bluuebunny/crossref_metadata_2025 huggingface dataset:
#4787 VITAMIN D AND PARATHYROID HORMONE PREDICT INCIDENT MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS STARTING HAEMODIALYSIS: A REAL-WORLD ANALYSIS
Authors: Mcdowell Garry , Downey Robert , Buckley Benjamin , Austin Philip , Lip Gregory , Rao Anirudh
Published: June 2023

Background and Aims

Despite its advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality, within 2 years of starting treatment. HD patients are known to suffer from vitamin D deficiency which has been linked to excess CV mortality and morbidity. We aimed to investigate the prognostic significance of vitamin D in predicting incident Major Adverse Cardiovascular Events (MACE) within 5 years of commencing HD.

Method

A retrospective cohort study was performed using electronic medical records from a global federated research network from the US (TriNetX). The TriNetX network was searched on 31st January 2023. The cohorts commenced HD post-diagnosis of End-Stage Kidney Disease. Data censoring for MACE was invoked prior to the index event of HD. Vitamin D (25-hydroxyvitamin D and 1,25 dihydroxy Vitamin D) concentrations were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender, and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95% CI for 5-year MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke, and all-cause mortality. All statistical analysis was performed on the TriNetX online platform.

Results

The results are shown below. There was no association between outcome and PTH at 55 pg/ml threshold. Only results that reached statistical significance (p<0.05) are shown. Patients with a 25-OH Vitamin D concentration <24 ng/ml or 1,25-diOH Vitamin D at <35 pg/ml had significantly more events, as shown below.

Conclusion

Circulating plasma levels of cholecalciferol and calcitriol are predictive of CV outcomes in patients commencing HD; however, the risk profile is different between low levels of active and inactive vitamin D. As the incident HD population are at increased risk of CV mortality and morbidity, cholecalciferol and calcitriol should be included in assessing overall risk.
#5352 INCIDENT ACUTE KIDNEY INJURY AND THE RISK OF DEMENTIA: THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT
Authors: Xu Hong , Xu Yang , Garcia-Ptacek Sara , Bruchfeld Annette , Eriksdotter Maria , Carrero Juan Jesus
Published: June 2023

Background and Aims

Preclinical studies suggest that acute kidney injury (AKI) leads to biochemical and pathological changes in the brain. However, whether developing AKI associates with the risk of dementia is not well explored. We here aimed to evaluate the association between developing AKI and the subsequent risk of dementia in general population.

Method

We included all adults with age ≥65 years, free from dementia diagnosis and with known kidney function in Stockholm during 2006-2019. The exposure was AKI (time varying): prevalent history of AKI was ascertained by clinical diagnoses, and new/incident AKI events during observation by both clinical diagnoses and transient creatinine elevations according to KDIGO criteria. The outcome was dementia diagnosis, first via confirmed cases in the Swedish registry of cognitive/dementia disorders (SveDem) and enriched with cases identified by two issued diagnoses of dementia in outpatient care or initiation of specific anti-dementia medications. We considered death, migration, and end of follow-up as censoring events and also explored risk associations with specific dementia subtypes. The association between developing AKI and study outcomes was evaluated through time-varying multivariate Cox regression, accounting for recurrent AKI events through weighted cumulative exposure metrics.

Results

We included 354,612 individuals with median 76 years (55% women). During median follow-up of 8.1 (IQR: 3.7, 12.1) years, there were 48,624 (14%) persons suffering at least one episode of AKI, and 47,765 (13%) diagnoses of dementia were recorded. The rate of dementia cases was 37.13 per 1000 person-year (95% CI 36.06-38.22) after developing AKI, which was approximately 2 times higher than the rate observed during the periods without AKI (18.47 [18.3-18.64]). After multivariable adjustment, developing AKI was associated with a 48% higher risk of having dementia [adjusted HR 1.48 (95%CI 1.43-1.53)]. This pattern was consistent for the dementia subtypes: the HRs for Alzheimer's dementia, Parkinson's disease dementia, and vascular dementia were 1.14 (1.07-1.21), 1.90 (1.37-2.65) and 1.24 (1.15-1.33) higher, respectively, after developing AKI. Among persons with recurrent AKIs, each additional AKI event was associated a 4% higher risk of dementia (adjusted HR: 1.04, 95% CI: 1.03-1.05). We observed similar results across subgroups of sex, baseline kidney function, history of hypertension, diabetes, and cardiovascular disease.

Conclusion

In this region-representative cohort, participants who experienced AKI were at increased risk of receiving a diagnosis of dementia.
#5635 SYSTEMIC OXALOSIS: AN OVERVIEW OF THE FINDINGS AND PREVALENCE IN PRIMARY HYPEROXALURIA
Authors: Deesker Lisa , Garrelfs Sander , Groothoff Jaap
Published: June 2023

Background and Aims

Systemic oxalosis is a severe co-morbidity that may arise in patients with primary hyperoxaluria type 1 (PH1). It is caused by precipitation of calcium oxalate crystals in organs besides the kidneys, as a result of high endogenous oxalate production. In this study, we aimed to provide an overview of the prevalence, features, screening modalities and factors that play a role in developing systemic oxalosis as cohort studies are currently lacking.

Method

A retrospective registry study was conducted using data from the OxalEurope registry, one of the largest registries of patients with PH1. All patients with primary hyperoxaluria and data on systemic oxalosis were identified. Data was analyzed using descriptive statistics, Chi-square tests, Mann-Whitney U tests and Kaplan Meier analyses.

