The genetical mechanism of chronic kidney disease in congenital anomalies of kidney and urinary tract, focused on renal renin-angiotensin system
| Project/Area Number |
20K17249
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | レニン・アンギオテンシン系 / 先天性腎尿路異常 / 多嚢胞性異形成腎 / 尿中アンギオテンシノゲン / 尿中アンギオテンシノーゲン / 腎臓学 / 小児科学 / 遺伝学 |
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| Outline of Research at the Start |
本研究は腎臓内レニンアンギオテンシンに着目し、未だに明らかでない先天性腎尿路異常患者における慢性腎臓病及び末期腎不全進展機序を解明するものである。まず日本人先天性腎尿路異常児に対しレニンアンギオテンシン系関連遺伝子の解析を網羅的に行う。さらに腎由来培養尿細管上皮細胞を用いてレニンアンギオテンシン系関連蛋白と間質線維化マーカー等を解析することで、慢性腎臓病進展メカニズムの解明を行う。加えて腎機能障害顕在化以前のレニンアンギオテンシン系阻害薬や活性酸素阻害薬による慢性腎臓病進展予防の疾患特異的新規治療法の開発を行う。
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| Outline of Final Research Achievements |
This study evaluated the relationship between unilateral multicystic dysplastic kidney (MCDK) and renin-angiotensin system, with a focus on a urinary angiotensinogen as a biomarker of the intra-renal renin-angiotensin system. We enrolled 7 children diagnosed with unilateral MCDK and 6 with solitary kidney in our institutions between 2010 and 2020, and 17 with healthy children as controls. There were no significant differences in the sex ratio, median age, gestational age and birth weight among MCDK, solitary kidney and control groups. Urinary angiotensinogen/Cr levels of the MCDK group (median: 8.7 μg/ng・Cr) was significantly higher than those of the solitary kidney and control groups (3.0 μg/ng・Cr, p= 0.004, 5.9 μg/ng・Cr, p= 0.01). The level of systolic blood pressure in the MCDK group was significantly higher than that in the solitary kidney group (111 vs 101 mmHg, p= 0.01). Our results showed that MCDK might be associated with intra-renal renin-angiotensin system.
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| Academic Significance and Societal Importance of the Research Achievements |
多嚢胞性異形成腎は、固有腎としての機能を有さず数年で自然退縮するが、その機序や病態は不明である。一方、近年レニンアンギオテンシン(RAS)系のうち、腎内局所RASが多くの慢性腎疾患や腎発生過程の在胎期間に関連が検証されているが、多嚢胞性異形成腎と腎内局所RASとの関連を検討した報告はない。今回の研究結果から片側多嚢胞性異形成腎は腎内RAS活性化との関連が示唆された。腎発生過程もしくは出生後経過のどちらに関与しているかは現時点では不明であるが、多嚢胞性異形成腎の自然退縮過程を含めた腎内RASの経時的変化を評価する計画であり、より病態の本質に迫ることが期待される。
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Report
(4 results)
Research Products
(5 results)
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[Presentation] Examination Of Relationship Between Multicystic Dysplastic Kidney And Intra-renal Renin-angiotensin System: A Pilot Study Of New Biomarker2022
Author(s)
Shingo Ishimori, Junya Fujimura, Tomoko Horinouchi, Tomohiko Yamamura, Nana Sakakibara, China Nagano, Kosuke Nishida, Kazumichi Fujioka, Takeshi Ninchoji, Kandai Nozu, Kazumoto Iijima
Organizer
14th Asian Congress of Pediatric Nephrology
Related Report
Int'l Joint Research
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