Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies

Masahiro Eriguchi, Ryusuke Yotsueda, kumiko torisu, Yasuhiro Kawai, Shoko Hasegawa, Shigeru Tanaka, Hideko Noguchi, Kosuke Masutani, Takanari Kitazono, Kazuhiko Tsuruya

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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.

Original languageEnglish
Pages (from-to)F322-F333
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number4
DOIs
Publication statusPublished - Feb 15 2016

Fingerprint

Podocytes
Angiotensinogen
Wounds and Injuries
Focal Segmental Glomerulosclerosis
Lipoid Nephrosis
Proteins
Puromycin Aminonucleoside
Kidney
Immunoelectron Microscopy
Renin

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies. / Eriguchi, Masahiro; Yotsueda, Ryusuke; torisu, kumiko; Kawai, Yasuhiro; Hasegawa, Shoko; Tanaka, Shigeru; Noguchi, Hideko; Masutani, Kosuke; Kitazono, Takanari; Tsuruya, Kazuhiko.

In: American Journal of Physiology - Renal Physiology, Vol. 310, No. 4, 15.02.2016, p. F322-F333.

Research output: Contribution to journalArticle

Eriguchi, Masahiro ; Yotsueda, Ryusuke ; torisu, kumiko ; Kawai, Yasuhiro ; Hasegawa, Shoko ; Tanaka, Shigeru ; Noguchi, Hideko ; Masutani, Kosuke ; Kitazono, Takanari ; Tsuruya, Kazuhiko. / Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies. In: American Journal of Physiology - Renal Physiology. 2016 ; Vol. 310, No. 4. pp. F322-F333.
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