In this national cohort, we found that higher prevalence of albuminuria and reduced kidney function was not associated with longer duration of Southeastern residence among either whites or blacks. Results were suggestive of an association between lifetime southeastern residence duration and increased risk of ESRD, but only among blacks. The interaction between race and southeastern residence duration for ESRD suggests effect modification by race, such that lifetime exposure to the Southeast appeared to be harmful for blacks but not whites. This effect modification persisted among those with lower but not higher income.
Diabetes and hypertension account for the majority of ESRD in the United States . Studies of diabetes have shown that it is more common among those living in the Southeast, often referred to as the “stroke belt” . In fact, a “diabetes belt”  that overlays the stroke belt has recently been proposed, based upon national survey prevalence estimates. Hypertension has also been associated with the duration of residence in the stroke belt in a dose-response manner (i.e., higher lifetime exposure to the stroke belt was associated with higher prevalence of hypertension) . In addition, racial disparities in both diabetes and hypertension persist, with blacks having higher prevalence of both conditions compared to whites in the United States . Given these established associations of diabetes and hypertension—strong risk factors for development and progression of CKD—with the U.S. southeastern states and race, we expected that longer residence in this region would be associated with higher prevalence of CKD and incidence of ESRD, and that the associations might be even stronger in blacks compared to whites.
However, in this national population-based cohort, while we did observe increasing prevalence of diabetes and, to a lesser extent, hypertension with higher duration of residence in the Southeast, the same was not true for the prevalence of albuminuria and reduced kidney function, or for incident ESRD. Differential CKD progression may partially explain these results. Faster progression among blacks is postulated to be responsible for decreased prevalence of CKD but increased ESRD incidence reported among blacks as compared to whites . Mortality also differs by race: blacks with CKD have higher mortality at every stage of CKD than comparable whites . Thus, racial differences in CKD prevalence and CKD-related mortality do not seem to account for the differences in progression to ESRD [9, 10]. However, higher early mortality and faster progression among blacks with CKD  may mean that this study, which recruited community-dwelling adults ≥45 years of age, was less likely to capture blacks with earlier vs. advanced-stage CKD. Additionally, if those with rapidly progressing CKD are more or less sensitive to geographic risk factors than those with slowly progressing CKD and were less likely to be captured in our study, our results may be under- or over-estimating the effect of southeastern residence duration on CKD, particularly among blacks.
Other important factors may partially account for our observed results. For example, higher income could offset deleterious effects of regional exposure in many ways, including: increasing quality of medical care received; facilitating higher adherence to healthier lifestyles and prescribed medical therapies; and improving residential neighborhood, in terms of crime, education, or pollution. Indeed, CKD has been shown to be more common in those with lower income, particularly among blacks [12–14]. Here, we found that the potential effect modifications by race for ESRD incidence were strongest in those with lower income. Those with lower income may have fewer opportunities to move for better educational and job opportunities, which in turn may affect their risk for incidence and progression of kidney disease.
Also, lifetime exposure (or cumulative life course exposure) to the southeastern United States may not be as important as other geographic factors, including early regional exposure (or critical period exposure). In fact, Howard et al. reported that early stroke belt exposure (place of birth, in childhood and/or adolescence) was more strongly associated with hypertension in REGARDS, compared to other periods. The authors found that early stroke belt exposure was a strong risk factor, particularly among black participants; whereas lifetime exposure was more strongly associated with hypertension in white participants. Similarly, southeastern U.S. place of birth and adult residence were both shown to be independently associated with stroke mortality, although childhood exposure was not available in this study . However, we found no association between southeastern residence during the first 18 years of life and prevalence of albuminuria or reduced kidney function. And, while protective and harmful effects were suggested for ESRD among whites and blacks, respectively, these results were neither statistically significant nor substantially different (in either race) from those obtained in our main analyses of lifetime exposure.
Residential mobility may also play a role. In general, higher residential mobility is thought to be associated with poorer health [16, 17] and there is some evidence of an association between higher mobility and higher prevalence of hypertension . However, it has been suggested that such an effect is highly dependent on age and health status at the time of migration . Our results among blacks suggest that increased residential mobility, at least in and out of the Southeast, may be partially protective against albuminuria, although the reverse effect (declining health leading to decreased mobility) cannot be entirely ruled out since the duration of albuminuria is unknown. Whether this can be explained by the reasons for moving—e.g., educational or occupational opportunities—or by explanations such as the “healthy migrant” effect or “salmon bias,” which are often invoked to explain superior health status of immigrant populations [19, 20], requires further research.
While these results demonstrate geographical variation specifically within the United States, they are likely to be relevant to international populations as well. For example, in Japan, another highly industrialized country, incidence rates of ESRD were shown to be higher in the northern vs. southern regions, mirroring known regional patterns of hypertension and stroke, despite a relatively racially homogenous population compared to the United States . However, recent studies show that the geographic differences in ESRD incidence have all but disappeared in the last decade in Japan , suggesting that interventions may be effective in reducing geographic disparities. In India, the identification of such existing geographic variations, as was seen with the national Indian CKD registry data, particularly with respect to the prevalence of hypertensive CKD , is critical to development and implementation of interventions that could reduce or eliminate disparities, as has occurred in Japan. Population genetic studies could help identify global subgroups, such as those of sub-Saharan African ancestry, who may be at higher risk . Such populations could be targeted for early interventions that could prevent the development of geographic disparities as these populations transition to having chronic disease as the main population health concern .
In addition to the limitations discussed above, there are other limitations worthy of mention. First, residence was self-reported and recall of all relocations to exact year may be somewhat flawed. Also, this exposure reflects duration of residence in the Southeast but not necessarily the amount of exposure to cultural, lifestyle, and/or environmental factors of the region, which may account for increased risk of disease, including CKD. Cohort effects could also an issue, although interactions between age and duration of southeastern residence were generally non-statistically significant, except in the models of ESRD in whites. Both albuminuria and reduced kidney function are based upon single measurements and some misclassification of CKD is likely. Without good measures of diabetes and hypertension control over time, we cannot ascertain whether these differ geographically and what effect these might have on CKD prevalence and ESRD incidence by region. Additionally, unmeasured genetic and environmental factors cannot be examined to determine the contributions of each to observed differences. ESRD is rare, leading to small numbers of events and possibly unstable estimates in southeastern exposure categories, particularly for income-stratified models. As with all observational studies, causal inference is limited. However, this study also has several strengths, including a large study sample size with adequate follow-up, ascertainment of ESRD through active follow-up, and a sampling scheme that provided adequate numbers of participants in both race and Southeastern residence.