End-stage Renal Disease Subjects Research Articles

#3127 Bedside cycling modulated the bone-resorption markers in patients with end-stage renal disease

Abstract Background and Aims Exercise provided multifactorial benefits in improving the health of the CKD patients. The exercise itself improved the bone remodeling. For CKD patients, chronic kidney disease mineral bone disorder (CKD-MBD) is an important complication and the treatment for renal osteodystrophy is unsatisfactory. The aim of study is to validate the role of bedside cycling in bone remodeling markers for patients with end-stage renal disease (ESRD). Method Participants were grouped into 4 groups: health control, chronic kidney disease (GFR 15∼60 ml/min) and ESRD (GFR<15 ml/min with maintenance dialysis). For ESRD patients, 12-week bedside cycling ((30 minutes per session; 3 times per week) were given for subjects. The pre-and post-exercise bone remodeling markers and clinical outcome were compared in ESRD with and without exercise in ESRD subjects. Results Bone formation markers (Bone specific alkaline phosphatase (15.57 ± 1.59 pg/dL) and Procollagen type 1 amino-terminal propeptide (1269.12 ± 116.34 pg/dL) were higher in ESRD patients with correlation with indoxyl sulfate and intact parathyroid hormone concentration(p < 0.05) respectively. In ESRD patients, the post-exercise concentration of Tartrate-resistant acid phosphatase 5b (3.64 ± 0.25 pg/dL to 4.23 ± 0.31 pg/mL, p = 0.003) and N-terminal telopeptide-1 (113.67 ± 20.53 pg/mL to 260.61 ± 30.9 pg/mL, p = 0.001)increased after 12 weeks of bed-side cycling. The hospitalization and mortality were similar between ESRD with or without exercise. Conclusion The bone formation marker concentration increased along with the severity of CKD. Bedside cycling increased the concentration of the bone resorption markers in ESRD patients.

Demographic and clinical risk factors for diagnosis of sleep disorders in ESRD patients

BackgroundSleep disturbances in patients with end-stage renal disease (ESRD) are common and more prevalent than in the general population. This study aims to assess the demographic and clinical risk factors for the diagnosis of sleep disorders in ESRD patients. MethodsThis study is a retrospective analysis of the United States Renal Data System (USRDS) to evaluate risk factors for the diagnosis of sleep disorders, including hypersomnolence, insomnia, restless leg syndrome (RLS), or obstructive or central sleep apnea (OSA/CSA). All ESRD subjects enrolled in the USRDS between 2004-2015 were eligible for inclusion. The risk factors analyzed were age, race, sex, ethnicity, access type, dialysis modality, and the Charlson Comorbidity Index (CCI). All statistical analysis was performed using SAS 9.4, and statistical significance was assessed using an alpha level of 0.05. Descriptive statistics on all variables overall and by each sleep diagnosis were determined. ResultsIncreasing age, black race, other race, and Hispanic ethnicity were associated with decreased risk of each sleep diagnosis while CCI was associated with increased risk. Females were at increased risk of RLS and insomnia while males were at increased risk of OSA/CSA. Catheter and graft access decreased risk of RLS but increased risk of insomnia compared to AVF access. Catheter access increased risk of OSA/CSA compared to graft access. Hemodialysis increased risk of OSA/CSA compared to peritoneal dialysis. ConclusionsSome ESRD patients are at an increased risk for diagnosis of sleep disorders based on age, race, sex, comorbid health conditions, and dialysis modality.

