Longitudinal Analysis Research Articles

Victory-in-freedom: Ukraine’s democratic resilience in the face of war

The article offers a rare systematic analysis of political attitudes in societies experiencing massive military invasions using statistical analysis of two original surveys conducted by the Ukraine National Academy of Sciences Institute of Sociology — a panel survey tracking the same respondents in three waves (N = 329, November 2021, June-July 2022, and June 2023) and an additional larger survey (N = 869, June 2023). Despite devastating suffering, Ukrainians’ support for democracy as a political system and for freedom of speech have stayed remarkably resilient over this time period. Cross-sectional (multiple ordinary least squares regression) and longitudinal (linear mixed-effects model regression) tests, as well as supplementary focus group conversations in all of Ukraine’s macro-regions, show that this democratic resilience is grounded in the victory-in-freedom synergy — a widespread sense of shared sacrifice that drives determination to win the war and restore Ukraine’s territorial integrity. In particular, we found a clearer understanding of the importance of political freedoms and fighting for victory among individuals who experienced loss and trauma and a strong appreciation across Ukraine’s society that victory is vital to preserve democracy. Survey data also demonstrates that democracy support has become more intrinsic to Ukrainian national identity and that the initial surge of democracy support among Ukrainians in the face of Russia’s invasion has been more than a short-term rallying-round-the-flag. In combination, these factors explain the Ukrainians’ sustained, spirited resilience in the face Russia’s mass savage invasion over more than a two-year period. Moreover, support for democratic ideals doesn’t mean Ukrainians write a blank check of trust to their government. Longitudinal analysis indicates that as the war progressed, and hardship persisted respondents held their democratic institutions accountable. At the same time, the results of our study indicate that sustaining this resilience would require not only battlefield successes, but also accountable governance, countering Russia’s media impacts, and sustaining family incomes. Our findings contribute to the literature on war and democracy by showing the importance of considering both the external context (war duration and impacts and the aggressor state type) and the mobilization of national identity in the face of aggression.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

Evolution of Child and Youth Mental Health in the Context of the COVID-19 Pandemic: A Longitudinal Analysis

Background: The COVID-19 pandemic generated uncertainty and disruption among the child and adolescent population. Multiple studies have documented a worsening of mental health following the pandemic. The main objective of this longitudinal study is to analyze the short-, medium-, and long-term evolution of the overall functioning of children and adolescents treated by a child and adolescent mental health team in the context of the COVID-19 pandemic. Methods: 420 patients aged 3 to 18 were assessed using the Global Assessment of Functioning (GAF) scale at three time points: during the lockdown, three months later, and three years later. Differences based on gender, diagnosis, and time were analyzed. Results: A significant improvement was observed in the short-term (three months) and long-term (three years) compared to the lockdown period. This improvement was maintained in all diagnostic subgroups except for mixed cases (severe mental pathology), which showed the least improvement. No significant differences were found between males and females. Conclusions: The child and adolescent population showed a greater capacity for adaptation to the lockdown than expected. Family support, decreased stress, and therapeutic intervention appear to have played an important role in improving mental health.

OrganoIDNet: a deep learning tool for identification of therapeutic effects in PDAC organoid-PBMC co-cultures from time-resolved imaging data.

Pancreatic Ductal Adenocarcinoma (PDAC) remains a challenging disease due to its complex biology and aggressive behavior with an urgent need for efficient therapeutic strategies. To assess therapy response, pre-clinical PDAC organoid-based models in combination with accurate real-time monitoring are required. We established stable live-imaging organoid/peripheral blood mononuclear cells (PBMCs) co-cultures and introduced OrganoIDNet, a deep-learning-based algorithm, capable of analyzing bright-field images of murine and human patient-derived PDAC organoids acquired with live-cell imaging. We investigated the response to the chemotherapy gemcitabine in PDAC organoids and the PD-L1 inhibitor Atezolizumab, cultured with or without HLA-matched PBMCs over time. Results obtained with OrganoIDNet were validated with the endpoint proliferation assay CellTiter-Glo. Live cell imaging in combination with OrganoIDNet accurately detected size-specific drug responses of organoids to gemcitabine over time, showing that large organoids were more prone to cytotoxic effects. This approach also allowed distinguishing between healthy and unhealthy status and measuring eccentricity as organoids' reaction to therapy. Furthermore, imaging of a new organoids/PBMCs sandwich-based co-culture enabled longitudinal analysis of organoid responses to Atezolizumab, showing an increased potency of PBMCs tumor-killing in an organoid-individual manner when Atezolizumab was added. Optimized PDAC organoid imaging analyzed by OrganoIDNet represents a platform capable of accurately detecting organoid responses to standard PDAC chemotherapy over time. Moreover, organoid/immune cell co-cultures allow monitoring of organoid responses to immunotherapy, offering dynamic insights into treatment behavior within a co-culture setting with PBMCs. This setup holds promise for real-time assessment of immunotherapeutic effects in individual patient-derived PDAC organoids.

