Mean Difference Research Articles

#2459 Matching-adjusted indirect comparison of eGFR in patients with immunoglobulin A nephropathy treated with Nefecon (TRF budesonide) or sparsentan

Abstract Background and Aims Primary immunoglobulin A nephropathy (IgAN) is an immune-mediated disease that can lead to kidney failure, need for dialysis and kidney transplantation, and early death. IgAN is the most common type of primary glomerulonephritis globally, with an estimated worldwide incidence of 2.5 per 100 000 individuals per year. Estimated glomerular filtration rate (eGFR) is a measure of renal function and is accepted as a surrogate endpoint for clinical trials evaluating kidney function deterioration. In December 2023, the US Food and Drug Administration (FDA) granted full approval to Nefecon (marketed as Tarpeyo® by Calliditas Therapeutics), a targeted-release formulation of budesonide, to reduce the loss of kidney function in adults with IgAN at risk of disease progression, based on the Phase 3 NefIgArd clinical trial. In February 2023, sparsentan (marketed as Filspari™ by Travere Therapeutics) was granted accelerated approval by the FDA to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein–creatinine ratio (UPCR) ≥1.5 g/g, based on the Phase 3 PROTECT study. Matching-adjusted indirect comparison (MAIC) is a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons. In this analysis, we aimed to compare the effects of Nefecon and sparsentan on kidney function deterioration in patients with IgAN, as assessed by eGFR. Method An anchored MAIC was performed to estimate the relative effect of Nefecon and sparsentan on the absolute eGFR change from baseline at 9, 12 and 24 months, with common comparators of optimized renin–angiotensin system inhibition for NefIgArd and irbesartan for PROTECT. Patient-level data from NefIgArd were used to select a population matched to PROTECT, and the following baseline characteristics were used to determine the weights: mean age (years), sex (% male), race (% white), mean eGFR (mL/min/1.73 m2), mean UPCR (g/g), urine albumin–creatinine ratio (UACR) (% with UACR >1.1 g/g), and urinary protein excretion (% with urinary protein excretion >1.8 g/day). Absolute change in eGFR was analyzed using a mixed model for repeated measures (MMRM) method, including baseline, 3-, 6-, 9-, 12-, 18- and 24-month data, baseline eGFR, baseline eGFR-by-time interaction, treatment, and treatment-by-time interaction. The MAIC weights were incorporated into the MMRM. A Bayesian fixed-effects network meta-analysis was performed on the relative effect from PROTECT and the weighted relative effect from NefIgArd, measured by the estimated absolute change from baseline in eGFR. Results The matching-adjustment of the NefIgArd patient population to the PROTECT population is shown in Table 1. The weighted NefIgArd population exhibits very similar baseline characteristics to the PROTECT population. The effective sample size of the weighted NefIgArd population is 208. Results from the anchored MAIC showed statistically and clinically significant favorable effects of Nefecon versus sparsentan on eGFR for all time points analyzed (Fig. 1). Mean differences in the absolute change in eGFR of 5.68 mL/min/1.73 m2 (95% credible interval [Crl] 3.14, 8.20; p < 0.001), 3.48 mL/min/1.73 m2 (95% Crl 0.97, 5.97; p = 0.006) and 3.28 mL/min/1.73 m2 (95% Crl 0.02, 6.51; p = 0.048) were observed when comparing Nefecon with sparsentan at 9 months vs 36 weeks, 12 months vs 48 weeks, and 24 months vs 106 weeks, respectively. Conclusion After accounting for differences in the patient populations from the NefIgArd and PROTECT trials, the anchored MAIC showed that treatment with Nefecon 16 mg/day for 9 months was associated with greater eGFR benefit compared with continuous treatment with sparsentan 400 mg/day over 2 years, with significant differences observed as early as 9 months after treatment initiation and sustained up to 2-years of follow-up.

Web-based Telemonitoring of Visual Function and Self-reported Postoperative Outcomes in Cataract Care: an International Multicenter RCT.

Comparing web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up. Eye clinics in the Netherlands, Austria and Germany. Randomized controlled trial with an embedded method comparison study [ClinicalTrials.gov: NCT04809402]. Routine cataract patients were randomized into two groups: the 'telemonitoring' group undertook web-based vision self-assessments and questionnaires from home, while the 'usual care' group received conventional care. All participants had a 4-6 week post-surgery clinic visit for safety and validation purposes. Outcomes included: the web-test's accuracy for assessing postoperative visual acuity (VA) and refractive error; adverse event rates; and patient reported outcome measurements (PROMs). 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (-0.03±0.14 logMAR) when compared to conventional ETDRS chart testing, with 95% limits-of-agreement ranging from -0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference 0.15±0.67 diopters), resulting in a poorer corrected distance VA compared to subjective refraction (mean 0.1 vs. -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROMs questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and NEI-VFQ-25) improved after surgery (mean improvement -0.80 and 16.70 respectively) and did not significantly differ between the two groups. The cataract patients in this study effectively provided postoperative outcome data via a web-interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes.

