Steroid-resistant nephrotic syndrome: impact of genetic testing
BACKGROUND AND OBJECTIVES: Mutations in several genes are known to cause steroid-resistant nephrotic syndome (SRNS), most commonly in NPHS1, NPHS2, and WT1. Our aims were to determine the frequency of mutations in these genes in children with SRNS, the response of patients with SRNS to various immun...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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King Faisal Specialist Hospital and Research Centre
2013-11-01
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| Series: | Annals of Saudi Medicine |
| Online Access: | https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2013.533 |
| _version_ | 1819080485591056384 |
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| author | Jameela A. Kari Sherif M. El-Desoky Mamdooh Gari Khalid Malik Virginia Vega-Warner Svjetlana Lovric Detlef Bockenhauer |
| author_facet | Jameela A. Kari Sherif M. El-Desoky Mamdooh Gari Khalid Malik Virginia Vega-Warner Svjetlana Lovric Detlef Bockenhauer |
| author_sort | Jameela A. Kari |
| collection | DOAJ |
| description | BACKGROUND AND OBJECTIVES: Mutations in several genes are known to cause steroid-resistant nephrotic syndome (SRNS), most commonly in NPHS1, NPHS2, and WT1. Our aims were to determine the frequency of mutations in these genes in children with SRNS, the response of patients with SRNS to various immunosuppressants, and the disease outcome, and to review the predictive value of genetic testing and renal biopsy result. DESIGN AND SETTINGS: A retrospective review was performed of the medical records for all children with SRNS who were treated and followed-up in the Pediatric Nephrology Unit of King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from 2002–2012. PATIENTS AND METHODS: We retrospectively reviewed the medical records of children above 1 year of age, who presented with SRNS to KAUH, Jeddah, Saudi Arabia, in the 10-year interval from 2002–2012 and for whom the results of genetic testing for NPHS1, NPHS2, and WT1 were available. We compared the clinical phenotype, including response to treatment and renal outcome to genotype data. RESULTS: We identified 44 children with a clinical diagnosis of SRNS in whom results of genetic testing were available. Presumably disease-causing mutations were detected in 5 children (11.4%) of which 3 (6.8%) had NPHS2 mutation and 2 (4.5%) had NPHS1 mutation. Renal biopsy revealed minimal change disease (MCD) or variants in 17 children, focal segmental glomerulosclerosis (FSGS) in 23 children, membranoproliferative changes (MPGN) in 2 children, and IgA nephropathy in another 2 children. Children with MCD on biopsy were more likely to respond to treatment than those with FSGS. None of those with an identified genetic cause showed any response to treatment. CONCLUSION: The frequency of identified disease-causing mutations in children older than 1 year with SRNS presented to KAUH was 11.4%, and these patients showed no response to treatment. Initial testing for gene mutation in children with SRNS may obviate the need for biopsy, and the use of immunosuppressive treatment in children with disease due to NPHS1 or NPHS2 mutations. Renal biopsy was useful in predicting response in those without genetic mutations. |
| first_indexed | 2024-12-21T19:45:38Z |
| format | Article |
| id | doaj.art-d85049ed83464114b746b0d6a0c76b5b |
| institution | Directory Open Access Journal |
| issn | 0256-4947 0975-4466 |
| language | English |
| last_indexed | 2024-12-21T19:45:38Z |
| publishDate | 2013-11-01 |
| publisher | King Faisal Specialist Hospital and Research Centre |
| record_format | Article |
| series | Annals of Saudi Medicine |
| spelling | doaj.art-d85049ed83464114b746b0d6a0c76b5b2022-12-21T18:52:20ZengKing Faisal Specialist Hospital and Research CentreAnnals of Saudi Medicine0256-49470975-44662013-11-0133653353810.5144/0256-4947.2013.533asm-6-533Steroid-resistant nephrotic syndrome: impact of genetic testingJameela A. Kari0Sherif M. El-Desoky1Mamdooh Gari2Khalid Malik3Virginia Vega-Warner4Svjetlana Lovric5Detlef Bockenhauer6From the Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi ArabiaFrom the Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi ArabiaFrom the Center of Excellence in Denomic Medicine Research, Jedah, Saudi ArabiaFrom the Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi ArabiaFrom the Pediatrics, University of Michigan, Ann Arbor, Michigan, United StatesFrom the Pediatrics, University of Michigan, Ann Arbor, Michigan, United StatesFrom the Renal Unit, Great Ormond Street Hospital, London, United KingdomBACKGROUND AND OBJECTIVES: Mutations in several genes are known to cause steroid-resistant nephrotic syndome (SRNS), most commonly in NPHS1, NPHS2, and WT1. Our aims were to determine the frequency of mutations in these genes in children with SRNS, the response of patients with SRNS to various immunosuppressants, and the disease outcome, and to review the predictive value of genetic testing and renal biopsy result. DESIGN AND SETTINGS: A retrospective review was performed of the medical records for all children with SRNS who were treated and followed-up in the Pediatric Nephrology Unit of King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from 2002–2012. PATIENTS AND METHODS: We retrospectively reviewed the medical records of children above 1 year of age, who presented with SRNS to KAUH, Jeddah, Saudi Arabia, in the 10-year interval from 2002–2012 and for whom the results of genetic testing for NPHS1, NPHS2, and WT1 were available. We compared the clinical phenotype, including response to treatment and renal outcome to genotype data. RESULTS: We identified 44 children with a clinical diagnosis of SRNS in whom results of genetic testing were available. Presumably disease-causing mutations were detected in 5 children (11.4%) of which 3 (6.8%) had NPHS2 mutation and 2 (4.5%) had NPHS1 mutation. Renal biopsy revealed minimal change disease (MCD) or variants in 17 children, focal segmental glomerulosclerosis (FSGS) in 23 children, membranoproliferative changes (MPGN) in 2 children, and IgA nephropathy in another 2 children. Children with MCD on biopsy were more likely to respond to treatment than those with FSGS. None of those with an identified genetic cause showed any response to treatment. CONCLUSION: The frequency of identified disease-causing mutations in children older than 1 year with SRNS presented to KAUH was 11.4%, and these patients showed no response to treatment. Initial testing for gene mutation in children with SRNS may obviate the need for biopsy, and the use of immunosuppressive treatment in children with disease due to NPHS1 or NPHS2 mutations. Renal biopsy was useful in predicting response in those without genetic mutations.https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2013.533 |
| spellingShingle | Jameela A. Kari Sherif M. El-Desoky Mamdooh Gari Khalid Malik Virginia Vega-Warner Svjetlana Lovric Detlef Bockenhauer Steroid-resistant nephrotic syndrome: impact of genetic testing Annals of Saudi Medicine |
| title | Steroid-resistant nephrotic syndrome: impact of genetic testing |
| title_full | Steroid-resistant nephrotic syndrome: impact of genetic testing |
| title_fullStr | Steroid-resistant nephrotic syndrome: impact of genetic testing |
| title_full_unstemmed | Steroid-resistant nephrotic syndrome: impact of genetic testing |
| title_short | Steroid-resistant nephrotic syndrome: impact of genetic testing |
| title_sort | steroid resistant nephrotic syndrome impact of genetic testing |
| url | https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2013.533 |
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