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Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

ABSTRACT: BACKGROUND:Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. OBJECTIVE:To measure the association between kidney function biomarkers and brain MRI findings in CKD. METHODS:In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. RESULTS:We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: eGFR 45-59; 74 controls: eGFR?60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. CONCLUSIONS:Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

SUBMITTER: Vemuri P

PROVIDER: S-EPMC5621389 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

Vemuri Prashanthi P Knopman David S DS Jack Clifford R CR Lundt Emily S ES Weigand Stephen D SD Zuk Samantha M SM Thostenson Kaely B KB Reid Robert I RI Kantarci Kejal K Slinin Yelena Y Lakshminarayan Kamakshi K Davey Cynthia S CS Murray Anne A

Journal of Alzheimer's disease : JAD 20170101 3

<h4>Background</h4>Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD.<h4>Objective</h4>To measure the association between kidney function biomarkers and brain MRI findings in CKD.<h4>Methods</h4>In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), an ...[more]

PMID: 27767995

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Project description:Rationale & objectivePatients with kidney failure have poor physical performance, but its trajectory is less clear. We examined physical function over the course of kidney disease, including the transition to dialysis.Study designObservational cohort.Setting & participantsCommunity-dwelling adults aged ≥45 years in the Brain in Kidney Disease (BRINK) cohort study.PredictorsEstimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR).OutcomesChange in physical performance using the Short Physical Performance Battery (SPPB) (primary) and gait speed (secondary).Analytical approachLinear mixed effects regression models.ResultsThe analytical cohort included 562 participants with mean age of 69.3 (SD, 9.8) years followed for up to 63 months. In total, 49.8% were women. In addition, 79.9% self-identified as White, and 15.3% self-identified as Black. In total, 48.8% had diabetes. Mean eGFR at baseline was 48.1 (SD, 24.3) mL/min/1.73 m2. In unadjusted analysis, lower eGFR was associated with greater decline in SPPB score (P trend < 0.001). The decline in SPPB score was larger among participants with lower eGFR, with a gradient from -0.15 (95% CI, -0.23 to -0.07) points per year for participants with eGFR ≥60 mL/min/1.73 m2 to -0.56 (95% CI, -0.84 to -0.27) for participants with eGFR <15 mL/min/1.73 m2 and -0.61 (95% CI, -0.90 to -0.33) after dialysis initiation. In covariate-adjusted models, SPPB did not continue to decline after dialysis initiation. In secondary analyses evaluating change in gait speed, gait speed continued to decline after dialysis initiation. Higher UACR was also associated with a greater decline in SPPB score and gait speed in unadjusted and adjusted models.LimitationsSmall number of participants started dialysis.ConclusionsWe found a graded association of chronic kidney disease stage and albuminuria with decline in physical performance. The decline in SPPB was not accelerated after dialysis initiation in covariate-adjusted models, whereas gait speed continued to decline.

Project description:The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results.Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2).Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR?60 mL/min/1.73 m(2).eGFR group.Performance on cognitive function tests and structural brain magnetic resonance imaging.Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years.Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ?60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs?30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised.Healthy cohort bias, competing risk for death versus cognitive decline.Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

