Kidney Week

Abstract: SA-PO1158

Precise Clinicopathologic Findings May Increase the Detection Rate of Gene Mutations in Pediatric Kidney Transplant Recipients with Focal Segmental Glomerulosclerosis

Session Information

• Transplantation: Clinical - Rejection, Recurrent Disease, Incompatibility
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Kaneko, Naoto, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Naoto Kaneko,

• Miura, Kenichiro, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Kenichiro Miura,

• Ando, Taro, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Taro Ando,

• Iida, Takaya, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Takaya Iida,

• Shiratori, Atsutoshi, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Atsutoshi Shiratori,

• Shirai, Yoko, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Yoko Shirai,

• Ishiwa, Sho, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Sho Ishiwa,

• Yabuuchi, Tomoo, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Tomoo Yabuuchi,

• Hashimoto, Taeko, Yamagata University, Yamagata-city, Japan

Taeko Hashimoto,

• Ishizuka, Kiyonobu, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Kiyonobu Ishizuka,

• Sato, Hidenori, Yamagata University Faculty of Medicine, Yamagata, Japan

Hidenori Sato,

• Harita, Yutaka, Dept. of Pediatrics, Tokyo University, Tokyo, Japan

Yutaka Harita,

• Hattori, Motoshi, Tokyo Women's Medical University, Shinjuku-Ku, TOKYO, Japan

Motoshi Hattori,

Background

Whole exome sequencing (WES) has enabled precision medicine in kidney transplant recipients with focal segmental glomerulosclerosis (FSGS), because individuals with a monogenic cause have a very low expectancy of posttransplant recurrence. However, it remains unknown whether all recipients with FSGS should undergo genetic testing. Here, we investigated the likelihood of detecting pathogenic mutations in recipients with FSGS divided into subgroups based on clinicopathologic findings.

Methods

Nineteen pediatric transplant recipients with FSGS were recruited and classified based on their clinical and pathologic findings. Adaptive, drug-induced and virus-associated FSGS were classified as secondary FSGS. Patients with family history of FSGS or extrarenal manifestations were classified as familial/syndromic FSGS. Patients who showed nephrotic syndrome (NS) and diffuse foot process effacement (FPE) in their native kidneys or had a history of recurrence in a previous transplantation were classified as presumed primary FSGS. We performed WES and examined a subset of 114 genes associated with FSGS in all patients.

Results

The results of classification and genetic testing are shown in Figure. WES revealed that 0 (0%) of 8 patients with presumed primary FSGS and 10 (91%) of the other 11 patients carried gene mutations known to cause FSGS. Three of 8 (38%) patients with presumed primary FSGS had posttransplant recurrence, while no recurrence was observed in the other patients.

Conclusion

The detection rate of pathogenic mutations known to cause FSGS was very high in the kidney transplant recipients after excluding individuals with secondary and presumed primary forms based on our precise clinicopathologic findings such as family history, extrarenal manifestations, NS and diffuse FPE.

The results of classification and genetic analysis

Funding

• Government Support - Non-U.S.