bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3004 Serum miRNAs as novel biomarkers and modulators of rapidly progressing chronic kidney disease in patients with diabetes
Authors: Mcdowall Callum , Shalamanova Liliana , Wilkinson Fiona , Pritchett James , White Stephen , Kalra Philip A 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD) is very common in diabetes, occurring in around 40% of patients. Without treatment, CKD can lead to end stage renal disease (ESRD), which requires costly dialysis and transplantation. Current treatments aim to prevent CKD or slow down its progression to ESRD. The speed of CKD progression is patient-specific, and at present there are no biomarkers which can predict which patient with diabetes will develop CKD; level of albuminuria is an important but variably reliable biomarker of speed of CKD progression.
The current methods for rapid identification of patients prone to accelerated CKD progression are limited, as they are based on measuring estimated glomerular filtration rate (eGFR) over prolonged periods of time, as well as albuminuria. Therefore, there is a clinical need for novel biomarkers that can predict early potential rapid CKD progression in patients.
The aim of this project is to determine whether serum microRNAs (miRs) can be used as biomarkers to predict the speed of CKD progression in diabetes patients, and to identify potential treatment targets associated with such dysregulated miRs.

Method
miRs were isolated from sera of 34 patients with type 2 diabetes classed with either slow or fast progressing CKD by their eGFR (n = 17; obtained from the Salford Kidney Study sample collection). Several miRs were found to be significantly dysregulated in fast progressing patients by using Next Generation Sequencing (NGS) of miRs in individual serum samples. An additional 49 diabetic CKD patient serum samples (slow (n = 29) or fast progressors (n = 20)) were used to validate the potential miR biomarker panel by qPCR.

Results
The NGS miR analysis of the initial 34 CKD patient sera produced a panel of 16 miRs that were either significantly upregulated or downregulated in the fast-progressing patients compared to slow progressors. The qPCR validation of this initial panel in 49 additional CKD patient serum samples demonstrated that 6 miRs were significantly upregulated in the fast-progressing patients. The levels of these miRs correlated with demographic and clinical parameters. ROC curve analysis revealed that the individual predictive power of each of those 6 miRs to define either a slow or fast progressing CKD patient was between 63-75%. Determination of a miR combination the strongest predictive power is ongoing.

Conclusion
A potential biomarker panel of 6 miRs has been identified and validated by qPCR, with each miR having a predictive power of between 63-75% for fast progression of CKD. A panel of miRs that could accurately predict progression speed of CKD patients could lead to faster and earlier diagnosis of patients to enable better treatment.
Work is ongoing to explore the predictive power of this miR biomarker panel, and potential novel therapeutic targets to prevent CKD or delay its progression to ESRD.
#2929 Plasma levels of brain injury markers NfL and GFAP are independently predicted by glomerular filtration rate in patients with chronic kidney disease
Authors: Axelsson Torunn , Zetterberg Henrik , Axelsson Markus , Svensson Maria K , Saeed Aso , Guron Gregor 
Published: May 2024

Abstract

Background and Aims
Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The aim of the present study was to measure brain injury biomarkers in plasma in a cohort of patients with CKD stages 3 and 4, without a diagnosis of cerebrovascular disease, and to determine factors that independently predicted plasma levels of these biomarkers.

Method
This was a cross-sectional cohort study including 110 patients with CKD stages 3 and 4, and 55 healthy, matched, controls, recruited from the outpatient clinic at Sahlgrenska university hospital, Gothenburg, Sweden. None of the included study subjects had a diagnosis of cerebrovascular disease, cognitive impairment, or any other neurological disease. Plasma concentrations of neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau (p-Tau231) were analyzed with ultrasensitive single molecule array (SIMOA). Measured GFR (mGFR) was determined by plasma clearance of ⁵¹Cr-EDTA. Values are medians [interquartile range]. For linear regression analyses standardised beta coefficients (β) are presented.

