Abnormal degree centrality in end-stage renal disease (ESRD) patients with cognitive impairment: a resting-state functional MRI study

Brain Imaging and Behavior - To investigate functional connectivity (FC) changes in end-stage renal disease (ESRD) patients with and without cognitive impairment (CI) by using resting-state...     

Neurovascular coupling dysfunction in end-stage renal disease patients related to cognitive impairment

We aimed to investigate the neurovascular coupling (NVC) dysfunction in end-stage renal disease (ESRD) patients related with cognitive impairment. Twenty-five ESRD patients and 22 healthy controls were enrolled. To assess the NVC dysfunctional pattern, resting-state functional MRI and arterial spin labeling were explored to estimate the coupling of spontaneous neuronal activity and cerebral blood perfusion based on amplitude of low-frequency fluctuation (ALFF)-cerebral blood flow (CBF), fractional ALFF (fALFF)-CBF, regional homogeneity (ReHo)-CBF, and degree centrality (DC)-CBF correlation coefficients. Multivariate partial least-squares correlation and mediation analyses were used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment and clinical characteristics. The NVC dysfunctional patterns in ESRD patients were significantly decreased in 34 brain regions compared with healthy controls. The decreased fALFF-CBF coefficients in the cingulate gyrus (CG) were associated positively with lower kinetic transfer/volume urea (Kt/V) and lower short-term memory scores, and were negatively associated with higher serum urea. The relationship between Kt/V and memory deficits of ESRD patients was partially mediated by the fALFF-CBF alteration of the CG. These findings reveal the NVC dysfunction may be a potential neural mechanism for cognitive impairment in ESRD. The regional NVC dysfunction may mediate the impact of dialysis adequacy on memory function.     

终末期肾病患者的抑郁症状

<正>随着透析技术的进步及医疗保险的贯彻实施,接受血液透析治疗的终末期肾病(End Stage Renal Disease,ESRD)患者越来越多,生存时间越来越长,ESRD患者的心血管系统、血液系统、骨骼疾病等躯体并发症与体征异常已引起人们的广泛关注,而ESRD患者可能出现的如神经衰弱、焦虑症、抑郁症、恐惧感等精神或神经症候群则容易被忽视。据统计,在普通人群中大约有1.1%～15%的男性和     

Fibrin clot structure in patients with end-stage renal disease

Fibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD). These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p < 0.001), less compactable (p < 0.001), and less susceptible to fibrinolysis (p < 0.001) than clots from controls. The maximum rate of turbidity increase was also higher for the patients than controls (p < 0.001), and scanning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p < 0.001). Patients had higher plasma concentrations of fibrinogen, C-reactive protein and interleukin 6 than controls. These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.     

Altered sleep structure in patients with end-stage renal disease

ObjectiveAlthough symptoms of sleep disturbances are widely recognized in end-stage renal disease (ESRD), the effect of uremia on sleep structure has not been well investigated. We hypothesized that compared to individuals without ESRD, those with ESRD would have altered sleep structure after controlling for the severity of sleep apnea (SA).MethodsWe studied 57 ESRD patients (42 men) and 57 controls (46 men) who had undergone polysomnography. Control subjects were matched to the ESRD patients by age, body mass index (BMI), frequency of periodic leg movements per hour of sleep, and the frequency of apneas and hypopneas per hour of sleep [apnea–hypopnea index (AHI)].ResultsThe AHI and the percentage of patients with an AHI ≥15 were similar between ESRD and control groups. However, total (p = 0.002), rapid eye movement (REM) (p = 0.007), and non-REM (p = 0.022) sleep times were lower in ESRD patients than in the control group. In a multivariable analysis adjusted for age, sex, AHI, BMI, arousal index, and diabetes, ESRD remained independently associated with lower REM (p = 0.021) and total sleep times (p = 0.026).ConclusionESRD is independently associated with reduced total and REM sleep times after controlling for the severity of SA and other variables. Although we could not identify the cause of reduced sleep times, these could be related to uremia or fluid overload or both. Accordingly, our data provide a strong rationale for examining the effects of intensifying dialysis on sleep structure in ESRD patients.     

