Multicenter Study Research Articles

#1043 Metabolomics and proteomics study on kidney function post-liver transplantation

Abstract Background and Aims Hepatorenal syndrome (HRS) is a serious complication characterized by kidney dysfunction in patients with advanced liver disease. The pathophysiology of HRS is poorly understood and involves a combination of hemodynamic, circulatory, inflammatory, and hormonal factors. While some patients with HRS restore kidney function after liver transplantation (LT), others continue to have impaired kidney function. Understanding the mechanisms associated with persistent kidney dysfunction is essential for developing effective treatments and stratifying patients for combined liver-kidney transplantation versus LT only. Method We analyzed serum samples from 10 patients of the multicenter prospective study (INAID CTOT14). Five of them had no HRS and maintained an eGFR > 50 ml/min post-LT. One patient with HRS recovered kidney function post-LT. Four patients with HRS failed to regain kidney function at one- and two-months post-LT (eGFR < 30 ml/min). We categorized the five patients without HRS and one patient with recovered eGFR as Normal Kidney Function (NKF) group and the other four patients as Impaired Kidney Function (IKF) group. Serum samples were collected at one (visit 1) and two months (visit 2) post-LT and stored at −80°C until analysis. Both untargeted metabolomics and proteomics analysis were conducted using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS) on Agilent® Q-TOF 6546. Data was analyzed by Agilent® Qualitative Workflow 10, Agilent® Profinder 10, MetaboAnalyst (V6.0), and Spectrum Mill MS software. Results A total of 150 metabolites were identified by LC-MS/MS based metabolomics. Principal component analysis (PCA) did not show significant differences between visit 1 and visit 2 samples (Fig. 1A). Therefore, visit 1 and visit 2 samples were analyzed together. With 12 samples in NKF and 8 samples in IKF group, the PCA score plot showed distinct clustering of the two groups (Fig. 1B). Volcano plot analysis was conducted to analyze metabolite differences between NKF and IKF. P-values were calculated using a Student's t-test, and differential metabolites were identified with a P-value cut-off of < .05 and a fold change > 2.0. The result revealed 37 downregulated and 13 upregulated metabolites when comparing NKF and IKF (Fig. 1C). Notably, creatinine was among the downregulated metabolites in the NKF group, validating the accuracy of our analysis. Untargeted proteomics analysis was also performed on all 20 samples. Using a P-value cut-off of .05 and a fold change >1.25, 43 proteins were found to be upregulated, and four proteins to be downregulated when comparing NKF to IKF. Fig. 2A lists the top 10 regulated proteins, with beta-2-microglobulin as the most significantly changed. Reactome® pathway analysis of these 47 proteins highlighted potential impacts on various biological pathways (Fig. 2B), providing potential valuable insights into the molecular alterations associated with kidney function post-LT. Conclusion Our comprehensive metabolomics and proteomics study characterized the molecular alterations associated with kidney function post-LT. The identified metabolites and proteins may provide valuable insights for understanding persistent kidney damage. Future research is warranted to confirm and correlate these findings with clinical outcomes, enhancing the applicability and significance of our results in the broader context of HRS and LT.

Follow-up computed tomography and unexpected hemostasis in non-operative management of pediatric blunt liver and spleen injury.

While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

The safety and clinical outcomes of endovascular treatment versus microsurgical clipping of ruptured anterior communicating artery aneurysms: a 2-year follow-up, multicenter, observational study

Background and objectiveCurrent data on the optimal treatment modality for ruptured anterior communicating artery (AComA) aneurysms are limited. We conducted this multicenter retrospective study to evaluate the safety and clinical outcomes of endovascular treatment (EVT) and microsurgical clipping (MC) for the treatment of ruptured AComA patients.MethodsPatients with ruptured AComA aneurysms were screened from the Chinese Multicenter Cerebral Aneurysm Database. Propensity score matching (PSM) was used to adjust for baseline characteristic imbalances between the EVT and MC groups. The safety outcomes included total procedural complications, procedure-related morbidity/death and remedial procedure for complication. The primary clinical outcome was 2-year functional independence measured by the modified Rankin scale (mRS) score.ResultsThe analysis included 893 patients with ruptured AComA aneurysms (EVT: 549; MC: 346). PSM yielded 275 pairs of patients in the EVT and MC cohorts for comparison. Decompressive craniectomy being more prevalent in the MC group (19.3% vs. 1.5%, p < 0.001). Safety data revealed a lower rate of total procedural complications (odds ratio [OR] = 0.62, 95% CI 0.39–0.99; p = 0.044) in the EVT group and similar rates of procedure-related morbidity/death (OR = 0.91, 95% CI 0.48–1.73; p = 0.880) and remedial procedure for complication (OR = 1.35, 95% CI 0.51–3.69, p = 0.657) between the groups. Compared with that of MC patients, EVT patients had a greater likelihood of functional independence (mRS score 0–2) at discharge (OR = 1.68, 95% CI 1.14–2.50; p = 0.008) and at 2 years (OR = 1.89, 95% CI 1.20–3.00; p = 0.005), a lower incidence of 2-year all-cause mortality (OR = 0.54, 95% CI 0.31–0.93; p = 0.023) and a similar rate of retreatment (OR = 1.00, 95% CI 0.23–4.40; p = 1.000).ConclusionClinical outcomes after treatment for ruptured AComA aneurysms appear to be superior to those after treatment with MC, with fewer overall procedure-related complications and no increase in the retreatment rate. Additional studies in other countries are needed to verify these findings.

