Impacts of RAS and renal perfusion on eGFR in hypertensive patients, independent of renal artery stenosis

Introduction Emerging evidence suggests that renal circulatory dysfunction may independently contribute to renal damage through mechanisms involving the renin-angiotensin system (RAS)1. While RAS activation is known to regulate glomerular hemodynamics2,3. Purpose This study investigates the impacts of RAS and renal circulation perfusion on estimated glomerular filtration rate (eGFR) in hypertensive patients, independent of renal artery hemodynamics. Methods This study enrolled 147 hypertensive patients. Imaging assessments comprised Renal nuclide, renal artery CTA/MRI (Computed tomography angiography/Nuclear Magnetic Resonance Imaging) .Laboratory analyses measured serum RAS components. Renal artery stenosis was graded based on CTA/MRI using a score: the higher, the narrower. Unilateral Renal perfusion peak counts＜180 counts/sec was defined as perfusion impairment. Patients were stratified into three groups: single injury,double normal and double injury. To mitigate pharmacological interference with RAS assessment, the perfusion peak of the impaired/lower perfusion was normalized to normal/higher perfusion（I/N ratio）. This normalized I/N ratio was used to quantify the severity of unilateral perfusion impairment. Statistical analyses included Kruskal-Wallis tests for intergroup comparisons and restricted cubic spline (RCS) regression for non-linear correlation analysis. Results In the cohort-wide analysis, unilateral/total renal perfusion parameters demonstrat a positive correlation with corresponding unilateral/total eGFR（P<0.001Conversely, no significant associations were observed between renal artery CTA/MRI-based stenosis scores and renal perfusion or eGFR (P=0.343,P=0.082).In the unilateral renal perfusion impairment group, plasma renin levels were initially significantly elevated during early-stage impairment. Notably, when I/N ratio decreased to 40-60% of contralateral value, renin levels plateaued . Further progression to severe impairment was associated with a secondary mild renin elevation(p=0.029).In the double normal group, plasma renin levels remained within the normal range at baseline. However, a increase in renin was observed as unilateral renal function declined ( p<0.001). In contrast, the double injury group (N=36) exhibited no significant renin elevation despite progressive bilateral perfusion deterioration (p=0.001).Renin represents pressure load and aldosterone represents volume load. Correlation analyses revealed a significant positive association between renin/aldosterone (R/G ratio) and eGFR ( p=0.047), whereas aldosterone/renin (G/R ratio) showed no significant correlation with eGFR ( p=0.091). Conclusions Renal perfusion, rather than renal artery emerged as the pivotal determinant of renal function. Distinct patterns of RAS activation depend on different spatiotemporal progression of renal circulatory impairment in hypertensive patients.R/G ratio (pressure/volume ratio) was associated with renal function.