Cognition may be related to arterial pulsatility index in HD patients.

AIMS: Hemodialysis (HD) patients have a heavy burden of subclinical cerebrovascular disease and cognitive changes consistent with a vascular etiology. Pulsatility index is associated with microangiopathy of cerebral blood vessels and an increased risk of cerebral infarction. The proposed study was to determine common carotid artery pulsatility index (CCAPI) and its relation to cognition in well-dialyzed HD patients with no history of stroke or dementia and matched controls. METHODS: Observational, cross-sectional study of CCAPI and cognition in 37 hemodialysis outpatients and 18 matched controls with normal kidney function. Non-parametric analyses were used to compare variables between groups. Multiple regression and ANOVA models were used to adjust for risk factor differences. RESULTS: Controls had a lower CCAPI than the HD group (1.7 ± 0.3 vs. 2.1 ± 0.4 cm/s, p = 0.006). HD patients scored significantly lower on all cognitive domains. Attention correlated with CCAPI in HD patients, independent of hypertension, diabetes, hyperlipidemia, and years on HD (r2 = -0.36, p = 0.01). CCAPI correlated with years on HD, independent of traditional cardiovascular risk factors. (r2 = 0.26, p = 0.04). CONCLUSION: In well-dialyzed hemodialysis patients with no history of stroke or dementia, CCAPI may correlate with cognitive function and represent a marker for underlying cerebral microvascular disease.

Increased presence of cognitive impairment in hemodialysis patients in the absence of neurological events.

BACKGROUND/AIMS: Cognitive impairment (CI) is highly prevalent among hemodialysis (HD) patients and is associated with increased morbidity and mortality. The aim was to compare cognitive function in HD patients with no history of stroke or dementia and well-matched controls. Studies are required to determine the impact of HD and chronic kidney disease-specific risks on CI. METHODS: 76 outpatients (50 receiving outpatient HD and 26 with normal kidney function matched for age and comorbidity) underwent a cross-sectional observational study. HD patients were well dialyzed and had optimal hemoglobin levels. A battery of eight neuropsychological tests was used. Outcomes included assessment scores of neurocognitive testing and prevalence and subtype of CI. RESULTS: Compared to controls, HD subjects had significantly lower composite scores for each tested cognitive domain. In each domain except memory, the percentage of subjects with impairment was significantly higher in HD subjects than controls. Differences between the groups were independent of vascular and dementia risk factors. 82% of HD subjects met criteria for CI versus 50% of controls. Non-amnestic subtype of CI was more prevalent in both groups. CONCLUSION: Well-dialyzed HD patients with optimized hemoglobin levels and with no history of stroke or dementia performed significantly worse on multiple measures of cognition compared to controls. A higher prevalence of non-memory impairment may suggest an underlying vascular versus neurodegenerative mechanism. HD and chronic kidney disease-specific risk factors may contribute to early CI not readily detected by routine screening methods.

Cognitive profile of chronic kidney disease and hemodialysis patients without dementia.

BACKGROUND/AIMS: The high risk and prevalence of dementia among patients with chronic kidney disease (CKD) and in those receiving hemodialysis (HD) may be preceded by mild cognitive impairment (MCI). We aimed to assess cognitive function in CKD and HD patients with no history of stroke or dementia, in order to identify and characterize early cognitive deficits. METHODS: 24 CKD and 27 HD male outpatients without history of cerebrovascular or neurodegenerative disease underwent comprehensive neuropsychological testing in an observational cross-sectional study. Test results were used to categorize patients into MCI subtypes. RESULTS: All subjects scored ≥28 on the Mini-Mental State Examination. The prevalence of executive function was at least 25% in both groups and memory impairment occurred in 13% of the HD patients and 15% of those with CKD. MCI occurred in 76% of the group and HD patients showed a higher prevalence of MCI compared to CKD patients (89 vs. 63%) with a preponderance (>70%) of cases across both groups classified as non-amnestic MCI. CONCLUSION: Predialysis CKD and HD patients have a high prevalence of MCI despite normal global cognitive function. MCI was more prevalent among the HD patients and deficits more frequently resulted in non-amnestic MCI.

Thrombocytopenia associated with use of a biocompatible hemodialysis membrane: a case report.