#1038 Progressive multifocal leukoencephalopathy in kidney transplant recipients: a retrospective multicenter nationwide cohort study

Abstract Background and Aims Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infectious disease affecting the central nervous system caused by JC virus. While extensively studied in patients with HIV infection, haematological malignancies, or undergoing immunotherapies, there is a lack of data concerning kidney transplant recipients (KTRs). Method We performed a retrospective, multicentric, nationwide study. We contacted all kidney transplantation centres in France to gather all cases of PML. We obtained the count of patients with a functional kidney allograft using the registry of the French regulatory agency. Results We collected 24 cases of PML. Between 2012 and 2021, the estimated minimal nationwide incidence of PML was 4.7/100 000 patient-years. The median duration from kidney transplantation to PML was 88 months (interquartile range: 9 to 355). Eight patients (33%) had been exposed to belatacept (median exposure: 18.5 months). Almost all patients underwent reduction or withdrawal of immunosuppressive drug doses and 13 (54%) received a specific treatment. Fifteen patients (65%) died within one year after diagnosis. Conclusion In this nationwide study, PML incidence rate in KTRs was at least 4.7/100 000 patient-years resulting in an alarming 65% mortality rate within a year despite immunosuppressants doses decrease or withdrawal. Further investigations are warranted to demonstrate the efficacy of specific treatments and confirm a potential association between belatacept exposure and PML occurrence, as suggested by our study.

#475 Association between hospital-acquired acute kidney injury and the risk of kidney cancer

Abstract Background and Aims The effects of hospital-acquired acute kidney injury (HA-AKI) on kidney cancer remain unclear. The study aimed to investigate the association between HA-AKI and kidney cancer by a large multicenter cohort study. Method The real-world cohort study included Chinese adults with at least two serum creatinine (SCr) tests within 7 days during hospitalization from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥26.5 μmol/l increase in serum creatinine concentration within 48 hours or a ≥50% increase over the baseline within 7 days. The primary outcome was a new diagnosis of kidney cancer, while the secondary outcomes included death attributed to kidney cancer and new diagnoses of other cancers of the urinary system. The Cox proportional hazard model was employed for analyses. Results Of the 342861 patients (median age, 57.06 [43.68, 68.54] yr; men, 179096 [52.2%]), 9337 patients experienced HA-AKI. During a mean follow-up of 2.03 years, 195 (0.57‰) patients with a new diagnosis of kidney cancer were detected. After multivariable adjustment, HA-AKI was significantly associated with a higher risk of kidney cancer (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.37-4.17, P = 0.003) and kidney cancer-specific death (adjusted HR, 3.19; 95% CI, 1.90-5.37, P < 0.001). We also found that relationships between HA-AKI and cancers of the urinary system, excluding kidney cancer, such as bladder cancer, prostate cancer, were not statistically significant. Conclusion HA-AKI was significantly associated with increased risk of kidney cancer and death attributed to kidney cancer. Our findings highlight the importance of monitoring HA-AKI patients for early detection of kidney cancer.

