Effective calcineurin inhibitor treatment in adult-onset steroid-resistant nephrotic syndrome with a novel splice donor site variant of TRPC6: a case report

被引：0

作者：

Nagasaka, Tomoki ^{[1
]}

Uchiyama, Kiyotaka ^{[1
,2
]}

Hama, Eriko Yoshida ^{[1
]}

Kojima, Daiki ^{[1
]}

Kaneko, Kenji ^{[1
]}

Yoshimoto, Norifumi ^{[1
]}

Yasuda, Itaru ^{[1
]}

Yamada, Mamiko ^{[3
]}

Miya, Fuyuki ^{[3
]}

Suzuki, Hisato ^{[3
]}

Tajima, Takaya ^{[1
]}

Yamaguchi, Shintaro ^{[1
]}

Hayashi, Kaori ^{[1
]}

Kanda, Takeshi ^{[1
]}

Hashiguchi, Akinori ^{[4
]}

Kosaki, Kenjiro ^{[3
]}

Itoh, Hiroshi ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Endocrinol Metab & Nephrol, 35 Shinanomachi,Shinjuku Ku, Tokyo 1608582, Japan

[2] Int Univ Hlth & Welf, Narita Hosp, Dept Nephrol, 852 Hatakeda, Narita, Chiba 2860124, Japan

[3] Keio Univ, Sch Med, Ctr Med Genet, 35 Shinanomachi,Shinjuku, Tokyo 1608582, Japan

[4] Keio Univ, Sch Med, Dept Pathol, 35 Shinanomachi,Shinjuku Ku, Tokyo 1608582, Japan

来源：

CEN CASE REPORTS | 2024年

关键词：

Steroid-resistant nephrotic syndrome; Minor glomerular abnormality; TRPC6; Calcineurin inhibitor; Splice donor site; CYCLOSPORINE-A; CHILDREN; MUTATIONS; TACROLIMUS; THERAPY;

D O I：

10.1007/s13730-024-00935-6

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Transient receptor potential canonical 6 (TRPC6) variants, which were initially detected in adult-onset familial focal segmental glomerulosclerosis (FSGS), were also identified in pediatric-onset one. Here, we present a patient with adult-onset steroid-resistant nephrotic syndrome (SRNS) who harbored a likely pathogenic TRPC6 variant and partially responded to calcineurin inhibitors (CNIs). A 44-year-old woman with stable rheumatoid arthritis, systemic lupus erythematosus, and Sj & ouml;gren's syndrome was presented with nephrotic syndrome. Her renal biopsy results showed minor glomerular abnormalities. Upon admission, she was treated with steroids for around 4 weeks, but it was ineffective. After 1-2 weeks of cyclosporine A (CyA) administration, urine output increased, renal function improved without a decrease in proteinuria, and she was discharged. Her renal function was maintained for 2 months, but after a CyA dose reduction, she was again admitted to the hospital due to relapsing edema, decreased urine output, and worsening renal function. CyA was replaced by tacrolimus (TAC). A second renal biopsy showed nearly the same findings as the first except for tubulointerstitial lesions. After 1-2 weeks of TAC administration, urine output increased, and renal function improved. However, urinary protein levels did not decrease as before. After discharge, a whole exome analysis revealed a heterozygous splice donor site variant NM_004621.6;c.2644 + 1G > A in TRPC6. Genetic testing identified a novel splice donor site variant of TRPC6 in a patient with adult-onset SRNS, which prevented unnecessary steroid continuation. The safety and efficacy of CNI in TRPC6 glomerulopathy must be evaluated in future larger studies with longer follow-up.

引用

页码：208 / 216

页数：9