March is here! The days are getting longer and spring is just around the corner. But did you know March is also National Kidney Month? This month, genetic counselor Mary-Beth Roberts explains the growing field of nephrogenetics and the role of the genetic counselor.
Renal Disease and the Genetic Counselor: Another Opportunity to Help Patients and Their Families
I had the good fortune of becoming acquainted with hereditary kidney disease in my first position out of graduate school. As a new general GC, I worked with a number of medical geneticists, including Dr. Xiangling Wang, who is double-boarded in nephrology and clinical genetics. As genetic counselors, we are accustomed to rarity, but I came to realize these qualifications are nearly unheard of. Kidney clinic was filled with what were, to me, novel and complex indications: focal segmental glomerulosclerosis (FSGS), atypical hemolytic-uremic syndrome, APOL1-mediated nephropathy, and refractory hypomagnesemia to name a few. A significant number of these referrals were conditions with variable penetrance and multifactorial inheritance and, at first, I struggled to find the best way to provide genetic counseling in the traditional sense. Many of the terms and concepts used by referring nephrologists required additional hours of research or detailed explanation, and I was woefully unfamiliar with many of our patients’ lived experiences managing renal diets, dialysis and organ transplant. The learning curve was steep indeed, but I became increasingly excited for ‘kidney days’ as I started to understand the life-changing impact genetic testing has for people with chronic kidney disease (CKD) and their families.
What is CKD?
CKD affects roughly 15 percent of Americans. Americans with recent African ancestry (ARAA) are at highest risk with around four times the rate of CKD compared with those of other ancestries. The prevalence of CKD caused by a genetic disorder ranges from 10-30 percent of adults, and 30-70 percent of children. There are over 600 genes in the ‘kidneyome’, and approximately 4-10 percent of CKD can be explained by copy number variants. With increasing adoption of next-generation sequencing for people with CKD, the phenotypic spectrum of conditions like Alport syndrome and others are evolving beyond our typical expectations, which supports the rationale for genetic work up for CKD of unknown etiology. In our experience with nearly 300 patients over the past 3-4 years, 40 percent of patients with a confirmed genetic diagnosis have had significant changes in their medical management. This includes initiating extra-renal screening for syndromic manifestations, early initiation of preventative therapies such as angiotensin-converting enzyme (ACE) inhibitors, ending use of therapies such as steroids or immunosuppressants in the case of genetic FSGS, or discontinuation of calcium supplementation to treat hypocalcemia in the presence of an activating CASR variant. Genetic testing and counseling also plays a critical role in living related donor selection for transplant.
Impact of Genetic Diagnosis
In addition to medical management, uncovering a genetic cause for personal or family history of CKD may have an important impact on perceptions of disease. CKD is considered by many to be, at least in part, due to modifiable lifestyle choices- especially in the presence of comorbidities such as obesity, chronic tobacco use, hypertension and/or diabetes. While a genetic kidney disease diagnosis can present its own set of health complications and relational challenges, it may also relieve some of the personal guilt and/or sense of responsibility associated with poor health. This is especially true of APOL1-mediated CKD, which affects up to 70 percent of ARAA with non-diabetic CKD; studies have indicated that strict control of blood pressure in this group has only a modest effect on slowing progression of CKD, suggesting that hypertension is part of the phenotype of APOL1-CKD rather than the underlying trigger.
Renal GC Network and Support
As my interest in genetic kidney disorders grew, so too did my desire to meet other genetic counselors with similar interests. The availability of CKD gene panels have increased significantly from 2018 to now as clinical laboratories seized on the opportunity to move into a new market. Even so, I had little awareness of the size, scope or make-up of the clinical practice of ‘nephrogenetics’ across the country. As a result, the NSGC Renal SIG was founded in late 2020 by myself and fellow genetic counselor Beth Jiorle, who was a medical science liaison for a commercial lab offering a large CKD panel at the time. Since then, interest in nephrogenetics has continued to grow across genetics and nephrology communities, and for me personally. Around 50 percent of my clinical practice is now made up of non-cancer kidney disease indications, and I continue to learn something new about this field on what feels like a daily basis. The challenges we face nationwide largely stem from the small number of providers with clinical expertise in this area, and lack of awareness of who, when, and how to refer kidney patients for genetic counseling. However, the landscape of genetic testing in nephrology is rapidly progressing, and a growing number of genetic counselors are counseling patients with hereditary kidney disease. The emerging specialty of nephrogenetics is truly an exciting and satisfying career path, and I whole-heartedly encourage more genetic counselors to embrace this fascinating field!