Effect of Argentine tango sessions on total physical activity time in patients with chronic inflammatory rheumatism: randomized, controlled, pilot study.

The aim of this study was to evaluate the effect of an Argentine Tango (AT) program on total physical activity (PA) time in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Prospective randomized controlled pilot study with two parallel groups. Participants were randomized 1:1 to attend a 24-week AT program from baseline to month6 for the immediate tango group (ITG) and a 12-week AT program from month3 to month6 for the wait-list control group (WLCG). Total PA time was measured at baseline, month3, and month6 using the Global Physical Activity Questionnaire-ONAPS and an accelerometer. Twenty-seven participants (15 RA and 12 SpA) were enrolled in the study. Thirteen participants in the WLCG and 14 in the ITG. At month3, there was no significant difference in the total PA time between the two groups. Longitudinal analyses revealed no significant difference between the two groups regarding PA, sedentary, fatigue, anxiety, depression, balance, physical performance, pain, and stress. However, body appreciation improved significantly in the ITG compared with the WLCG. Both groups showed improved physical abilities at 6month, including improvements in the 6-min walk test and timed up and go test. The ITG also reported reduced pain at months 3 and 6, while the WLCG exhibited improved balance at month 6. Although the AT program did not significantly increase total PA time in patients with CIR, it positively impacted body appreciation and physical abilities suggesting its potential as a complementary therapy. Key Points • Body appreciation significantly improved after a 24-week AT program, emphasizing the positive impact of dance on self-perception. • Both groups exhibited improved physical abilities at month 6, indicating a positive influence on participants' overall mobility and functional capacity. • The 24-week AT group reported reduced pain at months 3 and 6, and the 12-week AT group exhibited improved balance at month 6.

Longitudinal analysis of epigenome-wide DNA methylation reveals novel loci associated with BMI change in East Asians.

Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations. This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years. We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change. This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.

Trend in prevalence, associated risk factors, and longitudinal outcomes of sarcopenia in China: A national cohort study.

To estimate the contemporary trend in the prevalence of sarcopenia and evaluate its risk factors and the longitudinal associations with multiple chronic conditions and mortality among Chinese middle-aged and older adults. This was a nationwide, prospective cohort study using data from the China Health and Retirement Longitudinal Study. The definition of sarcopenia was based on the Asian Working Group for Sarcopenia 2019 algorithm. In the cross-sectional analysis, we estimated the trend in the weighted prevalence of sarcopenia from 2011 to 2015 and examined the associated risk factors for sarcopenia severity in 2011. In the longitudinal analysis, we assessed the longitudinal associations between sarcopenia and 14 chronic conditions and mortality during a 9-year follow-up. The weighted prevalence of sarcopenia remained consistently high in the overall population from 2011 (15.9%, 95% confidence intervals [CI]: 15.1, 16.6) to 2015 (15.0%, 95% CI: 14.3, 15.6; p for trend=0.075). A range of risk factors were independently associated with the severity of sarcopenia, including older age, female sex, lower socioeconomic status, smoking status, malnutrition, and several chronic conditions. Possible sarcopenic and sarcopenic individuals had higher odds of several chronic conditions (i.e., heart disease, chronic lung disease, and memory-related disease) and increased risks of mortality (possible sarcopenia: odds ratios (OR): 1.66, 95% CI: 1.37, 2.00; sarcopenia: OR: 1.69, 95% CI: 1.36, 2.11) in 9 years of follow-up. The prevalence of sarcopenia remained consistently high in the investigated population. Various risk factors were significantly associated with a higher prevalence of sarcopenia. Sarcopenic individuals had higher odds of several chronic conditions and increased risks of mortality, highlighting that the urgent need for dedicated efforts to improve the management of sarcopenic patients.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. There was a significant association of LE8 with death and cancer risk, especially for the young population.