#691 Validation of a prognostic model for adverse events in advanced chronic kidney disease in the Chinese population

Abstract Background and Aims Currently, the Grams model has been developed to estimate risks of adverse events among advanced chronic kidney disease (CKD) patients in western populations. Its utility is noteworthy as it predicts multiple adverse events within a single model while taking competing risks into account. While no external validation has been conducted among Asian, especially Chinese population, restricting further practical application and clinical benefits evaluation. Hence, we aimed to validate the performance of Grams model for estimating risks of major adverse events among Chinese CKD population. Method The Grams model was validated in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a multicenter prospective cohort study which involved 39 renal departments of 39 hospitals from 28 cities of 22 provinces in China. Participants with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 during baseline and follow-up were enrolled. The same predictors as those selected in the Gram model were considered, including age, sex, race, history of cardiovascular disease(CVD), smoking status, systolic blood pressure, diabetes mellitus, eGFR, and urine albumin-to-creatinine ratio (uACR). The outcomes included kidney replacement therapy(KRT), CVD and death within 2- and 4- year follow-up periods. The discrimination and calibration of the model were evaluated using the concordance index (C index), the ratio of observed and expected outcomes (O/E ratio), and the calibration curve. The clinical utility of the model was assessed through decision curve analysis. Intercept recalibration was used to update the model. Results Among 1333 included participants (54 (IQR, 43-64) years, 699(52.4%) male), 386(29.0%) developed KRT, 118(8.9%) developed CVD, 88(6.6%) died during the follow-up period. The Grams model showed a moderate to good discrimination for three outcomes, with the C index ranging from 0.656 to 0.720. According to the O/E ratios and calibration curves, the calibration for KRT was relatively accurate, but the model overestimated the predicted probability of CVD and death. Intercept recalibration led to closer alignment of observed and predicted risks. Decision curve analyses revealed the superior net benefit of the Grams model in guiding KRT preparation. Conclusion In summary, the Grams model exhibited moderate discrimination for predicting outcomes, with relatively accurate calibration for KRT but an overestimation of predicted probabilities for CVD and death, intercept recalibration improved the calibration of the model. Despite its limitations, the model offered a superior net benefit in guiding KRT preparation, suggesting its potential use in clinical decision-making process. Further investigations are warranted to improve the performance of the Grams model in Chinese population.

#357 Sex differences in the aldosterone-renin system must be taken into account during screening for primary aldosteronism

Abstract Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P < 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P < 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P < 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study

Abstract Background and Aims Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years. Method A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission. Results We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010. Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010. Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high. Conclusion The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

#1426 Association of intradialytic hypertension and mortality in a cohort of Spanish population

Abstract Background and Aims Intradialytic hypertension (IH) has been identified as an independent mortality risk factor in hemodialysis (HD) patients. The are a lack of a standardized definition of (IH). Recently, a definition of IH ≥30% of baseline sessions with an increase in pre-to post-HD systolic blood pressure (SBP) of ≥10 mmHg had the highest adjusted risk of mortality, compared with other threshold-based definitions (Singh AT, et al. Hypertension 2022;79:855–62) in American population. The aim of these study is to evaluate this definition of IH in our Spanish population. Method We conduct a retrospective multicenter non-interventional study in a Spanish cohort of patients receiving HD (3 sessions PER week) between 1-July 2021 and 30-June 2023 in Fresenius Medical Care Spain. Pre-post-HD SBP, HD parameters and blood test data were averaged over the 90-day exposure period from 1-April-2021 to 30-Jun- 2021. Cox models were fit to examine the association of ID ≥10 mmHg with all-cause mortality in the univariate and multivariate model adjusted for potential confounding variables. Results 3221 patients met the inclusion criteria, 59.6% men, median age 74 years. The mean of SBP pre HD systolic during the exposure period was 140.6 ± 21 mmHg. The mean follow-up was 22 months. 1620 (50.3%) met the definition of IH,379 (22.4%) of patients with IH died during the follow-up period, compared with 302 of 1587 (19%) individuals who did not meet criteria for IH. In the cox multivariate model, patients with IH, had a significant association with mortality HR: 1.19 [1.01-1.41]) p < 0.05 in a model adjusted for age, Charlson Index, weight loss, vintage, ultrafiltration, vascular access, OL-HDF and malnutrition, among others (Table 1). Conclusion Patients with IH (defined as ≥30% of baseline sessions with an increase in pre-to post-HD systolic blood pressure of ≥10 mmHg) have been associated with all-cause mortality (HR 1.19 [1.01-1.41]) in Spanish HD population, similar to previous studies in the American population.

