Article

Pathogenesis and therapy of focal segmental glomerulosclerosis: an update

Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Pediatric Nephrology (Impact Factor: 2.88). 11/2010; 26(7):1001-15. DOI: 10.1007/s00467-010-1692-x
Source: PubMed

ABSTRACT Focal and segmental glomerulosclerosis (FSGS) is an important cause of steroid-resistant nephrotic syndrome in adults and children. It is responsible for 5-20% of all cases of end-stage kidney disease (ESKD) in the United States. The pathogenesis of FSGS has not been fully elucidated; however, data from molecular studies of familial cases in the last two decades suggest that FSGS is a defect of the podocyte. The therapeutic agents available for treatment of FSGS are not very effective and only a small percentage of affected individuals will achieve complete remission. Recent data from molecular biology and molecular genetics has provided insight into the mechanisms of action of old agents and also identification of other novel therapeutic targets. This review focuses on recent advances in the molecular pathogenesis of FSGS and currently available therapeutic agents as well as potential novel therapies.

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    ABSTRACT: Background: Treatment of steroid-resistant nephrotic syndrome with a focal segmental glomerulosclerosis (FSGS) histological diagnosis can be challenging, particularly in the presence of ciclosporin resistance. The importance of mutations in genes encoding the structural proteins of podocytes has been recently recognized and may influence medical decision-making. The c.349G>A variant of the NPHS1 gene has been associated with a poorer prognosis in IgA nephropathy and nephrotic syndrome. Case Diagnosis/Treatment: To study the potential association of the NPHS1: c.349G>A sequence variant with renal disease, we analyzed five children in whom this variant had been identified and who all presented with nephrotic syndrome and the histological diagnosis of FSGS. Although this sequence variant was present in all cases, one patient had steroid-responsive nephrotic syndrome without relapse following standard initial therapy, three responded to a variety of treatments, and one patient was unresponsive. Conclusion: The NPHS1: c.349G>A sequence variant may either be independent of, or a modifying agent in, the progression of the disease, and does not preclude these and similar patients from appropriate treatment and entry into clinical trials. Larger trials are needed to evaluate the therapeutic response and long-term outcome of FSGS patients with different NPHS gene mutations.
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