Victor J. Del Brutto, MD

Liu B, Lau KK, Li L, Lovelock C, Liu M, Kuker W, et al. Age-Specific Associations of Renal Impairment With Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Transient Ischemic Attack and Stroke. Stroke. 2018

In this article, Bian Lui and colleagues assessed the association of renal impairment with imaging markers of small vessel disease (SVD). As shown in previous studies, small vessel disease usually coexists with renal damage and it has generally been considered that this association is related to simultaneous damage of both the cerebral and the renal microvasculature. The authors presented the results of a population-based study in which they studied age-specific associations of renal impairment and SVD burden adjusting for demographics and traditional vascular risk factors including premorbid blood pressure.

The study was conducted using the Oxford Vascular Study registry from Oxfordshire, United Kingdom. The analysis included 1028 patients with a transient ischemic attack or minor brain infarct that underwent brain MRI and baseline renal function measurement. Patients with systemic vasculitis, CADASIL and Fabry’s disease were excluded. The burden of SVD was determined by the presence of lacunar infarctions, cerebral microbleeds, enlarged basal ganglia perivascular spaces and white matter hyperintensities on brain MRI. Renal impairment was defined by an eGFR <60 mL/min per 1.73 m2. Remarkably, the authors used the premorbid creatinine within a year to avoid the influence of a recent vascular event in the measurement of baseline renal function.

The association between SVD and renal impairment was lost after adjusting for age, sex and history of hypertension. However, after stratifying by age, the link between these conditions was maintained in patients aged 60 years or younger (OR, 3.97; 95% CI, 1.69–9.32; P=0.002). This age-specific correlation was consistent when individual imaging markers of SVD were analyzed separately (see Figure).

Figure. Associations of renal impairment (adjusted odds ratio and 95% CI) and the presence of individual small vessel disease markers stratified by age.

Figure. Associations of renal impairment (adjusted odds ratio and 95% CI) and the presence of individual small vessel disease markers stratified by age.

Chronic kidney disease and SVD are conditions that, in the majority of cases, develop as a consequence of microvasculature damage. Aging, chronic hypertension and other traditional vascular risk factors are thought to drive the slow progression of these disorders. Therefore, it is expected that the correlation between SVD and kidney disease be attenuated in a model that includes vascular risk factors as confounders. However, the independent association found by the authors in patients below the age of 60 raises some questions: Is this subset of patients genetically predisposed to develop SVD? Are systemic diseases present in younger individuals (i.e., autoimmune conditions, infections) not related to traditional vascular risk factors responsible for microvasculature damage in the brain and the kidney simultaneously?

It is without a doubt that this study stresses the need for further understanding on the mechanism that leads to microvascular injury in younger patients. Furthermore, it highlights an interesting subgroup of patients for future research studies.

Regarding the clinical implications of this manuscript, the early recognition of renal impairment in younger individuals could identify patients that would benefit from early interventions to slow progression or prevent complications of SVD (i.e., low dose ASA for primary prevention of lacunar infarcts).