Venetoclax pharmacokinetics in subjects with end-stage renal disease undergoing hemodialysis.

e19042 Background: Venetoclax is a first-in-class Bcl-2 inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia(AML) and is currently being investigated as a treatment for t(11;14)-positive relapsed/refractory multiple myeloma (MM). Renal insufficiency is a common comorbidity in patients with hematologic malignancies, and no clinical study has been conducted to assess how end stage renal disease might affect venetoclax pharmacokinetics. This study aimed to assess the pharmacokinetics of venetoclax after oral administration of a single 100 mg dose of venetoclax in subjects with normal renal function and end-stage renal disease, including those undergoing hemodialysis. Methods: Venetoclax was administered as a single 100 mg dose to 7 healthy female subjects with normal renal function (eGFR > 90 ml/min) and 6 female subjects with end-stage renal disease (ESRD) (eGFR < 15 ml/min) both prior to hemodialysis (Period 1) and between hemodialysis days (Period 2). Intensive PK and protein binding samples were collected from all subjects. Arterial and venous samples were collected from ESRD subjects during hemodialysis to assess the effect of hemodialysis on the pharmacokinetics of venetoclax. Pharmacokinetic parameters were estimated using non-compartmental methods. Results: There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that hemodialysis did not affect the PK of venetoclax. The fraction unbound (fu) of venetoclax increased approximately 2-fold for subjects with ESRD compared to subjects with normal renal function.The unbound Cmax and AUC0-48 of ESRD subjects, between dialysis days were comparable to unbound Cmax and AUC0-48 observed in the normal renal function subjects. The harmonic mean t1/2 between groups (normal renal function vs. ESRD) ranged from 11 and 12.2 hours, demonstrating that end-stage renal disease did not affect the half-life of venetoclax. Conclusions: End-stage renal disease does not alter unbound venetoclax plasma concentrations and no dose adjustment is neededfor patients with renal insufficiency based on pharmacokinetics. Clinical trial information: NCT04810598 .

Knee and hip arthroplasty joint surgical site wound infection in end-stage renal disease subjects who underwent dialysis or a kidney transplant: A meta-analysis.

A meta-analysis study to assess the knee and hip arthroplasty joint surgical site wound infection (SSWI) in end-stage renal disease (ESRD) subjects who underwent dialysis or a kidney transplant (KT). A comprehensive literature examination till February 2023 was implemented and 1046 linked studies were appraised. The picked studies contained 5 471 898 subjects with total joint arthroplasty (TJA) at the baseline, 13 049 of them were haemodialysis or renal transplant, and 5 458 849 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of knee and hip arthroplasty SSWI in ESRD subjects who underwent dialysis or a KT by the dichotomous and continuous styles and a fixed or random model. Haemodialysis or renal transplant had a significantly higher postoperative SSWI (OR, 2.13; 95% CI, 1.73-2.62, P < .001) compared with control in TJA subjects. However, no significant difference was observed between haemodialysis and renal transplant in postoperative SSWI (OR, 0.93; 95% CI, 0.16-5.54, P=.94) and between haemodialysis or renal transplant and control in prosthetic joint infection (OR, 1.07; 95% CI, 0.25-4.55, P=.93) in TJA subjects. Haemodialysis had a significantly higher prosthetic joint infection (OR, 1.92; 95% CI, 1.21-3.03, P=.005) compared with renal transplant in TJA subjects. Haemodialysis or renal transplant had a significantly higher postoperative SSWI in TJA subjects. Also, haemodialysis had a significantly higher prosthetic joint infection compared with renal transplant in TJA subjects. Although precautions should be taken when commerce with the consequences because a low number of selected studies was picked for certain comparisons in this meta-analysis.

EEG Delta/Theta Ratio and Microstate Analysis Originating Novel Biomarkers for Malnutrition-Inflammation Complex Syndrome in ESRD Patients.

