End-stage Renal Disease Group Research Articles

Comparison of functional outcome after intracerebral hemorrhage in patients with or without end stage renal disease on hemodialysis: a propensity-score matched study

Abstract Background End stage renal disease (ESRD) requiring hemodialysis (HD) increases mortality among patients with intracerebral hemorrhage (ICH). The aim of this study is to investigate the clinical characteristics and outcome of ICH patients with ESRD on HD versus propensity-score matched controls. Methods This is a single center retrospective study. Consecutive ICH admissions at the University of California, Irvine Medical Center from January 1, 2018 to July 31, 2022 were analyzed. Results Among 347 ICH admissions that met inclusion criteria, 24 patients (6.92%) had ESRD on HD. Compared to patients without ESRD, patients with ESRD on HD had significantly higher rate of diabetes mellitus (79.2% vs. 36.8%, p < 0.01) and in-hospital mortality (25% vs. 7.43%, p < 0.01). There were no significant differences in demographics, other comorbidities, clinical characteristics, good (mRS score 0–3) or poor (mRS score 4–5) functional outcomes, rate of comfort care and the time to comfort care decision between the 2 groups. After propensity score matching, the ESRD group had a significantly higher in-hospital mortality rate (27.3% vs. 8%, p = 0.012) and a lower rate of obesity (9.1% vs. 34.1%, p = 0.02). Among patients who died during admission, ESRD on HD status did not inadvertently influence end-of-life care decisions. Univariate logistic regression and area under curve analysis showed that ICH score ≥ 3 was a predictor of increased mortality in both ESRD and non-ESRD groups. Conclusions ICH patients with ESRD on HD had significantly higher in-hospital mortality and lower rate of obesity than propensity score matched controls, suggesting a survival benefit from obesity. ICH score ≥ 3 is an independent predictor for poor outcomes in both ESRD and non-ESRD groups.

The prognostic role of activation of the complement pathways in the progression of advanced IgA nephropathy to end-stage renal disease

IntroductionThe role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN.MethodsRenal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses.ResultsDuring a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively).ConclusionComplement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage.

Impact of chronic kidney disease and end-stage renal disease on the mid-term adverse outcomes in diabetic patients with cardiovascular diseases

The evidence for the impact of renal dysfunction in patients with diabetes mellitus (DM) and first cardiovascular diseases on mid-term adverse outcomes remain scarce. This study included the data of patients with DM having first atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF) from the Taipei Medical University Clinical Research Database. A Cox proportional hazards regression model was used to assess the impact of chronic kidney disease (CKD) or end-stage renal disease (ESRD) on the 1-year mortality and recurrent ASCVD/CHF outcomes. We enrolled 21,320 patients with DM hospitalized for ASCVD or CHF; of them, 18,185, 2639, and 496 were assigned to the non-CKD, CKD, and ESRD groups, respectively. After propensity score matching, compared with the non-CKD group, the CKD and ESRD groups had higher mid-term all-cause mortality (adjusted hazard ratio 1.72 [95% confidence interval 1.48–1.99] and 2.77 [2.05–3.73], respectively), cardiovascular death (1.84 [1.44–2.35] and 1.87 [1.08–3.24], respectively), and recurrent hospitalization for ASCVD (1.44 [1.24–1.68] and 2.33 [1.69–3.23], respectively) and CHF (2.08 [1.75–2.47] and 1.50 [1.04–2.17], respectively). The advancing age was associated with mortality in CKD/ESRD groups. In CKD group, male sex was associated with all-cause mortality and recurrent ASCVD risk; the diuretics usage was associated with mortality and recurrent CHF risks. Our findings suggest that CKD and ESRD are significant risk factors for mid-term adverse outcomes in patients with DM and established cardiovascular diseases. Additionally, old age, male sex and diuretics usage requires attention. Further good quality studies are needed in the future.