#2234 A new formula for total body water in peritoneal dialysis patients

Abstract Background and Aims Peritoneal dialysis (PD) adequacy, assessed primarily by Kt/V, is crucial in routine clinical practice for detecting issues with PD treatment. This metric relies on urea levels and its volume (V) distribution, classically equivalent to total body water (TBW). TBW estimation, commonly achieved through the Watson and Watson (WW) formula, lacks dialysis patients in its original study, it also excluded patients with water metabolism disturbances, raising concerns about its generalizability to this population. Despite limitations, WW has been widely used in trials assessing optimal dialysis dosage in the PD population. Body composition monitoring (BCM) with bioimpedance (BI) offers a more reliable method for TBW determination, commonly used in dialysis programs for quantifying overhydration. However, its higher cost and limited availability compared to estimate formulas pose challenges. Thereby, this study aims to compare TBW values derived from the WW formula and BCM analysis with BI. Additionally, intends to create a new, patient-specific TBW formula based on biometric measurements for PD. Method We retrospectively analyzed adequacy measurements and BCM data from a Portuguese PD center. Patient information included age, sex, height, weight, and BCM-TBW and Percentage Body Fat (PBF). Derived parameters encompassed WW-derived TBW, Body Surface Area (BSA) via the DuBois formula and Body Mass Index (BMI). Statistical analysis, using Microsoft Excel 2017 and IBM SPSS version 25, with a p-value<0.05 considered significant, followed by a step-wise approach: Results 400 measurements were collected from 90 chronic PD patients. 25.1% (n = 23) were female (101 measurements), with a mean age of 56.2 ± 11.9 years. Mean weight was 74.0 ± 12.5 kg, BMI 26.4 ± 4.1 and BSA 1.80 ± 0.80. BCM TBW obtained was significantly lower compared to WW-TBW (33.7 and 38.4 litters respectively, mean difference −4.65 ± 4.17, P < .001). This difference correlated positively with increased PBF (ρ = 0.73, P < .001). BCM TBW correlated positively with weight, height, BMI and BSA (ρ = 0.62, ρ = 0.68, ρ = 0.28 and ρ = 0.62, respectively, with P < .001 overall), without correlation with age (ρ = 0.0, P = .99). For linear regression analysis, the first step was to exclude outlier values for BCM TBW using median ± 1.5 x interquartile range resulting in 383 measurements comprised between 22.15 and 44.95 L. A multiple linear regression using BSA, height, weight and sex to predict BCM TBW. The overall regression model was statistically significant (R2 = 0.59, F (4 378) = 138.17, P < .001). All the variables significantly contributed to the model at predicting BCM TBW (BSA: β = −0.283, P < .001; Height: β = 0.495, P < .001; Weight: β = 0.56, P < .001; Sex: β = 0.237, P < .001). Two formulas were extrapolated from this regression: Conclusion We present a pivotal formula for TBW calculation in PD patients, aiming to improve the correlation between provided Kt/V and clinical outcomes. This addresses the exclusion of diverse patient characteristics in previous studies. However, given the new evidence challenging the association between Kt/V and clinical outcomes in PD, it becomes imperative to appropriate measures for PD adequacy and subject them to examination in novel randomized clinical trials.

Role of nebulised magnesium sulfate in treating acute asthma in children: a systematic review and meta-analysis

ObjectivesTo review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children.MethodsThe authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published...

#1384 Obstructive sleep apnea and fluid management in the hemodialysis: are clinicians putting existing scientific evidence into practice?

Abstract Background and Aims Obstructive Sleep Apnea (OSA) prevalence was found to be higher in an intermittent hemodialysis (iHD) population of the French-speaking Switzerland than in the general population of the same geographical area. The high prevalence of OSA in iHD patients was linked to fluid overload. Interdialytic fluid management targeting a low dry weight showed to reduce OSA's severity, offering a novel therapeutic option in this population. The aims of this study were: 1) to assess the prevalence of confirmed OSA in an end-stage renal disease (ESRD) population undergoing iHD in the Italian-speaking area of Switzerland; 2) to assess the awareness of the treating nephrologists about the OSA's diagnosis of their patients; and 3) to evaluate whether nephrologists integrate the current knowledge in their fluid management strategy of iHD patients with OSA. Method We performed a multicenter, cross-sectional study between July 2022 and July 2023, screening all patients attending the four iHD units of the Ente Ospedaliero Cantonale (EOC), the public hospital network of Canton Ticino (Switzerland), and including those with confirmed OSA. For these patients, we collected anthropometric parameters, iHD protocol characteristics and fluid status from electronic patient dossiers. Fluid overload was measured by multifrequency bioelectrical impedance (Body Composition Monitor®, BCM®; Fresenius Medical Care). Nephrologists of the four iHD units were asked to identify patients with known OSA diagnosis, without consulting the medical dossiers, and were interviewed about their specific iHD strategy in patients with OSA. We compared the fluid management of patients identified as “OSA positive” and those with OSA diagnosis, but misclassified as “OSA negative” by the treating nephrologist. Results Out of 193 patients treated by iHD in the four HD units, 45 patients had a confirmed diagnosis of OSA and were included in this study. Mean age was 76.0 ± 7.5 y, 82.2% were men, mean BMI was 29.1 ± 4.5 kg/m2. They were treated 3 times per week, in mean for 3.76 ± 0.37 hours; 22 were treated by hemodialysis and 23 by hemodiafiltration. The 23% prevalence of diagnosed OSA observed in the study population was significantly lower than the 56% prevalence found in the French Switzerland iHD cohort (p < 0.001). Out of the 45 patients with diagnosed OSA, only 27 (60.0%) were correctly identified by the treating nephrologist. We found no difference in the dry weight target defined by the treating nephrologist between the patients correctly identified as “OSA positive” and those misclassified as “OSA negative”, both being close to the dry weight calculated with BCM® (mean difference 0.7 ± 2.3 vs 0.3 ± 1.4 kg; p = 0.564). The pre-dialysis fluid overload of the whole population was 2.4 ± 1.7 kg, being higher in the “OSA positive” group (2.9 ± 2.0 kg) than in the “OSA negative” group (1.8 ± 0.7 kg; p = 0.0172). However, we found no difference in post-dialysis achievement of dry weight between the groups (residual overweight 0.2 ± 1.0 and 0.1 ± 0.7 kg respectively; p = 0.672). In the interviews, only half of the nephrologists (4/8) were aware of the correlation between fluid overload and OSA, and two of them reported to integrate this knowledge in their fluid management strategy, even if not systematically. Conclusion Nephrologists' attention to sleep apnea in iHD patients seems to be low, despite its high prevalence in this population and scientific evidence supporting that targeting fluid overload is an effective option to improve OSA severity. However, nephrologists tried to achieve the dry weight very strictly in all patients, independently of OSA. More intensive training of nephrologists to the clinical and diagnostic peculiarities of OSA in patients with ESKD is required, in order to improve OSA diagnosis and targeted therapeutic care.

