认知功能衰退
混淆
肾功能
内科学
肾脏疾病
医学
认知
前瞻性队列研究
比例危险模型
队列
睡眠剥夺对认知功能的影响
蛋白尿
内分泌学
作者
Benjamin Lidgard,Nisha Bansal,Leila Zelnick,Andrew Hoofnagle,Jing Chen,Derek Colaizzo,Mirela Dobre,Katherine Mills,Anna Porter,Sylvia Rosas,Mark Sarnak,Stephen Seliger,James Sondheimer,Manjula Kurella Tamura,Kristine Yaffe,Bryan Kestenbaum
出处
期刊:Journal of the American Society of Nephrology
[American Society of Nephrology]
日期:2022-04-20
标识
DOI:10.1681/asn.2021111435
摘要
Background Persons with chronic kidney disease (CKD) are at high risk for cognitive impairment and progressive cognitive decline. Retention of protein-bound organic solutes that are normally removed by tubular secretion is hypothesized to contribute to cognitive impairment in CKD. Methods We followed 2362 participants who were initially free of cognitive impairment and stroke in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study. We estimated tubular secretory clearance by the 24-hour kidney clearances of eight endogenous solutes that are primarily eliminated by tubular secretion. CRIC study investigators assessed participants' cognitive function annually, using the Modified Mini-Mental State (3MS) Examination. Cognitive decline was defined as a sustained >5 point decrease in the 3MS score from baseline. Using Cox regression models adjusted for potential confounders, we analyzed associations between secretory solute clearances, serum solute concentrations, and cognitive decline. Results The median number of follow-up 3MS examinations was 6 per participant. There were 247 incident cognitive decline events over a median of 9.1 years of follow-up. Lower kidney clearances of five of the eight secretory solutes (cinnamoylglycine, isovalerylglycine, kynurenic acid, pyridoxic acid, and tiglylglycine) were associated with cognitive decline after adjustment for baseline eGFR, proteinuria, and other confounding variables. Effect sizes ranged from a 17% to 34% higher risk of cognitive decline per 50% lower clearance. In contrast, serum concentrations of the solutes were not associated with cognitive decline. Conclusions Lower kidney clearances of secreted solutes are associated with incident global cognitive decline in a prospective study of CKD, independent of eGFR. Further work is needed to determine the domains of cognition most affected by decreased secretory clearance and the mechanisms of these associations.
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