Predicting higher child BMI z-score and obesity incidence in Malaysia: a longitudinal analysis of a dynamic cohort study.

To target public health obesity prevention, we need to predict who might become obese i.e. predictors of increasing Body Mass Index (BMI) or obesity incidence. Predictors of incidence may be distinct from more well-studied predictors of prevalence, therefore we explored parent, child and sociodemographic predictors of child/adolescent BMI z-score and obesity incidence over 5 years in Malaysia. The South East Asia Community Observatory in Segamat, Malaysia, provided longitudinal data on children and their parents (n = 1767). Children were aged 6-14 years at baseline (2013-14) and followed up 5 years later. Linear multilevel models estimated associations with child BMI z-score at follow-up, adjusting for baseline BMI z-score and potential confounders. Predictors included parent cardiometabolic health (overweight/obesity, central obesity, hypertension, hyperglycaemia), and socio-demographics (ethnicity, employment, education). Logistic multilevel models explored predictors of obesity incidence. Higher baseline BMI z-score predicted higher follow-up BMI z-score both in childhood to late adolescence (0.60; 95% CI: 0.55, 0.65) and early to late adolescence (0.76; 95% CI: 0.70, 0.82). There was inconsistent evidence of association between child BMI z-score at follow-up with parent cardiometabolic risk factors independent of baseline child BMI z-score. For example, maternal obesity, but not overweight, predicted a higher BMI z-score in childhood to early adolescence (overweight: 0.16; 95% CI: -0.03, 0.36, obesity: 0.41; 95% CI: 0.20, 0.61), and paternal overweight, but not obesity, predicted a higher BMI z-score in early to late adolescence (overweight: 0.22; 95% CI: 0.01, 0.43, obesity: 0.16; 95% CI: -0.10, 0.41). Parental obesity consistently predicted five-year obesity incidence in early to late adolescence, but not childhood to early adolescence. An adolescent without obesity at baseline with parents with obesity, had 3-4 times greater odds of developing obesity during follow-up (incidence OR = 3.38 (95% CI: 1.14-9.98, mother) and OR = 4.37 (95% CI 1.34-14.27, father) respectively). Having a higher BMI z-score at baseline was a stronger predictor of a higher BMI z-score at follow-up than any parental or sociodemographic factor. Targeting prevention efforts based on parent or sociodemographic factors is unwarranted but early childhood remains a key period for universal obesity prevention.

Why circadian rhythmicity matters: associations between sleep irregularity and mental health conditions during the Covid-19 health crisis

Objective: To assess the association between sleep irregularity, anxiety, and depression while controlling for other sleep dimensions and using a longitudinal design. Methods: Longitudinal cohort study which started in April 2020 during the first French lockdown in the general population. Follow-up questionnaires were completed in June 2020, a period without lockdown measures. Participants were asked about their sleep (regularity, duration, timing, complaints) and their anxiety (General Anxiety Disorder-7) and depressive (Patient Health Questionnaire-9) symptoms. Results: A total of 3745 participants were included (mean age: 28.9 years) with 2945 women (78.6%). At baseline, 38.1% (1428) of participants reported irregular sleep timing, 23.8% (891) anxiety and 28.9% (1081) depressive symptoms. In cross-sectional analyses, irregular sleep timing was associated with a 2.5-fold higher likelihood of anxiety and a 4-fold higher likelihood of depressive symptoms compared to regular sleepers. Associations were not explained by the other sleep dimensions and persisted in a longitudinal analysis, with irregular sleep timing at baseline being associated with anxiety (OR = 3.27[1.58-6.76]) and depressive symptoms (OR = 3.45[1.66-7.19]) during follow-up. Conclusion: The results show a strong association between sleep irregularity and mental health. Furthers studies are needed to explore how sleep regularity could promote good mental health in non-clinical populations.

