James Post

Cerebrovascular effects of hemodialysis in chronic kidney disease

Patients with end-stage renal disease (ESRD) undergoing hemodialysis are known to suffer cognitive deficits and stroke of unknown etiology. It has been suspected that the treatment itself may contribute to the syndrome by unknown mechanisms, which we investigated in this study. End-stage renal disease patients on hemodialysis (n = 19) or peritoneal dialysis (PD, n = 5) were compared with 14 healthy controls. Subjects participated in magnetic resonance imaging (MRI) measurements of cerebral atrophy, cerebral blood flow (CBF) arterial spin labeled-MRI (ASL-MRI), quantitative Doppler blood flow through the internal carotid artery, and cerebral oxymetry. The Doppler and oxymetry procedures were also performed at the beginning and end of a single hemodialysis session. End-stage renal disease patients on hemodialysis showed significant cerebral atrophy, associated with longer hemodialysis duration and cognitive deficits, including focal bilateral lesions in the caudate nucleus and midbrain. Cerebral oxygenation was extremely low before dialysis (rSO2 41 ± 13, compared with 70 ± 2 in controls, P < 0.02) and improved only slightly after dialysis. Carotid blood flow was also very low at the start of dialysis (115 ± 28mL/sec, versus 193 ± 56 in controls, P < 0.005) but normalized at the end of the session (181 mL/sec). The PD patients showed intermediate values, between the hemodialysis and controls. Notably, duration of hemodialysis treatment predicted global gray-matter volume (r = −0.74), change of blood flow during dialysis (r = −0.65), and baseline rSO2 (r = −0.65). The findings suggest that ESRD patients on hemodialysis suffer low CBF during the interdialytic cycle. Coupled with low cerebral oxygenation levels and atherosclerosis, this may contribute significantly to the etiology of the observed cerebral atrophy, cognitive deficits, and high stroke prevalence.

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.

The renal safety of bowel preparations for colonoscopy : a comparative study of oral sodium phosphate solution and polyethylene glycol

Background  Rare cases of nephrotoxicity have been reported with oral sodium phosphate solution (OSPS).

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.

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.

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.

Clinical trial: the efficacy and safety of routine bowel cleansing agents for elective colonoscopy in persons with spinal cord injury – a randomized prospective single‐blind study

Background  As difficulty with evacuation is a common occurrence in individuals with spinal cord injury, preparation prior to colonoscopy may be suboptimal and, perhaps, more hazardous.

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.

Telenephrology: Providing Healthcare to Remotely Located Patients with Chronic Kidney Disease

Background: Chronic kidney disease (CKD) patients who live far (>30 miles) from their nephrologist experience lower rates of clinic visit adherence, limited access to treatment, and higher rates of hospitalization and mortality than patients who live in close proximity to their nephrologist. Strategies to minimize disparities between urban and remotely located CKD patients are needed. The purpose of this study was to determine whether adherence to clinic visits and clinical outcomes in the remote management of CKD via telenephrology is comparable to in-person conventional care. Methods: Renal clinic adherence and composite outcomes of death, end-stage renal disease (ESRD), or doubling of serum creatinine (Cr) were measured in geographically remote Hudson Valley VA Medical Center (HVVAMC) CKD patients enrolled in telenephrology (n = 112) and CKD patients enrolled in the Bronx VAMC renal clinic (n = 116). Results: Prior to implementing the telenephrology service, 53.1% of scheduled visits of rural HVVAMC patients to the Bronx VAMC renal clinic were either cancelled or were “no-shows.” This was reduced by nearly half (28.5%) after instituting telenephrology (p < 0.001). Moreover, the frequency of attending appointments was greater in the telenephrology (71.9%) vs. in-person Bronx VA cohort (61.0%). The incidence of the composite outcome of death, ESRD, or doubling of Cr was similar between both groups (p = 0.96) over 2 years of follow-up. Conclusions: Remote CKD care delivered through telenephrology improves renal clinic visit adherence while delivering comparable renal outcomes. Application of this technology is a promising method to provide access to care to rural CKD patients and to minimize the disparity between urban/rural patients.

T1093 Long Term Follow Up of Renal Function in Subjects Receiving Oral Sodium Phosphate for Bowel Preparation Prior to Colonoscopy: A Prospective Study

G A A b st ra ct s insertion in 22 subjects (6.1%) and blood came from the stomach into the catheter in 17 (4.7%). Proper catheter placement could be confirmed by the litmus paper turning red in 360 subjects (98.9%). Testing with litmus paper failed because 1) Considerable bile reflux into the stomach turned the paper yellow; 2) Large amounts of saliva flowing into the stomach made it difficult to interpret the color change. The test was repeated two hours later, demonstrating the paper turned red in the remaining subjects. Conclusions: Gastrostomy catheter replacement using a rod was a very safe procedure. Litmus paper allowed confirmation that the replacement catheter was properly positioned in the stomach whether or not bleeding occurred inside or outside the stomach. The procedure appears to provide an easy and useful means of catheter replacement to home or nursing-home settings where radiographic equipment is not available.