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Nephrology, Dialysis, Transplantation :... Sep 2013Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has... (Review)
Review
Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in the mid-nineteenth century, and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis). Additional studies showed that during life impaired renal function occurred in half of these subjects. As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se. Indeed, gout was removed from the textbooks as a cause of CKD, and the common association of hyperuricemia with CKD was solely attributed to the retention of serum uric acid that is known to occur as the glomerular filtration rate falls. Renewed interest in uric acid as a cause of CKD occurred when it was realized that invalid assumptions had been made in the arguments to dismiss uric acid as a risk factor for CKD. The greatest assumption was that the mechanism by which uric acid would cause kidney disease would be via the precipitation as crystals in the kidney, similar to the way it causes gout. However, when laboratory animals with CKD were made hyperuricemic, the renal disease progressed rapidly despite an absence of crystals in the kidney. Since this seminal study, there has been a renewed interest in the potential role uric acid may have in both acute and CKD. We briefly review some of the major advances that have occurred in this field in the last 15 years.
Topics: Animals; Humans; Rats; Renal Insufficiency, Chronic; Risk Factors; Uric Acid
PubMed: 23543594
DOI: 10.1093/ndt/gft029 -
Stroke Oct 2017There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with... (Observational Study)
Observational Study
BACKGROUND AND PURPOSE
There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults.
METHODS
We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. We examined the associations of spinal arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex.
RESULTS
Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; =14.58; <0.001). Arteriolosclerosis was more severe in the spinal cord than in the brain (cord: 4.10, SD=0.70; brain: 3.5, SD=0.98; =10.39; <0.001). The severity of spinal arteriolosclerosis was associated with spinal white matter pallor (=0.47; <0.001). Spinal arteriolosclerosis accounted for ≈3% of the variation in parkinsonism in models controlling for age, sex, brain arteriolosclerosis, and cerebrovascular disease pathologies. Further models showed that the association of spinal arteriolosclerosis and parkinsonism was not mediated via spinal white matter pallor.
CONCLUSIONS
Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.
Topics: Aged, 80 and over; Aging; Arteriolosclerosis; Brain; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Microvessels; Parkinsonian Disorders; Spinal Cord
PubMed: 28931619
DOI: 10.1161/STROKEAHA.117.017643 -
NeuroImage. Clinical 2021Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor...
Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/.
Topics: Aged; Alzheimer Disease; Arteriolosclerosis; Brain; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Reproducibility of Results
PubMed: 34330087
DOI: 10.1016/j.nicl.2021.102768 -
Veterinary Pathology Sep 1987
Topics: Animals; Arterioles; Arteriosclerosis; Cat Diseases; Cats; Female; Kidney
PubMed: 3672816
DOI: 10.1177/030098588702400519 -
Journal of Wound Care Apr 2022Martorell hypertensive ischaemic ulcers are often misdiagnosed and can be a clinical and therapeutic challenge. Controversy exists regarding both their underlying...
OBJECTIVE
Martorell hypertensive ischaemic ulcers are often misdiagnosed and can be a clinical and therapeutic challenge. Controversy exists regarding both their underlying triggers and the type of treatment that should be carried out. This study was designed to compare the effectiveness of punch grafting and conventional therapy in pain reduction.
METHOD
A single-centre retrospective study was performed, including 40 patients with a clinical diagnosis of a Martorell ulcer or post-traumatic ulcer secondary to arteriolopathy in the elderly, who were treated with punch grafting (n= 24) or conventional medical treatment (n=16).
RESULTS
There was a statistically and clinically significant reduction in pain after punch grafting. The minimal overall reduction was of three points in visual analogue pain scores. Of the patients who received punch grafting, 80% reported a VAS pain score of 0 at the third follow-up, in contrast with the 44% (n=4) patients who were treated without punch grafting. The mean time to epithelialisation was 82.1 days in patients who received conventional treatment and 43.5 days in those who received punch grafts.
CONCLUSION
Punch grafting is a simple, validated and cost-effective technique that can be performed on an outpatient basis, promotes wound healing and reduces pain. It may control pain and stimulate epithelialisation even if the wound does not present with optimum wound bed characteristics for graft taking. Pain reduction and faster epithelialisation are associated with improvements in patients' quality of life.