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge

BackgroundSARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients.MethodsIn a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin).ResultsOut of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups.ConclusionsThe study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Longitudinal plasma proteomic analysis of 1117 hospitalized patients with COVID-19 identifies features associated with severity and outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by highly heterogeneous manifestations ranging from asymptomatic cases to death for still incompletely understood reasons. As part of the IMmunoPhenotyping Assessment in a COVID-19 Cohort study, we mapped the plasma proteomes of 1117 hospitalized patients with COVID-19 from 15 hospitals across the United States. Up to six samples were collected within ~28 days of hospitalization resulting in one of the largest COVID-19 plasma proteomics cohorts with 2934 samples. Using perchloric acid to deplete the most abundant plasma proteins allowed for detecting 2910 proteins. Our findings show that increased levels of neutrophil extracellular trap and heart damage markers are associated with fatal outcomes. Our analysis also identified prognostic biomarkers for worsening severity and death. Our comprehensive longitudinal plasma proteomics study, involving 1117 participants and 2934 samples, allowed for testing the generalizability of the findings of many previous COVID-19 plasma proteomics studies using much smaller cohorts.

Associations between dietary diversity and high sensitive C-reactive protein among Japanese workers: findings of a cross-sectional and longitudinal study.

To clarify the association between dietary diversity and inflammatory status in Japanese workers. Of 1,460 men and women aged 20-64 years in 2010 (baseline), those who were followed-up at least once between 2011 and 2018 were included in this study; 1,433 participants and 745 participants were included in the cross-sectional and longitudinal analyses, respectively. Dietary intake was assessed using a food frequency questionnaire at baseline, and the dietary diversity score was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). High-sensitivity C-reactive protein (hs-CRP) was taken to indicate inflammatory status at the baseline and follow-up surveys. In the cross-sectional analysis using baseline data, a generalized linear model was used to calculate adjusted means and 95% confidence intervals (CIs) for hs-CRP according to the QUANTIDD score. In the longitudinal analysis, generalized estimating equations were used to calculate the adjusted mean (95% CI) for hs-CRP in follow-up according to the QUANTIDD score at baseline. In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups. These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.

#2938 The association between serum iron biomarkers and health-related quality of life in patients undergoing dialysis

Abstract Background and Aims Anemia is a very common complication of chronic kidney disease, affecting most patients undergoing dialysis. Iron deficiency, one of the causes of anemia, is generally a second consideration in the management of anemia. Nephrologists mainly focus on the correction of hemoglobin, often prescribing iron therapy for this indication only. However, iron has important physiological functions besides erythropoiesis. Conversely, iron overload can lead to oxidative stress and cellular damage. Therefore, nephrologists have been cautious to prescribe iron therapy to patients with already high serum iron levels. This caution has been underscored by studies linking higher levels of iron to increased mortality. Unfortunately, evidence is lacking regarding the impact of iron on important patient-reported outcomes like health-related quality of life (HRQoL). Therefore, the aim of this study is to explore the association between serum iron biomarkers, health-related quality of life (HRQoL) and the presence of anemia-related symptoms over a one-year period in patients undergoing dialysis. Method Data were obtained from the multicenter, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). Adult patients new to dialysis were included, and had a baseline and follow-up assessments at 3, 6 and 12 months, with measurements of serum iron biomarkers ferritin and transferrin saturation (TSAT). HRQoL, encompassing physical and mental HRQoL, was measured using the validated 12-item Short Form Health Survey (SF12, summary scores ranging from 0 to 100). The presence of anemia-related symptoms: fatigue, shortness of breath, restless legs and muscle cramps were assessed using the Dialysis Symptom Index. Patients were categorized into 4 groups depending on their ferritin levels (μg/L): &amp;lt;200, 200–500 (reference), &amp;gt;500–700 and &amp;gt;700, and into 3 groups depending on their TSAT levels (%) at baseline: &amp;lt;20, 20–39 (reference), and ≥40. Longitudinal analyses were conducted using sequential conditional mean models to adjust for time-independent and time-varying confounding. All analyses captured the overall association over a one-year follow-up. Results We included 1069 patients, of whom 76% started hemodialysis, the median age was 68, 66% were male, and 32% were receiving iron therapy. Over a one-year follow-up, patients with ferritin &amp;lt;200 μg/L had similar physical HRQoL (MD=0.5 ; 95% CI –2.4 to 3.3 ) and mental HRQoL (MD=0.04 ; 95% CI -2.0 - 2.0) compared to the reference group with ferritin between 200–500 μg/L. Patients with ferritin between 501–700 μg/L also had a similar physical and mental HRQoL mental HRQoL compared to those with ferritin between 200-500 μg/L. This was also found for patients with ferritin above 700 μg/L (Fig. 1). Similarly, patients with TSAT levels below 20% and patients with TSAT levels ≥40% had comparable physical and mental HRQoL compared the reference group of patients with a TSAT between 20-39% (Fig. 2). For the secondary objectives, we found no significant differences in the anemia-related symptoms fatigue, shortness of breath, restless legs, or muscle cramps between patients with various levels of ferritin nor between the various TSAT groups. Conclusion We found that dialysis patients with higher or lower levels of ferritin or TSAT did not have a significantly different physical or mental HRQoL over a one year-follow up after starting dialysis. Similarly, no significant differences were found in the presence of fatigue, shortness of breath, restless legs, and muscle cramps between patients with these higher or lower levels of serum iron markers. And although iron levels do have impact on clinical outcomes such as mortality, these results suggest that they do not influence patient reported outcomes such as physical and mental HRQoL.

