title: Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies.
abstract: Urinary protein (UP) is widely used as a clinical marker for podocyte injury; however, not all proteinuric nephropathies fit this model. We previously described the elevation of urinary angiotensinogen (AGT) accompanied by AGT expression by injured podocytes in a nitric oxide inhibition rat model (Eriguchi M, Tsuruya K, Haruyama N, Yamada S, Tanaka S, Suehiro T, Noguchi H, Masutani K, Torisu K, Kitazono T. Kidney Int 87: 116-127, 2015). In this report, we performed the human and animal studies to examine the significance and origin of urinary AGT. In the human study, focal segmental glomerulosclerosis (FSGS) patients presented with higher levels of urinary AGT, corrected by UP, than minimal-change disease (MCD) patients. Furthermore, AGT was evident in podocin-negative glomerular segmental lesions. We also tested two different nephrotic models induced by puromycin aminonucleoside in Wistar rats. The urinary AGT/UP ratio and AGT protein and mRNA expression in sieved glomeruli from FSGS rats were significantly higher than in MCD rats. The presence of AGT at injured podocytes in FSGS rats was detected by immunohistochemistry and immunoelectron microscopy. Finally, we observed the renal tissue and urinary metabolism of exogenous injected human recombinant AGT (which is not cleaved by rodent renin) in FSGS and control rats. Significant amounts of human AGT were detected in the urine of FSGS rats, but not of control rats. Immunostaining for rat and human AGT identified that only rat AGT was detected in injured podocytes, and filtered human AGT was seen in superficial proximal tubules, but not in injured podocytes, suggesting AGT generation by injured podocytes. In conclusion, the urinary AGT/UP ratio represents a novel specific marker of podocyte injury.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eriguchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Yotsueda
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Torisu
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Shoko
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Hideko
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan tsuruya@intmed2.med.kyushu-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000652:urine*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000652:urine; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000473:pathology*; D011507:Proteinuria / Q000139:chemically induced / Q000473:pathology* / Q000652:urine; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D000808:Angiotensinogen; D011692:Puromycin Aminonucleoside
keywords: angiotensinogen; focal segmental glomerulosclerosis; minimal-change disease; podocyte; proteinuric nephropathy