The magnitude of creatinine increase after cardiac surgery is associated in a graded manner with an increased risk of incident CKD, CKD progression, and mortality.

Background The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk of cognitive impairment (CI) in chronic kidney disease (CKD) patients. We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. Study Design Longitudinal observational cohort study of the epidemiology of CI in CKD. The primary aim is to characterize the association between (a) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, dialysis initiation, and (b) cognitive decline over 3 years in a CKD cohort with mean eGFR < 45 mL/min/1.73 m2. Setting & Participants Community-dwelling participants aged 45 years or older recruited from four health systems into two groups: reduced eGFR, defined as eGFR < 60 mL/min/1.73 m2 (non-dialysis-dependent), and control, defined as eGFR ≥ 60 mL/min/1.73 m2. Predictor eGFR group. Outcomes Performance on cognitive function tests and structural brain magnetic resonance imaging. Measurements Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. Results Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFR <45 (non-dialysis dependent, non-transplant), 45-<60, and ≥ 60 (controls) mL/min/1.73 m2, respectively. Mean eGFR in the reduced eGFR participants was 34.3 mL/min/1.73 m2. Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFR < 30 mL/min/1.73 m2 performed significantly worse than those with eGFR ≥ 30 mL/min/1.73 m2 on tests of memory, processing speed, and executive function. Participants with reduced eGFR overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. Limitations Healthy cohort bias, competing risk of death versus cognitive decline. Conclusions Cognitive function was significantly worse in participants with eGFR < 30 mL/min/1.73 m2. Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

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.