#1651 Urinary oxygen partial pressure: closely associated with hourly urine output induced by furosemide in patients with acute renal injury

Abstract Background and Aims Urine oxygen level, an indicator of kidney medullar oxygenation, is promising for predicting the onset of acute kidney injury (AKI). Furosemide, a commonly used diuretic in ICU, significantly increases urine output and is believed to change kidney medullar oxygenation. We monitored the longitudinal change of urinary oxygen partial pressure during bolus or pump administration of furosemide, aiming to describe the reaction pattern in an AKI-susceptible patient population. Method The prospective observational pilot study included seven adult patients in the ICU because of cardiac surgery or sepsis. We monitored the continuous urinary oxygen partial pressure for 8-24 hours through a device placed between the urinary catheter and collecting bag during furosemide administration, recorded hourly urine output simultaneously from a urine bag, and followed the patients in the hospital for the onset and development of AKI. Results We recruited three female patients and four male patients with an average age of 54 years and a medium of 5 days in ICU with an AKIN stage I of AKI during their hospital stay. None of them developed more severe stage AKI or required any kidney replacement therapy. We found a reverse correlation pattern between hourly urine output and urinary oxygen partial pressure. Specifically, the urine oxygen level dropped during urine volume increase caused by furosemide bolus administration and abolished by furosemide administration through a pump with more stable urine output. The paired t-test showed a significant increase in average urine oxygen level (mean difference = 21.2 mmHg, p = 0.044) recorded during the “high hourly urine output” period compared to the “low hourly urine period”. Conclusion We first found a drop in urinary oxygen partial pressure during the high urine output period elicited by bolus furosemide administration. It shed light on the confounding factors in AKI predicating during possible furosemide administration.

Cost-effectiveness of strength exercise or aerobic exercise compared with usual care for patients with knee osteoarthritis: secondary results from a multiarm randomised controlled trial in Norway

ObjectivesTo evaluate the 1-year cost-effectiveness of strength exercise or aerobic exercise compared with usual care for patients with symptomatic knee osteoarthritis (OA), from a societal and healthcare perspective.DesignCost-effectiveness analysis embedded...

#1103 Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients: a systematic review and meta-analysis

Abstract Background and Aims Delayed graft function (DGF) is more common in donors after cardiac death, especially expanded criteria donors and those with longer cold ischaemia time, older or with an increased serum creatinine. There is no agreement on the optimal immunosuppressive approach in patients at increased risk of DGF, with strategies including a delayed introduction of calcineurin inhibitors (CNI) or initial low dose CNI. Our aim was to evaluate the benefits and harms of delayed initiation of CNI or reduced CNI dose as initial immunosuppression therapy for kidney transplant (KT) recipients at high risk of DGF. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 07 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomized controlled trials (RCTs) and quasi-RCTs evaluating early vs delayed initiation of CNI or reduced vs standard initial dose of CNI in kidney transplant (KT) recipients at high risk of DGF. Three authors independently assessed study eligibility, and two assessed the risk of bias, certainty of evidence, extracted the data, and performed the analysis. Results were reported as risk ratios with 95% confidence intervals for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. Statistical analysis was performed using the random-effects model. Risk of bias was assessed with RoB2 and the certainty of the evidence according to GRADE methods. Results Thirteen studies were included (2386 randomized participants). Incidence of DGF (RR 1.09, 95% CI 0.89 to 1.32; I2 = 18%) and acute rejection (RR 0.98, 95% CI 0.72 to 1.33; I2 = 54%) were similar between early and delayed introduction of CNI, as well as between low vs standard dose of CNI (DGF: RR 1.16, 95% CI 0.90 to 1.50; I2 = 9%; acute rejection: RR 0.70, 95% CI 0.43 to 1.14; I2 = 58%). There were also no differences in secondary outcomes such as graft function, graft loss, risk of death, or infection. Conclusion In patients at high risk of DGF, the strategy of delaying CNI introduction or starting at a lower dose does not reduce the risk of DGF.

