期刊
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 15, 期 7, 页码 983-994出版社
AMER SOC NEPHROLOGY
DOI: 10.2215/CJN.13371019
关键词
nephrotic syndrome; pediatric nephrology; progression of renal failure; transplant outcomes; Rituximab; Exome; Radar; immunosuppression; Base Sequence; Genetic Testing; Renal Insufficiency; Biopsy; Disease Progression; Registries; Cohort Studies
资金
- Elizabeth Blackwell Institute for Health Research at the University of Bristol
- Medical Research Council's Global Challenges Research Fund
- Kidney Research UK
- Medical Research Council's Stratified Medicine Initiative
- National Institute for Health Research's RareDiseases Translational Research Collaboration
- Nephrotic Syndrome Trust
- Wellcome Trust's Institutional Strategic Support Fund
- MRC [G0800571] Funding Source: UKRI
Background and objectivesIntensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study of Nephrotic Syndrome cohort aimed to improve disease stratification by determining, in comprehensively genetically screened patients with steroid-resistant nephrotic syndrome, if there is an association between response to initial intensified immunosuppression and disease progression and/or post-transplant recurrence.Design, setting, participants, & measurementsPediatric patients with steroid-resistant nephrotic syndrome were recruited via the UK National Registry of Rare Kidney Diseases. All patients were whole-genome sequenced, whole-exome sequenced, or steroid-resistant nephrotic syndrome gene-panel sequenced. Complete response or partial response within 6 months of starting intensified immunosuppression was ascertained using laboratory data. Response to intensified immunosuppression and outcomes were analyzed according to genetic testing results, pattern of steroid resistance, and first biopsy findings.ResultsOf 271 patients, 178 (92 males, median onset age 4.7 years) received intensified immunosuppression with response available. A total of 4% of patients with monogenic disease showed complete response, compared with 25% of genetic-testing-negative patients (P=0.02). None of the former recurred post-transplantation. In genetic-testing-negative patients, 97% with complete response to first intensified immunosuppression did not progress, whereas 44% of nonresponders developed kidney failure with 73% recurrence post-transplant. Secondary steroid resistance had a higher complete response rate than primary/presumed resistance (43% versus 23%; P=0.001). The highest complete response rate in secondary steroid resistance was to rituximab (64%). Biopsy results showed no correlation with intensified immunosuppression response or outcome.ConclusionsPatients with monogenic steroid-resistant nephrotic syndrome had a poor therapeutic response and no post-transplant recurrence. In genetic-testing-negative patients, there was an association between response to first intensified immunosuppression and long-term outcome. Patients with complete response rarely progressed to kidney failure, whereas nonresponders had poor kidney survival and a high post-transplant recurrence rate. Patients with secondary steroid resistance were more likely to respond, particularly to rituximab.
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