Aspects of ethnicity on blood pressure regulating mechanisms and kidney function in a defined population

Abstract: Background: Middle Eastern immigrants represent a growing population in Sweden today. This group are at higher risk for type 2 diabetes than the native population, but are also shown to exhibit unique properties; despite an abundance in traditional cardiometabolic risk factors such as obesity, dearranged blood lipids and diminished physical acitivity, this group seem to exhibit lower blood pressure levels. Further, people with type 2 diabetes of Middle Eastern descent have lower all cause and cardiovascular mortality rates, as compared to the native Swedish population. This indicates that Middle Eastern immmigrants may exhibit protective mechanisms towards cardiovascular diseases (CVD) that remain to be unravelled. Renal function is closely related to blood pressure. Further, new evidence on mechanisms in relation to blood pressure regulation and renal function has emerged, including vascular ageing, i.e. gradual change in the vascular structure and the endogenous opioid marker Pro-Enkephalin (PENK), which is shown to exhibit a direct cardiodepressive effect on the kidneys.Aims: The general aim was to study potential differences across ethnicities on renal function, blood pressure and its regulating mechanisms as well as characteristics on diabetes and its complications - all of them, strongly associated with CVD. In specific, the aims were to study the contributing role of ethnicity (born in Iraq or Sweden) in each paper on: Renal function and its association with blood pressure (paper I), diabetes traits and incidence in diabetic complications (paper II), the biomarker PENK and its association with renal function (paper III) and arterial stiffness as an indicator of vascular ageing (paper IV). In this paper the aim was further to validate eGFR equations across a Middle Eastern ethnicity. Methods: The thesis is based on data from three different cohorts comparing Iraqi and Swedish born subjects: the MEDIM study (paper I and III), a population-based cross-sectional study, conducted in 2010-2012. The study included physical examinations, blood sampling and collection of information on lifestyle, comorbidity and medication. The ANDIS study (paper II), a longitudinal follow-up study, recruiting patients diagnosed with diabetes during 2008-2016 and followed for complications until 2017. The MEDIM 2019 population-based study (paper IV), a cross-sectional study conducted in 2019-2020 assessing iohexol clearance for determining measured GFR (mGFR), pulse wave velocity (PWV) as measurement of arterial stiffness, physical examinations, blood sampling and information on comorbidity, lifestyle and medication.Results: In paper I, Iraqi-born immigrants (n=1214) exhibited a better renal function as described by higher levels of estimated GFR (eGFR) in comparison to the Swedish-born control group (n=659) (96.5 vs 93.6 mL/min/1.73m2, p=0.009). Further, the association between blood pressure and renal function was significantly weaker in the Iraqi group as confirmed by a signification interaction (Pinteractino = Country of birth x eGFRCAPA=0.004). In paper II, a larger proportion of Iraqi-born immigrants (n=183) had insulin-deficient diabetes in comparison to the Swedish-born control group (n=7044) (27.9 vs. 16.2%, p<0.001) and a lower proportion had insulin-resistant diabetes (5.5 vs. 16.3%, p<0.001). The risk for chronic kidney disease (CKD) among diabetes patients was lower in the Iraqi-born group (HR 0.26, 95% CI 0.08-0.8). In paper III, levels of PENK did not differ between Iraqi-born immigrants (n=1263) and the Swedish-born control group (n=680), despite higher eGFR in the Iraqi group. The association between PENK and renal function was weaker in the Iraqi group as supported by a significant interaction (Pinteractino = Country of birth x PENK=0.031). In paper IV, PWV did not differ between Iraqi-born immigrants (n=31) and the Swedish-born control group (n=32). When comparing mGFR to eGFR based on various equations, the commonly used CAPA equation was less accurate in the Iraqi group. The results indicated that the CKD-EPI equations could be accurate equations in the Iraqi group.Conclusion: Iraqi born immigrants had a more favorable renal function, an insulin deficient diabetes trait and considerably lower risk for diabetic kidney disease, than for the native Swedish population. The impact on renal function of blood pressure as well as of the cardiodepressive opioid PENK was weaker among Iraqi-born immigrants, which may contribute to a preserved renal function in the Iraqi-born group. In the long run, a more favorable renal function and less susceptible kidneys could serve as an important advantageous mechanism in the protection against CVD among Iraqi-born immigrants.