Results

A total of 159 out of 291 (55%) screened PH1 patients were diagnosed with systemic oxalosis. In addition, 110 patients were recorded having no signs of systemic oxalosis at follow-up, however screening was not performed. Sixty-two patients had already developed systemic oxalosis at moment of diagnosis and systemic oxalosis was most often found in patients with ESKD (95%). The eyes, bones and heart are most frequently affected, nevertheless deposits occurred in many organs, as shown by obduction. Fundus photography (n = 16), X-ray (n = 43), and echocardiography (n = 59) are the modalities used most often to screen respectively the eyes, bones and heart. Patients who developed systemic oxalosis had significantly higher upper plasma oxalate levels (median 22 versus 175 umol/L, p<0.001). Furthermore, patients with systemic oxalosis had a significant higher mortality rate compared to patients without systemic oxalosis (48 out of 142 versus 10 out of 212, p<0.001), which difference persisted after correcting for ESKD (p<0.001). Kaplan Meier analysis (Figure 1) showed that pediatric patients with ESKD tended to developed systemic oxalosis more frequently than adults (p<0.001).

Conclusion

This is the first research to systematically study and report systemic oxalosis in patients with primary hyperoxaluria type 1. Systemic oxalosis is prevalent among PH1 patients, especially when ESKD is present, and may lead to significant morbidity and mortality. Patients with systemic oxalosis have a higher mortality rate and pediatric patients may develop systemic oxalosis more frequently than adults. Given the high incidence and possible implications, we would like to make an appeal on screening all patients with systemic oxalosis. Future research should focus on reliable screening modalities for early signs of systemic oxalosis.
#6737 ESTIMATED GLOMERULAR FILTRATION RATE BY FIVE DIFFERING MEASURES, RACE, GENETIC RISK AND PREDICTION OF CARDIOVASCULAR DISEASE AND MORTALITY
Authors: Tang Lei , Zeng Xiaoxi , Fu Ping
Published: June 2023

Background and Aims

Estimated glomerular filtration rate (eGFR), a significant measurement of chronic kidney disease (CKD), is associated with adverse health outcomes in the general population but whether its utility differs by race and genetic risk remains unclear. The current study aims to investigate the performance of CKD staging and risk prediction in cardiovascular disease and mortality based on five eGFR measures among people of different ethnic groups and genetic background.

Method

In this prospective cohort study, we included 431,126 participants from the UK Biobank, deriving hazard ratios and 95% confidence intervals from multivariable adjusted Cox proportional hazards models. C statistic and net reclassification improvement (NRI) were utilized for comparing the predictive benefit of eGFR measures when added to the traditional cardiovascular risk factors.

Results

Over a median of 13.4 (IQR 12.7-14.9) years of follow-up, 27,757 (6.4%) participants died from any cause, of which 3272 (0.8%) died primarily from CVD. 39,522 (9.2%) incident composite CVD hospitalization and 911 (0.2%) ESRD occurred. Two new eGFR equations refitted without race provided lower estimates in Black population but higher in other ethnic backgrounds than the corresponding old ones. The relative risk of adverse outcomes was generally greater in Blacks and participants with low genetic susceptibility to impaired kidney function. The superiority of cystatin C-based eGFR measures in risk prediction did not differ by race and genetic risk.

Conclusion

Eliminating the use of racial categories in eGFR calculation help enhance the access to specialist care and intervention at the early stage of CKD for Black population. Cystatin C-based eGFR measures can be extensively used in risk assessment in clinical practice.
#2499 ALBUMINURIA AND THE RISK OF CANCER: THE STOCKHOLM CREATININE MEASUREMENTS (SCREAM) PROJECT
Authors: Luo Li , Yang Yuanhang , Kieneker Lyanne M , Janse Roemer J , Bosi Alessandro , Mazhar Faizan , de Boer Rudolf A , de Bock Geertruida H , Gansevoort Ron T , Carrero Juan-Jesus
Published: June 2023

Background and Aims

Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. The few studies focusing on albuminuria provide results that vary considerably, probably due to a lack of consideration of eGFR, their limited sample sizes, and that different albuminuria measurement techniques were used. This study therefore aimed to investigate the eGFR independent risk of cancer incidence associated with albuminuria measured as ACR as well as by dipstick in a large Swedish population.

Method

We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer, 250,768 subjects with at least 1 urine albumin-creatinine ratio (ACR) test (primary cohort), and 433,850 subjects with at least 1 dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs, 95% CIs) crude, and additionally adjusted for confounders including baseline eGFR.

Results

During a median follow-up of 4.3 (IQR, 2.0-8.2) years, 21,901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR, 1.23; 95% CI, 1.19-1.28) and 40% (HR, 1.40; 95% CI, 1.31-1.50) higher risk of developing cancer, respectively, when compared to subjects with an ACR ≪30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung, and hematological cancer incidence (all P≪0.05). No significant associations of albuminuria with the incidence of melanoma, breast, and prostate cancers were found. Results were similar in the dipstick albuminuria cohort, and were robust in several sensitivity analyses.