The Malnutrition-Inflammation Score (MIS) was initially proposed to evaluate malnutrition-inflammation complex syndrome (MICS) in end-stage renal disease (ESRD) patients. Although MICS should be routinely evaluated to reduce the hospitalization and mortality rate of ESRD patients, the inconvenience of the MIS might limit its use. Cerebral complications in ESRD, possibly induced by MICS, were previously assessed by using spectral electroencephalography (EEG) via the delta/theta ratio and microstate analysis. Correspondingly, EEG could be used to directly assess MICS in ESRD patients, but the relationships among MICS and these EEG features remain inconclusive. Thus, we aimed to investigate the delta/theta ratio and microstates in ESRD patients with high and low risks of MICS. We also attempted to identify the correlation among the MIS, delta/theta ratio, and microstate parameters, which might clarify their relationships. To achieve these objectives, a total of forty-six ESRD subjects were willingly recruited. We collected their blood samples, MIS, and EEGs after receiving written informed consent. Sixteen women and seven men were allocated to low risk group (MIS ≤ 5, age 57.57 ± 14.88 years). Additionally, high risk group contains 15 women and 8 men (MIS > 5, age 59.13 ± 11.77 years). Here, we discovered that delta/theta ratio (p < 0.041) and most microstate parameters (p < 0.001) were significantly different between subject groups. We also found that the delta/theta ratio was not correlated with MIS but was strongly with the average microstate duration (ρ = 0.708, p < 0.001); hence, we suggested that the average microstate duration might serve as an alternative encephalopathy biomarker. Coincidentally, we noticed positive correlations for most parameters of microstates A and B (0.54 ≤ ρ ≤ 0.68, p < 0.001) and stronger negative correlations for all microstate C parameters (−0.75 ≤ ρ ≤ −0.61, p < 0.001). These findings unveiled a novel EEG biomarker, the MIC index, that could efficiently distinguish ESRD patients at high and low risk of MICS when utilized as a feature in a binary logistic regression model (accuracy of train-test split validation = 1.00). We expected that the average microstate duration and MIC index might potentially contribute to monitor ESRD patients in the future.

Abstract 12460: The Effect of Alirocumab on the Plasma Metabolome and Lipidome in End-Stage-Renal Disease

Introduction: Atherosclerotic disease is the major cause of morbidity and mortality among patients maintained on dialysis for end-stage renal disease (ESRD). Cardiovascular disease specifically accounts for almost 50% of deaths of these patients. In a pilot study to determine the safety of Alirocumab we investigated the plasma metabolome and lipidome in patients on dialysis and after treatment with a PCSK9 inhibitor. Methods: We recruited 14 subjects (10 male/4 female) from outpatient nephrology practices on hemodialysis (n=12) or peritoneal dialysis (n=2) for 3 months without complications. Subjects received Alirocumab (150 mg, i.m.) every 2 weeks. Blood was drawn from 13 subjects at baseline and after 12 weeks (6 injections) at completion of the trial. In addition, blood was drawn from 21 healthy controls. Plasma obtained was stored at -80 o C for biomarker analysis. Targeted metabolomic analysis allowed quantitative detection of 542 metabolites including 480 lipid species in 13 lipid classes. This analysis was performed by liquid chromatography mass spectrometry using the Quant 500 metabolomic kit. Results: Metabolomic analysis identified 152 metabolites significantly different (FDR p&amp;lt0.05) between control and ESRD subjects. Notably, various elevated metabolites as well as lower triglyceride and phosphatidylcholine lipid species. Twenty-three metabolites were significantly decreased after Alirocumab treatment (FDR paired t-test, p&amp;lt0.05), all of which were lipid species from the following classes: cholesterol esters, ceramides, hexosylceramides and sphingomyelins (Figure 1). Conclusions: Subjects with ESRD have dysregulation of lipid metabolism that may contribute to atherosclerosis. The effect of Alirocumab on plasma ceramides and sphingomyelins is of particular interest since increased levels in these lipid species have been shown to be associated with vascular disease and increased mortality.

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors.

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

Coronary Artery Calcium Score Correlates With Coronary Plaques And Calcification In End-stage Renal Disease Subjects Similar To Those Without Renal Disease (matched Cohort)

Introduction: Coronary artery plaques can be calcified, non-calcified, or mixed. Calcification in the coronaries is almost solely atherosclerotic and is easily quantified by Coronary Artery Calcium (CAC) score, which is highly predictive of cardiovascular events. Calcified, Non-Calcified Plaque levels and CAC score weight have not been studied adequately in End-Stage Renal Disease (ESRD) subjects, who generally have elevated Coronary Plaque and very high ASCVD risk. This study is to examine coronary plaque types, stenosis scores, and segments involved in ESRD subjects compared to matched non-ESRD subjects.

