The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria

• Published in: The Journal of urology p. 101097JU0000000000004147
• Main Authors: Breeggemann, Matthew C, Harris, Peter C, Lieske, John C, Tasian, Gregory E, Wood, Kyle D
• Format: Journal Article
• Language: English
• Published: United States 02-08-2024
• Subjects: genetic testing; nephrolithiasis; diagnosis; primary hyperoxaluria; calcium oxalate
• ISSN: 1527-3792

Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare but important forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. The conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease (CKD), and eventually kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in the setting of CKD when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1 (PH1). Increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. This narrative review addresses the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. We share our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. This information may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.