Conclusion

Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung, and hematological cancers.
#2528 APOL1 GENOTYPING AND PROTEINURIC KIDNEY DISEASE IN EUROPE
Authors: Knebelmann Bertrand , Bramham Kate , Mccafferty Kieran , Zaidan Mohamad , Torres Pablo Antonio Urena , Audard Vincent , Boffa Jean Jacques , Powell Thomas , Shahid Nauman , Echeverri Diego , Provenzano Christopher , Bauman John , Zamauskaite Aurelia , Delestre-Levai Irisz , Yang Yuan , Krause Silva , Ferreira Anna Carolina , Egbuna Ogo , Chertow Glenn
Published: June 2023

Background and Aims

Apolipoprotein L1 (APOL1) toxic gain-of-function variants (G1 or G2) are genetic factors driving a broad spectrum of progressive, proteinuric nephropathies referred to as APOL1-mediated kidney disease (AMKD). APOL1 genotyping is not routinely performed in kidney disease care, and prevalence of APOL1 variants among persons with chronic kidney disease (CKD) in Europe is not well known. These variants are common in persons of recent African ancestry. We report interim data of a global study estimating the prevalence of APOL1 genotypes in participants of recent African ancestry and proteinuric CKD, with a focus on data from Europe.

Method

Enrollment in this ongoing study will include up to 2,500 participants across different geographies who are of recent African ancestry and have focal segmental glomerulosclerosis (FSGS) or other proteinuric nondiabetic kidney disease (NDKD). The study includes a single visit during which blood samples are collected from participants to determine their APOL1 genotype using a validated polymerase chain reaction (PCR)-based assay. The percent of participants with two APOL1 variants and percent of participants in each genotype category (e.g., G1/G1, G1/G2, G2/G2) are assessed; genetic counseling services are available to participants, if desired.

Results

This interim analysis included 1,256 participants of whom 174 (13.9%) were from Europe. As shown in the table, among the 88 participants with FSGS and 86 participants with proteinuric NDKD, 54 (61.4%) and 32 (37.2%) have two APOL1 variants, respectively.

Conclusion

Our study will generate one of the largest global APOL1 genotyping data sets in participants with proteinuric kidney disease. These data begin to address a critical knowledge gap and highlight the importance of APOL1 genotyping in kidney disease care to identify AMKD, potentially optimize disease management, and enable referral for interventional clinical trials evaluating targeted therapies for AMKD.
#2775 USING A DEEP LEARNING MODEL TO EVALUATE PATHOLOGICAL INJURY OF DIABETIC KIDNEY DISEASE
Authors: Jin Feng Yong , Huang Yang , Huang Yu Lin , Zhao Qing , Wu Qin Yi , Ma Kun Ling
Published: June 2023

Background and Aims

Early diagnosis and evaluation play an important role in preventing the progression of diabetic kidney disease (DKD). Renal biopsy is the gold standard of DKD diagnosis. In 2010, the Renal Pathology Society (RPS) developed a consensus classification for DKD, which classifies DKD glomerular lesions and scores for tubulointerstitial lesion. However, as the pathologic heterogeneity of DKD patients and unparallel relationship between pathology features and clinical symptoms, it remains controversial whether is reliable to use RPS classification for renal outcomes prediction. Besides, the inconsistence between pathologists might magnify the gap between prediction and outcome. More reliable methods for DKD pathology assessment are needed. The development of machine learning (ML) algorithms especially convolutional neural networks (CNNs) enables it possible, which can provide automatic and precise analysis for complicated images. Thus, this study aimed to construct a ML-based model to assist and provide automatic decision supports to clinical doctors.

Method

We examined 204 DKD renal biopsied whole-slide images (WSIs) of Periodic Acid Schiff staining from Southeast University Institute of Nephrology whose database came from more than 30 hospital centers. All the WSIs were randomly annotated by three pathologists. We established a consecutive CNNs framework: DKD pathology evaluation system (DPES). It consists of three parts: 1. Based on classic UNet architecture, we developed a segmentation model whose backbone is replaced by ResNet 50 architecture for detecting glomeruli. 2. According to RPS classification, a CNN added with channel attention mechanism is built to discriminate sclerotic glomeruli, glomeruli with K-W node, and glomeruli with mesangial expansion. Through this method, the entire WSIs were divided into RPS grades I-IV. 3. For the analysis of tubulointerstitial lesion, we constructed a segmentation model as previous description to calculate the area of the atrophic tubule and its percentage of the total tubules.

Results

For glomerular assessment, compared with other ML networks, DPES achieved better performance in segmentation for glomeruli (Intersection over Union (IOU): 0.82, Precision: 0.89, Accuracy: 0.91) and tubulointerstitial (atrophy (TA): IOU: 0.9;Precision: 0.94; Accuracy: 0.95; non-tubular atrophy (NT): IOU: 0.84; Precision: 0.90; Accuracy: 0.93). Interstitial fibrosis and tubular atrophy (IFTA) from network compared with three pathologists didn’t show statistically difference.

Conclusion

Our findings demonstrated that the DPES achieved similar performance with three pathologists. It suggests that machine learning algorithms can generate reliable results and provide more supports for clinical decision.
#2819 BIOELECTRICAL IMPEDANCE PARAMETERS AS EARLIER PREDICTORS OF FRAILTY AND FUNCTIONAL IMPAIRMENT IN ECUADORIAN HEMODIALYSIS PATIENTS
Authors: Juan Santacruz , Armijo Kevin , Arévalo Vanessa , Santacruz Angel , Vásquez Ana , Gavilanes Verónica
Published: June 2023

Background and Aims

Functional impairment (FI) and frailty are highly prevalent in hemodialysis (HD) population and are associated with morbidity/mortality. Bioelectrical impedance analysis (BIA) is a non-invasive test to assess body composition and water distribution. Few is known about BIA parameters as predictors of frailty and FI. The aim of the study was to study BIA parameters associated with frailty and FI and to determine their prevalence among Ecuadorian adult patients on HD.