#510 Evaluating tolvaptan as a protective agent for cardiac insufficiency in peritoneal dialysis patients

Abstract Introduction Peritoneal dialysis serves as a highly effective renal replacement therapy, offering prolonged preservation of residual renal function, improved blood pressure regulation, and enhanced quality of life. While diuretics are generally considered safe and beneficial in this context, their efficacy may be limited in certain cases. Background and Aims The rationale behind investigating the potential benefits of tolvaptan in peritoneal dialysis stems from existing studies in Asia, where the use of tolvaptan has been approved in this population. These studies, conducted on patients undergoing peritoneal dialysis, indicate notable improvements in urine output and key heart failure indicators such as Left Ventricular Mass Index (LVMI) and Brain Natriuretic Peptide (BNP). Materials & Methods Recognizing the significance of these findings, a recent meta-analysis was conducted to comprehensively assess the collective data. The meta-analysis encompassed data from five pertinent studies involving a total of 70 peritoneal dialysis patients, with an average age of 66.1 ± 15 years. Participants received tolvaptan in doses of up to 15 mg, and the mean follow-up period was 8.2 ± 3.9 months. Results Results from the meta-analysis revealed a significant increase in urine volume in two out of four instances (Mean Difference [MD]= +554.5 cc [379,730], I²=61.5). While most studies did not indicate substantial changes in body weight or renal kt/V, a notable reduction in Left Ventricular Mass Index was evident in two studies (MD= -43.28 [-84.9,-1.6], I²=80.6%). Additionally, a substantial reduction in BNP was reported in one study, with no documented adverse events across the studies. Conclusion As an adjunct therapy, tolvaptan exhibits potential benefits in volume control, potentially contributing to improved cardiac function in peritoneal dialysis patients. The findings of this study align with existing research, highlighting the positive impact of tolvaptan on heart failure markers. Nevertheless, further high-quality studies are imperative to consolidate and validate these observed benefits in the peritoneal dialysis population.

#2651 Microwave tissue digestion and flame atomic absorption spectroscopy for measuring tissue sodium content in CKD patients

Abstract Background and Aims Skin and muscle sodium accumulation has been demonstrated in CKD patients and may contribute to progression of the disease. Various methods are available for measuring tissue sodium content. However, the accuracy and reproducibility of these methods remain unknown. Dry ashing is the most used digestion method, but is expensive, time consuming and has a risk of incomplete digestion. This study compared microwave digestion, dry ashing, and two electrolyte quantification methods for quantifying tissue sodium and potassium. Method We compared microwave digestion (Ethos LEAN Compact Microwave Digestion System, Milestone SRL) and dry ashing (Nabertherm S27) as sample preparation methods, and flame atomic absorption spectroscopy (FAAS, Model 425 Flame Photometer, Sherwood Scientific) and inductively coupled plasma optical emission spectrometry (ICP-OES, Varian 720-ES, Varian Inc.) as electrolyte quantification methods. Skin and muscle samples were obtained from rats and mice, and human skin samples were used. Tissues biopsies were cut in three pieces and digested separately. The methods were compared using interclass correlation coefficient (ICC) and Bland-Altman analysis. The third piece of tissue was microwave-digested by another operator to test inter-operator reproducibility by calculating the ICC and absolute overall mean difference. Results With microwave digestion and FAAS median (IQR) human skin concentration was 114.8 (99.2-157.0, n = 12) mmol/L, confirming tissue sodium storage. When including all tissues, FAAS and ICP-OES showed high agreement for sodium (ICC 0.98, bias –0.00008 mmol/g, n = 141 and potassium (ICC 0.98, bias –0.005 mmol/g, n = 141). Microwave digestion and ashing showed agreement for sodium (ICC 0.93, bias –0.002 mmol/g, n = 61) and potassium (ICC 0.93, bias –0.02 mmol/g, n = 61). The inter-operator agreement was good for sodium (ICC 0.95, absolute mean difference (SD) 0.044 mmol/g (0.073), n = 70) and potassium (ICC 0.96, absolute mean difference (SD) 0.031 mmol/g (0.032), n = 70). Conclusion Microwave digestion with FAAS is a reliable and consistent method for sodium and potassium trace analysis in animal and human tissues compared to ashing and ICP-OES, respectively. This method showed more quantification of cations than the most frequently reported method, representing an easier, and less time-consuming way to quantify tissue sodium in CKD research.

Clinical and cost-effectiveness of telemedicine among patients with type 2 diabetes in primary care: A systematic review and meta-analysis.

Telemedicine has been promoted as an effective way of managing type-2 diabetes (T2DM) in primary care. However, the effectiveness of telemedicine is unclear. We investigated the clinical and cost-effectiveness of different telemedicine interventions for people with T2DM, compared to usual care. We searched Medline, Embase, Cochrane, CINHAL, ProQuest and EconLit for randomized controlled trials (RCTs) that examined the effectiveness of telemedicine interventions on clinical outcomes (HbA1c, body mass index [BMI], weight, diastolic blood pressure [DBP], systolic blood pressure [SBP], fasting blood glucose, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, total cholesterol and triglyceride) in adults with T2DM, published in English from inception until 31 December 2022. Meta-analyses were conducted using random-effects models pooling mean differences, heterogeneity was quantified using the I2 statistic. Publication bias was assessed using funnel plots, Egger tests and trim and fill. Subgroup analyses included type of telemedicine intervention, telemedicine mode of delivery and type of healthcare professionals. This study was registered with PROSPERO, CRD 42022375128. Of the 4093 records identified, 21 RCTs, 10,732 participants from seven regions, were included. Reported interventions included telephone (k = 16 studies), internet-based (k = 2), videoconference (k = 2) and telephone and emails (k = 1). We observed no statistically significant differences between synchronous or asynchronous telemedicine interventions compared to usual care for HbA1c (-0.08%(-0.88 mmol/mol); 95% CI: -0.18, 0.02), BMI (0.51 kg/m2; 95% CI: -0.21, 1.22), SBP (-1.48 mmHg; 95% CI: -3.22, 0.26), DBP (3.23 mmHg; 95% CI: -0.89, 7.34), HDL-cholesterol (0.01 mmol/L; 95% CI: -0.03, 0.05), LDL-cholesterol (0.08 mmol/L; 95% CI: -0.22, 0.37), triglycerides (-0.08 mmol/L, 95% CI: -0.31, -0.15), total cholesterol (-0.10 mmol/L; 95% CI: -0.25, 0.04) and weight (-0.50 kg; 95% CI: -1.21, 0.21). Telemedicine was as effective as usual care in improving health outcomes of people with T2DM. They can provide a safe solution in times of rising demands for primary healthcare services, or in extreme events, like a global pandemic. More high-quality RCTs are needed on the cost evaluation of telemedicine.