Evaluation of Thyroid functions in Patients with End Stage Renal Disease in a Sample of Egyptian Populations

Abstract Background In most cases, hypothyroidism is not linked to kidney disease. However, hypothyroidism has been shown to hasten the development of chronic kidney disease (CKD). Aim of the Work to evaluate thyroid abnormalities in patients with end stage renal disease in a sample of Egyptian populations. Patients and Methods This study was conducted with 70 Egyptian Patients selected from Nephrology department in Theodor Bilharz Research Institute, in a case control study, they were categorized into 2 groups Group 1: Stage V renal disease group (n = 40): patients with eGFR &amp;lt;15 mL/min with no history of thyroid disease or receiving any thyroid medications. Group 2: Age and sex matched health population group (n = 30): with normal renal function with no history of thyroid disease or receiving any thyroid medications. All subjects underwent full thyroid profile, and estimated GFR. Results Symptoms of thyroid dysfunction were more frequent in end stage group, the difference statistically were significant only in muscle weakness. TSH was statistically significantly higher in cases with hypothyroidism. TGABs were statistically significantly higher in cases with hypothyroidism. Antimicrosomal antibodies recorded only in hypothyroid cases, the differences were statistically significant. FT3, TSH, TGABs and thyroid volume statistically had perfect diagnostic performance in diagnosing hypothyroidism among end stage renal disease group. Conclusion Frequency of hypothyroidism was higher in end stage renal disease patients compared to control group. So, it is important to keep monitoring thyroid functions in patients with advanced renal impairment that may enhance quality of life.

Complement C3a/C3aR and C5a/C5aR deposits accelerate the progression of advanced IgA nephropathy to end-stage renal disease

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732–0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079–9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

#2987 Describing inflammatory markers in end-stage renal disease and hemodialysis

Abstract Background and Aims There is an increased inflammatory state in patients with End-Stage Renal Disease (ESRD). It is crucial to investigate if the decline in renal function influences on the levels of infectious and inflammatory parameters, particularly procalcitonin (PCT) which exhibits the highest specificity for bacterial infections. Additionally, it would be useful establish a PCT cut-off-value for patients on renal replacement therapy and ESRD in the absence of infection, facilitating the differentiation between those with and without bacterial infection. The aim of this study is to analyze infectious and inflammatory parameters, including PCT, in ESRD and HD patients. A secondary objective is to explore the link among inflammatory markers between themselves and with some specific clinical conditions. Method A cross-sectional observational comparative study was conducted involving HD patients (Group 1) and ESRD (Group 2). We assessed PCT, C-Reactive Protein (CRP), Sedimentation Velocity (SV), and Ferritin, among others. Patients with active infection were excluded. For HD patients, analytical extraction was conducted before the midweek session. Results are presented as mean ± standard deviation for variables exhibiting a normal distribution, and as the median for variables displaying a non-normal distribution. Normality was assessed using the Shapiro-Wilk test. Group comparisons were conducted using Mann Whitney test for variables with a non-normal distribution. Relationships between parameters were examined using the Spearman correlation test and linear regression analysis. Significance was established at p &amp;lt; 0.05. The statistical software utilized was Jamovi (Version 2.3). Results We found in HD patients (Group 1) when compared to ESRD patients (Group 2) higher PCT levels, higher ferritin levels, and lower albumin levels, with statistical significance (Table 1). Conclusion There is a decrease in albumin levels and an increase in PCT, and ferritin levels in HD patients compared to ESRD patients. We observed that RCP, and ferritin were independent predictive factors of PCT levels, but, unexpected, diabetes was not. Given the fact that ESRD, and HD patients are in a chronic inflammatory status, it is difficult to assess the acute infectious severity in these patients. For that reason, the cut-off-values of inflammatory parameters in these patients in a non-infectious time-point needs to be clarified.

Clinical Features of Cardiac Calcified Amorphous Tumor: A Narrative Review.