Results
Characteristics of CKD patients and healthy controls are presented in Table 1. Plasma concentrations of NfL (37.5 [22.1-47.5] vs. 13.4 [10.5-16.7] ng/L, p &lt; 0.001), p-Tau231 (25.7 [19.1-38.7] vs. 13.9 [10.5-16.3] ng/L, p &lt; 0.001) and GFAP (190 [140-281] vs. 153 [116-211] ng/L, p = 0.001) were significantly elevated in patients with CKD vs. controls. In CKD patients, mGFR showed statistically significant inverse correlations to plasma concentrations of NfL, p-Tau231, and GFAP (Table 2). In multiple regression analyses, mGFR was associated with plasma levels of NfL (β = −0.457, p &lt; 0.001) and GFAP (β = −0.322, p &lt; 0.001) independently of diabetes, age, troponin-T, b-hemoglobin, and aortic pulse-wave velocity. However, mGFR was not significantly associated with plasma levels of p-Tau231 in a multiple regression analysis.

Conclusion
Plasma levels of brain injury markers NfL, p-Tau231 and GFAP were elevated in patients with CKD stages 3 and 4, without a history of cerebrovascular disease, compared to healthy controls. Furthermore, mGFR independently predicted plasma concentrations of NfL and GFAP in multiple regression models. These results raise the possibility that reduced GFR per se may be associated with subclinical brain injury.
#1164 Smoking cessation and atherosclerotic cardiovascular events and mortality in chronic kidney disease
Authors: Han Seung Hyeok , Joo Young Su , Koh Hee Byung , Park Jung Tak , Yoo Tae-Hyun , Oh Kook-Hwan , Kang Shin-Wook 
Published: May 2024

Abstract

Background and Aims
Smoking cessation is recommended to reduce excess atherosclerotic cardiovascular disease (ASCVD) and mortality in patients with chronic kidney disease (CKD). However, this recommendation is largely based on observational studies on the general population, involving participants with preserved kidney function. Therefore, we aimed to evaluate the association of smoking dose and smoking cessation duration with ASCVD and mortality in patients with CKD.

Method
We compiled a comprehensive pooled dataset comprising 66,245 participants with CKD from the KNOW-CKD and the UK Biobank cohort. Participants were categorized according to smoking dose and duration of smoking cessation base on a questionnaire. The primary outcome encompassed a composite of ASCVD or all-cause mortality. An ASCVD event was defined according to the ICD-10 codes in the claim and death register records.

Results
Over a median follow-up period of 13.2 years, 14,671 (22.1%) participants reached the primary outcome. Compared to never smokers, former and current smokers exhibited a 1.30- and 2.14-fold higher risk of the primary outcome, respectively. Among former smokers, the hazard ratios (HRs) (95% confidence intervals [CIs]) for smoking loads &lt;20 and ≥20 pack-years were 1.05 (1.00–1.10) and 2.14 (2.05–2.25), respectively. The increased risk of the primary outcome was attenuated by longer smoking cessation. The HRs (95% CIs) for smoking cessation of &lt;10 years, 10–20 years, and &gt;20 years were 1.75 (1.65–1.86), 1.43 (1.34–1.52), and 1.11 (1.06-1.16), respectively, compared with never smokers.

Conclusion
Among former smokers with CKD, the risk of ASCVD or mortality was substantially attenuated with less smoking load and a longer duration of smoking cessation. Our findings support the preexisting recommendations for smoking cessation to improve clinical outcomes in patients with CKD.
#1434 A study of the factors related to the change in eGFR after arteriovenous fistula creation in CKD patients and its impact on kidney prognosis
Authors: Hara Masatoshi , Nakai Kentaro , Tokumoto Masanori , Nakano Toshiaki 
Published: May 2024

Abstract

Background and Aims
Occasionally, we observe cases of transiently increased estimated glomerular filtration rate (eGFR) after arteriovenous fistula (AVF) creation in patients with chronic kidney disease (CKD). However, there is limited research on the factors influencing the change in eGFR after AVF creation and its impact on kidney prognosis.

