ホシノ　ジユンイチ   Hoshino Jiyun'ichi   星野　純一    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis
掲載誌名	正式名：Kidney international reports 略　 称：Kidney Int Rep ISSNコード：24680249/24680249
掲載区分	国外
巻・号・頁	6(5),pp.1346-1354
著者・共著者	Fujimaru Takuya, Kawanishi Kunio, Mori Takayasu, Mishima Eikan, Sekine Akinari, Chiga Motoko, Mizui Masayuki, Sato Noriaki, Yanagita Motoko, Ooki Yuki, Nagahama Kiyotaka, Ohnuki Yuko, Hamano Naoto, Watanabe Saki, Mochizuki Toshio, Nagatsuji Katsushi, Tanaka Kenichi, Tsukamoto Tatsuo, Tsushima Hideo, Shimamoto Mamiko, Tsuji Takahiro, Kuyama Tamaki, Kawamoto Shinya, Maki Kenji, Katsuma Ai, Oishi Mariko, Yamamoto Kouhei, Mandai Shintaro, Kikuchi Hiroaki, Ando Fumiaki, Mori Yutaro, Susa Koichiro, Iimori Soichiro, Naito Shotaro, Rai Tatemitsu, Hoshino Junichi, Ubara Yoshifumi, Miyazaki Mariko, Nagata Michio, Uchida Shinichi, Sohara Eisei
発行年月	2021/05/04
概要	INTRODUCTION:Recently, nephronophthisis (NPH) has been considered a monogenic cause of end-stage renal disease (ESRD) in adults. However, adult-onset NPH is difficult to accurately diagnose and has not been reported in a cohort study. In this study, we assessed the genetic background and clinicopathologic features of adult NPH.METHODS:We investigated 18 sporadic adult patients who were suspected as having NPH by renal biopsy. We analyzed 69 genes that cause hereditary cystic kidney disease and compared clinicopathologic findings between patients with and without pathogenic mutations in NPH-causing genes.RESULTS:Seven of 18 patients had pathogenic NPH-causing mutations in NPHP1, NPHP3, NPHP4, or CEP164. Compared with patients without pathogenic mutations, those with pathogenic mutations were significantly younger but did not significantly differ in the classic NPH pathologic findings, such as tubular cysts. On the other hand, the number of tubules with thick tubular basement membrane (TBM) duplication, which was defined as >10-μm thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. α-Smooth muscle actin (α-SMA)-positive myofibroblasts were detected inside thick TBM duplication.CONCLUSIONS:In adult patients with NPH, thick TBM duplication was the specific finding. Our analysis also suggested that older patients tended to have no pathogenic mutations, even when they were suspected to have NPH by renal biopsy. These findings could be the novel clinical clue for the diagnosis of NPH in adult patients.
DOI	10.1016/j.ekir.2021.02.005
PMID	34013113