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

Abstract

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.

• Authors: Yasushi Chiba, Chiyoko N Inoue
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 247 Issue 1 Pg. 35-40 (01 2019) ISSN: 1349-3329 [Electronic] Japan
• PMID: 30651406 (Publication Type: Case Reports, Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Cyclosporine
• Creatinine

Topics

• Adolescent
• Angiotensin Receptor Antagonists (therapeutic use)
• Biopsy
• Child
• Child, Preschool
• Creatinine (blood, urine)
• Cyclosporine (therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Frasier Syndrome (blood, drug therapy, urine)
• Humans
• Kidney (pathology)
• Kidney Diseases (blood, drug therapy, urine)
• Proteinuria (complications)