Method
In this single-center retrospective cohort study conducted from April 1, 2021, to July 31, 2023, 141 patients with CKD were enrolled. The participants were categorized into two groups: the increased eGFR group and the non-increased eGFR group after AVF creation. Factors contributing to increased eGFR after AVF creation were identified using through univariate and multivariate logistic regression analysis.
Predictive variables included demographic and clinical variables such as sex, age, presence of diabetes mellitus (DM), history of cardiovascular diseases, urinary protein level, systolic blood pressure (SBP) on admission, the use of RAAS inhibitors and diuretics, and smoking history. Additionally, the period from AVF creation to dialysis induction was compared between both groups by the Mann-Whitney U test.

Results
Mean age was 69.3 ± 12.4. 75.9% were male, and 48.2% had DM. Among the 141 patients, 44 (31.2%) experienced an increase in eGFR after AVF creation.
There was no significant difference in eGFR at the time of AVF creation between the increased eGFR group and the non-increased eGFR group (6.4 ± 1.5 vs. 6.2 ± 1.7 ml/min/1.73 m2, P = 0.56). Multivariate adjustment revealed that DM (Odds ratio [OR] 2.55, 95% confidence interval [95% CI] 1.01-6.45), hypertension (OR 0.97, 95% CI 0.95-0.99), and smoking history (OR 0.40, 95% CI 0.16–0.98) were associated with the eGFR increase after AVF creation. The time from AVF creation to dialysis induction was significantly longer in the increased eGFR group than in the non-increased eGFR group (median, 76.5 days vs. 42.0 days, P = 0.02).

Conclusion
Factors associated with accelerated atherosclerosis, such as hypertension and smoking, were significantly negatively correlated with increased eGFR. Conversely, DM was significantly associated with increased eGFR after AVF creation. Increased eGFR after AVF creation significantly prolonged the time to dialysis induction compared to the non-increased eGFR group.
#1466 Age- and kidney function-dependent life expectancy of patients after COVID-19
Authors: Siwy Justyna , Wendt Ralph , Peters Björn , Dudoignon Emmanuel , Banasik Miroslaw , Hecking Manfred , Spasovski Goce , Mischak Harald , Beige Joachim 
Published: May 2024

Abstract

Background and Aims
The life expectancy among survivors of SARS-CoV-2 infection may be influenced by age, pre-existing health conditions, and the severity of the initial infection. This study aimed to investigate the life expectancy in patients that survived the acute phase of COVID-19 and the association with kidney function.

Method
Survival data of 649 unvaccinated patients from our previous study “Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection” (CRIT-COV-U) [1] was collected until December 2023 in six different countries. These patients had been recruited within the first and second wave in 2020-2021 (mostly infected with wild-type virus) and had survived the acute phase of COVID-19 (CritCov-U study period 21 days after infection). The age dependent death rate in this cohort was compared to age- and sex-matched data of non-SARS-CoV-2 infected patients (n = 5192) extracted from human urinary database. The association of chronic kidney disease biomarker CKD273 with mortality was investigated in both cohorts using Kaplan-Meier analysis. Cox-regression analysis was used to assess variables associated with mortality in the COVID-19 population.

Results
Mortality was age dependent in both cohorts and markedly higher in patients who had survived the acute phase of COVID-19 in comparison to non-infected individuals (Fig. A-E). Within the first year after infection, mortality was up to 16.5 times higher in patients younger than 50 years in comparison to non-infected controls. Kidney status estimated by the CKD273 score was associated with a poor outcome in both COVID-19 patients and age- and sex-matched controls, respectively (Fig. F-G). The hazard ratio (HR) for mortality during the first year of follow-up for patients with the highest CKD273 score was 12.7, a huge increase in comparison to HR = 6.6 in the matched control group. In the Cox-regression model, CKD273 significantly contributed to death prediction, next to age and COVID-19 severity score at baseline.