Topics: Aged; Arteriolosclerosis; Humans; Leg Ulcer; Pain; Quality of Life; Retrospective Studies; Skin Transplantation; Skin Ulcer; Ulcer
PubMed: 35404703
DOI: 10.12968/jowc.2022.31.4.356 -
Journal of Neuropathology and... Mar 2021Locus coeruleus (LC) neurodegeneration is associated with cognitive deterioration during the transition from normal cognition to mild cognitive impairment (MCI) and...
Locus coeruleus (LC) neurodegeneration is associated with cognitive deterioration during the transition from normal cognition to mild cognitive impairment (MCI) and Alzheimer disease (AD). However, the extent to which LC degenerative processes differentiate cognitively normal, "resilient" subjects bearing a high AD pathological burden from those with MCI or AD remains unclear. We approached this problem by quantifying the number of LC neurons and the percentage of LC neurons bearing AT8 tau pathology, TDP-43 pathology, or a marker for DNA/RNA oxidative damage, in well-characterized subjects diagnosed as normal cognition-low AD pathology (NC-LP), NC-high AD pathology (NC-HP), MCI, or mild/moderate AD. In addition, the severity of pontine arteriolosclerosis in each subject was compared across the groups. There was a trend for a step-wise ∼20% loss of LC neuron number between the NC-LP, NC-HP and MCI subjects despite a successive, significant ∼80%-100% increase in tau pathology between these groups. In contrast, increasing pontine arteriolosclerosis severity scores and LC oxidative stress burden significantly separated the NC-LP/HP and MCI/AD groups via comparative, correlation, and regression analysis. Pontine perfusion, as well as LC neuronal metabolic and redox function, may impact noradrenergic LC modulation of cognition during the preclinical and prodromal stages of AD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Arteriolosclerosis; Brief Psychiatric Rating Scale; Cognitive Dysfunction; Cohort Studies; Diagnosis, Differential; Female; Humans; Locus Coeruleus; Male; Oxidative Stress; Pons; Resilience, Psychological
PubMed: 33709107
DOI: 10.1093/jnen/nlab017 -
Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study.Kidney International Reports Sep 2022
PubMed: 36090487
DOI: 10.1016/j.ekir.2022.05.036 -
Biomedicines Jul 2023The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the...
The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the cross-sectional association between smoking (current or former) and renal arteriolar hyalinosis and wall thickening with or without HU [uric acid (UA) level ≥ 7 and ≥5 mg/dL in men and women] in 87 patients with IgA nephropathy who underwent renal biopsy. Arteriolar hyalinosis and wall thickening were assessed by the semiquantitative grading of arterioles. The SMK/HU subgroup showed the highest indices for hyalinosis and wall thickening, followed by the non-SMK/HU, SMK/non-HU, and non-SMK/non-HU subgroups. Multiple logistic analysis showed that SMK/HU, but not SMK/non-HU, was significantly associated with an increased risk of higher-grade renal arteriolar wall thickening. However, this did not occur with hyalinosis compared to non-SMK/non-HU. The adjusted odds ratio (95% confidence interval, value) for SMK/HU was 12.8 (1.36-119, < 0.05) for wall thickening. An association between SMK and renal arteriolar wall thickening might be prevalent only among patients with HU and in patients with IgA nephropathy. Further prospective studies are needed to determine whether patients with HU and SMK history exhibit rapid eGFR deterioration.
PubMed: 37509692
DOI: 10.3390/biomedicines11072053 -
Alzheimer Disease and Associated...We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE).
OBJECTIVE
We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE).
METHODS
Using National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively.
RESULTS
In MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE.
CONCLUSIONS
Differences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.
Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoprotein E4; Cognitive Dysfunction; Disease Progression; Female; Humans; Intracranial Arteriosclerosis; Male; Mental Status and Dementia Tests; Neuropathology; Neuropsychological Tests; Retrospective Studies
PubMed: 32925200
DOI: 10.1097/WAD.0000000000000411 -
Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.Brain : a Journal of Neurology Jan 2014Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a...
Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Arterioles; Arteriolosclerosis; Autopsy; Brain; Capillaries; Cerebral Infarction; Cerebrovascular Disorders; Cohort Studies; Databases, Factual; Female; Hippocampus; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Logistic Models; Male; Odds Ratio; Sclerosis
PubMed: 24271328
DOI: 10.1093/brain/awt318