Dr. Xu et al. analyzed the association of kidney function with the risk of dementia in a registry of 329,822 residents of Stockholm (2006–2011), additionally assessing the association with decline in kidney function in 205,622 residents who had repeated measurements in the first year of observation. Over a median follow-up of 5 years, they found that both lower kidney function and steeper decline in kidney function were associated with the development of dementia. In response, Dr. Fischereder highlighted uncertainties about the causal association of kidney function with cognitive function and postulates that the association likely reflects common causes of renal impairment and cognitive decline such as microvascular disease. Dr. Fischereder noted potential implications of a true causal association for patients with iatrogenically decreased kidney function, such as living kidney donors. Although the authors adjusted their analyses for key comorbidities, Dr. Fischereder noted the increasing risk of dementia observed even in people with high estimated glomerular filtration rate (eGFR) in the cohort after this adjustment and suggested a subgroup analysis specifically in patients who are free of diabetes mellitus, hypertension, or tobacco use. Responding to these comments, the authors agree that causation cannot be inferred from their data but note other studies indicating an association between cognitive impairment and renal dysfunction. Regarding the underlying mechanisms, they point to experimental evidence that various uremia-induced processes may lead to dementia. They agree that chronic kidney disease may be a risk mediator for other vascular risk factors for dementia but also note that they found similar associations in people with and without diabetes or hypertension. They hypothesize that some people with especially high eGFR in the cohort may have had glomerular hyperfiltration or low muscle mass but are wary of conclusions based on dementia risk in that subgroup. They also caution against extrapolating their findings to kidney donors, noting that 10-year follow-up studies show a consistent increase in GFR for such individuals during the first few years postdonation, followed by a decline at a slower rate than controls. In summary, this exchange highlights the uncertain pathophysiologic mechanisms of the observed association between renal function and cognitive decline. At present, one might reasonably conclude that patients with renal impairment merit screening for cognitive disorders.