Vascular Disease Contributes to Cognitive Decline in Patients with Kidney Disease

Chicago—Underlying vascular disease likely explains the high risk of cognitive impairment in patients with kidney disease, according to study results presented at Kidney Week 2016 in November.

Although it is well known that patients with kidney disease are at high risk of cognitive decline, the relationship between the two conditions is unclear, wrote lead author Daniel Weiner, MD, an associate professor of medicine at Tufts University School of Medicine in Boston. To better understand this connection and probe the potential role of vascular disease in these conditions, Weiner and his colleagues analyzed baseline data from a substudy of the Systolic Blood Pressure Intervention (SPRINT) study called SPRINT-MIND.

The SPRINT-MIND study enrolled 9361 participants, including more than 2700 who in addition to kidney disease-related testing completed an extensive battery of cognitive tests and 637 who underwent brain imaging. When Weiner and his colleagues adjusted baseline study data for certain demographic and clinical characteristics, they found that having a higher albumin-to-creatine ratio (ACR) in the urine was associated with worse performance on tests of overall cognitive function, executive function, memory, and attention. In fact, the cognitive effect of each doubling of ACR was comparable to the effect of 6 to 14 months of aging.

Lower estimated glomular filtration rates (eGFR) also were associated with worse performance on tests of overall cognition and memory. Among patients who underwent brain imaging, higher ACRs were associated with abnormalities in the brain’s white matter, but lower eGFRs were not linked to such brain changes.

“The findings cement the association between kidney damage and cognitive functioning, suggesting that albumin in the urine and changes in brain structure are likely both representations of the same vascular process, just in different organs,” said Weiner in a press release. “This manifests with worse brain function, particularly in domains linked to cerebrovascular disease.”

The fact that the results came from a large study of a nationally representative population of patients with kidney disease suggests the results may be relevant to “tens of millions of US adults,” said Weiner.

“It’s a great study to take advantage of to look at these relationships,” said Anne Murray, MD, MSc, professor of medicine and geriatrics at the Hennepin County Medical Center’s Berman Center for Clinical Research in Minneapolis.

The results confirm previous studies that show vascular disease contributes to cognitive decline in patients with chronic kidney disease, Murray said. She noted evidence that the brain and kidneys share many common anatomic and vasoregulatory features; they are low resistance end organs exposed to high-volume blood flow, which may make them especially vulnerable to microvascular damage (Bugnicourt JM, et al. J Am Soc Nephrol 2013; 24:353–363).

“The results also highlight that memory is impaired to a greater extent than executive function, in contrast to some other studies,” said Murray. She noted, however, that this result is consistent with results from the Brain in Kidney Disease Study (BRINK) (Murray AM, et al. Am J Kidney Dis 2016; 67:593–600).

One of the study’s strengths is that it looked at both ACR and eGFR, which showed that multiple mechanisms are likely involved, Murray said. One limitation is that the mean eGFR was high and the mean ACR was low in this patient population. Only a small percentage of patients had eGFRs below 30, a point at which the risk of cognitive impairment is high, and memory loss becomes more predominant, Murray explained.

“So, it’s difficult to interpret the ‘dosage’ effect of lower ranges of eGFR and higher ACR on each outcome,” she said.

In the meantime, it is important for clinicians to be aware that patients with eGFRs below 45, especially those with eGFRs below 30, and even somewhat elevated ACRs may be experiencing cognitive decline, Murray said.

“Clinicians should suspect significant cognitive impairment and manage their care accordingly,” she said. For example, the patient may not be able to be compliant with their medications so physicians might suggest having a caregiver or family member supervise medication administration. If there are decisions that need to be made regarding access, placement, dialysis initiation, or being placed on the transplant list those discussions should be held with family members present in case the patient’s judgment is impaired,” she stressed. This is particularly important for patients starting dialysis who are likely to experience further cognitive declines after 3-6 months of dialysis, she noted.

“Cognitive Function and Kidney Disease: Baseline Data from the SPRINT Trial” (Abstract 744)

December 2016 (Vol 8, Issue 12)