Method

Observational-prospective-cohort study performed between January/2021 and October/2022 in one HD center. Clinical Frailty Scale (CFS) score ≥4 determined frailty diagnosis, and FI was labeled with Barthel Index (BI) <70. ROC curves were performed to determine the best cut-off for Phase Angle (PA) and Extracellular/Intracellular water ratio (E/I ratio) to predict frailty and FI (Fig. A). Pearson's correlation coefficient between PA and E/I ratio with CFS score and FI were calculated (Fig. B), and univariate logistic regression analysis was performed.

Results

A total of 115 patients were included. Baseline characteristics, findings and variables with statistical significance are resumed in Table 1. The AUC of PA to predict non-frailty patients and non-functional impaired patients was 0.87 (p<0.001) and 0. 79 (p<0.001), which corresponds to PA values of ≥4.35° and ≥3.62°, respectively. The AUC for E/I ratio to predict frailty and FI was 0.83 (p<0.0001) and 0.74 (p<0.0001), which corresponds to E/I ratio values of ≥0.97 and ≥0.99 respectively. Moderate-to-strong-negative correlation was found between PA and CFS score (r = −0.61, p<0.0001) as well as moderate-positive correlation between PA and BI (r = −0.47, p<0.0001) was found. Moderate-positive correlation between E/I ratio and CFS score (r = −0.56, p<0.0001) and moderate-negative correlation between E/I ratio with BI (r = −0.45, p<0.0001) were found. Univariate logistic regression analysis revealed that factors independently associated with frailty were age (OR = 1.04, CI-95%:1.02-1.06) and PA (≥4.35°) (OR = 0.17, CI-95%:0.11-0.24).

Conclusion

PA and E/I ratio obtained in a single non-invasive BIA can be used as screening tool, with sensitivity >80%, for earlier prediction of FI and frailty in HD patients allowing premature identification and intervention in this group of patients.
#3193 PERFORMANCE OF THE RACE-FREE CKD-EPI CREATININE-BASED EGFR EQUATION IN A DANISH COHORT WITH CHROMIUM-51-EDTA CLEARANCE MEASUREMENTS
Authors: Munch Philip Vestergaard , Heide-Jørgensen Uffe , Jensen Simon Kok , Birn Henrik , Vestergaard Søren , Frøkiær Jørgen , Sørensen Henrik Toft , Christiansen Christian Fynbo
Published: June 2023

Background and Aims

In 2021, an updated estimated glomerular filtration rate (eGFR) equation based on serum creatinine, age, and sex, but without a coefficient for race (CKD-EPI21) was developed and recommended for clinical use. However, the performance of the new equation has yet to be examined among specific groups such as patients with cancer.

Method

We compared the performances of the CKD-EPI21 equation and the original creatinine-based eGFR equation assuming non-Black race (CKD-EPI09-NB) in patients ≥18 years of age with measured GFR ascertained by chromium-51-EDTA plasma clearance at Aarhus University Hospital in Denmark during 2010–2018. We examined bias, accuracy, precision (defined as the interquartile range of the absolute bias), and correct classification of chronic kidney disease (CKD) stages (GFR ≥60, 30–59, and <30 ml/min/1.73 m2) using the chromium-51-EDTA clearance as the reference standard. Furthermore, we assessed the performance of the equations in the total cohort while stratifying by CKD stage. We assessed the performance in the total cohort and in cohorts of cancer patients and potential living kidney donors.

Results

In this predominantly White population, the CKD-EPI21 equation performed slightly better than the CKD-EPI09-NB equation, both when examining the total cohort (N = 4,668) and when examining cohorts of cancer patients (N = 3,313) and potential living kidney donors (N = 239). In the total cohort, the CKD-EPI21 equation demonstrated lower median absolute bias (−0.2 versus −4.4 ml/min/1.73 m2), higher accuracy (72% versus 70%) as well as equal precision (25 versus 25 ml/min/1.73 m2) and correct classification of CKD stages (86% versus 85%) when compared with the CKD-EPI09-NB equation. When we stratified by CKD stage, the CKD-EPI09-NB equation performed slightly better than the CKD-EPI21 equation among patients with a GFR < 60 ml/min/1.73 m2.

Conclusion

In a selected cohort of Danish patients with measured GFR, the CKD-EPI21 equation performed slightly better than the CKD-EPI21-NB equation except for patients with a GFR < 60 ml/min/1.73 m2.
#3743 MULTIDIMENSIONAL RISK ASSESSMENT OF KIDNEY ALLOGRAFT REJECTION USING DONOR DERIVED CELL-FREE DNA
Authors: Ursule-Dufait Cindy , Aubert Olivier , Brousse Romain , Gueguen Juliette , Racapé Maud , Legendre Christophe , Anglicheau Dany , Lefaucheur Carmen , Loupy Alexandre
Published: June 2023

Background and Aims

Post-transplantation patient care requires development and validation of non-invasive biomarkers to improve allograft monitoring and prevention from unnecessary and costly biopsies. Reports have suggested the association of donor derived cell-free DNA (dd-cfDNA) with allograft rejection. However, there is no proof of its added value on standard of care in large, unselected and deep phenotyped cohorts.

