Mendelian disease rare in adults with kidney stones, but nephrolithiasis risk may be high
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Key takeaways:
- Overall, 2.9% of adults with kidney stones had Mendelian disease, the study showed.
- Of kidney stone formers, 8.1% had monoallelic variants predisposing them to nephrolithiasis.
Mendelian disease is uncommon in adults with kidney stones, but variants leading to nephrolithiasis may be higher for these patients, according to study results.
“[For many] adult patients with kidney stones, the molecular pathogenesis of clinical traits associated with kidney stone formation (eg, hypercalciuria) remains unknown,” Manuel A. Anderegg, MD, PhD, of the department of nephrology and hypertension at the Bern University Hospital, University of Bern in Switzerland, and colleagues wrote. “Consequently, undifferentiated dietary and pharmacological preventive measures are initiated, but many patients continue to form stones.”
Researchers performed whole exome sequencing for 787 patients from the Bern Kidney Stone Registry who had at least one past kidney stone episode, as well as 114 non-kidney stone formers. Mean age of kidney stone formers was 47 years, and 18% were first timers.
Investigators examined 34 established nephrolithiasis genes and variants determined by American College of Medical Genetics and Genomics criteria. Researchers considered pathogenic or likely pathogenic variants as diagnostic as part of the study.
The aim was to determine the prevalence and traits of genetic diseases.
Researchers found disease linked to a single inherited gene mutation, or Mendelian disease, among 2.9% of kidney stone formers; cystinuria, vitamin D-24 hydroxylase deficiency and primary hyperoxaluria were the most common.
Of the kidney stone formers, 8.1% had monoallelic variants predisposing them to nephrolithiasis.
Anderegg and colleagues also found kidney stone formers were younger at the first stone event (30 vs. 36 years), were more likely to have cystine stones (23.4% vs. 1.4%) and were less likely to have calcium oxalate monohydrates stones (31.9% vs. 52.5%) vs. non-stone formers.
The phenotype of kidney stone formers with variants that may cause nephrolithiasis overlapped with patients without diagnostic variants, according to the researchers. In contrast, no Mendelian disease was found among non-stone formers, and pathogenic or likely pathogenic variants were also less frequent in this group compared with kidney stone formers (1.8% vs. 8.1%).
Researchers wrote that genetic testing has potential to identify whether adults with kidney stones have Mendelian disease or other gene variants that predispose them to nephrolithiasis so clinicians can tailor therapies or direct them to clinical trials.
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Anderegg MA, et al. Nephrol Dial Transplant. 2024;doi.org/10.1093/ndt/gfae074.
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