#620 Remaining life expectancy of Korean hemodialysis patients: how much longer can they live?

Abstract Background and Aims Hemodialysis (HD) patients have a higher mortality rate compared to general population. However, no study has investigated life expectancy in Korean HD patients so far. Therefore, this study aimed to calculate the remaining life expectancy among Korean maintenance HD patients and compare it to those of general population as well as HD patients from other countries. Method Baseline data were retrieved from HD quality assessment data from October to December 2015. Among the total number of patients who were alive at the beginning of 2016 (20,537 men and 14,404 women), a total of 22,439 (12,848 men and 9,591 women) were still alive at the end of 2021 while 12,502 (7,689 men and 4,813 women) were deceased during 6 years of follow-up. We used the life table method to calculate the expected remaining years of life in two-year increments. Results The mean age of the patients was 60.5 ± 12.4 years, and 58.7% were male. The average duration of HD was 5.63 ± 5.11 years. The most common cause of end-stage kidney disease was diabetes mellitus (42.0%), followed by hypertension (27.1%) and glomerulonephritis (10.9%). The remaining life expectancy for 60-year-old patients were 11.64 years for men and 14.64 years for women. The average remaining lifetimes of the HD population were only about a half of the general population (Fig.). Diabetic patients demonstrated shorter life expectancy compared to the patients with hypertension or glomerulonephritis. The remaining life expectancy of Korean HD patients was similar to that of Japanese and was almost double that of HD patients in Western countries such as Europe and United States. Conclusion HD population showed shorter life expectancy compared to the general population. Asian HD population seemed to demonstrate better patient survival compared to other countries. Longitudinal analysis should be warranted to analyze the effect of advanced dialysis technology upon improved survival rate among HD population.

