End-stage renal disease (ESRD) is manifested by uremia, which can include symptoms of anorexia, lethargy, nausea and vomiting, uremic pericarditis, seizures, muscle cramps, and coma.
Non-diabetic nephropathy (kidney disease) is a name given to a variety of kidney diseases that are not the result of diabetes mellitus. End-stage renal disease (ESRD) is manifested by uremia, which can include symptoms of anorexia, lethargy, nausea, vomiting, uremic pericarditis, seizures, muscle cramps, and coma.
The natural history of renal disease begins with an initial kidney injury. The subsequent clinical manifestations can vary from asymptomatic hematuria to dialysis-dependent renal failure. As renal dysfunction progresses, patients experience symptoms, including hypertension, bone disease, hyperkalemia, volume overload, metabolic acidosis, and anemia.
African Americans have a four to five times higher rate of ESRD than European Americans. In this population, the locus on chromosome 22 that contains APOL1 confers nearly all of the increased risk for nondiabetic nephropathy. Specifically, two sequence variants in the APOL1 gene are strongly associated with focal segmental glomerulosclerosis (FSGS; odds ratio = 10.5) and hypertension attributed ESRD (H-ESRD; odds ratio = 7.3), sickle cell nephropathy, and HIV nephropathy. In addition, preliminary clinical studies suggest transplanted kidneys with two APOL1 risk alleles have shorter graft survival than donor kidneys with zero or one APOL1 risk alleles.
The two APOL1 nephropathy risk variants are denoted G1 and G2. The G1 allele is composed of two nonsynonymous coding variants that are in complete linkage disequilibrium. The G2 allele is a six base pair deletion. The G1 and G2 alleles are mutually exclusive and there is no difference in risk of kidney disease when individuals with no risk alleles (G0) are compared to those with one risk allele. Two risk alleles—G1/G1, G2/G2, or G1/G2—are required to confer additional risk of kidney disease. Therefore, this pattern supports a recessive model of inheritance.
This test is indicated for:
Test outcomes:
| Gene | Protein | OMIM# | Locus |
|---|---|---|---|
| APOL1 | Apolipoprotein L1 | 603743 | 22q12.3 |
This test is performed by Sanger sequencing of exon 6 of APOL1. This test does not detect large deletions or variants in other coding exons or non-coding regions that could affect gene expression.
This assay is greater than 99.9% accurate in detecting variants in the sequence analyzed.
All samples must be accompanied with a completed requisition form. Please make sure any identifiers used on the specimen are provided on the paperwork. Consent page should be signed by a health care provider. Any incomplete or missing paperwork may delay the start of testing.
New York Residents only: In addition to the test requisition form, an informed test consent must also be reviewed with the ordering provider and signed by the patient.
Test code: lmAPOL1-pnlA_L
Turnaround time: 3 weeks
Specimen required:
If providing DNA, please provide the name and CLIA number of the lab performing the blood extraction.
The Laboratory for Molecular Medicine offers several billing options for our clients and their patients; however, we do not bill insurance companies and are unable to begin testing without accurate billing information.
