and mean height-adjusted TKV (Ht-TKV) of 664ml/m. The cohort was subdivided by groups based on eGFR stage (I, II, III), Ht-TKV (&lt;&gt;750ml/m) and genotype (PKD1 v PKD2/NMD) and correlated with HR-QOL scores. As expected, age, hypertension and Ht-TKV were significantly associated with eGFR stage. Of interest, flank pain was more frequently reported in patients with smaller kidneys (Ht-TKV&lt;750) and patients with PKD1 more likely to be hypertensive. All QOL scores (SF36) were significantly lower in patients with progressively lower eGFR except for emotional well-being whereas Symptom/problem (p=0.043) and Sleep (p=0.021) (KDQOL-SF1.3) were significantly worse in patients with lower kidney function. SF36 scores for Physical functioning (p=0.001), General health (p=0.026) and physical component summary (PCS) (P=0.019) decreased in patients with more advanced disease defined by larger kidneys (ht-TKV&gt;750).

Conclusion
In ADPKD patients with stage 1-3 chronic kidney disease (CKD), stepwise lower QOL scores were consistently found and significantly associated with decreasing eGFR. A notable reported item was disturbed sleep. Unexpectedly, patients with smaller kidneys reported significantly more flank pain. PKD1 patients and those with large kidneys were more likely to be hypertensive. Our results suggest that the impact of ADPKD on patients with stage 1-3 CKD is underestimated. Future work will investigate possible national differences and the relationship of HR-QOL with markers of disease within the entire cohort.
MO020EFFICACY AND SAFETY OF THE LONG-ACTING C5 INHIBITOR RAVULIZUMAB IN PATIENTS WITH POSTPARTUM ATYPICAL HAEMOLYTIC URAEMIC SYNDROME
Authors: Gäckler Anja , Dobronravov Vladimir , La Manna Gaetano , Denker Andrew , Liu Peng , Schoenermarck Ulf , Vinogradova Maria , Yoon Sung-Soo , Praga Manuel 
Published: June 2020

Abstract

Background and Aims
Atypical haemolytic uraemic syndrome (aHUS) triggered by pregnancy is a rare and under-recognised disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor built on eculizumab, with a maintenance dosing interval of 8 weeks, is efficacious in treating aHUS. In this analysis, we report outcomes in a subgroup of patients with postpartum-aHUS enrolled in the 311 study.

Method
This was a global, phase 3, single-arm, multicentre trial evaluating the efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete thrombotic microangiopathy (TMA) response (simultaneous platelet count normalisation [≥150 x 109/L], lactate dehydrogenase [LDH] normalisation [≤246 U/L] and ≥25% improvement in serum creatinine at 2 separate assessments ≥28 days apart) through the 183-day initial evaluation period. Additional efficacy endpoints were: time to complete TMA response, haematological normalisation (platelet count and LDH), dialysis requirement status, and change in eGFR.

Results
Eight patients with postpartum-aHUS (mean age 36 [±8] years) were diagnosed within 12 days of delivery. Seven patients were white and one was Asian. Six patients (75%) had received plasma exchange/infusion before ravulizumab therapy; five (63%) were on dialysis. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 32 days. Haematological normalisation was observed in all patients. By Day 29, all five patients on dialysis at baseline had discontinued dialysis, and by Day 183 all eight patients had improved CKD stage (defined based on eGFR value) by ≥1 category. Three possible treatment-related adverse events (non-serious) were noted in two patients (arthralgia and nasopharyngitis; urinary tract infection). All patients survived and no meningococcal infections occurred.

Conclusion
This is the first prospective analysis of a C5 inhibitor in postpartum-aHUS. Treatment with ravulizumab resulted in rapidly improved haematological and renal outcomes with no unexpected adverse events identified when administered at 8-weekly dosing intervals through intravenous infusion.
MO022URINARY PHOSPHATE/UREA RATIO, A NEW TOOL TO EVALUATE ADHERENCE TO PHOSPHATE DIETARY INTERVENTIONS IN CKD PATIENTS
Authors: Pendon-Ruiz de Mier M Victoria , Santamaria Rafael , Rodelo-Haad Cristian , Muñoz-Castañeda Juan R , Membrives Cristina , Lopez-Baltanas Rodrigo , Lopez-Zamorano M Dolores , Martin-Malo Alejandro , Caravaca Francisco , Soriano Cabrera Sagrario , Rodriguez Mariano 
Published: June 2020