Disruptions of brain structural network in end-stage renal disease patients with long-term hemodialysis and normal-appearing brain tissues

ObjectiveEnd-stage renal disease (ESRD) patients on hemodialysis were demonstrated to exhibit silent and invisible white-matter alterations which would likely lead to disruptions of brain structural networks. Therefore, the purpose of this study was to investigate the disruptions of brain structural network in ESRD patients.Materials and methodsThiry-three ESRD patients with normal-appearing brain tissues and 29 age- and gender-matched healthy controls were enrolled in this study and underwent both cognitive ability screening instrument (CASI) assessment and diffusion tensor imaging (DTI) acquisition. Brain structural connectivity network was constructed using probabilistic tractography with automatic anatomical labeling template. Graph-theory analysis was performed to detect the alterations of node-strength, node-degree, node-local efficiency, and node-clustering coefficient in ESRD patients. Correlational analysis was performed to understand the relationship between network measures, CASI score, and dialysis duration.ResultsStructural connectivity, node-strength, node-degree, and node-local efficiency were significantly decreased, whereas node-clustering coefficient was significantly increased in ESRD patients as compared with healthy controls. The disrupted local structural networks were generally associated with common neurological complications of ESRD patients, but the correlational analysis did not reveal significant correlation between network measures, CASI score, and dialysis duration.ConclusionGraph-theory analysis was helpful to investigate disruptions of brain structural network in ESRD patients with normal-appearing brain tissues.     

Dihydropteridine reductase activity: lack of association with serum aluminum levels and cognitive functioning in patients with end-stage renal disease

Although increased levels of aluminum (Al) are present in patients with dialysis encephalopathy (DE), it is unclear if the association is causal. The enzyme dihydropteridine reductase (DHPR) plays a critical role in neurotransmitter formation and its activity. Elevated levels of Al are reported to decrease DHPR activity, which would alter neurotransmitter metabolism, thus producing DE. We examined the association between erythrocyte DHPR activity and Al levels, attention/psychomotor skills, and depression in a group of 21 patients with end-stage renal disease. DHPR activity was not related to Al level, mental status, psychomotor ability, or depression score. After administration of deferoxamine (an Al chelating agent), Al level increased significantly but DHPR activity remained the same. Our results suggest that the mechanism for the development for DE does not involve alterations of neurotransmitter metabolism caused by Al-mediated reductions in DHPR activity.     

Macroscale neurovascular coupling and functional integration in end-stage renal disease patients with cognitive impairment: A multimodal MRI study

End-stage renal disease (ESRD) is associated with vascular and neuronal dysfunction, causing neurovascular coupling (NVC) dysfunction, but how NVC dysfunction acts on the mechanism of cognitive impairment in ESRD patients from local to remote is still poorly understood. We recruited 48 ESRD patients and 35 demographically matched healthy controls to scan resting-state functional MRI and arterial spin labeling, then investigated the four types of NVC between amplitude of low-frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, degree centrality, and cerebral blood perfusion (CBF), and associated functional networks. Our results indicated that ESRD patients showed NVC dysfunction in global gray matter and multiple brain regions due to the mismatch between CBF and neural activity, and associated disrupted functional connectivity (FC) within sensorimotor network (SMN), visual network (VN), default mode network (DMN), salience network (SN), and disrupted FC between them with limbic network (LN), while increased FC between SMN and DMN. Anemia may affect the NVC of middle occipital gyrus and precuneus, and increased pulse pressure may result in disrupted FC with SMN. The NVC dysfunction of the right precuneus, middle frontal gyrus, and parahippocampal gyrus and the FC between the right angular gyrus and the right anterior cingulate gyrus may reflect cognitive impairment in ESRD patients. Our study confirmed that ESRD patients may exist NVC dysfunction and disrupted functional integration in SMN, VN, DMN, SN and LN, serving as one of the mechanisms of cognitive impairment. Anemia and increased pulse pressure may be related risk factors.     