Incident Parkinson\u2019s disease in kidney transplantation recipients: a nationwide population-based cohort study in Korea

This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson’ disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson’s disease between 2007 and 2015. We established two control cohorts without a history of Parkinson’ disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson’s disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson’ disease. Risk of incident Parkinson’s disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson’s disease in KT recipients.

Macrophage and adipocyte interaction as a source of inflammation in kidney disease

In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.

Pharmacokinetics, Dialysability, and Safety of Gadopiclenol, a New Gadolinium-Based Contrast Agent, in Patients With Impaired Renal Function.

The aims of this study were to evaluate the pharmacokinetics (PK) of gadopiclenol, a new macrocyclic gadolinium based-contrast agent, in subjects with impaired renal function, and to assess its dialysability in subjects with end-stage renal disease (ESRD). This 2-center, open-label, phase 1 study included 5 successive cohorts of 8 adult subjects: healthy subjects (cohort 1), subjects with mild (cohort 2), moderate (cohort 3), severe (cohort 4) renal impairment, or ESRD (cohort 5), who received a single intravenous injection of gadopiclenol (0.1 mmol/kg). Blood and urine samples were collected at different time points in cohorts 1 to 4, and blood and dialysate samples were collected at each hemodialysis session (4-hour session on day 1, day 3, and day 5) in cohort 5. Gadopiclenol elimination and safety were assessed for up to 6 months. Pharmacokinetics parameters were calculated using noncompartmental analysis. A total of 40 subjects were included, with a mean age of 51.5 years (range, 18-71 years). No significant difference in the mean maximum concentration values and the distribution volume was observed among cohorts 1 to 4. Urinary excretion of unchanged gadopiclenol was delayed with the degree of renal impairment and ranged between 96% and 84% in subjects with mild to severe renal impairment. Compared with that of healthy subjects, the mean area under the plasma concentration curve was 54%, 148%, and 769% higher in subjects with mild, moderate, or severe renal impairment, respectively. The mean terminal half-life was prolonged with the degree of renal impairment (1.9, 3.3, 3.8, and 11.7 hours for cohorts 1-4). In ESRD subjects, gadopiclenol was effectively removed from the plasma (95% to 98%) after the first hemodialysis session. Gadopiclenol concentration in plasma was below the limit of quantification for all subjects after the second hemodialysis session. Gadopiclenol concentration was below limit of quantification in all plasma and urine samples collected at 1, 3, and 6 months. Five subjects (12.5%) experienced adverse events related to gadopiclenol, none serious and all resolved. Laboratory measurements, vital signs, and electrocardiography did not raise any safety concern. Gadopiclenol elimination half-life was prolonged in subjects with mild to severe renal impairment, yet its renal clearance remains complete or nearly complete. In ESRD subjects, gadopiclenol was effectively removed from the plasma after 1 hemodialysis session, and up to 3 hemodialysis sessions were sufficient to completely clear it. No safety concern was raised. Therefore, no dose adjustment seems necessary in this patient population.

