Genetic Testing and Stone Disease

Co-host: Kyle Wood, MD

Population analysis demonstrated that genetic conditions resulting in stone disease are magnitudes higher than those seen in clinical cohorts, suggesting underdiagnosis. Urologist play a unique role as we often times have many touch points with these patient given their presentation for stone disease. With the advancement of treatments, specifically in primary hyperoxaluria, it is essential that urologist play a more active role in the earlier diagnosis of patients. Genetic testing has become readily available at lower cost and much of the perceived barriers to genetic testing are addressed by current available programs.

Outline:

1. The contribution of genetics to kidney stone disease

2. Specific studies using genetic testing

3. Primary Hyperoxaluria as an example

4. Current Genetic Testing and Ease

5. The role of the Urologist

References:

- Hill AJ, Basourakos SP, Lewicki P, et al. Incidence of kidney stones in the United States: The Continuous National Health and Nutrition Examination Survey. J Urol. 2022;207(4):851-856.

- Singh P, Harris PC, Sas DJ, Lieske JC. The genetics of kidney stone disease and nephrocalcinosis. Nat Rev Nephrol. 2022;18(4):224-240.

- Goldfarb DS, Fischer ME, Keich Y, Goldberg J. A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int. 2005;67(3):1053-1061.

- Daga A, Majmundar AJ, Braun DA, et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 2018;93(1):204-213.

- Braun DA, Lawson JA, Gee HY, et al. Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol. 2016;11(4):664-672.

- Halbritter J, Baum M, Hynes AM, et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol. 2015;26(3):543-551.

- Knoers N, Antignac C, Bergmann C, et al. Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice. Nephrol Dial Transplant. 2022;37(2):239-254.

- Groothoff JW, Metry E, Deesker L, et al. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023;19(3):194-211.

- van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrol Dial Transplant. 2012;27(10):3855-3862.

- Hopp K, Cogal AG, Bergstralh EJ, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol. 2015;26(10):2559-2570.

- Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021;384(13):1216-1226.

- Baum MA, Langman C, Cochat P, et al. PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2. Kidney Int. 2023;103(1):207-217.

- Soliman NA, Nabhan MM, Abdelrahman SM, et al. Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center. Nephrol Ther. 2017;13(3):176-182.

- Schonauer R, Scherer L, Nemitz-Kliemchen M, et al. Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability. Am J Med Genet C Semin Med Genet. 2022;190(3):279-288.