Abnormal serotonergic control of prolactin and cortisol secretion in patients with seasonal affective disorder

The effects of the serotonergic agent d,l-fenfluramine (60 mg PO) or a placebo on serum prolactin (PRL) and cortisol levels were evaluated in seven patients (five men and two women) with seasonal affective disorders (SAD) and in eight normal controls (eight men and two women). Both groups were tested in fall/winter when patients with SAD suffered depressive symptoms and in spring/summer, when patients were euthymic. Spring/summer and fall/winter tests gave similar results. PRL and cortisol patterns were similar in all subjects after placebo, whereas both hormonal responses to d,l-fenfluramine were significantly lower in patients with SAD than in normal controls. Correlation studies between the two hormonal responses revealed that on both periods the amplitudes of PRL and cortisol increments were significantly and positively correlated in patients with SAD. These data show diminished serotonergic responsiveness in SAD regardless of the actual depressive status of the patients. They are consistent with a decrease of central serotonergic activity in SAD.     

Haemostatic profiles assessed by thromboelastography in patients with end-stage renal disease

Patients with end-stage renal disease (ESRD) have abnormalities in the cellular and plasmatic systems regulating blood homeostasis, which may contribute to their risk for thrombotic and bleeding complications. However, their relative contributions in this population are poorly understood. The aim of this study was to evaluate the distribution of enzymatic and cellular abnormalities in ESRD patients on haemodialysis as assessed by thromboelastography (TEG?). Whole blood samples were analysed by TEG in ESRD patients (n=70) and in a control group (n=70) of subjects with coronary artery disease. Profiles were constructed considering the maximum amplitude (MA), a marker of platelet function, and reaction time (R), a marker of thrombin generation, values. R values were higher in ESRD patients compared with the control group (8.2 ± 2.8 vs. 5.7 ± 1.9 minutes [min], p <0.0001), while there were no differences in MA (66.7 ± 8.1 vs. 66.2 ± 6.6 mm, p=0.562). Normal manufacturer defined coagulation (2-8 min) and aggregation (51-69 mm) parameters were present in 31% of ESRD patients compared with 56% of controls (p=0.006). A hypocoagulable status was observed in 42.9% of ESRD patients compared with 8.9% in the control group (p<0.0001). There were no differences in platelet function, which showed a hyperaggregable status in 41.4% versus 35.7% of cases (p=0.603). Abnormalities in both parameters were observed in 15.7% of ESRD patients versus 1.4% in the control group (p= 0.004), which were more common among older patients (p= 0.005). In conclusion, patients with ESRD have an elevated prevalence of abnormal haemostatic profiles, which may contribute to their elevated risk of bleeding and thrombotic complications.     

Medical decision-making and information needs in end-stage renal disease patients

Health information and decision-making are increasingly important to patients with diverse illnesses. The aim of this study was to examine health information needs and decision-making in individuals with end-stage renal disease (ESRD) and to examine the influence of age and gender. A self-report survey was administered to 197 consecutive ESRD patients receiving renal replacement therapy. Their mean age was 52.8 years; 58.2% were male, 64.3% were on hemodialysis, and 35.7% on peritoneal dialysis. Actual participation levels in decision-making were not necessarily in agreement with the preferred degree of participation. Eighty percent of patients wanted the health care team (HCT) to make their treatment decisions for them, but only 40% of those who preferred autonomous and 30% of those who preferred shared decision making with their HCT reported that this was their actual experience. Consequently, many more patients perceived that their decision-making was made by their HCT than preferred this. No significant gender differences were observed; however, older participants preferred and experienced their HCT make their treatment decisions (P<.05). All patients wanted high levels of information with some differences by gender and age. HCT should strive to ascertain and meet the information needs and treatment decision-making roles preferred by individual patients.     

Risk factors for selective cognitive decline in dialyzed patients with end-stage renal disease: evidence from verbal fluency analysis

Although dialyzed patients often have cognitive problems, little is known about the nature of these deficits. We hypothesized that, in contrast to semantic fluency relying mainly on temporal lobes, phonemic fluency, preferentially depending on functions of frontal-subcortical systems, would be particularly sensitive to the constellation of physiological pathological processes associated with end-stage renal disease and dialysis. Therefore, we longitudinally compared phonemic and semantic fluency performance between 49 dialyzed patients and 30 controls. Overall, patients performed below controls only on the phonemic fluency task. Furthermore, their performance on this task declined over time, whereas there was no change in semantic fluency. Moreover, this decline was related to the presence of hypertension and higher blood urea nitrogen. We suggest that these findings may be due to a combination of vascular and topic effects that impact more on fronto-subcortical than temporal lobe networks, but this speculation requires direct confirmation.     