Conclusion
SARS-CoV-2 infection during the first and second wave increased the risk of mortality in the follow-up period beyond the acute phase of the first 21 days. Kidney function appears to be a key element in the underlying molecular pathology of this process, indicating the importance of kidney-protective measures. Of note, among those who survived the acute phase of COVID-19, increase in mortality within the first year after infection compared to a non-infected control group was highest in the younger individuals.
#2282 Outcomes of renal amyloidosis: 8 years experience of tertiary center
Authors: Peres Nadiesda , Da Costa José Oliveira , Marchão Natália , Gameiro Joana , Rodrigues Natacha , Pereira Marta Sofia Henriques , Nogueira Estela , Jorge Sofia , Lopes José António , Godinho Iolanda 
Published: May 2024

Abstract

Background and Aims
Amyloidosis is a disease caused by the extracellular deposition of amyloid material that leads to organ dysfunction. Renal involvement is frequent and is characterized by amyloid fibrils pathologic deposition in glomeruli, vessels and interstitium. The most common presentation is nephrotic-range proteinuria or nephrotic syndrome and can progress to end stage kidney disease (ESKD). Prognosis is usually poor, especially with cardiac and severe renal involvement that requires renal replacement therapy. The goal of this study was to analyse the outcomes of patients with amyloidosis followed at the nephrology clinic in our centre.

Method
Descriptive analysis of all confirmed amyloid patients, followed by the Nephrology department from January 2015 to June 2023.

Results
We identified 49 patients with a mean age of 64 ± 16 years [18-88], mainly Caucasian (n = 47, 82%) and male (n = 28, 57%). The majority of patients were diagnosed through renal biopsy (26, 53%). The most common amyloid type was AL (n = 18, 38%), followed by ATTR (n = 16, 33%) and AA (n = 12, 25%). In 3 patients the amyloid type couldn't be characterized. Renal presentation was mostly as CKD 28/49 (57%), 15/49 (30.6%) as nephrotic syndrome and 6/49 (12%) patients as AKI. At presentation, almost half of the patients (24/49, 49%) had nephrotic-range proteinuria, with a mean proteinuria of 6.72 ± 6.12 g/d [0.103-19.8] and mean sCr was 2.6 ± 3.1 mg/dl [0.5-18.9].
AL amyloidosis had an almost equal distribution between lambda (9/18, 50%) and kappa chain (8/18, 44%, one unknown). Extrarenal involvement was frequent, mainly cardiac (12/18, 67%). Also 12/18 (67%) patients needed dialysis after a mean of 9 ± 15 months post-diagnosis, 16/18 (89%) received treatment and mortality was 61%, in mean 16 ± 17 months post-diagnosis, mainly due to disease progression.
AA amyloidosis was secondary to chronic infection in 7/12 (58%), 3/12 (25%) autoimmune diseases and in 2/12 (17%) unknown. Extrarenal involvement was less frequent, also mainly cardiac (3/12, 25%). 7/12 (58%) patients needed dialysis after a mean of 97 ± 117 months post-diagnosis and mortality was 58%, in mean 46 ± 66 months post-diagnosis, mainly due to acute infection. Two patients were diagnosed already on dialysis.
Regarding ATTR amyloidosis, all patients had a positive genetic test, extrarenal involvement was very frequent (13/16, 81%), mostly cardiac and peripheric nervous system. No patients required dialysis during follow-up, and one patient died of unknown cause.

Conclusion
In our cohort, renal AL and AA amyloidosis had poor prognosis, with a high progression to ESKD and very significant mortality, irrespective of treatment. Conversely, ATTR amyloidosis patients had lower progression to dialysis and death, probably as a consequence of disease-modifying therapies instituted in recent years.
#606 Impact of real-world off-label dose of apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease
Authors: Shin Ho Sik , Kil Song Yi , Park Byung Hwa , Kim Ye Na , Jung Yeonsoon , Rim Hark 
Published: May 2024

Abstract

Background and Aims
Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD).

Method
Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban.

