PMID- 37231123 OWN - NLM STAT- MEDLINE DCOM- 20230922 LR - 20231201 IS - 1432-198X (Electronic) IS - 0931-041X (Print) IS - 0931-041X (Linking) VI - 38 IP - 11 DP - 2023 Nov TI - Intrarenal renin-angiotensin system activation and macrophage infiltrations in pediatric chronic glomerulonephritis. PG - 3711-3719 LID - 10.1007/s00467-023-06026-5 [doi] AB - BACKGROUND: The current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin-angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis. METHODS: We measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs). RESULTS: Baseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01). CONCLUSIONS: The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis. CI - (c) 2023. The Author(s). FAU - Hattori, Tomoki AU - Hattori T AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. AD - Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan. FAU - Fujioka, Keisuke AU - Fujioka K AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. FAU - Nagai, Takashi AU - Nagai T AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. FAU - Kondo, Shuji AU - Kondo S AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. FAU - Kagami, Shoji AU - Kagami S AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. FAU - Hirayama, Masahiro AU - Hirayama M AD - Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan. FAU - Urushihara, Maki AU - Urushihara M AUID- ORCID: 0000-0002-6431-3239 AD - Department of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Kuramoto-cho 3-18-15, Tokushima, Tokushima, 770-8503, Japan. urushihara@tokushima-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230525 PL - Germany TA - Pediatr Nephrol JT - Pediatric nephrology (Berlin, Germany) JID - 8708728 RN - 11002-13-4 (Angiotensinogen) RN - 0 (Chemokine CCL2) RN - 11128-99-7 (Angiotensin II) RN - 0 (Immunosuppressive Agents) SB - IM MH - Humans MH - Child MH - *Renin-Angiotensin System MH - Angiotensinogen/urine MH - Kidney/metabolism MH - Chemokine CCL2 MH - *Glomerulonephritis/metabolism MH - Angiotensin II/metabolism MH - Chronic Disease MH - Immunosuppressive Agents/pharmacology/therapeutic use MH - Macrophages/metabolism PMC - PMC10514104 OTO - NOTNLM OT - Angiotensinogen OT - CD68 OT - Monocyte chemoattractant protein-1 OT - Pediatric chronic glomerulonephritis OT - Renin-angiotensin system COIS- The authors have no competing interests to declare that are relevant to the content of this article. EDAT- 2023/05/26 01:05 MHDA- 2023/09/22 06:43 PMCR- 2023/05/25 CRDT- 2023/05/25 23:25 PHST- 2022/12/26 00:00 [received] PHST- 2023/04/25 00:00 [accepted] PHST- 2023/04/21 00:00 [revised] PHST- 2023/09/22 06:43 [medline] PHST- 2023/05/26 01:05 [pubmed] PHST- 2023/05/25 23:25 [entrez] PHST- 2023/05/25 00:00 [pmc-release] AID - 10.1007/s00467-023-06026-5 [pii] AID - 6026 [pii] AID - 10.1007/s00467-023-06026-5 [doi] PST - ppublish SO - Pediatr Nephrol. 2023 Nov;38(11):3711-3719. doi: 10.1007/s00467-023-06026-5. Epub 2023 May 25.