A cardiac calcified amorphous tumor (CAT) is a non-neoplastic cardiac mass composed of calcified nodules surrounded by amorphous fibrous tissue in a context of degeneration and chronic inflammation. Although CAT cases are increasingly reported, its clinical manifestation remains unclear. We aimed to conduct a narrative review of CAT and identify its clinical characteristics. We conducted a comprehensive literature search using PubMed, with the keyword "Cardiac Calcified Amorphous Tumor" to identify relevant articles. A total of 113 articles published between 1997 and 2022 were retrieved. The clinical features allowing for assess patient background, differences with and without end-stage renal disease (ESRD), symptom-related factors, risk factors for embolism caused by CAT, and features of CAT, such as shape, location, mobility, pathology, and treatment, were statistically analyzed in 106 criteria-matched cases. The mean patient age was 60.2 ± 18.6 years, with 45 men and 61 women. Of the data collected from 21 countries, 52 patients were from Japan. Mobile CAT was more common in the chronic renal failure group. Linear, club-shaped, and spindle-shaped CAT tended to be mobile and more common in the ESRD group as well as located in the mitral valve region. The shape, mobility, location, and underlying mechanism of CAT depended on the presence or absence of ESRD. The risk of embolism was considered high because mobile CAT was more common in the ESRD group, and CAT originated in the mitral valve region. Hence, early diagnosis based on periodic examination in patients with ESRD and aggressive surgical treatment are necessary.

Oxidative stress in patients with coronavirus disease and end-stage renal disease: a pilot study

BackgroundOxidative stress, an imbalance between reactive oxygen species production and antioxidant capacity, increases in patients with coronavirus disease (COVID-19) or renal impairment. We investigated whether combined COVID-19 and end-stage renal disease (ESRD) would increase oxidative stress levels compared to each disease alone.MethodsOxidative stress was compared among three groups. Two groups comprised patients with COVID-19 referred to the hospital with or without renal impairment (COVID-ESRD group [n = 18]; COVID group [n = 17]). The third group (ESRD group [n = 18]) comprised patients without COVID-19 on maintenance hemodialysis at a hospital.ResultsThe total oxidative stress in the COVID-ESRD group was lower than in the COVID group (p = 0.047). The total antioxidant status was higher in the COVID-ESRD group than in the ESRD (p < 0.001) and COVID (p < 0.001) groups after controlling for covariates. The oxidative stress index was lower in the COVID-ESRD group than in the ESRD (p = 0.001) and COVID (p < 0.001) groups. However, the three oxidative parameters did not differ significantly between the COVID and COVID-ESRD groups.ConclusionsThe role of reactive oxygen species in the pathophysiology of COVID-19 among patients withESRD appears to be non-critical. Therefore, the provision of supplemental antioxidants may not confer a therapeutic advantage, particularly in cases of mild COVID-19 in ESRD patients receiving hemodialysis. Nonetheless, this area merits further research.

End-stage renal disease should not Be considered a contraindication for veno-arterial extracorporeal membrane oxygenation

BackgroundThis study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methodsAdult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P < 0.01) and had more comorbidities. Extracorporeal cardiopulmonary resuscitation (ECPR) was used more frequently in the ESRD group (66.1% versus 51.6%; P < 0.001). The ESRD group had higher in-hospital mortality rates (72.7% versus 63.3%; P = 0.03). In the ECPR subgroup, there was no difference of survival between ESRD and others(P = 0.56). In the multivariate Cox regression, ESRD was not an independent predictor for mortality (P = 0.20). ConclusionESRD was not an independent predictor of in-hospital mortality after VA-ECMO. The survival of ESRD patients was not inferior to those without ESRD when receiving ECPR. Therefore, ESRD should not be considered a contraindication to VA-ECMO in adults.

Clinicopathological characteristics and predictors of outcome of rapidly progressive glomerulonephritis: a retrospective study.

