Along with a detailed family history, this is a critical first step in differential diagnosis. It rules out etiologies for hematuria, a key early sign of Alport, and can also detect signs of possible CKD progression, such as proteinuria and declining GFR.1,2
Cannot identify 2 important aspects of Alport: the genetic variants in COL4A3/4/5 that define the disease and the structural changes to the glomerular basement membrane (GBM) these variants cause.1
Hematuria and other lab findings can overlap with other disorders, so additional steps are needed for a definitive diagnosis.3 By the time these clinical signs are detectable via urine or blood, kidney damage has already occurred.1
Biopsy can identify the splitting and lamination of the GBM that are characteristic of Alport, refining a possible diagnosis.1 Histological analysis can also provide some prognostic information by evaluating the extent of abnormal collagen deposition.3
Biopsies do not provide the genetic information that can reveal likely patient prognosis and potential risk to family members based on the inheritance pattern.1
A study of 75 patients in 47 families with inherited CKD who underwent biopsy found that genetic testing refined or changed the diagnosis for 79% of patients and would have changed recommended treatment in 26%.4
Genetic testing can provide a non-invasive, highly specific assessment of the COL4A3/4/5 mutations that define Alport syndrome.1 It can also find details on mutation location and type that reveal likely prognosis, informing treatment strategy.3 These details also inform the risk of inheritance for family members and future offspring to help guide family counseling and monitoring.5
Importantly, by identifying the source of Alport syndrome even in the absence of obvious or severe clinical signs, genetic testing can diagnose family members before irreversible kidney damage has occurred.1, 3
Advanced genetic testing is not yet standardized in nephrology and results reporting may be unfamiliar. The pathogenicity of all genetic variants is not yet known, so the clinical significance of some findings may not be clear.3
Genetic testing for Alport syndrome and several other rare forms of chronic kidney disease is more accessible than ever before. Find out the eligibility requirements for no-charge genetic testing through KIDNEYCODE.
There are both sex-linked and non sex-linked inheritance patterns of Alport syndrome. Genetic testing can do more than confirm an Alport syndrome diagnosis by helping you identify the inheritance pattern of the condition and how that might affect patient progression.1
Sex-linked Alport syndrome
As the name implies, XLAS is inherited via the X chromosome in a variant of COL4A5. XLAS has been considered the most common inheritance pattern, though expanded genetic testing is changing our understanding of Alport prevalence.1 XLAS causes more severe symptoms and more rapid progression to kidney failure in males, virtually all of whom will reach end-stage kidney disease. Females with XLAS may experience less severe symptoms but can still progress to kidney failure. Females with XLAS should not be considered merely “carriers.”5
Non sex-linked Alport syndrome
Autosomal genetic variants are inherited via chromosome 2 rather than the X chromosome. Both males and females with ADAS show no difference in disease severity and can experience kidney failure later in life compared with those living with XLAS.5
ARAS affects both males and females equally, and the severity of disease is identical to males with X-linked disease.5,6
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