#1934 Association between transient AKI and all-cause mortality in critically ill patients according to baseline BUN/SCr ratio and diuretics use

Abstract Background and Aims Previous studies have yielded inconsistent results regarding the prognosis of transient acute kidney injury (AKI). We aimed to assess the risk of mortality and kidney outcomes in critically ill patients with transient AKI according to BUN/SCr ratio (BCR) level and diuretics treatment at baseline. Method We conducted a multicentre retrospective cohort study of critically ill patients, including 131,034 patients from China (CRDS) and 9,778 patients from US (MIMIC-IV) spanning from 2012 to 2021. Transient AKI was defined as AKI that recovered within two days. Study outcomes included one-year all-cause mortality and the occurrence of major adverse kidney events (MAKE). The associations between transient AKI and study outcomes were compared in patients stratified by BCR level and diuretics use at baseline. Results Of 140,812 eligible patients, 3,863 were diagnosed with AKI according to KDIGO criteria and classified as having transient AKI. In patients with a baseline BCR level ≤ 20 (N = 79,883), transient AKI was associated with 42% and 58% increased risk of mortality and MAKE, respectively, compared to those without AKI. However, these associations were not significant in those with a BCR level > 20 (N = 60,929) (P for interaction < 0.05). Similar modified effects of diuretics on the outcomes of transient AKI were also observed. The associations of transient AKI with mortality and MAKE were both significantly different in patients with (N = 26,140) or without (N = 114,672) diuretics treatment before AKI (P for interaction < 0.05). Conclusion The effects of transient AKI on mortality and kidney outcomes in critically ill patients were modified by the BCR level and diuretics use before AKI.

#1067 The impact of hemodialysis (HD) versus hemodiafiltration (HDF) on the effect of intradialytic exercise: a multicentre cohort study

Abstract Background and Aims Diminished physical function in HD patients is a critical issue, necessitating strategic approaches to enhance the efficacy of exercise therapy. The differential impacts of HD and HDF on solute clearance, albumin loss, uremic conditions, and malnutrition could influence the success of exercise interventions. Presently, empirical evidence for this is lacking. This investigation explores how HD and HDF modalities influence the efficacy of exercise therapy administered during dialysis sessions. Method This study encompassed intradialytic resistance exercises, involving 414 patients with end-stage renal disease across 10 centers. Participants were voluntarily enlisted in an exercise regimen during their dialysis sessions. The intradialytic regimen comprised stretching and four types of resistance exercises utilizing elastic tubes, conducted thrice weekly over six months. Parameters such as 10-meter walking speed, knee extensor muscle strength, serum albumin levels (Alb), normalized protein catabolic rate (nPCR), and Creatinine Generation Rate (%CGR) were assessed pre-and post-intervention. Statistical analysis included propensity score matching to adjust for baseline characteristics, segregating patients into HD and HDF cohorts. Changes in the aforementioned indicators before and after intervention (Δ) were calculated. Analytical methods included paired t-tests for within-group comparisons and independent t-tests for between-group comparisons of Δ values. A 5% risk threshold was established for statistical significance. Ethical clearance was obtained from the Seirei Christopher University Ethics Committee. Results A propensity score matching yielded 70 matched pairs. There were no significant differences in baseline subject characteristics after propensity score matching. Within-group analyses in the HD group revealed significant improvements in 10-meter walking speed (1.42 ± 0.41→1.60 ± 0.46 m/s, p = 0.000), knee extensor strength (44.3 ± 14.7→49.6 ± 13.8%, p = 0.000), and a reduction in Kt/V (1.69 ± 0.32→1.64 ± 0.32, p = 0.006) after six months. The HDF group significantly enhanced 10-meter walking speed (1.54 ± 0.40→1.72 ± 0.40, p = 0.000), knee extensor muscle strength (51.7 ± 17.1→57.4 ± 17.7%, p = 0.000), nPCR (0.88 ± 0.15→0.94 ± 0.18, p = 0.009), and %CGR (106.3 ± 23.2→112.9 ± 25.2, p = 0.002) (pre to post value, respectively). There are no significant differences in other variables between pre- and post-values in each group. Comparative analysis between groups demonstrated a significantly lower ΔAlb (HD 0.04 ± 0.24 HDF −0.05 ± 0.27, p = 0.045)and a higher 7, p =0(HD 1.47 ± 18.2 HDF 6.65 ± 17.2, p = 0.004)in the HDF group compared to the HD group. Conclusion The study demonstrated a notable HDF group improvement in %CGR, an indicator of muscle mass, despite a decrease in albumin levels. This suggests that albumin loss due to HDF minimally affects the augmentation of physical function. The findings suggest integrating exercise therapy with HDF may positively influence protein consumption and muscle mass enhancement.