#1277 Comparing advanced glycation end products removal in super high-flux hemodialysis versus high-volume hemodiafiltration: a randomized, crossover study

Abstract Background and Aims Expanded hemodialysis using super high-flux membrane, is a promising therapy for effectively clearing middle molecule uremic toxins. However, its impact on advanced glycation end products (AGEs), which is related to an increase in cardiovascular mortality [1], remains inconclusive. Previous studies demonstrated that AGEs increased over time in patients treated with high-flux hemodialysis (HD) [2, 3] while remaining stabilized in online hemodiafiltration (ol-HDF) [3]. This study aims to compare the longitudinal tissue AGEs measured by skin autofluorescence (SAF) between super high-flux hemodialysis (SHF-HD) and high-volume post-dilution ol-HDF. Method In this open-label prospective cross-over 24-week trial, twenty-two prevalent HD patients were randomly assigned to undergone two sequences of 24-week treatment periods: SHF-HD followed by high-volume postdilution ol-HDF or vice versa, with a 4-week wash-out period with high-flux HD between. SAF was measured at baseline and 24 weeks. Midweek pre-HD measurements of beta-2 microglobulin (B2M), serum albumin, normalized protein catabolic rate (NPCR) and Kt/V were obtained every 8 weeks. The amount of dialysate albumin was collected by continuous sampling of spent dialysate method and determined by immunoturbidimetric assay Results Seventeen out of twenty-two patients completed the study. At baseline, SAF levels (3.88 ± 0.14 vs 3.99 ± 0.14 AU, p = 0.463) and pre-HD B2M (22.66 ± 1.41 vs 21.09 ± 1.41 mg/L, p = 0.228) were similar between the SHF-HD and ol-HDF groups. After 24 weeks, SAF levels showed no significant change in SHF-HD (from 3.88 ± 0.14 to 3.91 ± 0.14 AU, p = 0.846) and ol-HDF (from 3.99 ± 0.14 to 3.95 ± 0.14 AU, p = 0.796), with a mean difference of change 0.06 (95% CI −0.34, 0.47, p = 0.75). Similarly, mid-week pre-HD serum B2M at 24 weeks exhibited no significant change in the SHF-HD group (22.66 ± 1.41 to 22.18 ± 1.47 mg/L, p = 0.722) and the ol-HDF group (21.09 ± 1.41 to 21.83 ± 1.45 mg/L, p = 0.577), with a mean difference of change −1.22 (95% CI −4.94, 2.49, p = 0.519). The spKt/V urea did not exhibit any notable differences. Furthermore, pre-HD levels of all small uremic toxins after the 24-week periods did not differ between both groups. Nutritional status measured by serum albumin and NPCR were comparable despite higher dialysate albumin loss in postdilution ol-HDF group (0.82 ± 0.04 vs 1.92 ± 0.12 g, p < 0.001 in SHF-HD and ol-HDF, respectively) Conclusion After 24 weeks of treatment, SHF-HD demonstrated levels of AGEs, pre-HD serum B2M, and serum albumin comparable to high-volume ol-HDF. If high-volume postdilution ol-HDF is not feasible, SHF-HD may serve as a valuable alternative treatment for stabilizing AGEs in chronic hemodialysis patients.

#2576 Effect of dialysis versus conservative care on all-cause mortality in older patients with advanced CKD: nationwide Swedish cohort study

