Abstract
High renin angiotensin-aldosterone system (RAAS) activity is associated with target organ damage. Soluble (pro)renin receptor [s(P)RR] forms part of the RAAS cascade and is associated with kidney damage through both angiotensin II-dependent and -independent pathways. Additionally, s(P)RR levels are higher in hypertension and chronic kidney disease (CKD) patients. However, little is known regarding ethnic and sex differences in s(P)RR levels and its potential associations with kidney function in young healthy adults. Identifying these associations in young populations is essential for identification of areas of intervention to prevent CKD. This study aimed to compare levels of s(P)RR across ethnic and sex groups and determine s(P)RR associations with markers of kidney function, including estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (uACR) and alpha 1-microglobulin (uA1M). The study included 1156 young healthy Black and White South Africans aged 20-30 years (Men, N = 555; Women, N = 601). We measured uA1M, albumin and creatinine in urine to calculate uACR. s(P)RR, cystatin C and creatinine were measured in serum and eGFR was calculated. Independent t-tests and multiple regression analyses were carried out to compare groups and explore associations. s(P)RR levels were higher in White participants, and higher in White men than in women (all p < 0.001). eGFR was higher in both Black men and women than in White men and women (both p ≤ 0.001). Both uA1M and uACR were higher in Black men than in White men (both p ≤ 0.003). We observed an independent negative association between eGFR and s(P)RR in Black women only (Adj.R(2) = 0.309; Std. β=-0.141; p = 0.026), while uA1M associated positively with s(P)RR in the White group only (Adj.R(2) = 0.063; Std. β = 0.115; p = 0.018). No associations were evident between uACR and s(P)RR in any of the groups. The positive association between uA1M and s(P)RR suggest that s(P)RR may contribute to kidney damage in young White participants through pathways associated with inflammation and fibrosis. A better understanding of mechanisms linking s(P)RR to kidney damage may lead to discovery of areas of therapeutic interventions for the prevention and treatment of CKD in different population groups. Trial registration ClinicalTrials.gov NCT03292094. Registration date 2017-09-12.