Genetic Background and Clinicopathologic Features of Adult-onset Nephronophthisis

Takuya Fujimaru, Kunio Kawanishi, Takayasu Mori, Eikan Mishima, Akinari Sekine, Motoko Chiga, Masayuki Mizui, Noriaki Sato, Motoko Yanagita, Yuki Ooki, Kiyotaka Nagahama, Yuko Ohnuki, Naoto Hamano, Saki Watanabe, Toshio Mochizuki, Katsushi Nagatsuji, Kenichi Tanaka, Tatsuo Tsukamoto, Hideo Tsushima, Mamiko ShimamotoTakahiro Tsuji, Tamaki Kuyama, Shinya Kawamoto, Kenji Maki, Ai Katsuma, Mariko Oishi, Kouhei Yamamoto, Shintaro Mandai, Hiroaki Kikuchi, Fumiaki Ando, Yutaro Mori, Koichiro Susa, Soichiro Iimori, Shotaro Naito, Tatemitsu Rai, Junichi Hoshino, Yoshifumi Ubara, Mariko Miyazaki, Michio Nagata, Shinichi Uchida, Eisei Sohara

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1346-1354
Number of pages9
JournalKidney International Reports
Volume6
Issue number5
DOIs
Publication statusPublished - 2021 May

Keywords

  • adult-onset kidney disease
  • chronic kidney disease
  • human genetics
  • nephronophthisis
  • renal cystic disease
  • renal pathology

ASJC Scopus subject areas

  • Nephrology

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