Prospective Application of the Erythrocyte Sedimentation Rate (ESR) as a Possible Inflammatory Marker in Feline Patients

The application of the erythrocyte sedimentation rate (ESR) in feline medicine is currently unavailable, while in canine medicine it has been rediscovered due to the introduction of an automated ESR device. Our aims were to (1) define the reference interval (RI) of the ESR in healthy cats, (2) evaluate the ESR values between healthy and ill cats, (3) evaluate relationships between the ESR and some inflammatory markers, and (4) assess ESR changes in different durations of illness (acute, chronic, or acute-on-chronic). A prospective multicentric cohort study on 200 client-owned cats: 57 healthy cats and 143 ill cats for the other aims. Healthy cats were blood donors, or young cats underwent desexing procedures. Ill cats with full clinical medical records, hematobiochemical profiles, and diagnostic procedures to reach a final diagnosis were included. The ESR was performed with MINI-PET using the same K3-EDTA tubes used for CBC, with no additional sample required. The total leukocyte count (WBC), neutrophil-to-lymphocyte ratio (NLR), fibrinogen, serum amyloid A, and albumin/globulin ratio (A/G) were concurrently measured. Based on the clinical presentation and the final diagnosis, cats were classified as having the following: acute, chronic, and acute-on-chronic conditions. The RI of the ESR ranged between 1 and 23 mm/h. Ill cats showed a significantly higher ESR (median 29 mm/h; range 12–46 mm/h) than healthy cats (median 10 mm/h; range 1–12 mm/h; p<0.0001). The ESR was positively correlated only with fibrinogen (p<0.001; r = 0.43). Cats with acute-on-chronic diseases had the highest ESR (median 47 mm/h; range 35–56 mm/h) compared with acute (median 16 mm/h; range 14–42 mm/h; p=0.003) and chronic cats (median 14 mm/h; range 10–31 mm/h; p<0.0001). Although further studies are needed, the ESR could be a useful ancillary inflammatory marker in cats, specifically in cats with acute diseases, with or without an underlying chronic condition.

#1008 Prognostic impact of low skeletal muscle quality on 3-year mortality in initial-dialysis patients

Abstract Background and Aims Myosteatosis represents the infiltration of fat into the skeletal muscle in the early stages of sarcopenia, and has been suggested to be associated with adverse outcomes in patients undergoing dialysis. Skeletal muscle density (SMD) determined by computed tomography (CT) is commonly used to assess myosteatosis, but SMD is affected by contrast resulting in inaccurate measurements. Recently, indices for muscle quality measurements determined by muscle area have been developed. Thus, We aimed to investigate the relationship between a novel muscle area index and mortality in initial-dialysis patients and analyse variables related to myosteatosis using the cutoff values. Method This 3-year multicentric retrospective study enrolled a total of 782 initial-dialysis patients from four centres between 2014 and 2019 in China. SMD skeletal muscular area (SMA) normal attenuation muscle area (NAMA) intermuscular adipose tissue area (IMAT) was measured and skeletal muscle index (SMI) total attenuation muscle area (TAMA) NAMA/TAMA index was calculated on CT images at the level of the first lumbar vertebra. The relationship between NAMA/TAMA index and all-cause and cardiac death outcomes was analyzed. And the sex-specific optimal cut-off values of L1-NAMA/TAMA index were determined in relation to all-cause mortality. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors for death. Results A total of 782 patients were enrolled. The optimal cut-off values of NAMA/TAMA index were 48.76 for males and 58.02 for females. Pearson's correlation coefficient between L1-NAMA/TAMA index and L1 SMD was 0.589 (P < 0.001), no significant association between L1-NAMA/TAMA index and L1 SMI was observed (P > 0.05), similarly, no significant association between L1 SMD and L1 SMI (P > 0.05). Multivariate regression analysis revealed that the low L1-NAMA/TAMA index group had lower risks of all-cause death (hazard ratio 0.988; 95% confidence interval 0.977–0.999, P = 0.041) and cardiac death (hazard ratio 3.74; 95% confidence interval 1.43–9.79, P = 0.007). Conclusion Our findings demonstrate that L1-NAMA/TAMA index acquired via CT scan is of great prognostic value on all-cause and cardiac death in patients undergoing initial-dialysis.

#1573 Effects of haemodialysis coupled with hemadsorption on uremic toxins removal, oxidative stress and cellular death.