Abstract Background and Aims Conservative care is emerging as an alternative to dialysis in older patients with advanced chronic kidney disease (CKD). However, high-quality evidence comparing the effect of dialysis versus conservative care on patient survival is lacking. Previous observational studies suffered from avoidable biases, such as immortal time bias and lead time bias, and adjusted for limited confounders. This study aimed to assess the effects of dialysis versus conservative care on mortality in older patients with advanced CKD. Method The target trial emulation framework was used to design and analyze this observational study. We conducted a nationwide observational cohort study using data from the Swedish Renal Registry between 2007-2021. We included all nephrologist-referred patients with eGFR < 20 ml/min/1.73 m2 who had a registered decision for dialysis or conservative care. Eligible patients were required to be ≥ 65 years with a Davies Comorbidity Score ≥ 2 or ≥ 80 years. The primary endpoint was 5-year all-cause mortality. Inverse probability of treatment weighting was used to adjust for 50 baseline confounders, including demographics, comorbidities, medication use, blood pressure, laboratory measurements, hospitalizations, and calendar year. Patients in the non-overlapping region of the propensity score distribution were excluded since they had an absolute indication for dialysis or conservative care. Cox proportional hazards regression was used to estimate intention-to-treat hazard ratios (HRs) with 95% confidence intervals (CIs), and the Kaplan-Meier estimator was used to estimate absolute risks. Additionally, we calculated the 5-year restricted mean survival times (RMST) and the 5-year RMST difference between dialysis and conservative care arms. To test the robustness and consistency of our main results, we performed a subgroup analysis in patients aged ≥80. Results Of 2834 eligible patients, 1903 had a registered choice for dialysis and 931 for conservative care. The median age was 81 years, 36.1% were female and median eGFR was 13.1 ml/min/1.73 m2. During the 5-year follow-up period, 29 conservative care patients started dialysis and 430 patients died before starting dialysis. After weighting, all confounders were balanced (standardized mean difference < 0.10). Compared to dialysis, conservative care was associated with a higher absolute 5-year risk of death (91.8% vs. 74.1%), corresponding with an absolute risk difference of 17.6% (95% CI 13.3%-21.9%) (Fig. 1). The adjusted hazard ratio for conservative care vs. dialysis was 2.3 (95% CI 2.0-2.6). The 5-year restricted mean survival times were 34.8 (95% CI 33.2-37.3) months for dialysis and 21.5 (95% CI 19.4-23.6) months for conservative care groups. The 5-year RMST difference was 13.3 months (95% CI 10.8-16.6), meaning that dialysis patients would live on average 13.3 months longer over a 5-year follow-up period than conservative care patients (Table 1). The results were consistent among people ≥ 80 years (adjusted HR 2.2, 95% CI 1.9-2.5; 5-year RMST difference 9.4 months, 95% CI 7.2-13.9). Conclusion In older patients with advanced CKD under nephrologist care, conservative care was associated with a higher risk of mortality than dialysis. These findings could improve the shared decision-making process with patients on the choice of kidney failure treatment.

Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis

ObjectiveVarious stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models.MethodsThe PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots.ResultsThirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = −2.50, 95% CI: –3.07 to –1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation.ConclusionThe evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

#1519 Nutritional impact of ketoanalogue supplementation with protein-restricted diets in advanced chronic kidney disease

Abstract Background and Aims The benefits and risks of a protein-restricted diet supplemented with ketoanalogues (KA) in patients with chronic kidney disease (CKD) are still being explored. Combining KA supplementation with a protein-restricted diet may potentially preserve the glomerular filtration rate (GFR) in CKD patients. However, concerns about protein-energy wasting and the nutritional benefits of KA supplementation remain uncertain. Previous systematic reviews have often included crossover or non-randomized studies and combined data from CKD and dialysis patients, potentially introducing heterogeneity when assessing the effects of KA supplementation in CKD patients. We aim to provide an updated and comprehensive assessment of the impact of combining KA supplementation with a protein-restricted diet on the nutritional status of advanced CKD patients compared to the effects of a protein-restricted diet alone. Method We conducted systematic literature searches of PubMed, Embase, Scopus, and Cochrane Library up to September 2023. We selected parallel-design randomized controlled trials comparing KA supplementation to a low- or very low-protein diet (VLPD) versus a low-protein diet (LPD) alone in adults with stages 3-5 CKD. Outcomes included serum albumin, triceps skinfold (TSF), and mid-arm muscle circumference (MAMC). Pooled estimates of effect measures were calculated using the random-effects model and presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Given the variation in CKD stages among the included studies, subgroup analyses were conducted based on baseline renal function (GFR < 20 vs. ≥ 20 mL/min/1.73 m²). To assess the robustness of our meta-analyses, we conducted sensitivity analyses by excluding studies with an in-trial follow-up duration of less than one year. Results We identified 13 trials with 974 participants and a median follow-up of 12 months. KA supplementation combined with an LPD or a VLPD significantly increased TSF compared to an LPD alone (SMD, 0.25; 95% CI, 0.04, 0.45; P = 0.02; Fig. 1). No significant differences were observed in serum albumin (SMD, 0.28; 95% CI, -0.05, 0.61; P = 0.10; Fig.) and MAMC (SMD, 0.10; 95% CI, -0.12, 0.32; P = 0.37; Fig. 1). KA supplementation significantly increased serum albumin in patients with a baseline GFR ≥ 20 mL/min/1.73 m² (SMD 0.52; 95% CI, 0.20, 0.84; P = 0.001), but not in those with a baseline GFR < 20 mL/min/1.73 m² (SMD, -0.04; 95% CI, -0.41, 0.34; P = 0.85), and this difference between the subgroups was statistically significant (P = 0.03; Fig. 2). Sensitivity analysis that excluded studies with an in-trial follow-up duration of less than one year yielded results similar to the main analysis, except that the difference in TSF between the intervention and control arms became nonsignificant. Conclusion In patients with stages 3-5 CKD, KA supplementation with a protein-restricted diet did not adversely affect nutritional status. These findings remained consistent in sensitivity analyses of RCTs with a follow-up of more than one year and in subgroup analyses based on baseline GFR. The addition of KAs to protein-restricted diets improved serum albumin levels in patients with a baseline GFR of ≥ 20 mL/min/1.73 m². Our analyses confirmed the efficacy and safety of KA supplementation on nutritional status in advanced CKD patients over a one year follow-up period.

