Kenichiro Miura1, Naoto Kaneko1, Taeko Hashimoto1,2, Kiyonobu Ishizuka1, Yoko Shirai1, Masataka Hisano3, Hiroko Chikamoto1, Yuko Akioka1,4, Shoichiro Kanda1,5, Yutaka Harita5, Toshiyuki Yamamoto6, Motoshi Hattori7. 1. Department of Pediatric Nephrology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan. 2. Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan. 3. Department of Nephrology, Chiba Children's Hospital, Chiba, Japan. 4. Department of Pediatrics, Saitama Medical University, Saitama, Japan. 5. Department of Pediatrics, The University of Tokyo, Tokyo, Japan. 6. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. 7. Department of Pediatric Nephrology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan. hattori@twmu.ac.jp.
Abstract
BACKGROUND: Establishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20-30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined. METHODS: Pediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing. RESULTS: Twenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS. CONCLUSIONS: Our systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence. A higher resolution version of the Graphical abstract is available as Supplementary information.
BACKGROUND: Establishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20-30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined. METHODS: Pediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing. RESULTS: Twenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS. CONCLUSIONS: Our systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence. A higher resolution version of the Graphical abstract is available as Supplementary information.
Authors: An S De Vriese; Sanjeev Sethi; Karl A Nath; Richard J Glassock; Fernando C Fervenza Journal: J Am Soc Nephrol Date: 2018-01-10 Impact factor: 10.121
Authors: Agnieszka Bierzynska; Hugh J McCarthy; Katrina Soderquest; Ethan S Sen; Elizabeth Colby; Wen Y Ding; Marwa M Nabhan; Larissa Kerecuk; Shivram Hegde; David Hughes; Stephen Marks; Sally Feather; Caroline Jones; Nicholas J A Webb; Milos Ognjanovic; Martin Christian; Rodney D Gilbert; Manish D Sinha; Graham M Lord; Michael Simpson; Ania B Koziell; Gavin I Welsh; Moin A Saleem Journal: Kidney Int Date: 2017-01-20 Impact factor: 10.612
Authors: Lutz T Weber; Burkhard Tönshoff; Ryszard Grenda; Antonia Bouts; Rezan Topaloglu; Bora Gülhan; Nikoleta Printza; Atif Awan; Nina Battelino; Rasmus Ehren; Peter F Hoyer; Gregor Novljan; Stephen D Marks; Jun Oh; Agnieszka Prytula; Tomas Seeman; Clodagh Sweeney; Luca Dello Strologo; Lars Pape Journal: Pediatr Transplant Date: 2020-12-30