Abstract Background and Aims The retention of middle-molecules and Protein Bound Uraemic Toxins (PBUT) in dialysis patients are directly linked to specific clinical complications such as anaemia, inflammation and cardiovascular disease leading to increased mortality. These toxins, not adequately cleared by current dialysis techniques, could be removed by adsorption as demonstrated in numerous studies on dialysis patients. Furthermore, in dialysis patients there's an increased inflammation and oxidative stress only partially attenuated by biocompatibility of newly developed membraned. This pathologic inflammatory response lead to tissue damage and cellular death. A particular form of programmed cellular death involving red blood cells is called Eryptosis and is detectable as changes in the morphology and in the shape of human erythrocytes. The aim of this study was to assess the safety of dialysis coupled with hemadsorption (HA+HD) in terms of biocompatibility and efficacy in terms of removal of middle-molecules and PBUTs. Method This was a preliminary analysis of a multicentre observational study that evaluated 4 dialysis session focusing on 7 chronic dialysis patients of our dialysis centre. Patients were treated with HA+HD with HA130 cartridge (Jafron) only in the early-week dialysis session and then returned to their usual prescription. Blood samples were taken before and after dialysis session in order to measure Eryptosis as a marker of biocompatibility and few uremic toxins to assess the efficacy of the treatment by using Removal Ratio. Eryptototic RBCs were identified by FS (cell volume dimension) and FITC_AnnexinV-binding (Beckman Coulter, Brea, CA, USA) using Navios Flow Cytometer (Beckman Coulter, Brea, CA, USA). A minimum 100.000 events were collected on each sample. Statistical analysis was performed using the SPSS Software package. A p-value of <0.05 was considered statistically significant. Results This study was carried out on 7 patients (4 women) with a mean age of 65.7 ± 11.5 years and a median dialysis vintage of 33 months (IQR 28-51). All patients had AVF with Qb of 330 ml/min. Dialysis length was 210 minutes. We didn't find any differences between Eryptosis values measured before and after dialysis (Table 1), and between different timepoints. We found significant reduction of PTH (pre: 391.5 ng/L, IQR 206.5-602.8 vs post: 162.0 ng/L, IQR 95.0-363.3; p=0.005) and β2-microglobulin (pre: 23.10 mg/L, IQR 22.1-24.1 vs post: 6.72 mg/L, IQR 6.2-8.3; p>0.005) throughout the dialysis session coupled with hemadsorption (Fig. 1). Conclusion In this preliminary analysis, we found that the association of Dialysis with Hemadsorption allows a great removal of middle molecular-weight uremic toxins without compromise biocompatibility and thus represent a better treatment option in patients with high retention of these toxins.

#2155 Evaluating the health-related quality of life of patients undergoing haemodialysis: highlights from a multicentric nationwide study

Abstract Background and Aims Haemodialysis (HD) represents the most common renal replacement therapy for end-stage renal disease worldwide. Despite recent advances in HD the health-related quality of life (HRQoL) should be monitored in conjunction with clinical variables to optimize a comprehensive treatment. Method From June to July 2022, all patients from 47 clinics were included. Among other key relevant clinical variables, HRQoL was assessed by using the Kidney Disease Quality of Life Short Form (KDQOL-SF™ 1.3).It`s generic part is summarised in the physical component summary (PCS) and mental component summary (MCS). The specific part evaluates 11 domains: symptom/problem list; effects of kidney disease on daily life; burden of kidney disease; work status; cognitive function; quality of social interactions; sexual function; sleep; social support; dialysis staff encouragement; and patient satisfaction. All scores range from 0 (worst) to 100 (best). To ensure comparability of results, mean ± SD values are outlined, even though non-parametric tests were used to test associations. Results A total of 3,595 patients (67.3% male) completed the KDQOL (out of 4259 HD patients treated during study period). Most of them (67.18%) were over 60yo of age, and 65.67% had a severe comorbidity index score. In addition, 50.54% had a native AV fistula and only 3.92% were incident HD. PCS scores reported were higher in over 75yo (47.68 ± 10.63) rather than normative population (40.16 ± 11.62), indicating an overall good physical function. However, MCS values (33.17 ± 9.36) were indicative of substantial impact. Gender differences were noted across almost all disease-specific and generic domains (all p < 0.05). Severe comorbidity scores were associated with lower scores in certain renal specific domains and MCS. Finally, incident HD patients reported lower satisfaction and poorer perceived overall health (p-values = 0.001). Conclusion Although PCS scores reported were reasonable, a remarkable impact on mental health was found. Moreover, a differential impact of patient's HRQoL was captured based on gender and other variables highlighting the need of individualised evaluation and management of HD patients.

Early impact of nirsevimab on ambulatory all-cause bronchiolitis: a prospective multicentric surveillance study in France.

After implementation of nirsevimab in 2023 in France as compared with 2022-2023, we found a 52.7%, 95% CI [46.4-58.9]) decrease in all-cause bronchiolitis in children <3 months with the lowest number of bronchiolitis cases in this population since 2017.

