Abstract: PUB181
Utility of Genetic Testing in CKD with Nephrotic-Range Proteinuria
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Mogensen, Jodie Dianne, Baylor College of Medicine, Houston, Texas, United States
- Shah, Maulin, Baylor College of Medicine, Houston, Texas, United States
Introduction
Recent advancements in genetics are transforming clinical practice in all medical fields, including nephrology.
Case Description
We present a 55-year-old female with a past medical history of obesity, hypertension, and a BRCA-1 variant of uncertain significance (which she underwent hysterectomy and salpingo-oophorectomy for), referred for chronic kidney disease (CKD) with nephrotic proteinuria. Kidney biopsy was inconclusive and complicated by post-procedural bleeding requiring hospitalization. Genetic testing revealed a pathogenic variant in COL4A4. While she had no overt signs of Alport’s syndrome, including family history, ophthalmic or otologic complications, additional testing revealed mild sensorineural hearing loss.
Discussion
This case exemplifies the emerging potential of genetic testing for the evaluation of CKD with nephrotic proteinuria. Generally, kidney biopsies are the “gold standard” workup when the etiology of a nephrotic proteinuria is unclear on initial evaluation. However, due to advancements in less invasive secondary work-up, such as serologic testing, clinicians can often solidify a diagnosis and treatment plan for select patients with glomerular diseases without a biopsy. Genetic testing ought to become a more common, minimally invasive tool to avoid unnecessary or risky biopsies. In fact, current KDIGO guidelines for glomerular diseases dictate that conditions such as Alport’s, Fabry, and familial FSGS can be treated without a confirmatory biopsy; notably, these diseases are all detectable on a genetic panel. Moreover, genetic testing is a more sensitive and accurate diagnostic tool than using a combination of clinical features, family history, and biopsy results in some conditions: Alport’s syndrome is an example of this phenomenon. Due to its elusive clinical nature, guidelines suggest testing for COL4A3–COL4A5 genes in patients with persistent proteinuria >0.5 g/d, steroid-resistant nephrotic syndrome, or FSGS. Furthermore, ongoing genetic research in conditions that cause nephrotic range proteinuria, such as FSGS and steroid-resistant nephrotic syndrome, suggests an optimistic future where genetic testing may complement or eliminate the need for a biopsy.
Currently, kidney biopsy remains an invaluable and relatively safe procedure to evaluate nephrotic-range proteinuria. However, our case highlights the value of genetic testing as a less invasive and risky tool.