Project description:Rationale & objectiveChronic kidney disease (CKD) is associated with impaired physical performance. However, the association between albuminuria, a marker of vascular endothelial dysfunction, and physical performance has not been fully characterized. We hypothesized that estimated glomerular filtration rate (eGFR) and albuminuria would be independently associated with physical performance.Study designCross-sectional analysis.Setting & participantsA total of 571 adults with and without CKD.PredictorsCreatinine-based eGFR (eGFRCr) and cystatin C-based eGFR (eGFRCysC) and urine albumin to creatinine ratio (UACR).OutcomeShort Physical Performance Battery (SPPB).Analytical approachUnivariate and multivariable logistic regression models were used to examine associations of eGFR and UACR with impaired physical performance.ResultsOf the 571 participants (mean age, 69.3 years), 157 (27.5%) had eGFRCr (mL/min/1.73m2) <30, 276 (48.3%) had eGFRCr 30-<60, and 138 (24.2%) had eGFRCr ≥60; 303 (55.3%) participants had eGFRcysC <30, 141 (25.7%) had eGFRcysC 30-<60, and 104 (19.0%) had eGFRcysC ≥60. Impaired physical performance was observed in 222 (38.9%) participants. Separate univariate analyses showed that lower eGFRCr, lower eGFRCysC, and higher UACR were associated with higher odds of impaired physical performance. In the adjusted model with eGFRCr or eGFRCysC, UACR, and covariates, UACR retained a statistically significant association with impaired physical performance (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 1.21-3.47 for UACR from 30-300 mg/g vs <30 mg/g and adjusted OR, 1.93; 95% CI, 1.01-3.69 for UACR >300 mg/g vs <30 mg/g), but eGFRCr and eGFRCysC did not.LimitationsCross-sectional analysis, estimated rather than measured GFR.ConclusionsOnly UACR was associated with worse physical performance in the fully adjusted model, suggesting that vascular endothelial function and inflammation may be important mechanisms of decreased physical function. Similar results were found using eGFRCr or eGFRCysC, suggesting that confounding based on muscle mass does not explain the lack of an association between eGFRCr and physical performance.

Project description:Disproportionately enlarged subarachnoid space hydrocephalus (DESH), characterized by ventriculomegaly, high convexity/midline tight sulci, and enlarged sylvian fissures on brain MRI has been increasingly recognized as a distinct diagnostic imaging entity that falls within the larger category of idiopathic normal pressure hydrocephalus. Normal pressure hydrocephalus has been previously characterized as a CSF dynamics disorder based on abnormalities on nuclear medicine cisternography: radiotracer in the lateral ventricles and absent or delayed ascent of radiotracer over the cerebral convexity. The purpose of this work was to evaluate for differences in nuclear medicine cisternography between patients with vs without DESH and thereby provide support for the concept that DESH is a structural imaging marker of a CSF dynamics disorder. The study included 102 patients (mean age 71 years, range 46-86, 38 females), 58 patients with cisternogram performed to evaluate suspected normal pressure hydrocephalus (mean age 73 years, range 46-86 years, 24 female) and 44 patients evaluated for headache (mean age 68 years, range 60-82 years, 14 female). All patients had an MRI of the brain performed within 13 months of the cisternogram. Cisternogram imaging, typically acquired at 0.5, 1, 2, 4, and 24 h post injection, was evaluated for the time at which radiotracer reached the basal cisterns, presence of persistent radiotracer in the lateral ventricles, time radiotracer first entered the lateral ventricles, presence of radiotracer over the cerebral convexity, and time at which radiotracer was first visualized over the cerebral convexity. MRI features of ventriculomegaly (defined as Evans' index ≥ 0.3) and high convexity tight sulci (HCTS) were recorded. Based on the MRI features, patients were grouped according to presence or absence of DESH (ventriculomegaly and HCTS). Those without DESH were separated into groups of ventriculomegaly alone, HCTS alone, and neither ventriculomegaly nor HCTS. Cisternogram metrics were compared between MR-defined groups. Patients with DESH showed a higher frequency of radiotracer in the lateral ventricles and delayed or absent ascent over the cerebral convexity compared to those without DESH, higher frequency of ventricular radioactivity vs those with HCTS alone, and shorter time to ventricular radioactivity compared to those with ventriculomegaly alone. Patients with ventriculomegaly or HCTS alone had a higher frequency of radiotracer in the lateral ventricles and delayed ascent of radiotracer over the cerebral convexity compared to those with neither ventriculomegaly nor HCTS. These findings support DESH and the individual components of ventriculomegaly and HCTS as markers of disordered CSF dynamics.

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Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

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Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

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