MP43-07 RESULTS OF A PHASE 2 STUDY OF RELOXALIASE IN SUBJECTS WITH ADVANCED OXALATE DISORDERS

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (MP43)1 Apr 2020MP43-07 RESULTS OF A PHASE 2 STUDY OF RELOXALIASE IN SUBJECTS WITH ADVANCED OXALATE DISORDERS Felix Knauf, John Lieske, Mira Keddis, Annamaria Kausz, and Charles Scales* Felix KnaufFelix Knauf More articles by this author , John LieskeJohn Lieske More articles by this author , Mira KeddisMira Keddis More articles by this author , Annamaria KauszAnnamaria Kausz More articles by this author , and Charles Scales*Charles Scales* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000898.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hyperoxaluria (HOx) is a major risk factor for kidney stones, and can also lead to chronic kidney disease (CKD). With decreasing kidney function, plasma oxalate (POx) levels rise, resulting in oxalate deposition in the kidneys and other organs. There is an unmet need in patients with Enteric Hyperoxaluira (EH) and Primary Hyperoxaluira (PH), in whom the systemic and renal oxalate burden can contribute to worsening CKD, potentially leading to end-stage renal disease (ESRD). Reloxaliase is an oral, oxalate-specific enzyme therapy that is designed to degrade oxalate in the gastrointestinal (GI) tract, thereby reducing urinary oxalate (UOx). This study was conducted to evaluate whether reloxaliase can reduce UOx and POx in subjects with PH or severe EH and CKD. METHODS: This 12-week, open-label study of reloxaliase enrolled subjects with EH with CKD and hyperoxalemia (UOx ≥40 mg/24h, eGFR <45 mL/min/1.73m2 and POx >5 μmol/L, n=9 [6 with ESRD]), and PH (UOx ≥40 mg/24h, n=5) who received reloxaliase 7,500 u 5x/day with meals and snacks. POx and 24h UOx were obtained at baseline, Weeks 4, 8 and 12; UOx was not collected in ESRD subjects (eGFR <15 ml/min or dialysis). RESULTS: At the time of this report, 14 subjects were enrolled. In the EH subjects, there was a robust reduction in both UOx and POx as shown in the table below. No consistent effect was observed in PH subjects with normal kidney function. Reloxaliase was well tolerated, there were no study drug related serious adverse events. CONCLUSIONS: A substantial reduction in both POx and UOx was demonstrated in EH subjects with CKD. The mechanism of action of reloxaliase, to degrade oxalate in the GI tract, aligns with the pathophysiology of EH which involves excess oxalate absorption. To our knowledge, this is the first demonstration of a pharmacological therapy for POx reduction in subjects with EH and advanced CKD. This study suggests potential for reloxaliase to address an unmet need in subjects with EH and CKD, as this therapy could reduce systemic oxalate burden. Further clinical studies are warranted. Source of Funding: Allena Pharmaceuticals © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e649-e649 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Felix Knauf More articles by this author John Lieske More articles by this author Mira Keddis More articles by this author Annamaria Kausz More articles by this author Charles Scales* More articles by this author Expand All Advertisement PDF downloadLoading ...

Quality of life patients on hemodialysis in Kerala

Background: End Stage Renal Disease (ESRD) is on the rise in the recent years which carries with it emotional, physical, psychological, social, and existential burdens that impact their Quality of life (QOL). The QOL describes life satisfaction and life concerns and are affected by health and illness. Maintenance of QOL with the effects of chronic illness is a challenging, multifaceted, complex endeavour for patients, their families and the health professionals. Objective: To assess the kidney disease related quality of life in patients with ESRD, its association with selected demographic, socio economic, disease and treatment related characteristics of ESRD patients.&#x0D; Materials and methods: Descriptive survey was conducted on 112 participants diagnosed with ESRD and on hemodialysis at least for a minimum duration of 1 month, were recruited from both government and private hospitals through purposive sampling as per the inclusion and exclusion criteria. The Kidney Disease Quality of Life (KDQOLTM-36) and Personal Data Sheet were used to assess the QOL and to obtain information as per the objectives. Descriptive analysis and Chi square test were used to analyze the data.&#x0D; Results: Majority of the ESRD subjects had poor quality of life in all the domains, higher proportion being in the burden of illness (71.4%) and effects of illness (68.8%) domains. There was a significant association between the burden of illness and marital status(p=.01), type of bystander(p=.01); symptom and type of bystander(p=.03)&#x0D; Conclusion: Majority of the ESRD patients had low KDQOL scores indicating poor quality of life in all the domains requiring intervention. This emphasizes the need to identify as well as manage QOL among them and develop appropriate intervention

Fractal Analysis of Cardiac Fibrosis Patterns Derived From Magnetization Transfer Contrast MRI in Patients With End-Stage Renal Disease.