#2573 Effect of pre-transplant dialysis modalities on delayed graft function

Abstract Background and Aims Kidney transplantation represents the optimal treatment for end-stage renal disease patients. Benefits and disadvantages of different pre-transplant dialysis modalities and the effects on post-transplant outcomes remain unclear, but many authors identify peritoneal dialysis (PD) such a “bridge” versus renal transplantation. Method We analyze a consecutive series of 249 renal transplanted patients (mean age 48 ± 11 years, 67% males) between June 1998 and February 2016 with a low prevalence of comorbidities (diabetes 2%, hypertension 31%, previous cardiovascular events 2%). The median follow-up was 136 months [interquartile range (IR) 91-197 months]. The pre-transplant treatment was hemodialysis (HD) in 215 patients (86%) and peritoneal dialysis (PD) in the remaining 34 patients (14%). The majority of patients received a cadaveric donor organ (219 patients, 88%). Results Delayed Graft Function (DGF) was registered in 151 patients (61%). Analyzing pre-transplant dialysis treatment, 15 patients about 34 (44%) on pre-transplant PD had DGF vs 136/215 (63%) on pre-transplant HD treatment (P = 0.03). Remarkable PD patients were older (48 ± 12 years) than HD patients (44 ± 11 years), but this difference did not rise statistical significance (P = 0.09); similarly the prevalence of living donors were higher (13%) in the group of HD patients respect the group of PD patients (9%, P = 0.53). In a longitudinal analysis the last estimated Glomerular Filtration Rate (eGFR) was lower in patients with DGF (44, IR 19-66 ml/min/1,73 m2) vs patients without DGF (48, IR 35-73 ml/min/1,73 m2, P = 0.04), but no substantial differences was noted at the end of observation in eGFR between the two groups of patients (HD, eGFR 45, IR 25-68 ml/min/1,73 m2 vs PD eGFR 46, IR 24-67 ml/min/1,73 m2). Conclusion Results of this study confirm that PD treatment can be considered an optimal “bridge” for renal transplantation probably because peculiar characteristic of this dialysis modality (such us long term preserved diuresis and residual renal function respect HD patients) impacts positively on recovery of renal function. Further study need to clarify these controversial points.

#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) &amp;gt;75th percentile, 2) 75th-25th percentile, and 3) &amp;lt;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 (&amp;gt;75th, 75th-25th, and &amp;lt;25th groups, respectively). Results in the cross-section analysis (T1) &amp;lt;25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the &amp;gt;75th group. Using hierarchical linear modeling, the &amp;lt;25th exhibited higher cf-PWV than the &amp;gt;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 &amp;lt;25th group compared to the &amp;gt;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 &amp;lt;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.

#1832 Unraveling enteric peritonitis risk factors: the role of nutrition

Abstract Background and Aims Malnutrition estimated to have a prevalence of 30-50% among peritoneal dialysis (PD) patients. It independently correlates with increased patient morbidity and a lower technique survival, and it is exacerbated by protein loss through peritoneal fluid. Enteric-origin peritonitis in PD patients represents a severe complication also linked to elevated morbidity, hospitalizations, and inferior technique survival. However, the association between both is not well established. This study aims to analyze malnutrition-related as well as general risk factors and their association with peritonitis type (enteric/cutaneous). Method A longitudinal and retrospective observational analysis was conducted on PD patients with peritonitis at Hospital La Fe from 2012 to 2023. Demographic data (age, gender, obesity, diabetes, immunosuppression, polycystic kidney disease), analytical parameters (albumin, total proteins, potassium, phosphorus), number of exchanges, adequacy, surgical interventions, and/or catheter placement 6 months prior were analyzed for their association with peritonitis type (Cutaneous/Enteric/Mixed). Recurrences and peritonitis without microbial isolation were excluded. Results We collected data about 109 peritonitis cases; 59.6% cutaneous, 38.5% enteric, and 1.8% mixed, from 61 predominantly male patients (68.9%) with a mean age of 61.35 years. Common germs were S. epidermidis in cutaneous peritonitis and E. coli in enteric peritonitis. Obesity (27.9% of the sample), immunosuppression (16.4%), and hypoalbuminemia (56%) were statistically significantly associated with enteric peritonitis development (p 0.08, p 0.039, and p 0.036, respectively). No statistically significant differences were found for peritonitis type and gender, diabetes, residual renal function, hypokalemia, hypophosphatemia, and underdialysis. 85.3% of peritonitis cases involved manual exchanges, and 14.7% automated PD. While no statistically significant association was found between modality and peritonitis type, more manual exchanges correlated with increased peritonitis cases. Peritoneal catheter insertion and other surgical interventions in the previous 6 months were not significantly related to peritonitis type. Conclusion The presence of malnutrition-related factors such as hypoalbuminemia and obesity increases the risk of developing enteric peritonitis, likely linked to digestive bacterial translocation to peritoneal fluid facilitated by malnutrition. Ensuring preventive nutritional strategies is imperative for these patients.

