Limited data are available on the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end stage renal disease (ESRD) among individuals with chronic kidney disease (CKD). We conducted a collaborative meta-analysis of 21,688 participants selected for CKD from 13 cohorts. After adjustment for potential confounders and albuminuria, a 15 mL/min/1.73 m2 lower eGFR below 45 mL/min/1.73 m2 was significantly associated with mortality (pooled hazard ratio [HR] 1.47 [95% CI: 1.22–1.79]), and ESRD (pooled HR 6.24 [95% CI: 4.84–8.05]). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eight-fold higher albumin:creatinine ratio (ACR) or protein:creatinine ratio (PCR) was significantly associated with mortality (pooled HR 1.40 [95% CI: 1.27–1.55]), without evidence of significant heterogeneity. An eight-fold higher ACR or PCR was also strongly associated with ESRD (pooled HR 3.04 [95% CI: 2.27–4.08]), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD. The associations are stronger for ESRD than for mortality. The observed associations are consistent with CKD classification based on eGFR stages, and suggest that albuminuria provides additional prognostic information among individuals with CKD.
Age-associated loss of kidney function has been recognized for decades. With aging, many subjects exhibit progressive decreases in glomerular filtration rate (GFR) and renal blood flow (RBF), with wide variability among individuals. The fall in GFR is due to reductions in the glomerular capillary plasma flow rate, and the glomerular capillary ultrafiltration coefficient. In addition, a primary reduction in afferent arteriolar resistance is associated with an increase in glomerular capillary hydraulic pressure. These hemodynamic changes occur in concert with structural changes, including loss of renal mass; hyalinization of afferent arterioles and in some cases, development of aglomerular arterioles; an increase in the percentage of sclerotic glomeruli; and tubulointerstitial fibrosis. Aging is associated with altered activity and responsiveness to vasoactive stimuli, such that responses to vasoconstrictor stimuli are enhanced, while vasodilatory responses are impaired. Changes in the activity of the renin-angiotensin and nitric oxide systems appear to be particularly important, as is the modulating effect of gender. These changes may predispose the older kidney to acute kidney injury, including normotensive ischemic nephropathy, as well as progressive chronic kidney disease.
Objective: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD).Methods: Letter ("FAS") and semantic ("animal") fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n ϭ 71), semantic dementia (SemD; n ϭ 21), and progressive nonfluent aphasia (PNFA; n ϭ 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n ϭ 51; PNFA, n ϭ 11; SemD, n ϭ 10). Results:Patients with SemD were disproportionately impaired on the semantic fluency measure.Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/ lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative illness associated with frontal and temporal lobe atrophy. Conclusions:1 Clinical subgroups of patients with FTLD include a decline in behavior, comportment, and executive functioning (bvFTLD) 2,3 ; semantic dementia (SemD) 4 associated with fluent progressive aphasia, impaired word comprehension, and poor object knowledge; and progressive nonfluent aphasia (PNFA) 5 associated with effortful speech and impaired grammatic comprehension. Imaging studies have shown that these patients have different distributions of cortical atrophy. 6Recent research has demonstrated that these FTLD subgroups can present with impaired executive control as seen by reduced performance on tests of letter ("FAS") and semantic ("animals" 7,8 ) fluency. Because autopsy-confirmed patients with FTLD produce differing patterns of impairment on letter as compared with semantic fluency tests, these tests may help differentiate between Alzheimer disease (AD) and FTLD and between FTLD subtypes. [9][10][11][12] Functional neuroimaging studies of healthy adults associate these tasks with partially distinct activation patterns.
Patient: A man with semantic dementia, as demonstrated by clinical, neuropsychological, and imaging studies.Main Outcome Measures: Music performance and magnetic resonance imaging results.Results: Despite profoundly impaired semantic memory for words and objects due to left temporal lobe atrophy, this semiprofessional musician was creative and expressive in demonstrating preserved musical knowledge. Conclusion:Long-term representations of words and objects in semantic memory may be dissociated from meaningful knowledge in other domains, such as music.
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