Method

We enrolled 1134 kidney transplant recipients having concomitant evaluation of allograft histology, anti-HLA DSA and functional parameters between April 2013 and June 2018 in the derivation cohort, representing 1415 biopsies. Dd-cfDNA was measured in plasma at the time of the biopsy. Diagnoses were performed using Banff 2019 criteria. 171 AMR, 34 TCMR and 17 mixed rejections occurred. Parameters associated with rejection were assessed using uni- and multivariable logistic regression. We then developed a risk model using the variables that were independently associated with kidney rejection. The validation cohort comprised 1929 evaluations including 499 evaluations in one Belgian center and 1430 evaluations in nine North American centers.

Results

Higher levels of dd-cfDNA were observed for AMR and TCMR or both compared to other diagnoses (Fig. 1A). Dd-cfDNA incrementally increased with Banff acute lesions without significant increase for chronic lesions. In multivariable analysis, the variables independently associated with rejection were anti-HLA DSA (P<0.0001), dd-cfDNA (P<0.0001), eGFR (P<0.033), proteinuria (P = 0.016), and previous history of rejection (P<0.0001). Dd-cfDNA remained independently associated with kidney allograft rejection in validation cohorts from Belgium (P = 0.0006) and North America (P<0.0001). Discrimination of the model without dd-cfDNA was 0.777 and 0.821 with its inclusion, showing its added value (Fig. 1B). The good discrimination performances of the model with dd-cfDNA were also confirmed in the validation cohorts from Belgium (AUC: 0.815) and North America (AUC: 0.826).

Conclusion

We here demonstrate the independent and added value of dd-cfDNA in addition to conventional features to predict rejection. This first integrative system shows improved performance for patient monitoring and could help physicians in decision-making process.
#3819 THE PROTECTIVE EFFECT OF INTERLEUKIN-1 RECEPTOR ANTAGONIST ON KIDNEY FUNCTION: A MENDELIAN RANDOMIZATION STUDY
Authors: Cho Jeong Min , Joo Kwon Wook , Kim Jung-Hyun , Kim Dong Ki , Park Sehoon
Published: June 2023

Background and Aims

Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation.

Method

We performed two-sample summary-level mendelian randomization (MR) analysis (Fig. 1). Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for eGFR were obtained from CKDGen database. A replication analysis was performed in the independent UK Biobank data. As a main MR analysis, multiplicative random-effect inverse-variance weighed method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighed-median methods, were also implemented.

Results

We tested the causal estimates from nine ILs on eGFR traits. Among ILs, we found that genetically predicted serum IL-1ra level showed consistently significant association (P <0.05) with eGFR, also supported by significant (P <0.05) pleiotropy-robust MR results. Using 20 SNPs (18 of pQTL and 2 of eQTL SNPs), genetically predicted higher serum IL-1ra level was significantly associated (<0.05) with higher eGFR in multiplicative random effect IVW analysis (Fig. 2). In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome (Fig. 3).

Conclusion

These findings support the clinical importance of IL-1 associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1ra.
#3988 MARS – A NOVEL SCORE TO PREDICT THE RISK OF ACUTE KIDNEY INJURY AFTER LIVING DONOR LIVER TRANSPLANT
Authors: Rana Abhyudaysingh , Bansal Shyam , Saraf Neeraj , Choudhary Narendra , Mahapatra Amit , Sethi Sidharth , Soin Arvinder
Published: June 2023

Background and Aims

Acute kidney injury is common in liver transplant recipients with adverse effect on graft and patient outcomes. There are many studies on incidence, risk factors and outcomes of AKI post-LT in deceased donors, there is paucity of data about AKI in living donor liver transplant recipients (LDLT). LDLT is a difficult and prolonged surgery with inherent risk to donors, so it practised in only few centres across the world however there is little data of AKI in living donor liver transplant recipients (LDLT).

Method

This prospective observational study was undertaken to assess incidence, risk factors, patient graft outcomes and to develop a novel prediction model to identify recipients at risk for post-transplant AKI at the earliest possible time point after living donor liver transplantation in a tertiary care large volume centre in northern India.

Results

Incidence of AKI in our study was 31.7% with 13.5% requiring renal replacement therapy. Male gender, history of hepatorenal syndrome, use of intraoperative inotropes (Indicating Post reperfusion injury), MELD score >14, preoperative proteinuria >0.5 gram/day & estimated GFR <90 ml/min/1.73 m2 were significant risk factors for AKI within 1 month post-LDLT in logistic regression model. We devised a risk prediction score (The MARS score) which had a sensitivity of 81.36%, specificity of 88.19%, positive predictive value of 76.9%, negative predictive value of 91.06% and overall accuracy of 86.02% to predict AKI. AKI was associated with longer hospital stay, higher mortality and led to higher occurrence of chronic kidney disease after a median follow up period of 724 (635 – 794) days.

Conclusion

Our risk model (MARS) with an AUC of 0.925 performed better than all previously reported scores in DDLT & LDLT .The variables in our AKI risk prediction are simple to extract and use making it favourable in resource limited settings where access to newer biomarkers of kidney injury is limited. There is a need to apply the score in other cohorts to validate its applicability.
#4216 FEASIBILITY ANALYSIS OF AN ULTRASOUND-GUIDED PLACEMENT OF TUNNELED HEMODIALYSIS CATHETERS
Authors: Kächele Martin , Bettac Lucas , Hofmann Christopher , Herrmann Hannes , Brandt Amelie , Schroeppel Bernd , Schulte-Kemna Lena
Published: June 2023

Background and Aims

Radiographic fluoroscopy (RAD) is the current standard for placement of tunneled central venous catheters (CVC) for hemodialysis. RAD requires structural and personnel infrastructure and exposes the patient to ionizing radiation. Here, we investigate the feasibility of solely ultrasound-guided placement of tunneled central venous dialysis catheters.