OBJECTIVE. The purpose of this study is to use fractal analysis to characterize diffusely fibrotic, focally fibrotic, and healthy myocardium in patients with end-stage renal disease (ESRD) on the basis of previously published magnetization transfer (MT) contrast images. MATERIALS AND METHODS. The MT ratio values of patients with ESRD (n = 34) and healthy control subjects (n = 19) were used to construct anatomically faithful 3D left ventricular reconstructions. Established MT ratio threshold values were used to define healthy, diffusely enhanced, focally enhanced, and total enhanced tissue domains. The fractal dimension (FD) for reach domain was calculated using a 3D box-counting algorithm. RESULTS. Patients with ESRD showed a higher FD across all fibrotic domains compared with control subjects, in whom diffusely and focally enhanced myocardium showed largely planar distributions (mean [± SD] FD, 2.12 ± 0.02 and 1.92 ± 0.09, respectively), whereas the combined domain was fractal in 3D (mean FD, 2.41 ± 0.04). The FD and volume of fibrotic tissue were logarithmically correlated in the population with ESRD. Fractal analysis of MT-weighted cardiac MRI data revealed that the geometric characteristics of cardiac scar in patients with ESRD transition from fractal in 2D to planar in 2D to fractal in 3D as scar volume increases. CONCLUSION. Fatal arrhythmias in individuals with ESRD are increasingly attributed to cardiac fibrosis. Histologic analysis reveals that fibrosis progresses via a fractal expansion pattern. The method presented in this study can be applied to characterize the irregular space-filling morphometry of any pathologic substrate identified by contrast enhancement across noninvasive imaging modalities.

Assessing cardiovascular risk in the prerenal transplant population: Comparison of myocardial perfusion imaging and coronary angiography with risk factor stratification.

Patients with end-stage renal disease (ESRD) have a higher incidence of coronary artery disease (CAD). Hence, it is crucial to evaluate CAD before renal transplantation. This study compares the utility of pharmacologic single-photon emission computed-tomography (SPECT) imaging directly to coronary angiography for diagnosis of CAD with correlation to cardiovascular risk factors. Retrospective review of asymptomatic renal failure patients who underwent both SPECT and coronary angiography to identify obstructive CAD between the years 2008-2016. Ninety-four ESRD subjects were evaluated. Myocardial perfusion SPECT study found, when compared to coronary angiography demonstrated for CAD, the sensitivity of 93.3% with a specificity of 73.4%. Importantly, the negative predictive value for coronary artery disease was 96%. With seven or more cardiac risk factors, 66.7% of patients had obstructive coronary artery disease. Among all the risk factors examined, patients with a previous history of coronary artery disease had a 68% risk of obstructive coronary artery disease. Comparing myocardial perfusion imaging SPECT findings with coronary angiography in patients with ESRD, a sensitivity of 93.3% and a specificity of 73% were observed. Of all the risk factors examined, patient with the previous history of CAD was the single most significant risk factor for CAD in 68% of cases.

