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Albuminuria Predicts Cognitive Decline Independent of Kidney Function

Albuminuria and an eGFR below 60 mL/min per 1.73 m2 are independent predictors of the risk for cognitive decline with albuminuria the stronger predictor of the two….

Lead author Manjula Kurella Tamura, MD, from Stanford University School of Medicine in California, explained that, “Chronic kidney disease is identified by the presence of either persistent albuminuria or low glomerular filtration rate.” “Both markers have been associated with cognitive impairment, but it is not clear whether these markers are independent of each other.”

In evaluating data from 19,442 individuals participating in the Renal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Dr. Tamura and her colleagues found that individuals with albuminuria were 1.31 to 1.57 times more likely to develop cognitive impairment than those without albuminuria.

Interestingly, the association was strongest among those with albuminuria and normal kidney function (eGFR ≥60 mL/min per 1.73 m2). Those with eGFR below 60 mL/min per 1.73 m2 had a higher risk of developing cognitive impairment only if they did not have albuminuria.

“In a large national cohort of American adults, we found that albuminuria was associated with a 37% to 44% higher risk for cognitive impairment among individuals with normal or high estimated GFR, but not among individuals with lower GFR,” Dr. Tamura explained.

“Conversely, low GFR was associated with a 30% higher risk for cognitive impairment among individuals without albuminuria, but not among individuals with albuminuria.” GFR was estimated in patients with a serum creatinine and albumin-to-creatinine ratio that was measured on a single voided urine sample obtained at baseline.

The patients’ cognitive function was assessed annually, with impairment defined as a score of 4 or lower on the 6-item screener at the last study follow-up visit among individuals who did not show cognitive impairment at baseline. The mean follow-up period was 3.5 ± 1.3 years.

At baseline, a total of 6999 participants (8.1%) had albuminuria (albumin-to-creatinine ratio ≥10 mg/g) and 1884 (10%) had stage 3 to 4 chronic kidney disease (eGFR <60 mL/min per 1.73 m2).

During follow-up, 1575 participants (8.1%) developed cognitive impairment. Incident cognitive impairment was associated with albuminuria, with an odds ratio (OR) of 1.23 (95% confidence interval [CI], 1.11 – 1.37). Those with an eGFR below 45 mL/min per 1.73 m2 had an OR of 1.36 (95% CI 1.08-1.71) for incident cognitive impairment.

Incident cognitive impairment occurred in 10.1% of participants with albuminuria, in 18.8% with eGFR below 45 mL/min per 1.73 m2, in 13.4% with both conditions, and in 6.7% with neither condition.

Albuminuria and low eGFR were separately associated with incident cognitive impairment after adjustment for factors including demographics, diabetes, hypertension, cardiovascular disease, and tobacco and alcohol use. The fully adjusted OR for cognitive impairment among those with albuminuria, compared with those with neither condition, was 1.25 (95% CI, 1.12 – 1.40). For subjects with an eGFR below 45 mL/min per 1.73 m2, the OR was 1.78 (95% CI, 1.23 -2 .57); for those with both albuminuria and low eGFR, the OR was 1.41 (95% CI, 1.05 – 1.88).

The odds ratios were similar when 60 mL/min per 1.73 m2 was used as the cut-off for low eGFR.

“The findings suggest that albuminuria and low GFR are complementary risk factors for cognitive impairment, and that they may identify different targets for interventions to slow cognitive decline,” Dr. Tamura said. “Clinicians may use this information to more accurately identify persons with chronic kidney disease who are at risk for cognitive impairment.”

Little is known about the relationship of early decrements of kidney function with cognitive impairment in the general population. This study by Dr. Tamura [and colleagues] took advantage of the REGARD database to address this gap in knowledge.

The study benefits from the fact that the participants were living in the community rather than selected from kidney disease clinics or other select populations. Moreover, the REGARD dataset is exceptionally large; nearly 7000 individuals [were] included in this study.

The authors found that low levels of urine albumin-to-creatinine ratio were strongly associated with cognitive impairment, independent of eGFR, and much stronger than the association of eGFR with cognitive impairment.

This finding suggests that both albumin-to-creatinine ratio and cognitive impairment reflect endothelial dysfunction and vascular disease more globally.

Because albumin-to-creatinine ratio is readily available, easy to obtain, and inexpensive to measure, it may provide another method to identify individuals at greater risk for cognitive impairment

Renal Week 2010: American Society of Nephrology 43rd Annual Meeting. Abstract SA-FC359. Presented November 20, 2010.