Globally, there are regional and time-based variations in the prevalence, etiology, and prognosis of rapidly progressive glomerulonephritis (RPGN). Prognosis of RPGN is poor, with a higher risk of death and end stage renal disease (ESRD) even with immunosuppressive medications. In the Middle East and North Africa, the studies on this disease are very limited. Therefore, we determined the predictors of outcome of RPGN. We retrospectively assessed 101 adult patients over age of 18, diagnosed with RPGN based on renal biopsy illustrating crescents in ≥ 50% of the glomeruli. Patients who had crescents in their renal biopsies that were < 50% and those who refused to consent to a renal biopsy were excluded. We categorized the patients into 3 groups based on immunohistochemistry; type I, type II and type III. Then, depending on renal loss, we divided them into ESRD and non-ESRD groups. The clinical history and physical examination were retrieved. Additionally, 24-hour urine protein, urine analysis, renal function tests, serum albumin, complete blood count, antinuclear antibodies, anti-double stranded DNA antibodies, ANCA antibodies and serum complement levels were checked. Each patient underwent a kidney biopsy for immunohistochemistry and light microscopy. The percentage of crescentic glomeruli, number of sclerosed glomeruli, tertiary lymphoid organ (TLO), neutrophil infiltration, endocapillary or mesangial hypercellularity, interstitial fibrosis with tubular atrophy (IFTA) were analyzed. Primary outcomes (remission, ESRD and mortality) and secondary outcomes were assessed. Type II was the most frequent cause of RPGN (47.5%), followed by type III (32.7%) and type I (19.8%). 32 patients (31.7%) died during follow up, whereas 60 patients (59.4%) developed ESRD. In 41 patients (40.6%), remission occurred. Oliguria, serum creatinine, and need for HD at presentation were significantly increased in ESRD group compared to non-ESRD group (P < 0.001 for each). Mesangial proliferation, IFTA, TLO formation, sclerotic glomeruli and fibrous crescents were also significantly increased in ESRD group in comparison to non-ESRD group (P < 0.001 for each). Glomerulosclerosis (P = 0.036), and IFTA (P = 0.008) were predictors of ESRD. Infections (P = 0.02), respiratory failure (P < 0.001), and heart failure (P = 0.004) were mortality risk factors. Type II RPGN was the most common. Infection was the most frequent secondary outcome. Oliguria, glomerulosclerosis, the requirement for hemodialysis at presentation, IFTA and TLO formation were predictors of ESRD. Respiratory failure, heart failure and infections were significant predictors of mortality.

Blunted cerebral hemodynamic responses to incremental exercise in patients with end-stage renal disease.

The aims of this study were to compare cerebral hemodynamics and maximal oxygen uptake (VO2peak) in patients with end-stage renal disease (ESRD) vs. age-matched healthy controls during maximal exercise. Twelve patients with ESRD and twelve healthy adults (CTR group) performed exhaustive incremental exercise test. Throughout the exercise test, near-infrared spectroscopy allowed the investigation of changes in oxyhemoglobin (∆O2Hb), deoxyhemoglobin (∆HHb), and total hemoglobin (∆THb) in the prefrontal cortex. Compared to CTR, VO2peak was significantly lower in ESRD group (P < 0.05). Increase in ∆THb (i.e., cerebral blood volume) was significantly blunted in ESRD (P < 0.05). ESRD patients also had impaired changes in cerebral ∆HHb and ∆O2Hb during high intensity of exercise (P < 0.05). Finally, no significant correlation was observed between VO2peak and changes in cerebral hemodynamics parameters in both groups (All P > 0.05). Maximal exercise highlights subtle disorders of both hemodynamics and neuronal oxygenation in the prefrontal cortex in patients with ESRD. This may contribute to both impaired cognitive function and reduced exercise tolerance throughout the progression of the disease.

Hemodynamic and neuromuscular basis of reduced exercise capacity in patients with end-stage renal disease.

The present study aimed to characterize the exercise-induced neuromuscular fatigue and its possible links with cerebral and muscular oxygen supply and utilization to provide mechanistic insights into the reduced exercise capacity characterizing patients with end-stage renal disease (ESRD). Thirteen patients with ESRD and thirteen healthy males (CTR group) performed a constant-force sustained isometric contraction at 50% of their maximal voluntary isometric contraction (MVC) until exhaustion. Quadriceps muscle activation during exercise was estimated from vastus lateralis, vastus medialis, and rectus femoris EMG. Central and peripheral fatigue were quantified via changes in pre- to postexercise quadriceps voluntary activation (ΔVA) and quadriceps twitch force (ΔQtw,pot) evoked by supramaximal electrical stimulation, respectively. To assess cerebral and muscular oxygenation, throughout exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin (∆O2Hb), deoxyhemoglobin (∆HHb), and total hemoglobin (∆THb) in the prefrontal cortex and in the vastus lateralis muscle. ESRD patients demonstrated lower exercise time to exhaustion than that of CTR (88.8 ± 15.3s and 119.9 ± 14.6s, respectively, P < 0.01). Following the exercise, MVC, Qtw,pot, and VA reduction were similar between the groups (P > 0.05). There was no significant difference in muscle oxygenation (∆O2Hb) between the two groups (P > 0.05). Cerebral and muscular blood volume (∆THb) and oxygen extraction (∆HHb) were significantly blunted in the ESRD group (P < 0.05). A significant positive correlation was observed between time to exhaustion and cerebral blood volume (∆THb) in both groups (r2 = 0.64, P < 0.01). These findings support cerebral hypoperfusion as a factor contributing to the reduction in exercise capacity characterizing ESRD patients.