#2947 Exploring various approaches for assessing fatigue in patients receiving hemodialysis using the CONVINCE study population

Abstract Background and Aims In nephrology, there is a growing interest in identifying patients’ priorities to achieve meaningful outcomes. A particular relevant outcome in end stage kidney disease is fatigue, with prevalence ranging from 60% to 97% in patients receiving hemodialysis. Different approaches for assessing fatigue exist. The objective of this study was to investigate how self-reported peri-/intra-dialytic and post-dialysis fatigue relate to overall fatigue levels and to certain risk factors of patients receiving hemodialysis. Method The CONVINCE trial is an international multi-center, prospective, randomized, open label, controlled trial, comparing all-cause mortality of high-flux hemodialysis with high-dose hemodiafiltration. Patient-related outcomes (PROs) were examined as secondary outcomes. Fatigue was assessed using tailored short forms from the Patient-Reported Outcome Measurement Information System (PROMIS) to measure overall fatigue, the newly developed Convince Dialysis Fatigue Scale (CDFS) to capture peri-/intra-dialytic fatigue and the Convince Time to Recovery (CTTR-1) to measure post-dialysis fatigue. PROs were collected every 3 months for 24 months, except for CTTR-1 and a PROMIS fatigue short form, which were collected on a monthly basis from the 1st to 5th months. To investigate the agreement between overall fatigue, peri-/intra-dialytic and post-dialysis fatigue, Spearman's correlation was calculated. In addition, we examined whether general health, depression, physical function, sex and dialysis vintage were related to peri-/intra-dialytic, post-dialysis and overall fatigue in a cross-sectional study design (irrespective of dialysis modality). To test for change over time as well as differences between groups Cohen's d effect sizes were calculated. Results Data for PROs was collected from 1282 participants at baseline and 804 after 24 months. The PROMIS fatigue score and the CDFS correlated strongly at each measurement point (Spearman r≥0.67). The PROMIS fatigue score and CTTR-1 correlated moderately (Spearman r≥0.41). We found large effect sizes for mean differences for peri-/intra-dialytic fatigue between patients with/without at least mild depression (Cohen's d 1.27 (95%CI 1.11 to 1.44)) as well as between patients with/without at least moderately impaired physical function (Cohen's d 1.04 (95% CI 0.89 to 1.19)). Patients, who reported CTTR-1 ≥12 hours, showed also large effect sizes for mean differences for overall fatigue between patients with/without at least mild depression (Cohen's d 0.9 (95% CI 0.48 to1.39)) as well as between patients with/without at least moderately impaired physical function (Cohen's d of 1.1 (95% CI 0.7 to 1.67)). In almost half of the patients, the time to recovery was > 4 hours, and patients who reported having to recover for a longer time after dialysis were, on average, more fatigued overall. Overall fatigue, with an observed mean change of 2.10 (SD 9.69) of PROMIS fatigue score, and peri-/intra dialytic fatigue, with an observed mean change of 1.98 (SD 6.98) of CDFS, showed a small increase over the study course. Prevalence of clinically relevant overall fatigue, as defined by a PROMIS fatigue score ≥59, was 15.9% at baseline and increased to 19.8 % after 24 months. Conclusion The three fatigue measurements correlated moderately to strongly and showed small change over time. The relations of various risk factors with fatigue, including self-reported depression, were similar, irrespective of the measure used, indicating that the discrimination between these constructs is imperfect. Furthermore, we discovered that the overall level of fatigue in the study population was comparable to the general population and the prevalence of clinically relevant fatigue was less than reported previously. This is surprising, given the emphasis on fatigue as a significant outcome for patient receiving dialysis. To assess the experience and impact of fatigue in patients receiving hemodialysis, greater attention is warranted, particularly in the timing of fatigue, the time span studied, and the severity of fatigue, especially when investigating a specific fatigue treatment.

A Meta-Analysis of 3-Nitrooxypropanol Dietary Supplementation on Growth Performance, Ruminal Fermentation, and Enteric Methane Emissions of Beef Cattle

This study aimed to evaluate the effects of dietary supplementation with 3-nitrooxypropanol (3-NOP) on growth performance, ruminal fermentation, and enteric methane emissions of beef cattle using a meta-analytic approach. The final meta-analysis database included results from 15 scientific articles. The response variables were analyzed through random effects models, where the results were reported as weighted mean differences (WMD) between the treatments without 3-NOP and those supplemented with 3-NOP. The dietary inclusion of 3-NOP decreased (p < 0.001) dry matter intake but did not affect (p > 0.05) average daily gain and increased (p < 0.05) feed efficiency. In the rumen, 3-NOP supplementation increased (p < 0.01) the pH and ruminal concentration of propionate, butyrate, valerate, isobutyrate, and isovalerate. In contrast, dietary supplementation with 3-NOP decreased (p < 0.001) the rumen concentration of ammonia nitrogen, total volatile fatty acids, acetate, and the acetate/propionate ratio. Furthermore, daily methane (CH4) emission, CH4 yield, and CH4 emission as a percentage of gross energy ingested decreased (p < 0.001) in response to 3-NOP dietary supplementation. In conclusion, dietary supplementation with 3-nitrooxypropanol can be used as a nutritional strategy to improve feed efficiency and ruminal fermentation in beef cattle and, at the same time, reduce enteric methane emissions.

