BACKGROUND: Urinary angiotensinogen (AGT) was reported as a marker of renal injury in chronic kidney disease patients. However, the main source of urinary AGT is unknown in proteinuric patients because the disrupted filtration barrier might cause AGT filtration. We investigated the origin and the clinical importance of urinary AGT in proteinuric IgA nephropathy (IgAN) patients. METHODS: In patients with biopsy-proven IgAN, urinary and plasma AGT was measured using a sandwich ELISA and compared with intrarenal AGT expression. The patients were followed up for 3 years. RESULTS: Natural logarithm of the urinary AGT/creatinine (ln (urinary AGT/Cr)) was positively correlated with intrarenal expression of AGT (ln (urinary AGT/Cr) versus AGT/β-actin, r = 0.620, P < 0.0001; ln (urinary AGT/Cr) versus AGT density, r = 0.452, P = 0.007). Ln (urinary AGT/Cr) showed a positive correlation with urinary protein/creatinine ratio (PCR) but a negative correlation with estimated glomerular filtration rate (eGFR). Regression analyses showed that ln (urinary AGT/Cr) was a significant determinant of urinary PCR and eGFR 3 years after biopsy. CONCLUSIONS: Urinary AGT reflects intrarenal AGT expression and correlates with the extent of proteinuria and renal function. Our study indicates the intrarenal compartment as the main source of urinary AGT, suggesting its clinical implication as an important biomarker in proteinuric IgAN patients.
BACKGROUND: Urinary angiotensinogen (AGT) was reported as a marker of renal injury in chronic kidney diseasepatients. However, the main source of urinary AGT is unknown in proteinuric patients because the disrupted filtration barrier might cause AGT filtration. We investigated the origin and the clinical importance of urinary AGT in proteinuric IgA nephropathy (IgAN) patients. METHODS: In patients with biopsy-proven IgAN, urinary and plasma AGT was measured using a sandwich ELISA and compared with intrarenal AGT expression. The patients were followed up for 3 years. RESULTS: Natural logarithm of the urinary AGT/creatinine (ln (urinary AGT/Cr)) was positively correlated with intrarenal expression of AGT (ln (urinary AGT/Cr) versus AGT/β-actin, r = 0.620, P < 0.0001; ln (urinary AGT/Cr) versus AGT density, r = 0.452, P = 0.007). Ln (urinary AGT/Cr) showed a positive correlation with urinary protein/creatinine ratio (PCR) but a negative correlation with estimated glomerular filtration rate (eGFR). Regression analyses showed that ln (urinary AGT/Cr) was a significant determinant of urinary PCR and eGFR 3 years after biopsy. CONCLUSIONS: Urinary AGT reflects intrarenal AGT expression and correlates with the extent of proteinuria and renal function. Our study indicates the intrarenal compartment as the main source of urinary AGT, suggesting its clinical implication as an important biomarker in proteinuric IgANpatients.
Authors: Lodi C W Roksnoer; Koen Verdonk; Anton H van den Meiracker; Ewout J Hoorn; Robert Zietse; A H Jan Danser Journal: Curr Hypertens Rep Date: 2013-04 Impact factor: 5.369
Authors: Hui Lin; Frank Geurts; Luise Hassler; Daniel Batlle; Katrina M Mirabito Colafella; Kate M Denton; Jia L Zhuo; Xiao C Li; Nirupama Ramkumar; Masahiro Koizumi; Taiji Matsusaka; Akira Nishiyama; Martin J Hoogduijn; Ewout J Hoorn; A H Jan Danser Journal: Pharmacol Rev Date: 2022-07 Impact factor: 18.923