Results
Among 635 patients with AF and CKD (76.9 ± 10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P = 0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P = 1.000; off-label overdose vs. standard dose, P = 1.000; off-label underdose vs. off-label overdose, P = 0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P = 0.005).

Conclusion
Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.
#990 Association between frailty and chronic kidney disease: findings from CHARLS
Authors: Liu Fang , Jiamin Yuan 
Published: May 2024

Abstract

Background and Aims
Frailty is a complex age-related clinical condition characterized by a decline in physiological capacity of several organ systems, with a resultant increased susceptibility to stressors. Little is known about the association between frailty and chronic kidney disease (CKD) among Chinese adults. The present study sought to investigate the relationship between frailty and CKD based on a large, nationally representative survey.

Method
The participants were 4231 adults aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS). Based on the FRAIL scale, frailty and prefrailty were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between frailty and CKD. Cox proportional hazards regression models were used to examine the effect of frail status and frail components on CKD.

Results
We found that prevalence of frailty in CKD individuals was 13.9% while in patients without CKD was 8.4%. The prevalence of CKD in robust group was 6.0%, in prefrail group was 10.1% and in frail group was 14.0%. In frail status, after adjusted, the incidence of CKD was 1.713 (95% CI 1.109-2.646) in the frail group compared with robust group (P = 0.015). While there was no statistical difference in the incidence of CKD among the prefrail group and robust group. In frail components, after adjusted, weight loss was associated with higher risk of CKD [HR (95% CI): 1.617 (1.170-2.235)].

Conclusion
We found that the prevalence of frailty was relatively high in the population. In frail status, both prefrail and frail were associated with a higher risk of CKD. In frail components, weight loss was associated with an increase incidence of CKD. Frailty is reversible, so early identification of frailty may reduce the incidence of CKD and improve the adverse consequences associated with CKD.
#1880 Disease outcomes associated with decreased estimated glomerular filtration rate: a Phenome-wide association study
Authors: Li Chunyang , Yang Wanyi , Zeng Xiaoxi 
Published: May 2024

Abstract

Background and Aims
This study aimed to identify associations between decreased creatinine-based estimated glomerular filtration rate (eGFR) and a broad range of related outcomes.

Method
Polygenic risk score (PRS) was calculated using PLINK1.9 software according to the tutorial with summing of risk alleles weighted by the effect sizes of 347308 white participants in UK Biobank. Genome-wide association study (GWAS) summary statistical data of creatinine-based eGFR from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phe codes = 7.52 × 10−5) to correct for multiple testing.

Results
Totally, 19857 SNPs (pruned by r2 &lt; 0.1 within the 250 kb region, P &lt; 0.01) from base data were retained for PRS calculation. Our Phe was identified that one standard deviation (SD) decrease in the PRS of eGFR significantly associated with chronic renal failure (OR = 1.27, 95% CI: 1.25-1.30, P = 1.66 × 10−158), intestinal malabsorption (OR = 1.18, 95% CI: 1.13-1.22, P = 1.76 × 10−16), other hypothyroidism (OR = 1.06, 95% CI: 1.04-1.07, P = 4.98 × 10−13), calculus of kidney and ureter (OR = 0.92, 95% CI: 0.89-0.94, P = 4.91 × 10−11), gout (OR = 1.07, 95% CI: 1.05-1.10, P = 2.34 × 10−8), chronic nephritic syndrome (OR = 1.21, 95% CI: 1.12-1.30, P = 3.20 × 10−7), Hypertensive renal disease (OR = 1.15, 95% CI: 1.09-1.21, P = 4.72 × 10−7), acute renal failure (OR = 1.04, 95% CI: 1.02-1.06, P = 4.58 × 10−6), glaucoma (OR = 0.95, 95% CI: 0.93-0.98, P = 2.16 × 10−5) and unspecified renal failure (OR = 1.10, 95% CI: 1.05-1.16, P = 2.70 × 10−5).

Conclusion
Genetically predicted deceased eGFR associated with a series of disease outcomes, providing evidence for prevention of following diseases in patients with kidney function impairment.