Kidney Week

Abstract: SA-PO669

Kidney Pathological Findings in MYH9-Related Disease

Session Information

• Pediatric Nephrology - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

• Nakatani, Ryo, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan

Ryo Nakatani, MD

• Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan

Kenichiro Miura, MD, PhD

• Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan

Yoko Shirai, MD, PhD

• Ohtsuka, Yasufumi, Saga Daigaku Igakubu Daigakuin Igakukei Kenkyuka, Saga, Saga, Japan

Yasufumi Ohtsuka, DrMed, PhD

• Ohwada, Yoko, Dokkyo Ika Daigaku, Shimotsuga-gun, Tochigi, Japan

Yoko Ohwada

• Konomoto, Takao, Miyazaki Daigaku Igakubu Daigakuin Ikagaku Kangogaku Kenkyuka, Miyazaki-gun, Miyazaki, Japan

Takao Konomoto, MD, PhD

• Morohashi, Tamaki, Nihon Daigaku Igakubu Daigakuin Igaku Kenkyuka, Itabashi-ku, Tokyo, Japan

Tamaki Morohashi, DrMed, PhD

• Tsugawa, Koji, Hirosaki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Hirosaki, Aomori, Japan

Koji Tsugawa, DrMed, DrPH

• Taneda, Sekiko, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan

Sekiko Taneda, MD, PhD

• Honda, Kazuho, Showa Daigaku Daigakuin Igaku Kenkyuka Igakubu, Shinagawa-ku, Tokyo, Japan

Kazuho Honda, MD, PhD

• Kunishima, Shinji, Gifu Iryo Kagaku Daigaku, Seki, Gifu, Japan

Shinji Kunishima, PhD

• Ishikura, Kenji, Kitasato Daigaku Igakubu, Sagamihara, Kanagawa, Japan

Kenji Ishikura, MD, PhD

• Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan

Motoshi Hattori, MD, PhD

Background

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, progressive kidney failure, and sensorineural hearing loss. There are limited data of kidney pathological findings of MYH9-RD because of the low platelet count. Although focal segmental glomerulosclerosis (FSGS) and glomerular basement membrane (GBM) abnormalities similar to Alport syndrome have been anecdotally described, no comprehensive studies have been performed.

Methods

We conducted a cross-sectional nationwide survey in Japan. Questionnaires were initially sent to 145 institutions. We asked the eligible patients if a kidney biopsy had been performed. Eight kidney biopsy samples from seven patients were finally included in the study. All pathological samples were examined by pediatric nephrologists and pathologists at our institution. This study was supported by “Research on Rare and Intractable Diseases, Health and Labor Sciences Research Grants” from the Ministry of Health, Labour and Welfare (Grant No. 20FC1028), Japan.

Results

All seven patients had pathogenic variants in the MYH9 gene: R702C in three patients, R702H in two patients, D1424H in one patient, and Q1068_L1074dup in one patient. The median ages at onset of proteinuria and kidney biopsy were 7 years and 11 years, respectively. Mesangial matrix expansion was observed in all samples, and two samples also showed FSGS. Immunofluorescence study showed significant depositions of immunoglobulin and complement in two samples: IgG and C1q in one patient and IgA and C3 in one patient. Electron microscopy showed segmental foot process effacement, endothelial cell swelling, and electron-dense deposits (EDD) in eight, six, and five samples, respectively. GBM abnormalities such as thinning, thickening, and splitting of the lamina densa were observed in three samples.

Conclusion

Mesangial matrix expansion and focal foot process effacement were commonly observed in MYH9-RD patients. In addition, a variety of pathological findings including immunoglobulin and complement depositions with EDD and GBM abnormalities were also observed. These results may have important implications for the disease mechanism and treatment of MYH9-RD.