Abstract

Background and Aims
In chronic kidney disease (CKD) patients, phosphate (P) restriction is crucial for the control of mineral metabolism. Many reports indicate that P intake doesnot correlate with 24-hour phosphaturia. Different sources of P (organic or inorganic) have different intestinal absorption rates. Different proportions of organic and inorganic P in diet might be the reason for the lack of correlation between phosphorus intake and phosphaturia. Therefore, we aimed to evaluate if the source of dietary P rather than the total amount of P ingested determines total phosphaturia and it was accessed to what extent inorganic P intake modifies phosphaturia

Method
A 3-day dietary survey was performed in 71 stages G2-3 CKD patients with metabolic syndrome to estimate the amount and source of P in the diet. Blood and 24-hour urine-samples were collected. Total phosphaturia, fractional excretion of P (FeP%), urinary P/eGFR ratio (mg/day/GFR that reflects the urine P excretion relative to renal function), P/creatinine ratio, urinary urea /Cr ratio, and urinary P/urea ratio (that reflects daily intestinal absorption of P relative to the amount of proteins absorbed and metabolized) were evaluated. P/urea ratio was categorized into tertiles and contrasted in terms of the other variables analyzed (T1=&lt;0.027 mg/mg, T2=0.027-0.033 mg/mg, T3= &gt;0.033 mg/mg). Statistics were performed using R 3.6.2, RStudio, Tidyverse, and tableone v0.10.0 packages.

Results
Patients` age was 61±9 years, and eGFR was 68±21 ml/min/1.73m2. Estimated P intake was 869±289 mg/day. According to sources, P intake was 64% from animal sources, 22% from vegetable sources, and 14% from inorganic P. Total P intake did not correlate with urinary P (r=0.18, p=0.12), urinary P/eGFR (r=-0.32, p=0.79), or FeP (r=-0.08, p=0.48). Figure 1 shows that patients ingesting more P have a greater intake of inorganic P. There was a correlation between P intake and P/Urea ratio (p=0.008). Patients in the upper urinary P/urea tertile showed the highest daily P intake (p=0.04), and inorganic P (p=0.03). These patients from tertile 3 also showed the highest amount of urinary P excretion (p=0.04).

Conclusion
Urinary P/urea reflects the total P intake and, more importantly, provides information about the amount of inorganic P. Therefore, the P/urea ratio may be used to guide the appropriate nutritional advice for CKD patients.
MO024WHAT IS THE BEST PREDICTABLE LIPID SUBFRACTION FOR CARDIOVASCULAR OUTCOMES AND ALL-CAUSE MORTALITY IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE?
Authors: Kim Yaerim , Yoon Jeongsoo , Paek Jin Hyuk , Park Woo Yeong , Jin Kyubok , Han Seungyeup , Joo Kwon Wook , Kim Dong Ki 
Published: June 2020

Abstract

Background and Aims
Dyslipidemia is an essential parameter for the prediction of cardiovascular disease (CVD). We aimed to investigate the most valuable subfraction of lipid for predicting CVD in patients with chronic kidney disease (CKD).

Method
We retrospectively reviewed the National Health Insurance Service database for people who received nationwide health screening in 2009. All subjects exposed with lipid-lowering agent before screening were excluded. The population was divided as control, early CKD (eGFR 45-60 ml/min/m2), and advanced CKD (eGFR &lt;45 ml/min/m2) by estimated glomerular filtration rate. Each subfraction of lipid profile, including LDL, TG, HDL, and TG/HDL, was categorized by decile, and the reference was the fifth decile. The end-point of the study was major adverse cardiovascular events (MACCE). The hazard ration (HR) of MACCE was calculated using Cox regression models after adjustment of multiple covariates.

Results
A total of 3,634,915 examiners were included in this study, with 66,810 (1.8%) and 404,315 (11.1%) in advanced and early CKD, respectively. For all populations, LDL, TG, HDL, and TG/HDL showed a linear relationship to MACCE. Except HDL, all subfraction showed positive correlation with the risk for MACCE: adjusted HR (aHR) in tenth decile, 1.45 (1.42-1.49) in LDL; 1.25 (1.22-1.28) in TG; 1.30 (1.27-1.33) in TG/HDL; 0.88 (0.85-0.90) in HDL. Although these patterns were similar in TG, HDL, and TG/HDL for all-cause mortality, only LDL showed different pattern for the two outcomes. In the subgroup analysis using LDL, according to the renal function, the significance for the outcomes and a linear pattern was decreased in the advanced CKD group. For the TG/HDL, although the significance was deceased, the linear pattern has maintained in the advanced CKD group (Fig 1).

Conclusion
The pattern and significance of lipid subfraction were different according to the grade of renal function. Thus, TG/HDL should be additionally considered with LDL as a target variable in patients with advanced CKD.