Abstract
Purpose: It has long been hypothesized that renin angiotensin system (RAS) is heterogeneously activated in the kidney and is associated with the development of hypertension, but the mechanism by which RAS hyperactivity occurs is unclear. In this study, we hypothesized that narrowing of the lumen of afferent arteriole in chronic kidney disease (CKD) is associated with increased renal RAS, and investigated whether renal arteriolar remodeling is related to urinary angiotensinogen (UAGT), an index of renal RAS. Methods: Of 172 patients who underwent renal biopsy between 2010 and 2013 at our department, 54 patients with UAGT data and less than 10 arterioles and those on RAS inhibitors were excluded. IgA nephropathy was the most common primary disease (57.4%). Microvascular remodeling was assessed by measuring the wall to lumen ratio (WLR), which was calculated as (outer diameter of arteriole - lumen diameter of arteriole)/interstitial lumen diameter. In addition to clinical parameters, we examined the association of WLR with high-sensitivity C-reactive protein (CRP), oxidative stress markers (dROM), flow-dependent vasodilatory response (%FMD), and UAGT. Results: The mean age and eGFR were 38 years and 81 mL/min/1.73 m2, respectively; Log UAGT showed a positive correlation with Log WLR, LDL, and Log dROM, respectively, and a negative correlation with eGFR. Multiple regression analysis showed that Log WLR was significantly associated with Log UAGT independently of factors such as eGFR and urinary protein (β; = 0.38, p = 0.04). Conclusions: Our results suggest that renal arrteriolar remodeling may be associated with increased renal RAS in CKD patients.
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