SAT-061 THE COMPARATIVE IMPACT OF DIALYTIC MODALITIES ON ELECTRIC MYOCARDIAL REPOLARIZATION INHOMOGENEITIES

Patients with end stage renal disease (ESRD) on dialysis have increased all cause and CV mortality, a significant proportion of this being represented by sudden unexplained (cardiac) death, most probably secondary to malignant ventricular arrhythmias. QT dispersion (QTd), defined as the difference in duration between the longest and the shortest QT interval on electrocardiogram (ECG), may be considered as a direct measure of the regional heterogeneity of myocardial repolarization and also an approximation for repolarization abnormalities. The aim of our study was to investigate the effect of the dialytic modalities on ECG abnormalities (QT interval, QT dispersion) and to find its important modulators, as markers of arrhythmia and sudden death in a large population of dialysis patients. We compared 68 HD patients (4 h/HD session, F100 dialysers); mean age 41.5 ±11.2 years; mean dialysis vintage 55.2 ± 38.3 months, with 63 PD patients (4 exchanges of 2000 ml/day, glucose/Na/Ca/K/Mg = 1.5/134/1.75/2/0.5 mmol/l), mean age 50.9 ± 15.2 years; mean dialysis vintage 34.7 ± 20 months. The QT interval was calculated as an average of three consecutive complexes, and corrected for heart rate using the Bazett's formula (QTc=QT/(R–R)1/2). Echocardiography was performed in all patients; Na+, K+, Ca2+, PO4, pH and BP levels were also determined. Follow-up was performed to analyze the overall survival and to determine the potential impact of inhomogeneities in myocardial repolarization and dialytic method on patient survival. The mean values for QTc and QTdc were 428.8 ± 34.1 ms and 39.3 ± 32.1 ms. Overall, QTc significantly correlated (univariate analysis) with the LVM and QTdc with serum ionized Ca and LVM (p < 0.05 for all). Stepwise multiple linear regressions showed Ca2+ to be the only independent predictor for QTdc. In CAPD patients, the mean value for QTc was 426.8 ± 40.7 ms (27% patients with abnormal QTc interval) and for QTdc = 43.2 ± 42.7 ms. In the HD subgroup, the mean value for QTc was 430.3 ± 27.2 ms (33.8 % abnormal QTc interval), p = NS vs CAPD; QTdc valuewas 35.7 ± 16.9 ms. In both dialysis groups (univariate analysis) QTc significantly correlated with LVM; QTd and QTdc only correlated with serum ionized Ca (p < 0.05). In Cox analysis model significant predictors for survival were gender (p=0.009), serum potassium (p = 0.007) and QTc (p = 0.005). The difference in QTc between HD and PD, unadjusted for confounders, was 14.9 % greater in PD vs HD patients (p = NS). QTc significantly correlated with LVM (r = 0.223, p = 0.039), QTd and QTdc correlated with serum ionized Ca2+ (r = 0.335, p = 0.000; r = 0.375, p = 0.000 respectively) and LVM (r = 0.240, p = 0.026; r = 0.23, p = 0.032 respectively). Stepwise multiple linear regression showed Ca2+ to be the only independent predictor for both QTd (adjusted R2 = 0.18; beta = 0.44) and QTdc (adjusted R2 = 0.19; beta = 0.45). Our study, the largest to date and with follow-up survival analysis, thoroughly describes the characteristics of CAPD and HD patients, supporting the lack of a significant different impact between these two dialytic modalities on ECG abnormalities. We also confirm the paramount influence of subjacent structural cardiac abnormalities on arrhythmia risk. Calcium represents probably the most relevant electrolyte for this pathology, in ESRD subjects on renal replacement therapy.

Risk Estimation of Aortic Stiffness in Patients with End Stage Renal Disease under Maintenance Haemodialysis

Background: The stiffness of the large elastic arteries increase the morbidity and mortality. Objective: The purpose of the present study was to estimate the risk of aortic stiffness among end stage renal disease patients under maintenance haemodialysis.&#x0D; Methodology: This case-control study was carried out in the Department of Nephrology at National Institute of Kidney Diseases and Urology (NIKDU), Dhaka and National Institute of Cardiovascular Disease and Hospital (NICVD), Dhaka, Bangladesh from January 2013 to December 2014 for a period of two (02) years. Chronic kidney disease in stage 5 [CKD-5(D)] patients older than 18 years on maintenance haemodialysis (MHD) for more than 3 months were designated as case group and age and sex matched non CKD patients were considered as control group. Serum calcium, serum albumin, serum phosphate and iPTH were estimated by semi-automated biochemistry analyzer from the Department of Biochemistry of NIKDU, Dhaka and NICVD, Dhaka. Plain X-ray abdomen in lateral view was performed for all patients.&#x0D; Result: A total number of 100 patients were enrolled for this study of which 50 patients were in end stage renal disease (ESRD) group and the rest 50 patients were in non-CKD group. Mean (±SD) aortic stiffness index was significantly higher (P&lt;0.001) among ESRD population (3.27±1.70) compared to non CKD group of population (2.00±0.73). Mean (±SD) serum calcium (corrected) level was significantly high (P&lt;0.001) in ESRD patients (9.79±0.87) compared to non CKD group of population (9.13±0.70). Mean (±SD) serum phosphate level was significantly higher (P&lt;0.001) in ESRD patients (5.71±0.96) compared to non CKD group of population (4.20±0.59). However, mean (±SD) iPTH level showed no significant difference between ESRD (25.33±51.98) and non CKD group of population (38.53±19.52).&#x0D; Conclusion: In conclusionaortic stiffness is significantly higher among ESRD subjects.&#x0D; University Heart Journal Vol. 14, No. 2, Jul 2018; 67-70

