Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis

被引：8

作者：

Nagano, China ^{[1
]}

Hara, Shigeo ^{[2
]}

Yoshikawa, Norishige ^{[3
]}

Takeda, Asami ^{[4
]}

Gotoh, Yoshimitsu ^{[5
]}

Hamada, Riku ^{[6
]}

Matsuoka, Kentaro ^{[7
]}

Yamamoto, Masaki ^{[8
]}

Fujinaga, Shuichiro ^{[9
]}

Sakuraya, Koji ^{[9
]}

Kamei, Koichi ^{[10
]}

Hamasaki, Yuko ^{[11
]}

Oguchi, Hideyo ^{[11
]}

Araki, Yoshinori ^{[12
]}

Ogawa, Yayoi ^{[13
]}

Okamoto, Takayuki ^{[14
]}

Ito, Shuichi ^{[15
]}

Tanaka, Seiji ^{[16
]}

Kaito, Hiroshi ^{[17
]}

Aoto, Yuya ^{[1
]}

Ishiko, Shinya ^{[1
]}

Rossanti, Rini ^{[1
]}

Sakakibara, Nana ^{[1
]}

Horinouchi, Tomoko ^{[1
]}

Yamamura, Tomohiko ^{[1
]}

Nagase, Hiroaki ^{[1
]}

Iijima, Kazumoto ^{[18
,19
]}

Nozu, Kandai ^{[1
]}

机构：

[1] Kobe Univ, Dept Pediat, Grad Sch Med, Kobe, Hyogo, Japan

[2] Kobe City Med Ctr Gen Hosp, Dept Diagnost Pathol, Kobe, Hyogo, Japan

[3] Takatsuki Gen Hosp, Clin Res Ctr, Takatsuki, Osaka, Japan

[4] Nagoya Daini Hosp, Dept Nephrol, Japanese Red Cross Aichi Med Ctr, Nagoya, Aichi, Japan

[5] Nagoya Daini Hosp, Japanese Red Cross Aichi Med Ctr, Dept Pediat Nephrol, Nagoya, Aichi, Japan

[6] Tokyo Metropolitan Childrens Med Ctr, Dept Nephrol, Tokyo, Japan

[7] Tokyo Metropolitan Childrens Med Ctr, Dept Pathol, Tokyo, Japan

[8] Seirei Hamamatsu Gen Hosp, Dept Pediat, Hamamatsu, Shizuoka, Japan

[9] Saitama Childrens Med Ctr, Div Nephrol, Saitama, Japan

[10] Natl Ctr Child Hlth & Dev, Div Nephrol & Rheumatol, Tokyo, Japan

[11] Toho Univ, Fac Med, Dept Nephrol, Tokyo, Japan

[12] Natl Hosp Org Hokkaido Med Ctr, Dept Pediat Nephrol, Sapporo, Hokkaido, Japan

[13] Hokkaido Renal Pathol Ctr, Sapporo, Hokkaido, Japan

[14] Hokkaido Univ, Dept Pediat, Grad Sch Med, Sapporo, Hokkaido, Japan

[15] Yokohama City Univ, Grad Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan

[16] Kurume Univ, Dept Pediat & Child Hlth, Sch Med, Kurume, Fukuoka, Japan

[17] Hyogo Prefectural Kobe Childrens Hosp, Dept Nephrol, Kobe, Hyogo, Japan

[18] Hyogo Prefectural Kobe Childrens Hosp, Kobe, Hyogo, Japan

[19] Kobe Univ, Dept Adv Pediat Med, Grad Sch Med, Kobe, Hyogo, Japan

来源：

KIDNEY360 | 2022年 / 3卷 / 08期

关键词：

clinical nephrology; Columbia classification; end stage kidney disease; focal segmental glomerulosclerosis; genetic renal disease; genotype-phenotype correlation; histopathology; nephrotic syndrome; variant; GLOMERULAR-FILTRATION-RATE; NEPHROTIC SYNDROME; PRESENTING FEATURES; JAPANESE CHILDREN; VARIANTS; EQUATION; FSGS;

D O I：

10.34067/KID.0000812022

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：

Background Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients. Methods This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates. Results The distribution of histologic variants according to the Columbia classification was 45% (n=53) FSGS not otherwise specified, 21% (n=25) cellular, 15% (n=18) perihilar, 13% (n=16) collapsing, and 6% (n=7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P < 0.001). Conclusions We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS.

引用

页码：1384 / 1393

页数：10

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