Steroid Resistant Nephrotic Syndrome/FSGS Panel
There is evidence that much of the kidney disease in the U.S. has a genetic component. Family history of renal disease was one of only four known independent risk factors for progression to end-stage renal disease (ESRD) identified in a large study cohort.(1) Other studies have shown a three to nine-fold increased risk of ESRD in people with a family history of ESRD.(2) One recent study looking at patients with steroid-resistant nephrotic syndrome (SRNS), which most commonly shows FSGS on biopsy, identified a single gene etiology in approximately 30% of patients.(3) Another study detected definitively pathogenic or probably pathogenetic variants in 70% of patients with a family history of disease and 15% of sporadic cases.(4) These results indicate that determining possible genetic etiologies for renal disease should be an integral component of the patient’s evaluation.
Inherited nephropathies involving many different genes often have overlapping clinical and morphologic findings. Therefore, testing for these genetic conditions stands to greatly benefit from sequencing techniques which enable evaluation of numerous genes simultaneously. The steroid-resistant nephrotic syndrome panel utilizes next generation sequencing (NGS) to detect variants in 33 genes which are described in this disease (see a full list of genes below).
Arkana is a laboratory with specialized expertise in the classification of renal disease. Therefore, if the patient has had a renal biopsy performed, this tissue can be used as a source of DNA for genetic testing. Alternatively, DNA can be extracted from a peripheral blood sample that has been sent along with the renal biopsy. The physicians at Arkana will incorporate evaluation of the clinicopathologic findings into the report. This will enable us to provide a complete diagnosis of the patient’s kidney disease including genotype-phenotype correlation by an expert in the field.
Reasons for Testing:
Detection of genetic variant leading to steroid-resistant nephrotic syndrome. There is some evidence that patients with a genetic etiology of SRNS will be less likely to respond to immunosuppressive therapy(5) and less likely to recur in the transplant.(6) It also provides information that might be valuable to patients for family planning purposes.
Method: Next generation sequencing and/or direct (Sanger) sequencing
Test performed: bi-weekly
Turnaround time: 3 months
Genes interrogated include:
ACTN4, ADCK3, APOL1, CD2AP, CLCN5, COL4A4, COL4A5, COQ2, COQ6, CRB2, DDX53, DGKE, FAT1, INF2, ITGA3, ITGB4, LAMB2, MYH9, MYO1E, NPHS1, NPHS2, OCRL, PAX2 , PDSS2, PLCE1,PODXL, PTPRO, SCARB2, SMARCAL1, TRPC6, TTC21B, VEGFA, WT1
Acceptable specimens include:
Peripheral blood (preferred): At least 2 ml in Lavender top (EDTA) tube shipped overnight at room temperature
Previously extracted DNA: 10ul suspended in TE buffer at 100 ng/ul, Transport overnight in frozen state (dry-ice) M-Th
Samples must have two patient identifiers, preferably the patient’s name and date of birth.
Each sample must be accompanied by a requisition form with the declaration signed by the ordering provider.
Please call Arkana Laboratories to request a kit.
Arkana Laboratories Molecular Division
10810 Executive Center Drive, Suite 100
Little Rock, AR 72211
Co-Director: Chris Larsen, MD
Co-Director: Jon D. Wilson, MD
Lab Manager: Marjorie Beggs, PhD
Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS. Risk Factors for End-Stage Renal Disease: 25-Year Follow-up. Arch Intern Med 2009; 169: 342-350.
Satko SG, Freedman BI, Moossavi S. Genetic factors in end-stage renal disease. Kidney Int Suppl 2005 94: S46-S49.
Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2015; 26: 1279-1289.
McCarthy HJ, Bierzynska A, Wherlock M, et al. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2013; 8: 637-648.
Giglio S, Provenzano A, Mazzinghi B, et al. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. J Am Soc Nephrol 2015; 26: 230-236.
Maas RJ, Deegens JK, van den Brand JA, Cornelissen EA, Wetzels JF. A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation. BMC Nephrol 2013; 14: 1-8.