Method

We evaluated prospectively collected single center data of 134 consecutive patients who underwent CVC implantation between 2020 and 2021 regarding feasibility, safety, and catheter function. We used the inset guidewire to visualize the position of the catheter tip. In the case of inadequate visibility by ultrasound, we additionally used intracardiac ECG recording or agitated saline. A total of 1844 catheter days were assessed. As a historical control, we analyzed the position of 50 CVCs placed by RAD. Optimal CVC position was defined to be in between the cavoatrial junction (CAJ) and the right atrium (RA), according to the guidelines.

Results

The catheters were placed on the right side in 117 (87%) cases. The primary success rate for optimal position and function was 97,7% (n = 131). Placement solely by ultrasound was possible in 130 (97%) cases. There were no immediate procedure-associated complications related to the new technique. Effective blood flow averaged 292 +/- 39 ml/min. Of all ultrasound-placed catheters, 6% were in the vena cava superior (RAD 24%), 70% in the CAJ (RAD 60%), and 24% in the RA (RAD 16%), resulting in a rate of 94% with optimal position.

Conclusion

Placement of CVCs for hemodialysis solely by ultrasound is an effective and safe alternative to fluoroscopy-assisted placement.
#5349 CYCLIN D1 AMELIORATES ACUTE KIDNEY INJURY BY IMPROVING FATTY ACID OXIDATION VIA AMPK PATHWAY
Authors: Huang Yuliang , Chen Junzhe , Shao Xiaofei , Li Jinxiang , Tang Ying
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a life-threatening condition. The absence of oxygen during the acute ischemic phase would disturb energy metabolism and cause kidney tubular epithelial cell damage. Fatty Acid Oxidation (FAO) is the main source of energy production of renal proximal tubular epithelial cells. Timely promoting FAO, increasing supplies of energy, and promoting cell proliferation are essential to improve kidney injury, but there is no clinically recognized effective treatment for this. Cyclin D1(CCND1), a member of the cell cycle family, plays a vital role in cell proliferation. Our previous study found that CCND1 improved AKI accompanied with increased fatty acid oxidation. Therefore, we investigated the role and molecular basis for CCND1 involvement in fatty acid oxidation of AKI.

Method

CCND1 was evaluated in AKI in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6J mice (wild type). The protective role of CCND1 in AKI was investigated in a mouse model of ischemia-reperfusion AKI treated by ultrasound-microbubble-mediated kidney-specifically transferring CCND1-expressing plasmids in male C57BL/6J mice (wild type). Eight-week-old male C57BL/6J mice (wild type) were subjected to bilateral renal artery occlusion for 30min followed by 24h of reperfusion. We evaluated FAO, proliferation, and autophagy in vitro and in vivo. In addition, we evaluated the concentrations of blood urea nitrogen and creatinine, evaluated kidney ultrastructure and so on.

Results

In vivo studies had shown that activation of CCND1 can prevent AKI-induced lipid accumulation, kidney tubule injury and kidney function declined after ischemia-reperfusion injury. Compared to test control, the treatment significantly (p < 0.05) lowered the concentrations of blood urea nitrogen and creatinine. Kidney specific overexpression of CCND1 promoted FAO, promoted proliferation and reduced apoptosis. Mechanistically, CCND1 activated the AMPK pathway, which increased the expression of phosphorylation AMP activated protein kinase (p-AMPK) and upregulated FAO. On the contrary, inhibiting the expression of CCND1 exacerbated impairment of FAO and disturbed energy metabolism.

Conclusion

Thus, CCND1 improved FAO and reduced lipid accumulation via active AMPK pathway in kidney proximal tubular epithelial cells (PTECs). Hence, reconstruction of the expression of CCND1 may be a novel therapeutic strategy for treating AKI.
#5485 CHRONIC KIDNEY DISEASE NOR STROMAL CELL-DERIVED FACTOR 1Α PEPTIDE (SDF-1A) BIO-FUNCTIONALIZATION ALTER RODENT VASCULAR IN SITU TISSUE FORMATION
Authors: Krebber Merle , Bessseling Paul , Driessen Rob , Söntjens Serge , Janssen Henk , Teraa Martin , Fledderus Joost , Dankers Patricia , Bouten Carlijn , Verhaar Marianne
Published: June 2023

Background and Aims

The systemic pro-inflammatory environment of chronic kidney disease (CKD) could influence neo-tissue formation of in situ tissue engineered vascular access grafts. Here, we studied in-graft tissue formation and inflammation in a rat CKD model. Moreover, we explored graft bio-functionalization with stromal cell-derived factor 1α peptides (SDF-1α), a progenitor cell chemotactic which may improve cell engraftment.

Method

Pristine or SDF-1α bio-functionalized vascular grafts (1,2 mm ID, 2 cm length, 250–300 μm wall thickness) were created from biodegradable, polycarbonate-bisurea (PC-BU) electrospun meshes. Abdominal aorta interposition grafts were implanted in female Sprague Dawley rats (n = 53) that underwent sham surgery or CKD induction by 5/6th nephrectomy. Explanations and analyses were performed after two (n = 25) or twelve (n = 9) weeks.