Altered brain texture features in end-stage renal disease patients: a voxel-based 3D brain texture analysis study.

Cognitive impairment in patients with end-stage renal disease (ESRD) is associated with brain structural damage. However, no prior studies have investigated the relationship between brain texture features and the cognitive function in ESRD patients. This study aimed to investigate changes in brain texture features in ESRD patients and their relationships with cognitive function using voxel-based 3D brain texture analysis (TA), and further predict individual cognitive-related brain damage in ESRD patients. Forty-seven ESRD patients and 45 control subjects underwent whole-brain high-resolution 3D T1-weighted imaging scans and neuropsychological assessments. The voxel-based 3D brain TA was performed to examine inter-group differences in brain texture features. Additionally, within the ESRD group, the relationships of altered texture features with neuropsychological function and clinical indicators were analyzed. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of brain texture features for cognitive-related brain damage in ESRD patients. Compared to the control group, the ESRD group exhibited altered texture features in several brain regions, including the insula, temporal lobe, striatum, cerebellum, and fusiform gyrus (p < 0.05, Gaussian random-field correction). Some of these altered texture features were associated with scores from the Digit Symbol Substitution Test and the Trail Making Test Parts A (p < 0.05), and showed significant correlations with serum creatinine and calcium levels within the ESRD group (p < 0.05). Notably, ROC curve analysis revealed that the texture features in the right insula and left middle temporal gyrus could accurately predict cognitive-related brain damage in ESRD patients, with the area under the curve values exceeding 0.90. Aberrant brain texture features may be involved in the neuropathological mechanism of cognitive decline, and have high accuracy in predicting cognitive-related brain damage in ESRD patients. TA offers a novel neuroimaging marker to explore the neuropathological mechanisms of cognitive impairment in ESRD patients, and may be a valuable tool to predict cognitive decline.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Safety and effectiveness of remdesivir for the treatment of COVID-19 patients with end-stage renal disease: A retrospective cohort study

BackgroundRemdesivir has been used to treat severe coronavirus 2019 (COVID-19); however, its safety and effectiveness in patients remain unclear. This study aimed to investigate the safety and effectiveness of remdesivir in patients with COVID-19 with end-stage renal disease (ESRD). MethodsThis retrospective study used the Chang Gung Research Database (CGRD) and extracted data from 21,621 adult patients with COVID-19 diagnosed between April 2021 and September 2022. The patients were divided into groups based on their remdesivir use and the presence of ESRD. The adverse effects of remdesivir and their outcomes were analyzed after propensity score matching. ResultsTo compare the adverse effects of remdesivir, propensity scores were used for one-to-one matching between patients with and without ESRD treated with remdesivir (N=110). There were no statistically significant differences in heart rates, blood glucose levels, variations in hemoglobin levels before and after remdesivir use, or liver function between the two groups after remdesivir use. A comparison was made between patients with ESRD using remdesivir and those not using remdesivir after propensity score matching (N=44). Although a shorter length of stay (LOS), lower intensive care unit (ICU) admission rate, and lower intubation rate were noted in the ESRD group treated with remdesivir, the difference was not statistically significant. ConclusionRemdesivir is safe for use in patients with COVID-19 and ESRD; no increased adverse effects were noted compared with patients without ESRD. However, the effectiveness of remdesivir use in patients with COVID-19 and ESRD remains uncertain.

Venetoclax pharmacokinetics in participants with end-stage renal disease undergoing haemodialysis.