Disrupted brain functional networks in patients with end-stage renal disease undergoing hemodialysis

Patterns of change in whole-brain functional networks remain poorly understood in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). We conducted a prospective research to investigate the topological properties of whole-brain functional networks in those patients using a graph-based network analysis. Resting-state functional magnetic resonance imaging was performed on 51 ESRD patients (25 HD and 26 nondialysis patients) and 36 healthy controls (HCs). We compared the topological properties of brain functional networks among the three groups, and analyzed the relationships between those significant parameters and clinical variables in ESRD patients. Progressively disrupted global topological organizations were observed from nondialysis patients to HD patients compared with HCs (all p < 0.05 after Bonferroni correction). HD patients, relative to HCs, showed significantly decreased nodal centralities in the left temporal pole: superior temporal gyrus, bilateral median cingulate and paracingulate gyri, bilateral hippocampus, bilateral parahippocampal gyrus, and bilateral amygdala, and showed increased nodal centralities in the orbital part of the bilateral middle frontal gyrus, left cuneus, and left superior occipital gyrus (all p < 0.05 after Bonferroni correction). Furthermore, nodal centralities in the bilateral hippocampus were significantly decreased in HD patients compared with nondialysis patients (p < 0.05 after Bonferroni correction). Dialysis duration negatively correlated with global efficiency in ESRD patients undergoing HD (r = −0.676, FDR q = 0.004). This study indicates that ESRD patients exhibit disruptions in brain functional networks, which are more severe in HD patients, and these alterations are correlated with cognitive performance and clinical markers.     

Abnormal brain activity patterns during spatial working memory task in patients with end-stage renal disease on maintenance hemodialysis: a fMRI study

Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.

     

Contingent negative variation before and after hemodialysis among patients with end-stage renal disease

OBJECTIVE: To investigate changes in contingent negative variation (CNV) induced by uremia and to study the effects of hemodialysis. METHODS: Fifteen right-handed healthy subjects and 12 patients with end-stage renal disease (ESRD) were studied. CNV was recorded from the Fz, Cz and Pz (using the International 10-20 System) referenced to linked ear lobes, using an S1 (click)-S2 (flashes)-key press paradigm. The amplitude of initial CNV (iCNV) was calculated as the average amplitude at 550-750 ms after S1. The amplitude of late CNV (lCNV) was the mean amplitude of the last 200 ms before S2. Testing was repeated for the patient group at pre- and post-hemodialysis observations. Neuropsychological measurements, a trail making test (TMT) and mini-mental state examination (MMSE), were conducted at each time. RESULTS: The mean amplitudes of iCNV and lCNV at the vertex (Cz) were both significantly lower in the patient group than in the control group (P<0.05). TMT were also significantly different between patient and control groups (P<0.05)), however MMSE showed no significant difference. There were no significant correlations between the values of neuropsychological tests and the parameters of CNV. Both iCNV and lCNV were not significantly different between the pre- and post-dialysis tests. CONCLUSION: CNV negativity in patients with ESRD reflects diffuse nonlocalizing neurological symptoms of uremia rather than a selective involvement of the frontal lobes. It is likely to reflect dysfunction in the frontal-subcortical circuit. In addition, hemodialysis seemed to have no significant effect on executive brain function in these patients with ESRD.     

Depression, perception of illness and mortality in patients with end-stage renal disease.

A role of depression in affecting outcome in patients with end stage renal disease (ESRD) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospectively. To assess whether depression or perception of illness influences survival in patients treated for ESRD, we prospectively evaluated fifty-seven patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14). Patients were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity. A cognitive item subset of the BDI (CDI) was used as an additional measure of depression. One and two years later, records were examined to determine survival. When initial results of the assessment of survivors and non-survivors were compared, at one year follow-up, there were no differences in mean age, duration of dialysis, severity scores, BDI or IEQ scores. The initial mean CDI scores in the group of non-survivors, however, were significantly greater than the scores in the survivor group. At two year follow-up, CDI scores were significantly different between groups, and were significant in a hazards regression. Disease severity, age and duration of dialysis were also significantly related to mortality at two year follow-up. We conclude cognitive depression is an important, early, indicator of grave prognosis in patients treated for ESRD. Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients.     

