Increased urinary excretion of angiotensinogen is associated with risk of chronic kidney disease.

Is urinary angiotensinogen ready for prime time as a biomarker of CKD?... Mills et al represent a leap forward in this exciting field and holds considerable promise to one day positively impact the care of patients with CKD...The effect of intrarenal reninangiotensin system (RAS) activity on risk of chronic kidney disease (CKD) has not been well studied in human subjects. We investigated the association between urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, and risk of CKD in 201 patients and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 m(2) or presence of albuminuria ( epsilon 30 mg/24 h). Compared to controls, median urinary angiotensinogen excretion (45.4 versus 7.4 g/24 h, P 0.0001) and angiotensinogen-to-creatinine ratio (26.3 versus 4.4 g/g, P 0.0001) were significantly higher in patients with CKD. Log-transformed urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were inversely correlated with eGFR (r 0.59 and 0.57, both P 0.0001) and positively correlated with log-transformed urinary albumin excretion (r 0.89 and 0.87, both P 0.0001). After adjusting for multiple covariables, including the use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, diuretics and statins, the odds ratios (95 confidence interval) for CKD comparing the highest tertile to the lowest two tertiles of urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were 6.70 (3.43, 13.1; P 0.0001) and 6.45 (3.34, 12.4; P 0.0001), respectively. These data indicate the intrarenal RAS may play an important role in the etiology of CKD, and urinary angiotensinogen may be a useful clinical biomarker for the identification of patients at a high risk for CKD.