Results

At two weeks, survival and graft patency were 100%. Explant cellularity and collagen content were not significantly different between sham and CKD rats and were not influenced by SDF-1α. Endothelial cell coverage (RECA+) and smooth muscle cell presence (αSMA+) were visually similar irrespective of disease or bio-functionalization. Elastin+ (p = 0,11), pan-(CD68+, p = 0,08) and anti-inflammatory macrophage (CD163+, p = 0,52) surface area, as well as (anti-)inflammatory gene expression were not significantly different between groups. The twelve-week CKD-group was taken out of experiment prematurely due to rapid disease progression. In addition, preliminary death due to vascular rupture occurred in four animals (n = 2 pristine and n = 2 SDF-1α) in the twelve-week sham animals. While patent, all remaining sham explants at twelve weeks (n = 9) showed severe vascular dilatation and calcifications (Von Kossa+). No differences in inflammatory and neo-tissue markers were found between twelve-week sham pristine and SDF-1α grafts or between explants over time.

Conclusion

CKD did not significantly alter inflammation or tissue formation of in situ tissue engineered vascular grafts. Additionally, SDF-1α bio-functionalization did not significantly alter cell engraftment or tissue formation. Mechanical stability of the graft appears to be the primary driver of neo-tissue formation. Future emphasis on in vitro to in vivo translation should be on the fine balance between tissue formation on one hand and fiber resorption on the other hand.
#5551 THE TROPONIN LEVEL AND ITS INFLUENCE ON RENAL AND CARDIOVASCULAR EFFECTS IN RENAL TRANSPLANT RECIPIENTS
Authors: Heleniak Zbigniew , Naik Marcel , Osmanodja Bilgin , Eleftheriadis Georgios , Schmidt Danilo , Debska-Slizien Alicja , Halleck Fabian , Budde Klemens
Published: June 2023

Background and Aims

Cardiovascular (CV) morbidity and mortality are highly prevalent in renal transplant recipients (RTRs). As such, assessments of CV status using troponin concentrations could help to identify patients at risk for death or CV events and as a predictor for deterioration of graft function. The aim of the study was to investigate the biomarker troponin for the prediction of adverse renal and cardiovascular outcomes in stable RTRs.

Method

305 stable RTRs with a median age of 53 years, (60.6% male) transplanted between 1994 and 2018 were enrolled in the study. General characteristics are shown in Table 1. At baseline, troponin, NT-pro BNP, carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) were measured. Troponin was measured during a routine baseline visit in stable RTR without cardiac symptoms. The median troponin concentration (11 ng/l) was used as cut-off. Patients were divided into two groups high (≥11 ng/l) and low (<11 ng/l) troponin and followed for 54 months. During this time CV events (stroke, myocardial infarction, peripheral artery thrombosis) death, graft loss and deterioration of renal graft function (increasing creatinine ≥30%) or proteinuria (urine protein creatinine ratio UPCR ≥500 mg/g) were monitored.

Results

At baseline, significant differences were observed between groups in terms of creatinine, eGFR, troponin, UPCR, PP, and PWV. In the group with baseline troponin ≥11ng/l, more patients had coronary artery disease/peripheral obliterans artery disease (CAD/POAD), heart failure (HF), and diabetes. Baseline troponin correlated only weakly with age (R = 0.47), cfPWV (R = 0.41), eGFR (R = −0.52). During follow-up, patients with high troponin experienced more frequently an increase in creatinine ≥30% (32.9% vs 13%), doubling creatinine (11.2% vs 3.1%), an increase in UPCR (22.4% vs 9.2%), graft loss (16.1% vs 1,8%), death (13.3% vs 0%), and CV events (6.3% vs 4.9%).

Conclusion

1. Age, arterial stiffness, and eGFR only have a weakly impact on troponin in stable RTR. 2. Higher troponin is associated with poor outcomes and might be useful not only for the identification of patients with high-risk CV events but also for the deterioration of allograft function.
#5611 ASSOCIATION BETWEEN LOSS OF IMMUNE CHECKPOINT PROGRAMMED CELL DEATH PROTEIN 1 AND ACTIVE ANCA-ASSOCIATED RENAL VASCULITIS
Authors: Tampe Björn
Published: June 2023

Background and Aims

Immune checkpoint inhibitors (ICIs) have made an important contribution on the survival of patients with certain cancers. ICIs interrupt co-inhibitory signalling pathways mediated by programmed cell death protein 1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen (CTLA-4) that result in the elimination of cancer cells by stimulating the immune system. Immune-related adverse events have also been described and attributed to an enhanced immune system activation. Recent observations have suggested dysregulation of immune checkpoints in active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Therefore, we here aimed to analyze abundance of immune checkpoint molecules PD-1/PD-L1 and its implications in ANCA-associated renal vasculitis.

Method

We here analyzed intrarenal PD-1 and PD-L1 by immunostaining in a total number of 15 kidney biopsies with ANCA-associated renal vasculitis in correlation with glomerular and tubulointer-stitial lesions. For independent validation, publicly available datasets were analyzed for PD-1 expression (encoded by PDCD1).

