In a cohort of patients with chronic kidney disease (CKD), having a more advanced stage of renal dysfunction was associated with an increased risk for incident cognitive impairment.
Previous studies have linked CKD to cognitive decline, especially when proteinuria is present, yet few population studies have examined both estimated glomerular filtration rate (eGFR) and proteinuria across the CKD spectrum in relation to cognitive impairment.
Researchers analyzed data of 5607 adults with CKD (mean age, 59.6 years; 56.3% men) who were free of cognitive impairment at baseline from a US-based cohort to assess associations between the severity of CKD (based on eGFR and the urinary protein-to-creatinine ratio [UPCR]) and the risk for incident cognitive impairment.
Participants underwent evaluation of global cognition and domains of verbal memory, delayed recall, attention, processing speed, and executive function.
Fasting blood and urine samples were collected to assess kidney function and proteinuria; eGFR was categorized as G1-G2 (≥ 60 mL/min/1.73 m2), G3a (45-59 mL/min/1.73 m2), G3b (30-44 mL/min/1.73 m2), and G4-G5 (< 30 mL/min/1.73 m2) and UPCR as normal to mildly increased (< 150 mg/g), moderately increased (150-500 mg/g), and severely increased (> 500 mg/g). The median follow-up duration ranged from 4-6 years.
Each 1-SD decrease in baseline eGFR was associated with a 21% increase in the risk for impairments in attention and processing speed (hazard ratio [HR], 1.21; P = .006); however, this association was attenuated after adjusting for UPCR. Each 1-SD increase in log-transformed UPCR was associated with a 21% increase in the risk for impairments in attention and processing speed (HR, 1.21; P = .01) and a 16% increase in the risk for impairment in executive function (HR, 1.16; P = .02); the associations remained nominally significant even after adjusting for eGFR.
Patients with a combined eGFR < 60 mL/min/1.73 m2 and UPCR ≥ 150 mg/g had a 38% increased risk for impairment in global cognition compared with those with better kidney function (HR, 1.38; P = .003).
“Although significant findings were observed in individual analyses of both the eGFR and the UPCR, the UPCR was shown to be a more robust determinant when modeled together…. These findings underscore CKD severity as a risk factor for cognitive decline across the CKD spectrum,” the authors reported.
The study was led by Zhijie Huang, PhD, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana. It was published online in JAMA Network Open. The study primarily used UPCR instead of urinary albumin-to-creatinine ratio. It excluded individuals with end-stage kidney disease, potentially limiting generalizability to those with most advanced CKD. Annual or biennial cognitive tests may have been subject to practice effects and ceiling effects, potentially attenuating observed associations. Despite adjusting for numerous lifestyle and clinical risk factors, residual confounding may persist.
(Medscape)
The study was supported by grants from National Institute of Diabetes and Digestive and Kidney Diseases and multiple institutional grants. Some authors reported receiving personal fees from industry and grants outside the submitted work; one served as an advisor to a research collaborative and as a journal editor.