Tohoku J. Exp. Med., 2019 January, 247(1)

Once-Daily Low-Dose Cyclosporine A Treatment with Angiotensin Blockade for Long-Term Remission of Nephropathy in Frasier Syndrome

YASUSHI CHIBA1,2 and CHIYOKO N. INOUE1

1Department of Pediatrics, Red Cross Sendai Hospital, Sendai, Miyagi, Japan
2Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Miyagi, Japan

Cyclosporine A is known to be effective in some genetic podocyte injury. However, the efficacy of cyclosporine A depends on the degree of histopathological findings, and the relationship between long-term use and renal prognosis remains unknown. Frasier syndrome is a rare genetic disorder caused by intronic mutations in WT1, and is characterized by progressive glomerulopathy, a 46,XY disorder of sex development, and an increased risk of gonadoblastoma. We report here a 16-year-old phenotypically female patient with Frasier syndrome. A renal biopsy at the age of seven years showed segmentally effaced podocyte foot processes with no evidence of glomerulosclerosis. Steroid-resistant proteinuria progressed to the nephrotic range at the age of 10 years, which responded to once-daily administration of cyclosporine A with low two-hour post-dose cyclosporine A (C2) levels; she then achieved stable partial remission in combination with renin-angiotensin system (RAS) blockade. At the age of 12 years, examinations for delayed puberty confirmed the diagnosis of Frasier syndrome. The second renal biopsy showed widespread foot process effacement and a minor lesion of segmental glomerulosclerosis without findings suggestive of cyclosporine A nephropathy. She maintained partial remission and normal renal function with the continuation of once-daily low-dose cyclosporine A. The C2 levels required for the remission were between 212 and 520 ng/ml. Cyclosporine A dosages sufficient for maintaining the C2 levels were 1.1-1.2 mg/kg per day. In conclusion, the long-lasting treatment of once-daily low-dose cyclosporine A with RAS inhibition was effective for induction and maintenance of partial remission in Frasier syndrome.

keywords —— cyclosporine A; Frasier syndrome; lisinopril; podocytes; telmisartan

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Tohoku J. Exp. Med., 2019, 247, 35-40

Correspondence: Yasushi Chiba, M.D., Ph.D., Department of Pediatrics, Tohoku Rosai Hospital, 4-3-21 Dainohara, Aoba-ku, Sendai, Miyagi 981-8563, Japan.

e-mail: ychiba-ped@tohokuh.johas.go.jp