#2751 CD14++CD16+ monocytes and CD8+ T cells are independently associated with annual change in eGFR and proteinuria in kidney transplant recipients

Abstract Background and Aims Immune cellular responses are implicated in all clinical aspects of kidney transplantation. There is little data regarding the additional value of regular monitoring of immune cells subsets expression in kidney transplant recipients (KTRs). The aim of our prospective study was a longitudinal follow-up analysis of monocytes subpopulations, natural killer (NK) cells and lymphocytes subsets including regulatory T cells (Tregs) in the circulation of KTRs and potential clinical correlations. Method 48 stable KTRs were initially enrolled. All KTRs were under immunosuppressive regimen with corticosteroids, mycophenolate mofetil or mycophenolate acid and calcineurin inhibitors (CNIs). Exclusion criteria were history or development during follow-up of acute rejection, cardiovascular disease, malignancy and active or chronic infections. Patients were followed for 12 months. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+ and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+ B lymphocytes, CD3+ CD4+ T cells, CD3+CD8+ T cells and Tregs (CD4+CD25+ FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry at baseline (T0) and after 12 months (T1). Clinical and laboratory parameters were recorded at T0 and T1. Delta (Δ) eGFR and Δ spot urine protein to creatinine ratio (ΔUPCR) were defined as their respective differences between T1 and T0. Likewise, Delta (Δ) of immune cells subtypes or laboratory indices was defined as their respective difference between T1 and T0. Results 35 KTRs (mean age 53 ± 9.28 years, 71% males, mean transplant vintage 96 ± 66 months, 63% on Tacrolimus and 37% on Cyclosporine) were included in the final analysis. Significant differences were observed between T0 and T1 in monocytes number (653 ± 244 and 538 ± 197/μL respectively, p = 0.001), monocytes percentage (7.6 ± 2.9 and 6.6 ± 2.2% respectively, p = 0.006) as well as in the number of classical CD14++CD16- monocytes (534 ± 225 and 452 ± 185/μL respectively, p = 0.04). The rest immune cells subsets did not show any significant differences between T0 and T1. Mean eGFR declined from 58 ± 17 at T0 to 53 ± 18 ml/min/1.73 m2 at T1 (p = 0.004). No significant changes were observed between T0 and T1 in median UPCR [0.16 (IRQ, 0.09-0.56) at T0 and 0.16 (IQR, 0.10-0.70) gr protein/gr creatine at T1, p = 0.489], in median CRP [4.0 (IQR, 3-7) at T0 and 5 (IQR, 2.5-7.5) mg/L) at T1, p = 0.919], in mean ESR (20 ± 14 at T0 and 22 ± 19 mm/hour at T1, p = 0.381) or other parameters, including CNIs blood levels. ΔeGFR was correlated with the T0 percentage of monocytes (rho = 0.359, p = 0.037), the T0 number and T0 percentage of CD14++CD16+ monocytes (rho= 0.502, p = 0.003 and rho = 0.438, p = 0.008 respectively). On the other hand, a borderline inverse correlation was observed between ΔeGFR and ΔCD14++CD16+ monocytes number (rho = −0.339, p = 0.05). Additional correlates of ΔeGFR included serum albumin at T0 (rho = 0.395, p = 0.021) and Δuric acid (rho = 0.567, p = 0.000). At stepwise linear regression analysis, CD14++CD16+ monocytes (β = 0.338, p = 0.04) and Δuric acid (β = 0.477, p = 0.006) remained independent significant correlates of ΔeGFR. ΔUPCR was significantly correlated with the percentage of B-lymphocytes (rho = 0.385, p = 0.027) and CD4+ T-cells (rho = 0.352, p = 0.044) at T0, and inversely correlated with the T0 percentage of T-lymphocytes (rho = −0.402, p = 0.02) and CD8+ T cells (rho = −0.603, p = 0.000) as well as with Δhemoglobin (rho = −0.385, p = 0.027). At stepwise linear regression analysis, only the CD8+ T cells percentage at T0 remained independently correlated to ΔUPCR (β = –0.379, p = 0.03). Conclusion The results of our study indicate that intermediate CD14++CD16+ monocytes are associated with annual eGFR change whereas CD8+ T cells negatively correlate with the annual trend of proteinuria change in KTRs. Further research is needed to clarify underlying pathophysiological mechanisms for these findings. Finally, future studies including larger cohorts and with longer follow-up are required to specify the potential utility of immune subpopulations monitoring as potential prognostic biomarkers in KTRs.

