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An Efficient Sieving Method to Isolate Intact Glomeruli from Adult Rat Kidney
Published on: November 1, 2018
Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a
Meenakshi Sambharia1, Prerna Rastogi2, Christie P Thomas1,3,4,5
1Division of Nephrology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
Abstract:
Focal segmental glomerulosclerosis (FSGS) is not a disease, rather a pattern of histological injury occurring from a variety of causes. The exact pathogenesis has yet to be fully elucidated but is likely varied based on the type of injury and the primary target of that injury. However, the approach to treatment is often based on the degree of podocyte foot process effacement and clinical presentation without sufficient attention paid to etiology. In this regard, there are many monogenic causes of FSGS with variable presentation from nephrotic syndrome with histological features of primary podocytopathy to more modest degrees of proteinuria with limited evidence of podocyte foot process injury. It is likely that genetic causes are largely underdiagnosed, as the role and the timing of genetic testing in FSGS is not established and genetic counseling, testing options, and interpretation of genotype in the context of phenotype may be outside the scope of practice for both nephrologists and geneticists. Yet most clinicians believe that a genetic diagnosis can lead to targeted therapy, limit the use of high-dose corticosteroids as a therapeutic trial, and allow the prediction of the natural history and risk for recurrence in the transplanted kidney. In this manuscript, we emphasize that genetic FSGS is not monolithic in its presentation, opine on the importance of genetic testing and provide an algorithmic approach to deployment of genetic testing in a timely fashion when faced with a patient with FSGS.
Insights
Genetic causes of Focal Segmental Glomerulosclerosis (FSGS) are underdiagnosed. Genetic testing can guide targeted therapies and predict disease progression, improving patient outcomes.
Area of Science:
- Nephrology
- Genetics
- Histopathology
Background:
- Focal segmental glomerulosclerosis (FSGS) represents a pattern of kidney injury, not a distinct disease, with diverse underlying causes.
- Current treatment approaches often prioritize histological findings and clinical presentation over etiological investigation, potentially overlooking genetic origins.
- Monogenic causes of FSGS present variably, ranging from nephrotic syndrome to milder proteinuria, highlighting diagnostic challenges.
Purpose of the Study:
- To emphasize that genetic FSGS is not a uniform condition and its presentation varies significantly.
- To underscore the critical importance of genetic testing in the diagnosis and management of FSGS.
- To propose a structured, algorithmic approach for the timely implementation of genetic testing in FSGS patients.
Main Methods:
- Review of existing literature on the genetic basis of FSGS.
- Analysis of clinical presentations and histological findings in genetically diverse FSGS cases.
- Development of a practical algorithm for genetic testing deployment in FSGS.
Main Results:
- Genetic causes of FSGS are likely underdiagnosed due to established diagnostic pathways.
- Genetic testing offers potential for targeted therapies, reduced reliance on empirical high-dose corticosteroids, and prediction of disease course.
- The interpretation of genetic findings requires integrated nephrology and genetics expertise.
Conclusions:
- A genetic diagnosis in FSGS can lead to personalized treatment strategies and improved prognostic accuracy.
- Integrating genetic testing into the standard workup for FSGS is crucial for comprehensive patient care.
- The proposed algorithm aims to facilitate timely and appropriate genetic evaluation for patients with FSGS.
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