Submit your picks! | @NephMadness | @nephmadness.bsky.social | NephMadness 2025

Nora Franceschini

Dr. Franceschini is a Professor of Epidemiology and Genetics at the University of North Carolina at Chapel Hill, and a board-certified nephrologist. Her research interest is the genetics of kidney diseases, including genetic testing.

Competitors for the Genetics Region

Team 1: Genetics in FSGS vs Team 2: Genetic Counseling

Image generated by Evan Zeitler using DALLE-E 3, accessed via ChatGPT at http://chat.openai.com, February 2025. After using the tool to generate the image, Zeitler and the NephMadness Executive Team reviewed and take full responsibility for the final graphic image.

Genetic testing is an underutilized yet powerful tool in nephrology, offering insights that can refine diagnosis, guide treatment, and even shape transplant decisions. When kidney disease is suspected to have a genetic cause, testing can help identify whether DNA variations are at play—offering clarity not only for patients but also for potential living donors within their families.

Genetic kidney disease can have a monogenic etiology (in which DNA variations in a single gene are responsible for the disease) or a complex polygenic etiology (in which genetic variation at many genomic regions and other risk factors confer risk to disease).  Most genetic tests are available for monogenetic disorders to identify rare genetic protein-changing variants (mutations) related to changes in protein quantity or function leading to kidney disease and other clinical manifestations.  One major exception are APOL1 genetic variants, which are common in individuals of African ancestry,  and confer risk for chronic kidney disease through a complex mechanism.

A prime example, focal segmental glomerulosclerosis (FSGS), is one of the most common diagnoses in kidney biopsies of patients with chronic kidney disease, but only a subset of patients will have a genetic cause. Many genetic variants and genes have been identified for FSGS, including those on APOL1. Non-syndromic monogenic causes of FSGS include, for example, mutations on genes of type IV collagen (COL4A3, COL4A4, and COL4A5), a structural protein in the glomerular basement membrane of the kidney related to Alport syndrome and thin basement membrane disease. Alport syndrome diagnosis can be missed when relying only on clinical and histologic patterns supporting genetic testing in some settings.

Medical care is a team sport, with multiple players needed to reach the goal of providing the best clinical care for patients.  For genetic kidney diseases, depending on the complexity of the diagnosis, the team will include nephrologists, medical and laboratory genetics experts, kidney pathologists and genetic counselors. Pre-test and post-test counseling is recommended for all individuals undergoing genetic testing to explain risks and benefits including costs, incidental findings and other harms. Counseling can be provided by a nephrologist or a genetic counselor expert.

But before the team takes the field, nephrologists must develop a game plan and that starts with thinking genetics. Recognizing  when a genetic workup is warranted,  understanding testing options in different settings, and the actionable role of a genetic diagnosis on patient care for therapy, prognosis or transplant options including for living-donor relatives.  Genetic testing in FSGS is the winner for the strategy “think genetics” and its adoption as a tool in clinical care. Genetic counseling is a very important part of getting the team into action for test implementation and follow-up of findings but only after a decision is made for genetic testing.

– Guest Post written by Nora Franceschini

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

Click to read the Genetics Region

Submit your picks! | @NephMadness | @nephmadness.bsky.social | NephMadness 2025