Risk Estimation of Aortic Stiffness in Patients with End Stage Renal Disease on Maintenance Haemodialysis

Background: The stiffness of the large elastic arteries increase the morbidity and mortality. The purpose of the present study was to estimate the risk of aortic stiffness among end stage renal disease patients on maintenance haemodialysis.&#x0D; Methods: This cross-sectional study was carried out in the Department of Nephrology at National Institute of Kidney Diseases and Urology (NIKDU), Dhaka and National Institute of Cardiovascular Disease and Hospital (NICVD), Dhaka, Bangladesh from January 2013 to December 2014 for a period of two years. Chronic kidney disease in stage 5 [CKD-5(D)] patients older than 18 years on maintenance haemodialysis (MHD) for more than 3 months were designated as case group and age and sex matched non CKD patients were considered as control group. Serum calcium, serum albumin, serum phosphate and iPTH were estimated by semi-automated biochemistry analyzer from the Department of Biochemistry of NIKDU, Dhaka and NICVD, Dhaka. Plain Xray abdomen in lateral view was performed for all patients.&#x0D; Result: A total number of 100 patients were enrolled for this study of which 50 patients were in end stage renal disease (ESRD) group and the rest 50 patients were in non-CKD group. Mean (±SD) aortic stiffness index was significantly higher (P&lt;0.001) among ESRD population (3.27±1.70) compared to non CKD group of population (2.00±0.73). Mean (±SD) serum calcium (corrected) level was significantly high (P&lt;0.001) in ESRD patients (9.79±0.87) compared to non CKD group of population (9.13±0.70). Mean (±SD) serum phosphate level was significantly higher (P&lt;0.001) in ESRD patients (5.71±0.96) compared to non CKD group of population (4.20±0.59). However, mean (±SD) iPTH level showed no significant difference between ESRD (25.33±51.98) and non CKD group of population (38.53±19.52).&#x0D; Conclusion: In conclusion, aortic stiffness is significantly higher among ESRD subjects.&#x0D; Birdem Med J 2019; 9(1): 59-62

A refined method of quantifying deceleration capacity index for heart rate variability analysis

BackgroundPhase-rectified signal averaging (PRSA) was often applied to assess the cardiac vagal modulation. Despite its broad use, this method suffers from the confounding effects of anomalous variants of sinus rhythm. This study aimed to improve the original PRSA method in deceleration capacity (DC) quantification.MethodsThe refined deceleration capacity (DCref) was calculated by excluding from non-vagally mediated abnormal variants of sinus rhythms. Holter recordings from 202 healthy subjects and 51 patients with end-stage renal disease (ESRD) have been used for validity. The DCref was compared to original DC (DCorg) by the area under receiver operating characteristic curve.ResultsExperimental results demonstrate that the original and refined DCs calculated from 24-h, 2-h, and 30-min Holter recordings are significantly lower in patients with ESRD than those in the healthy group. In receiver operating characteristic curve analysis, the DCref provides better performance than the DCorg in distinguishing between the patients with ESRD and healthy control subjects. Furthermore, the refined PRSA technique enhances the low frequency and attenuates high frequency components for spectral analysis in ESRD patients.ConclusionsThe DCref appears to reduce the influence of non-vagally mediated abnormal variants of sinus rhythm and highlighting the pathological influence. DCref, especially assessed from short-term electrocardiography recordings, may be complementary to existing autonomic function assessment, risk stratification, and efficacy prediction strategies.

An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28\xa0days to

BackgroundCalcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.MethodsIn this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing.ResultsMedian plasma cinacalcet tmax was 1 h (range 0.5–4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults.ConclusionsIn conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.