Biocompatibility of a dialyzer membrane has been defined largely by the degree to which it activates complement. Modifications of the cellulose membrane and the development of synthetic membranes have minimized the activation of complement and its associated complications. However, less is known about the blood-dialyzer membrane interactions that may occur in membranes made of the same synthetic polymer. A patient is described who developed dialysis-associated thrombocytopenia using a Fresenius Medical Care Optiflux polysulfone membrane (F-160) that significantly improved when switched to the polysulfone Asahi REXEED 25S membrane (AR-25S). A comparison of postdialysis d-dimer level suggests that the F-160 membrane activated the coagulation pathway to a greater extent than the AR-25S. Subtle differences between the internal surfaces of the membranes that are manufacturer specific may be responsible for exposing this patient's unique predisposition to thrombosis and thrombocytopenia. Despite the advances in membrane biocompatibility, differences may exist among membranes made of the same synthetic polymer.

Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons.

Aging is characterized by increasing inflammation and oxidant stress (OS). Reduced renal function was present in more than 20% of normal-aged individuals sampled in the National Health and Nutrition Examination Survey (NHANES) cross-sectional study of the US population. Longitudinal studies in the United States and Italy showed that renal function does not decline in some individuals, suggesting that a search for causes of the loss of renal function in some persons might be indicated and interventions to reduce this outcome should be sought. Because advanced glycation end products (AGEs) induce both inflammation and OS, accumulate with age, and primarily are excreted by the kidney, one outcome of reduced renal function in aging could be decreased AGE disposal. The build-up of AGEs with reduced renal function could contribute to inflammation, increased oxidant stress, and accumulation of AGEs in aging. In fact, results from a longitudinal study of normal aging adults in Italy showed that the most significant correlation with mortality was the level of renal function. A clear link between inflammation, OS, AGEs, and chronic disease was shown in studies of mice that showed that reduction of AGE levels by drugs or decreased intake of AGEs reduces chronic kidney disease (CKD) and cardiovascular disease of aging. The data support a role for AGEs in the development of renal lesions in aging mice and reveal that AGEs in the diet are very important contributors to renal and cardiovascular lesions. AGEs signal through two receptors, one of which is anti-inflammatory (AGER1) and the other is proinflammatory (RAGE). Overexpression of AGER1 protects against OS and acute vascular injury. The reduction of AGEs in the diet is as efficient in preventing aging-related cardiovascular and renal lesions in mice as that seen with calorie restriction. Studies in normal adults of all ages and those with CKD suggest that the findings in mice may be directly applicable to both aging and CKD. Namely, the dietary content of AGEs determines the serum levels of AGEs and inflammatory mediators and urine AGE levels in both normal subjects and CKD patients. Importantly, reduction of AGEs controls these changes in both normal subjects and CKD patients, and the phenotypic changes in AGER1 are reduced in CKD patients by decreasing the amount of AGEs consumed with the diet. These data suggest that the changes in renal function in normal aging may be subject to control and this subject deserves renewed attention.

Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

Iron deficiency in patients with chronic kidney disease: potential role for intravenous iron therapy independent of erythropoietin.

UNLABELLED: The prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients. All new hemodialysis patients entering a single hemodialysis unit between July 1999 and April 2002 were included in the study. The admission laboratory tests and the Health Care Financing Administration (HCFA) 2728 form were examined to determine the prevalence of erythropoietin use, anemia (Hb<11 g/dl), and iron deficiency (ferritin<100 ng/ml and transferrin saturation %<20%). In a second part of the study, the effect of intravenous iron gluconate replacement in patients with stage III & IV chronic kidney disease was examined. Anemia was present in 68% of all patients starting hemodialysis. Iron deficiency was a common feature occurring in 29% of patients taking erythropoietin (49% of all patients) and 26% of patients without erythropoietin (51% of all patients). Following the administration of intravenous iron gluconate to four patients, there was a significant rise in hemoglobin levels from 10.6+/-0.19 to 11.7+/-g/dl (p=0.02). CONCLUSION: Iron deficiency is common in predialysis patients. Replenishing iron stores in anemic patients with chronic kidney disease significantly increases hemoglobin levels and should be considered as an integral part of the therapy for treating anemia in the predialysis population.