#2285 Potentially modifiable factors influencing longitudinal health-related quality of life for those with chronic kidney disease in the NURTuRE-CKD cohort

Abstract Background and Aims Factors affecting poor health-related quality of life (HRQoL) for people with chronic kidney disease (CKD) have been previously described in literature, and worse HRQoL is associated with CKD progression and death. Little emphasis has been placed on which factors may be potentially modifiable, and longitudinal HRQoL outcome analyses in non-dialysis dependent CKD cohorts are few in number. Baseline analysis of the NURTuRE-CKD cohort identified several associations between these factors and HRQoL and these associations can now be examined with longitudinal data. Method The NURTuRE-CKD cohort study recruited 2996 participants with non-dialysis dependent CKD between 2017-2019, collecting biochemical, anthropometric, sociodemographic, medical history and patient reported outcome measure (PROM) data. Face-to-face follow-up repeated these measures. Longitudinal worsening overall HRQoL was the main outcome of interest, represented by mapped EQ-5D-3L index value and visual analogue score (VAS). Multivariable linear mixed effects models were fitted in R using the lmer and lmerTest packages. Models for index value were fit separately for each independent variable of interest and collated, as well as fitting models with all variables of interest. Models were adjusted for available confounders, repeated measures and follow-up time. P-values were adjusted for multiple testing using false discovery rate correction. Results 2054/2996 (68.6%) had complete HRQoL data at follow-up, of whom most had CKD stage G3a-G4 (n = 1597, 77.8%). 1817 (88.5%) were white and 1196 (58.2%) were male. Mean age was 63.7 (SD ±14.5) years and the mean number of comorbidities was 3.7 (SD ±2.2). Median (IQR) time between baseline and follow-up was 518 (410) days. At follow-up, mean mapped EQ-5D-3L index value was 0.72 (SD ±0.3) and mean VAS score was 70.4/100 (SD ±20.6). 1595 (77.7%) reported problems in at least one EQ-5D-5L dimension, with 255 (12.4%) developing issues since baseline. 1203 (58.6%) reported worse HRQoL index values at follow up and 910 (44.3%) reported worse VAS. The dimension with the highest number of newly reported issues at follow-up was ‘usual activities’ with 301 (14.7%). Multivariable linear mixed methods models showed independent associations with worse HRQoL (Figs 1 and 2) for those on ten or more medications (β −0.118, CI −0.137 to −0.100, p &amp;lt; 0.001), current smokers (β −0.036, CI −0.067 to −0.006, p = 0.0.012), obesity (β-0.059, CI −0.080 to-0.039, p &amp;lt; 0.001), haemoglobin of &amp;lt;100g/L (β-0.044, CI −0.073 to-0.016, p = 0.014), hospital anxiety and depression scale scores of 8 or above for anxiety (β-0.146, CI −0.161 to-0.130, p &amp;lt; 0.001) and depression (β-0.202, CI-0.219 to −0.186, p &amp;lt; 0.001), worse health literacy (β −0.099, CI −0.136 to −0.063, p &amp;lt; 0.001), and pain (β −0.148, CI −0.161 to −0.135, p ≤ 0.001), weakness (β −0.106, CI −0.120 to −0.092, p &amp;lt; 0.001) and shortness of breath symptoms (β −0.074, CI −0.087 to −0.060, p &amp;lt; 0.001). Conclusion Potentially modifiable factors influencing longitudinal worsening of HRQoL for people with CKD include polypharmacy, smoking, obesity, anaemia, depression and anxiety, limited health literacy, pain, weakness and shortness of breath symptoms. This highlights the need for high quality randomised controlled trials to test interventions addressing these factors with reported HRQoL outcomes. Further work in this cohort is required, examining a third timepoint for HRQoL and linked clinical outcome data.