Renal insufficiency is a common comorbidity in patients with haematological malignancies. This study aimed to assess how end-stage renal disease (ESRD) might affect the pharmacokinetics of venetoclax, a Bcl-2 inhibitor, in participants with ESRD undergoing haemodialysis. Venetoclax was administered as a single 100-mg dose to 6 female participants with ESRD (estimated glomerular filtration rate <15 mL/min) both prior to haemodialysis and between haemodialysis days and 7 healthy female participants with normal renal function (estimated glomerular filtration rate >90 mL/min). Intensive pharmacokinetic and protein binding samples were collected from all participants. Arterial and venous samples were collected from ESRD participants during haemodialysis to assess the effect of haemodialysis on venetoclax pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that haemodialysis did not affect the pharmacokinetics of venetoclax. The fraction unbound (fu ) of venetoclax was ~2-fold higher for participants with ESRD compared to participants with normal renal function. The unbound maximum plasma concentration and area under the plasma concentration-time curve from time 0 to 48 h were comparable between ESRD and normal function groups. The mean half-life ranged from 10.4 to 12.2h across groups, demonstrating that ESRD did not affect the half-life of venetoclax. No new safety signals were observed during this study. ESRD and dialysis do not alter unbound venetoclax plasma concentrations. No pharmacokinetics driven dose adjustment is needed for patients with renal insufficiency.

Abstract 13012: Impact of End-Stage Renal Disease on Short-Term Outcomes Among Adults Undergoing Percutaneous Mitral Valve Repair

Introduction: Patients with end-stage renal disease (ESRD) are predisposed to multiple complications following invasive and non-invasive procedures. With the recent introduction of percutaneous mitral valve repair (PMVR), there needs to be more data on ESRD patients' outcomes following such procedures. Our analysis aims to bridge data via national hospitalization records. Methods: We used de-identified data of adults(ages 18 and more) undergoing PMVR between 2016-2020 via the National Inpatient Sample. Patients were separated into two groups based on the presence of a diagnosis of ESRD. We excluded all other forms of Chronic kidney disease classifications from our control group. Differences in outcomes were studied via logistic regression models. Results: Between 2016-2020, a total of 24680 procedures of PMVR were performed in the United States that met our selection criteria. Among them, 1655 (6.7%) patients were reported with a diagnosis of ESRD, while 23025 (93.3%) were without any diagnosis of CKD or ESRD. Patients with ESRD consisted of a younger cohort (mean age 68.68 years) compared to the non-ESRD group (mean age 77.39 years, p&lt;0.01). Furthermore, the ESRD group showed a higher mean Charlson Comorbidity Index Score (CCI) score (6.47) compared to the non-ESRD group (score of 2.20). Most procedures were conducted in Urban teaching centers (90.4% of non-ESRD patients and 93.4% of ESRD patients). ESRD patients recorded higher odds of sepsis (aOR 1.747, 95% CI 1.191-2.560, p&lt;0.01), major bleeding (aOR 8.316, 95% CI 7.336-9.426, p&lt;0.01), postprocedural respiratory failure (aOR 2.531, 95% CI 1.441-4.445, p&lt;0.01), and mortality (aOR 2.109, 95% CI 1.513-2.940, p&lt;0.01). The two groups showed no differences in acute myocardial infarction events (aOR 1.235, 95% CI 0.899-1.697, p=0.193) during their hospitalization for the procedure. Conclusions: Patients with ESRD experienced poorer outcomes following PMVR as they had higher odds of mortality, postprocedural respiratory failure, major bleeding, and sepsis. Thus, physicians must adequately address the potential complications with and without the procedure and closely monitor the post-operative progress.

Indoxyl sulfate induced frailty in patients with end-stage renal disease by disrupting the PGC-1α-FNDC5 axis.