#443 LEVIL evaluates the impact of HDx on HR-QoL and symptoms, including durability-of-effect and variability

Abstract Background and Aims Current hemodialysis (HD), utilizing conventional high-flux dialyzers, is handicapped by clearance limitations (larger-sized uremic toxins), which contribute to poor health-related quality-of-life (HR-QoL) and symptom-burden. Recent international consensus and guideline-setting efforts have explicitly prioritized identification and management of symptoms and subjective experience, whilst also acknowledging the lack of tools available to fully appreciate and continuously monitor these challenges. This study aimed to utilize dynamic patient-reported-outcome-measurement tool (PROM), London Evaluation of Illness (LEVIL-developed in-house), to iteratively interrogate patient-experience and to confirm previously reported HR-QoL benefits of the use of expanded hemodialysis (HDx) using medium cut-off dialyzer (extending the spectrum of uremic toxins being addressed). Furthermore, this study aimed to extend appreciation of effects on patient subjective experience to include durability-of-effects, variability of symptom-measures and impact of HDx withdrawal. Methods We conducted a multi-centre interventional study in 47 patients established on conventional thrice weekly centre-based HD in Ontario, Canada. Study protocol was 15-months in length with five phases 1) one-month observation (high-flux-HD), 2) three-months HDx 3) two-month wash-out (high-flux-HD), 4) six-months HDx, 5) three-month wash-out (high-flux-HD). HR-QoL and symptom-burden were evaluated using LEVIL throughout study. Results HDx-therapy improved HR-QoL [p 0.0006 (19% from baseline)] and a variety of symptoms including general wellbeing [p 0.005 (23%)], energy [p 0.004 (33%)], sleep-quality [p 0.001 (33%)], pruritus [0.003 (30%)], pain [p 0.01 (19%)], restless leg syndrome [p 0.0006 (15%)], mood [p 0.02 (12%)], appetite [ p 0.03 (9%)], breathlessness [p 0.001 (9%)], and HD-recovery [p 0.004 (26%)]. Response was more pronounced in those with poorer HR-QoL and higher symptom-burden. Improvements were durable over time with continued use with less symptom-variability (range 10-35% improvement). Improvements diminished gradually with return to high-flux-HD. The drivers of poor HR-QoL were largely general-wellbeing, energy, sleep-quality, pruritus, and bodily pain. Conclusion Use of a dynamic PROM effectively allowed appreciation of HR-QoL burden in HD-patients. Use of HDx-therapy results in improved patient subjective outcomes that are durable and associated with significantly lower variation in important symptom-domains than patients experience with receiving conventional high-flux-HD.

#2293 Cardiac autonomic neuropathy: an independent risk factor for renal decline in diabetic kidney disease

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the UK and worldwide. Due to its unpredictability and incurable nature, novel risk factors associated with incidence and progression of DKD need to be identified. One such factor is cardiac autonomic neuropathy (CAN). Many studies over last 30 years had demonstrated a significant relationship between CAN and incidence and progression of DKD using estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) as end points. However, no prospective studies have looked into relationship between CAN diagnosed by gold standard cardiac autonomic reflex tests (CARTs) and DKD with different prognostic risks as per KDIGO classification. The aim of the study is to examine this relationship further. Method Data from 91 participants (type 1 and type 2 DM) with eGFR &amp;gt;30 ml/min/1.73 m2 who underwent assessment for CAN using CARTs as per O'Brien's and Ewing's criteria during baseline visits performed between 2007 and 2010 were collected. Additional participants (n = 113) were also recruited in 2021 as part of iBEAt study which is an EU-funded, multi-centre renal imaging study to identify novel biomarkers for DKD. Data analysis for 204 participants in total was performed for this study. CAN was defined as 2 or more abnormal CARTs out of 5 (Table 1). The level of prognostic risk was calculated based on eGFR (G1-G5) and UACR (A1-A3), following KDIGO risk table from 2012 CKD guidelines. eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation and UACR was assessed by early morning urine sample. Participants were categorised as follow: low risk, moderate risk and high risk. Due to limited numbers of participants with G3 in eGFR, we have combined ‘high risk’ and ‘very high risk’ into one group. CAN was divided into 2 groups—with and without CAN. Differences in proportions were examined using chi-square test. The association between baseline CAN and risk of renal decline was assessed using multinominal logistic regression adjusted for baseline age, HbA1c, ACEi/ARBs use, retinopathy status, total cholesterol and triglyceride. If significant differences were found, individual groups were compared by Bonferroni post hoc test. All analyses were performed in SPSS (version 29.0) and correlations were considered significant if p &amp;lt; 0.05. Results We analysed data of 204 participants (130 T1DM, 74 T2DM), 44.6% (n = 91) of them were women, mean (SD) age at baseline visit was 51 (15.7) years, eGFR 82.6 (13) ml/min/1.73 m2, UACR 5.2 (21.8) mg/mmol, duration of diabetes at baseline 19.7 (12.3) years and 36.8% had hypertension. Baseline eGFR and UACR were available for 198 and 193 participants respectively. Of these, 42.9% (85/198) had G1, 47.5 (94/198) had G2 and 9.6 (19/198) had G3. For UACR, 80.8% (156/193) had A1, 15.5% (30/193) had A2 and 3.6% (7/193) had A3. 53.4% (103/204) of participants had CAN and 46.6% (101/204) had no CAN. A higher proportion of participants was in low prognostic risk category 77.8% (154/198), followed by 13.1% (26/198) with moderate risk and 9.8% (18/198) with high risk for CKD progression. The risk of DKD progression was significantly associated with presence of CAN in multinominal logistic regression analysis (p = 0.020). The presence of CAN was closely related to low risk (95% CI: 1.44 to 22.04, p = 0.013) and moderately increased risk (95% CI: 1.03 to 24.7, p = 0.04). The participants with moderate and high risk had lower eGFR (p &amp;lt; 0.001) and higher UACR with increased risk (p &amp;lt; 0.001) (Table 2). This finding was independent of baseline age, HbA1C, retinopathy, ACEI/ARB use, type of diabetes, cholesterol and triglyceride levels at baseline as measured by logistic regression. Conclusion To our knowledge, this is one of the first studies to examine the relationship between presence of CAN in three stages of prognostic risk in DKD. We demonstrated that presence of CAN was an independent risk factor for decline in renal function in DKD. Further large prospective studies are required to confirm the findings of this study and examine the underlying mechanisms how CAN leads to greater risk of DKD.

