Journal
KIDNEY INTERNATIONAL REPORTS
Volume 6, Issue 5, Pages 1346-1354Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ekir.2021.02.005
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Funding
- Japan Society of the Promotion of Science [19K17730, 25221306, 16H05314, 19H01049, 19H03672, 15K15327, 16K15467, 18K19534, 17H06657, 20K22926, 19K17733]
- Health Labor Science Research Grant from the Ministry of Health Labor and Welfare, AMED [JP18ek0109304]
- Yukiko Ishibashi Foundation
- Salt Science Research Foundation [1925, 2030]
- LVSEM Study Group of Renal Biopsy and Hitachi High Technologies Corporation in Japan [007]
- Grants-in-Aid for Scientific Research [17H06657, 19K17733, 19K17730, 18K19534, 19H03672, 19H01049, 20K22926, 15K15327] Funding Source: KAKEN
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This study analyzed the genetic background and clinicopathologic features of adult NPH in 18 sporadic adult patients, finding that thick TBM duplication is a specific finding in adult NPH. Patients with pathogenic mutations were significantly younger, and older patients tended to have no pathogenic mutations even when suspected to have NPH by renal biopsy.
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-mu m thickness, was significantly higher in patients with genetically proven adult NPH than in those without pathogenic mutations. alpha-Smooth muscle actin (alpha-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.
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