#462 Initiation of SGLT2i vs GLP1-RA and incidence of AKI in persons with type 2 diabetes mellitus

Abstract Background and Aims Adverse kidney outcomes, including acute kidney injury (AKI), are frequent complications in people with diabetes mellitus type 2. In large placebo-controlled randomized trials, both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown efficacy in reducing the risk of kidney outcomes; however, no trial has compared the kidney protective effects of these drug classes head-to-head. We therefore conducted an emulated target trial to compare the effect of SGLT2i to that of GLP1-RA on the incidence of AKI. Method Using routinely collected data from nationwide Danish population-based registries, we included all adults with diabetes mellitus type 2 initiating SGLT2i or GLP1-RA in 2015-2020. Patients with prevalent kidney failure (defined as eGFR < 15 mL/min/1.73m2, dialysis, or kidney transplant), and patients initiating GLP1-RA marketed specifically for treatment of obesity were excluded. We assessed demographic and diabetes-related baseline characteristics along with comorbidities and comedication. We used propensity scores, estimated by logistic regression, to compute stabilized inverse probability of treatment weights, which were applied in all analyses to reduce confounding. Using an intention to treat approach, we followed patients from treatment initiation until the first of death, emigration, or end of follow-up (31 December 2021). Using creatinine measurements from in- and outpatient settings, we applied the KDIGO definition of AKI to record each episode of AKI during follow-up. We estimated the risk of a first AKI episode over time using the Aalen-Johansen estimator. Furthermore, to estimate the mean number of AKIs over time, i.e., including recurrent AKIs, we used the mean cumulative count estimator. Both estimators account for the competing risk of death. Comparing SGLT2i to GLP1-RA, we reported differences in risks and counts at 1, 3 and 5 years of follow-up. Finally, we estimated all-cause mortality using the Kaplan-Meier estimator. We used bootstrapping to obtain 95% confidence intervals (95% CI). Results We included 68 010 individuals, of which 44 034 (65%) initiated SGLT2i, and 23 976 (35%) initiated GLP1-RA. Initiators of SGLT2i were slightly older (median age 63 vs 62 years) and more often male (63% vs 56%) than initiators of GLP1-RA, but with similar diabetes duration (7 vs 7 years). The annual number of initiators of each drug in Denmark increased over the study period. Compared to GLP1-RA, initiators of SGLT2i generally had better estimated glomerular filtration rate (eGFR) at baseline (9% vs 18% had eGFR < 60 mL/min/1.73m2), more frequently used metformin (91% vs 84%), but less frequently insulin (11% vs 28%). Initiators of SGLT2i had a lower prevalence of hospital-diagnosed retinopathy (7% vs 9%), neuropathy (5% vs 6%), and obesity (13% vs 23%) than initiators of GLP1-RA. After inverse probability of treatment weighting, each variable was well balanced with absolute standardized mean differences below 0.02. During a median follow-up of 2.8 years, the weighted absolute risks of first time AKI at 1, 3, and 5 years were 4.8%, 11.2%, and 17.0% for initiators of SGLT2i, and 5.4%, 12.3%, and 19.1% for initiators of GLP1-RA, resulting in AKI risk differences of −0.6% (95% CI: −1.0% to −0.3%), −1.0% (95% CI: −1.7% to −0.5%), and −2.0% (95% CI: −3.0% to −1.1%). The mean cumulative counts showed a similar pattern, with SGLT2i initiators experiencing slightly fewer AKI episodes than GLP1-RA initiators on average (Fig. 1). After 5 years, an estimated 10.3% of SGLT2i initiators and 9.6% of GLP1-RA initiators had died, resulting in a risk difference of 0.7% (95% CI: -0.1% to 1.5%). Conclusion People with diabetes mellitus type 2 who initiated SGLT2i had slightly lower weighted incidence of AKI over 5 years than those initiating GLP1-RA.

The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis.

Sarcopenia describes the age-related decline in skeletal muscle mass and strength that is driven, at least in part, by an imbalance between rates of muscle protein synthesis (MPS) and muscle protein breakdown. An expanding body of literature has examined the effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) ingestion on MPS rates in older adults, with mixed findings. The aim of this systematic review and meta-analysis was to investigate the effectiveness of n-3 PUFA ingestion in stimulating rates of MPS and whole-body protein synthesis in healthy adults and clinical populations. Searches were conducted of the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until December 2022 for articles on randomized controlled trials comparing the effect of n-3 PUFA ingestion vs a control or placebo on rates of MPS and whole-body protein synthesis. The search yielded 302 studies, of which 8 were eligible for inclusion. The random effects inverse-variance model was used and standardized mean differences (SMDs) with 95%CIs were calculated to assess the pooled effect. Risk of bias was assessed by the Cochrane Risk-of-Bias 2 tool. The main analysis indicated no effect of n-3 PUFA supplementation on MPS rates (k = 6; SMD: 0.03; 95%CI, -0.35 to 0.40; I2 = 30%; P = .89). Subgroup analysis based on age, n-3 PUFA dose, duration of supplementation, and method used to measure fractional synthetic rate also revealed no effect of n-3 PUFA ingestion on MPS. In contrast, the main analysis demonstrated an effect of n-3 PUFA ingestion on increasing whole-body protein synthesis rates (k = 3; SMD: 0.51; 95%CI, 0.12-0.90; I2 = 0%; P = .01). n-3 PUFA ingestion augments the stimulation of whole-body protein synthesis rates in healthy adults and clinical populations. PROSPERO registration no. 42022366986.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing noFA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.