Results

We here observed a predominant tubulointerstitial expression of PD-1 that is decreased in ANCA-associated renal vasculitis. Moreover, loss of tubulointerstitial PD-1 correlated with active ANCA-associated renal vasculitis. Consistent to the observed association with active glomerular and tubulointerstitial lesions, we identified that interstitial PD-1 correlated with tubular and/or glomerular PD-L1 positivity. Finally, PD-1 was associated with decreased local synthesis of complement factor B. Interestingly, we did not observe a correlation between PD-1 and complement C5 or its C5a receptor. Combined with our observations, this may implicate a link between im-paired PD-1/PD-L1 signalling, complement factor B, and active ANCA-associated renal vasculitis.

Conclusion

These findings could be of relevance because experimental data have already been described that PD-1 agonism can be used therapeutically to attenuate autoimmunity in multiple disease models. Furthermore, targeted therapy against complement C5/C5a receptor and factor B are both available and currently evolving in the treatment of AAV. Therefore, this pilot study expands our current knowledge and describes a potential interplay between immune checkpoints and the alternative complement pathway in active ANCA-associated renal vasculitis.
#6522 CYSTATIN C-BASED ESTIMATED GLOMERULAR FILTRATION RATE AND RISK OF STROKE IN THE GENERAL POPULATION
Authors: Xiao Fei , Liao Jinlan
Published: June 2023

Background and Aims

Previous results on the association between estimated glomerular filtration rate (eGFR) and strokes are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and possibly has biased the association with stroke risks. We hypothesized that eGFR was independently associated with the risk of stroke in the general population. Herein, we investigated the linear and nonlinear associations of the cystatin C-based eGFR (eGFRcys) with the risk of total stroke and its subtypes in the UK Biobank participants.

Method

In this cohort study, we included 462,307 UK Biobank participants (94.5% Whites, 54% women, aged 56±8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were the incidences of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias.

Results

During averaged follow-up of 10.11 years, 4,427 incident strokes occurred, among which 3,447 were ischemic and 1,163 were hemorrhagic. After adjustment of confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 ml/min/1.73 m2 decrement in eGFRcys were 1.10 (1.06-1.12) for total stroke and 1.11 (1.08-1.15) for ischemic stroke. A similar pattern was observed with eGFRcr although the association was weaker. When either eGFR was below 75 ml/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. However, when eGFRcys was above 75 ml/min/1.73 m2, the risks did not significantly differ but seemingly decreased as eGFRcys exceeded 105 ml/min/1.73 m2. A U-shape relationship was witnessed if eGFRcr was used instead. There was null association between eGFR and hemorrhagic stroke.

Conclusion

The risks of total stroke and ischemic stroke increased exponentially when the eGFR fell below 75 ml/min/1.73 m2.
#6667 EFFECTIVENESS AND SAFETY OF APIXABAN, RIVAROXABAN AND WARFARIN IN PATIENTS WITH ADVANCED CKD AND ATRIAL FIBRILLATION: A NATIONWIDE US COHORT STUDY
Authors: Fu Edouard , Desai Rishi , Paik Julie , Kim Dae , Zhang Yichi , Mastrorilli Julianna , Cervone Alexander , Lin Joshua
Published: June 2023

Background and Aims

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced CKD or on dialysis are lacking. We compared the effectiveness and safety of apixaban, rivaroxaban and warfarin in patients with AF and CKD stages 3 to 5, including those on dialysis.

Method

We conducted a new-user, active-comparator, cohort study using data from two nationwide U.S. claims databases, Medicare and Optum Clinformatics® Data Mart Database (01/01/2013–03/31/2022). We included patients with nonvalvular AF and CKD who newly initiated warfarin vs. apixaban (N = 169,702), or rivaroxaban vs. apixaban (N = 129,396). CKD stages were determined based on a validated claims-based algorithm. The primary outcome was a composite of ischemic stroke or major bleeding to represent the net benefit of treatment. Secondary outcomes included the individual components of the primary outcome and all-cause death. We used 1:1 propensity score matching to adjust for 80 confounders. Adjusted hazard ratios (aHRs) were estimated with Cox regression analyses and absolute rate differences per 1000 person years (aRDs) with generalized linear regression in the propensity score matched sample.

Results

Compared with apixaban, warfarin and rivaroxaban were associated with a higher risk of the composite endpoint, regardless of CKD stage. Comparing warfarin vs. apixaban, the aHRs were 1.5 (1.3–1.6), 1.4 (1.0–1.9) and 1.3 (1.2–1.5) for CKD stages 3, 4, and 5/dialysis, respectively (p-value for heterogeneity 0.31); corresponding aRDs were 27.2 (20.4, 30.0), 32.9 (−4.3, 70.2), and 36.9 (21.7, 52.2) (p-value for heterogeneity 0.51). Comparing rivaroxaban vs. apixaban, the aHRs were 1.5 (1.4–1.7), 1.7 (1.4–2.2) and 1.3 (0.9–1.8) (p-value for heterogeneity 0.38) for CKD stages 3, 4, and 5/dialysis, respectively; corresponding aRDs were 27.1 (12.3, 41.8), 53.2 (29.8, 76.6), and 20.7 (−28.9, 70.2) (p-value for heterogeneity 0.16). The higher rate of the primary endpoint for warfarin and rivaroxaban was driven by a higher risk of bleeding, with similar rates of ischemic stroke.

Conclusion

In patients with AF and CKD, apixaban was associated with a net benefit compared with rivaroxaban or warfarin, which was primarily driven by lower rates of bleeding. Benefits were consistent across severity of CKD.