Q&A: How Severe CKD Can Cause Cognitive Impairment

In an interview with Pharmacy Times, Tanika N. Kelly, PhD, MPH, professor in the Division of Endocrinology, Diabetes and Metabolism at the University of Illinois College of Medicine in Chicago, discussed her study finding that patients with both reduced estimated glomerular filtration rate (eGFR) and significant proteinuria—hallmark signs of chronic kidney disease (CKD)—face a 38% increased risk of global cognitive impairment, with proteinuria emerging as the stronger predictor due to its link to microvascular brain damage. Kelly recommended that pharmacists probe beyond standard medication counseling, utilize tools such as pill organizers and family support systems, and consider using the Montreal Cognitive Assessment (MoCA) to screen high-risk patients with CKD for early cognitive decline.

Pharmacy Times: Could you briefly explain the results of your study?

Tanika N. Kelly, PhD, MPH: Previous studies have found that those with kidney disease are at higher risk of developing cognitive impairment compared [with] those without kidney disease. This study is among the first to examine how the severity of kidney disease predicts the future development of cognitive impairment. We show that those with more severe disease, based on 2 common measures of kidney function (eGFR rate and proteinuria), are at increased risk of cognitive impairment compared [with] those with less severe disease. These findings highlight more advanced kidney disease as an important predictor of future cognitive decline.

Pharmacy Times: The study data showed that a higher urinary protein to creatinine ratio was more consistently associated with cognitive impairment than a lower eGFR, particularly in domains of attention, processing speed, and executive function. What does this suggest about the pathophysiological mechanisms linking proteinuria to brain health?

Kelly: Proteinuria is intimately linked with not just kidney health but the health of cells that line small blood vessels throughout the body, including the brain. Our findings suggest that proteinuria may signal increased susceptibility to microvascular disease processes in the brain and a higher risk of developing related cognitive impairment in the future.

Pharmacy Times: Patients with both a reduced eGFR and significant proteinuria had a 38% increased risk of global cognitive impairment. How should this combined risk profile influence how clinicians, including pharmacists, approach treatment for these patients?

Kelly: While eGFR and proteinuria are both indicators of kidney function, they may capture unique biological pathways underlying CKD. In our study, although proteinuria was a stronger predictor of cognitive impairment compared [with] eGFR, associations were strongest when both were examined together. In other words, they are complementary measures that, together, may better predict the development of cognitive impairment.

Pharmacy Times: Given that cognitive impairment can affect a patient’s ability to understand medication instructions, adhere to complex regimens, and recognize adverse effects, what practical steps would you recommend pharmacists take when caring for patients with advanced CKD?

Kelly: This is an important question. In addition to asking patients if they have any questions about their medications, probing deeper about how patients ensure that they take their medications properly, particularly if they seem confused, could be helpful. Pharmacists have the opportunity to recommend simple and affordable tools like pill box organizers that make it easier for patients to not only remember which pills to take at different times throughout the day but also to visibly identify when they may have forgotten to take medication. Likewise, there is an opportunity to inquire about whether support systems, like family members, are in place to make sure they remain [adherent] to complex medication regimens.

Pharmacy Times: Are there validated, feasible screening tools for cognitive impairment that you would recommend pharmacists use in the ambulatory CKD setting, and at what stage of CKD would you suggest initiating that screening?

Kelly: There are numerous screening tools designed to quickly assess early symptoms of dementia or mild cognitive impairment. For example, [MoCA] is widely used in clinical settings to identify those with early signs of dementia. This test can be administered by any trained and certified health professional and can be completed in 10 to 15 minutes. That being said, our study was not designed to evaluate whether cognitive screening in CKD by pharmacists [or other health care providers] could facilitate better [adherence to] complex treatment regimens. Such research might be an important next step to provide such recommendations.

Pharmacy Times: What are the most important limitations pharmacists and other clinicians should keep in mind when applying these findings to individual patient care?

Kelly: In addition to CKD, there are many other risk factors that need to be taken into account when thinking about screening an individual patient with CKD for cognitive impairment. Factors such as age and other comorbid conditions that may also increase dementia risk should be taken into account. Most importantly, a patient’s (or their family’s) notice of changes in memory, behavior, or other cognitive functioning is likely among the most important indicators that screening for early cognitive changes should be considered.