#664 Childhood Takayasu arteritis: a multicentre retrospective study

Abstract Background and Aims Takayasu arteritis (TA) is a rare, large vessel vasculitis affecting mainly the aorta and its major branches. Data on paediatric TA (pTA) is very scarce. The aim of this study was to characterize clinical presentation, therapy and outcome of pTA in a global study population. Method We conducted an international multicentre retrospective observational study of children diagnosed with pTA. Inclusion criteria were an age of less than 18 years at initial presentation in the year 2000 or more recently. Clinical data were collected from patients’ charts by the treating paediatric rheumatologist or nephrologist; data were fully anonymised for analysis purposes. Follow-up data was collected up to 2 years after diagnosis. Results 198 patients from 20 countries were included (76% female). The median age at disease onset was 12 years. Arterial hypertension (67%), a difference in pulses between limbs (65%) and fatigue (66%) were the most common symptoms at presentation. The gastrointestinal system was the second most affected organ system. The median eGFR (estimated glomerular filtration rate) at baseline was 105 ml/min/1.73 m2. Renal artery stenosis was documented in 58% of all patients and in 37% there was need for an invasive renovascular procedure. In 25 of 32 (78%) patients who had either a positron emission tomography–magnetic resonance imaging (PET-MRI) or PET-computed tomography (CT) there was evidence of active inflammation mainly of the aorta. 67% of all patients showed thickened wall abnormalities and 31% had arterial dilatations in a major vessel on any one or more anatomical imaging modality such as ultrasound, CT or MRI. Immunosuppressive treatment was primarily steroids, cyclophosphamide and methotrexate, 37% of all patients were treated with monoclonal antibodies of which 65% received an anti-tumor necrosis factor (TNF) antibody, 31% an anti-Interleukin 6 (IL-6) antibody and 4% an anti-B-cell antibody. Dialysis was necessary in 7% and one patient underwent kidney transplantation. Seven patient deaths (4%) were documented at the most recent follow-up. The renal function after two years was median eGFR 102 ml/min/1.73 m2, with 67% showing normal function, 31% presenting with chronic kidney disease (CKD) stage 1, 1% with stage 2, 1% with stage 3 and no patients showed stages 4 and 5. A quarter of the patients (27%) were still symptomatic at the 2-year follow-up. The median systolic blood pressure was 117 (interquartile range 107–125) mmHg. 64% of all patients still had antihypertensive treatment, and 87% were still on immunosuppressive therapy. Conclusion Our study represents the largest paediatric cohort of children diagnosed with Takayasu arteritis. Several organ systems were involved at onset and the clinical spectrum was highly variable. We will in our further analyses in more detail describe the outcome in relation to presenting symptoms and treatment.