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.

Purpose Angiotensin-converting enzyme (ACE) inhibitors are recommended for patients with chronic kidney disease (CKD) because they slow disease progression. But physicians’ concerns about the risk of hyperkalemia (elevated serum potassium level), a potentially fatal adverse effect, may limit optimal management with ACE-inhibitors. We synthesized known predictors of hyperkalemia into a prognostic risk score to predict the risk of hyperkalemia. Methods We assembled a retrospective cohort of adult patients with possible CKD (at least one estimated glomerular filtration rate (eGFR) value less than 60 mL/min/1.73m2) who started an ACE-inhibitor (i.e., incident users) between 1998 and 2006 at a health maintenance organization. We followed patients for hyperkalemia: (1) potassium value > 5.5 mmol/L; or, (2) diagnosis code for hyperkalemia. Cox regression synthesized a priori predictors recorded in the electronic medical record into a risk score. Results We followed 5,171 patients and 145 experienced hyperkalemia, a 90-day risk of 2.8%. Predictors included: age, eGFR, diabetes, heart failure, potassium supplements, potassium-sparing diuretics, and a high dose for the ACE-inhibitor (lisinopril). The risk score separated high-risk patients (top quintile, observed risk of 6.9%) from low-risk patients (bottom quintile, observed risk of 0.7%). Predicted and observed risks agreed within 1% for each quintile. The risk increased gradually in relation to declining eGFR with no apparent threshold for contraindicating ACE-inhibitors. Conclusions The risk score separated high-risk patients (who may need more intensive laboratory monitoring) from low-risk patients. The risk score should be validated in other populations before it is ready for use in clinical practice.

OBJECTIVE-We assessed the representation of numerosity in corticobasal syndrome (CBS), a neurodegenerative condition affecting the parietal lobe.METHOD-Patients judged whether a target numerosity (e.g., "3") falls between two bounding numerosities (e.g., "1" and "5"). We manipulated the format for representing numerosity (Arabic numerals or dot arrays), the size of the gap between the two bounding numerosities, the absolute magnitude of the numerosities, and the order for presenting the bounding numerosities. In a subset of patients with available imaging, we related performance to cortical atrophy using voxel-based morphometry (VBM).RESULTS-CBS patients were significantly impaired overall (65.7% ±16.2 correct) compared to healthy seniors (96.6% ± 2.4 correct), and required three times longer than controls to judge correct stimuli. This deficit was equally evident for Arabic numeral and dot array formats. Controls were significantly slower with smaller gaps than larger gaps, consistent with the greater challenge distinguishing between numerosities that are more similar to each other than very different numerosities.However, CBS patients were equally slow and inaccurate for all gap sizes. Controls also were significantly slower with larger numerosities than smaller numerosities, but CBS patients were equally slow and inaccurate with all numerosity magnitudes. VBM revealed significant cortical atrophy in parietal and frontal regions in CBS compared to controls, including the intraparietal sulcus.CONCLUSIONS-These observations are consistent with the claim that the representation of numerosity is degraded in CBS.

Objective: To use multimodal neuroimaging to evaluate the influence of heterogeneous underlying pathology in corticobasal syndrome (CBS) on the neuroanatomical distribution of disease.Methods: We performed a retrospective evaluation of 35 patients with CBS with T1-weighted MRI, diffusion tensor imaging, and neuropathologic, genetic, or CSF evidence of underlying pathology. Patients were assigned to 2 groups: those with evidence of Alzheimer pathology (CBS-AD) and those without Alzheimer pathology (CBS-non-AD). Group comparisons of CBS-AD and CBS-non-AD assessed clinical features, gray matter (GM) cortical thickness, and white matter (WM) fractional anisotropy.Results: CBS-AD was found in 34% (n 5 12) and CBS-non-AD in 66% (n 5 23) of CBS patients.Clinical evaluations revealed that CBS-non-AD had a higher frequency of asymmetric rigidity compared to CBS-AD, but groups otherwise did not differ in dementia severity, impairments in cognition, or rates of extrapyramidal symptoms. We found frontoparietal GM and WM disease in each group compared to healthy, demographically comparable controls, as well as multimodal neuroimaging evidence of a double dissociation: CBS-non-AD had WM disease in the corpus callosum, corticospinal tract, and superior longitudinal fasciculus relative to CBS-AD, and CBS-AD had reduced temporoparietal GM relative to CBS-non-AD, including the precuneus and posterior cingulate. Conclusions:Patients with CBS have a pathology-mediated dissociation of GM and WM disease.Multimodality neuroimaging may be useful for improving in vivo pathologic diagnosis of CBS. Corticobasal syndrome (CBS) is a neurodegenerative condition characterized by lateralized extrapyramidal features and cortically mediated cognitive dysfunction.1 The underlying pathology of CBS is heterogeneous, and clinical features appear to be insufficient to identify an individual's histopathologic abnormality during life.2,3 The most common neuropathologic causes of CBS include corticobasal degeneration, a 4-repeat form of tau pathology associated with frontotemporal lobar degeneration (FTLD), 4 and Alzheimer disease (AD). 2,5,6 Multimodal neuroimaging studies suggest that AD and FTLD can be dissociated on the basis of gray matter (GM) and white matter (WM) neuroimaging. 7,8 Specifically, GM atrophy was evident in both AD and FTLD in T1-weighted MRI studies, but diffusion tensor imaging (DTI) revealed more WM disease in FTLD than in AD. Additional neuroimaging evidence suggests that tau pathology, the most common form of underlying pathology in CBS, is associated with substantial WM imaging changes 9 and that these findings converge with neuropathologic evidence of WM disease burden in 4-repeat tauopathy.9,10 However, prior evidence of greater WM pathology in FTLD disorders has been based on clinically heterogeneous study samples; therefore, it is not clear whether a dissociation of GM and WM disease is

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