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Abstract: FR-PO714

Tubular Basement Membrane Duplication and Cell Interposition Are Distinctive Histological Findings in the Adult Patients Genetically Diagnosed with Nephronophthisis-Related Ciliopathies

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Fujimaru, Takuya, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Nagata, Michio, University of Tsukuba, Tsukuba, Japan
  • Mandai, Shintaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Chiga, Motoko, Tokyo Medical and Dental University, Tokyo, Japan
  • Kikuchi, Hiroaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Ando, Fumiaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Yutaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Susa, Koichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Isobe, Kiyoshi, Tokyo Medical and Dental University, Tokyo, Japan
  • Iimori, Soichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Naito, Shotaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Okado, Tomokazu, Tokyo Medical and Dental University, Tokyo, Japan
  • Rai, Tatemitsu, Tokyo Medical and Dental University, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
Background

Unlike pediatric patients, nephronophthisis-related ciliopathys (NPHP-RCs) are often suspected only after renal biopsy in adult patients, because they usually have no specific extra-renal complications of NPHP-RCs. However, histological findings of NPHP-RCs, such as microcyst and interstitial fibrosis, are also commonly seen in any chronic tubulointerstitial disorders in general. In addition, comprehensive genetic testing is not easily available. Therefore, identification of representative histopathologic pattern of NPHP-RCs is useful for precise diagnosis of adult patients.

Methods

We analyzed 16 adult patients who were suspected as NPHP-RCs by renal biopsy. All patients had no extrarenal findings (retinitis pigmentosa and liver function disorder) and no family history of NPHP-RCs. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes that cause nine types of hereditary cystic kidney diseases, including NPHP-RCs.

Results

Through the analysis, six patients were genetically diagnosed with NPHP-RCs, including three patients with homozygous NPHP1 mutations and three patients with a compound heterozygous mutation in NPHP3, NPHP4, or CEP164, respectively. At the time of renal biopsy, the patients diagnosed genetically as NPHP-RCs were significantly younger than those without mutations (median, 30 years old vs 69 years old, P = 0.02). Regarding the pathological findings, tubular basement membrane (TBM) duplication and cell interposition in TBM of intact tubules were significantly more common in the patients with NPHP-RCs (83% vs 20%, P = 0.035, 83% vs 10%, P = 0.008, respectively).

Conclusion

Our study revealed that disorders of TBM could be specific findings in the adult patients genetically diagnosed with NPHP-RCs. These findings are potentially beneficial for optimal diagnosis of adult NPHP-RCs and are suggestive of the pathogenesis of the diseases.

Funding

  • Government Support - Non-U.S.