Intrarenal Renin-Angiotensin System Activation Alters Relationship Between Systolic Blood Pressure and Progression of Chronic Kidney Disease

Background: Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown. Methods: We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic blood pressure (SBP). The urinary angiotensinogen-to-creatinine ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy. Results: During 10 550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and urinary angiotensinogen-to-creatinine ratio on the risk of the primary outcome ( P value for interaction=0.019). In patients with urinary angiotensinogen-to-creatinine <3.65 μg/gCr, the hazard ratios (95% CIs) for SBP 120 to 129, 130 to 139, and ≥140 mmHg were 1.46 (1.07–1.99), 1.71 (1.25–2.35), and 2.40 (1.73–3.32), respectively, compared with SBP <120 mmHg. However, these associations were not observed in patients with urinary angiotensinogen-to-creatinine ≥3.65 μg/gCr. Conclusions: In this prospective CKD cohort, higher SBP was associated with CKD progression when urinary angiotensinogen levels were low, while this association was not seen when urinary angiotensinogen levels were high. This finding suggests that intrarenal renin-angiotensin system activity may modify the relationship between SBP and adverse kidney outcome.