Sarcopenia or frailty is common among patients with chronic kidney disease (CKD). The protein-bound uremic toxin indoxyl sulfate (IS) is associated with frailty. IS induces apoptosis and disruption of mitochondrial activity in skeletal muscle. However, the association of IS with anabolic myokines such as irisin in patients with CKD or end-stage renal disease (ESRD) is unclear. This study aims to elucidate whether IS induces frailty by dysregulating irisin in patients with CKD. The handgrip strength of 53 patients, including 28 patients with ESRD, was examined. Serum concentrations of IS and irisin were analyzed. CKD was established in BALB/c mice through 5/6 nephrectomy. Pathologic analysis of skeletal muscle was assessed through haematoxylin and eosin and Masson's trichrome staining. Expression of peroxisome proliferator-activated receptor-gamma coactivator PGC-1α and irisin were analyzed using real-time polymerase chain reaction and Western blotting. Handgrip strength was lower among patients with ESRD than among those without ESRD. In total, 64.3% and 24% of the patients in the ESRD and control groups had low handgrip strength, respectively (p < 0.05). Serum concentrations of IS were significantly higher in the ESRD group than in the control group (222.81 ± 90.67 μM and 23.19 ± 33.28 μM, respectively, p < 0.05). Concentrations of irisin were lower in the ESRD group than in the control group (64.62 ± 32.64 pg/mL vs. 99.77 ± 93.29 pg/mL, respectively, p < 0.05). ROC curves for low handgrip strength by irisin and IS were 0.298 (95% confidence interval (CI): 0.139-0.457, p < 0.05) and 0.733 (95% CI: 0.575-0.890, p < 0.05), respectively. The percentage of collagen was significantly higher in mice with 5/6 nephrectomy than in the control group. After resveratrol (RSV) treatment, the percentage of collagen significantly decreased. RSV modulates TGF-β signaling. In vitro analysis revealed that IS treatment suppressed expression of PGC-1α and FNDC5 in a dose-dependent manner, whereas RSV treatment attenuated IS-induced phenomena in C2C12 cells. IS was positively correlated with frailty in patients with ESRD through the modulation of the PGC-1α-FNDC5 axis. RSV may be a potential drug for reversing IS-induced suppression of the PGC-1α-FNDC5 axis in skeletal muscle.

Identification of Cell-Cell Communications by Single-Cell RNA Sequencing in End Stage Renal Disease Provides New Insights into Immune Cell Heterogeneity.

Impaired immune system characterized by low-grade inflammation is closely associated with kidney chronic kidney disease (CKD) progression. To reveal the alterations of the function, component, and intercellular communication of immune cells during the progression of CKD. We conducted a case-control study enrolling regular hemodialysis patients and healthy controls. Clinical data, serum and peripheral blood mononuclear cell (PBMC) samples were collected. Flow cytometry and single-cell RNA sequencing were performed to quantitatively analyze the immune cell subsets and T-cell subsets of PBMCs. scRNA data of GSE140023 containing mouse unilateral ureteral obstruction (UUO) models were analyzed the heterogeneity of immune cells. Overall reduction in peripheral blood lymphocyte subsets in patients with end-stage renal disease (ESRD) was observed. A higher ratio of Th17/Treg, Th1/Treg, and b-cell/Treg in the ESRD group was associated with a decrease in eGFR, PTH, and ferritin. Among T cell subsets identified by scRNA analysis, Th17 cells were significantly increased in the ESRD and UU0 group. TFH, Th1, and Th2 cells are located at the final stage in the developmental tree, while Treg and memory CD8+ T cells are at the beginning site. Early developmental differentiation of Th17, Th1, and Tfh cells was observed in the ESRD and UUO group. Analysis of intercellular communication between t-cell subpopulations identified two major input and output signaling pathways: the CD40 and macrophage inhibitory factor (MIF) pathways. The MIF signaling pathway primarily mediates intercellular communication among th17 effects, CD8+ t-cell, and Th17-Treg in the ESRD group, the serum level of MIF showed significant upregulation, which was closely related to Th17/Treg cells. A global immune imbalance was closely associated with the deterioration in renal function and complication development. The MIF signaling pathway mediates Th17/Treg communication and promotes the trans-differentiation of Treg cells to Th17 cells in CKD progression.

Altered resting-state cerebellar-cerebral functional connectivity in patients with end-stage renal disease

Background End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes. Methods Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients. Results ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p < 0.05). The altered cerebellar-cerebral FC was associated with the Montreal Cognitive Assessment Scale score (p < 0.05), and correlated with serum creatinine and uric acid levels within the ESRD group (p < 0.05). Conclusions The study indicates that cerebellar-cerebral FC is involved in the neural substrates of cognitive impairment in ESRD patients. The findings may provide clinically relevant new neuroimaging biomarkers for the neuropathological mechanisms underlying cognitive impairment of ESRD.