血清色氨酸水平与终末期肾病患者抑郁的关系

目的:探讨终末期肾病患者抑郁发生与色氨酸及其代谢产物水平之间的关系。方法:将94例行维持性血液净化治疗的终末期肾病患者纳入研究,选取25名健康志愿者为对照组,以贝克抑郁量表(BDI)评分,将终末期肾病检测患者分为抑郁组(≥14分)和非抑郁组(14分)。检测几组的血清白细胞介素-6(IL-6)、色氨酸、犬尿氨酸、以及常规生化指标。结果:终末期肾病患者的IL-6、犬尿氨酸水平明显高于对照组(P0.01),色氨酸水平明显低于对照组(P0.01)。在94例透析患者中,抑郁组19例,非抑郁组75例;发生率为20.2%。抑郁组的血红蛋白、色氨酸水平明显低于非抑郁组(P0.05),IL-6、犬尿氨酸水平明显高于非抑郁组(P0.05)。终末期肾病患者BDI评分与IL-6、犬尿氨酸水平呈正相关(分别为r=0.294,P=0.004;r=0.217,P=0.038),犬尿氨酸与IL-6水平呈正相关(r=0.244,P=0.019)。结论:炎症介质升高可能使犬尿氨酸水平增加,色氨酸水平下降,导致终末期肾病患者发生抑郁。     

Renal pathology in end-stage renal disease associated with paraplegia

In the present study we report the renal pathological findings from autopsy material along with relevant clinical data on 21 spinal cord injury patients with end-stage renal disease (SCI-ESRD) treated with maintenance haemodialysis. These data are compared with the relevant clinical and post-mortem findings on 43 ambulatory dialysis patients who expired during the same time period. The SCI-ESRD patients exhibited markedly different clinical and renal histopathological data when compared to the ambulatory--ESRD group. Chronic pyelonephritis and amyloidosis dominated the findings and were the major causes of renal insufficiency. Acute pyelonephritis, papillary necrosis, calculous disease, pyonephrosis and perinephric abscess formation were also more frequently present in the SCI-ESRD patients. Hypertension and nephrosclerosis, which were common findings in the ambulatory--ESRD patients were comparatively rare in the SCI-ESRD patients. In addition, the incidence of acquired cystic disease (ACD) was considerably less in the SCI-ESRD group. Although the reasons for these findings are not entirely clear several possible explanations are given. Infection with gram negative sepsis was the predominant cause of death in the SCI-ESRD patients, while death secondary to cardiovascular disease predominated in the ambulatory-ESRD group. Furthermore, the urinary tract and infected decubitus ulcers were determined to be the major source for sepsis in the SCI patients. From these findings it would follow that more effective prevention and control of these infections would result in not only a lower incidence of renal failure but also a substantially reduced morbidity and mortality in chronic SCI.     

Gabapentin-induced myoclonus in end-stage renal disease

PURPOSE: We analyzed the occurrence and clinical features of myoclonus in patients with end-stage renal disease (ESRD) who were treated with gabapentin (GBP). METHODS: We reviewed the medical records of patients with ESRD who were treated with GBP and hospitalized during an 18-month period and analyzed clinical details such as type of myoclonus, doses of GBP, electroencephalographic (EEG) findings, and relation of symptoms to GBP exposure and dosage. RESULTS: Three of 71 patients had myoclonus with GBP doses ranging from 9 mg/kg to 20 mg/kg and within 4 months of treatment onset. Myoclonus was characterized as multifocal, involving all extremities in the three patients. EEG did not show epileptiform discharges with the myoclonus. Myoclonus resolved in the three individuals within 4-15 days after GBP was discontinued. CONCLUSIONS: GBP increases the risk of myoclonus in ESRD. Myoclonus in these individuals was more disabling than that in patients with normal renal function, and discontinuation of GBP is required to restore normal function.