The Role of Genetic Testing in Tolvaptan Decision Making: A Case of Atypical Cystic Kidney Disease Associated With CYP24A1
4 affiliations
- 1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
- 2Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL
- 3Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, MN
- 4Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN
Abstract
Autosomal dominant polycystic kidney disease (PKD) is a genetically heterogenous group of disorders, most often caused by mutations in polycystin-1 ( PKD1 ) or polycystin-2 ( PKD2 ), for which tolvaptan is the only Food and Drug Administration--approved therapy to slow disease progression in rapidly progressive cases. However, atypical genetic causes of cystic kidney disease present unique diagnostic and therapeutic challenges, as these patients may have recessive forms of PKD that are poorly represented in clinical trials and not approved for tolvaptan. We present the case of a 45-year-old man with bilateral kidney cysts initially diagnosed with autosomal dominant PKD and referred for a second opinion regarding tolvaptan initiation. Comprehensive genetic testing revealed homozygous CYP24A1 missense mutations (c.1147G>C, p.Glu383Gln). Although traditionally associated with infantile hypercalcermia, CYP24A1 deficiency has been recently described in a case series of patients with cystic kidney disease. Laboratory findings confirmed elevated 1,25-dihydroxyvitamin D levels associated with suppressed parathyroid hormone and hypercalciuria. Given the absence of evidence supporting tolvaptan efficacy in this patient's recessive form of PKD, combined with the side effects and cost of the drug, therapy was not recommended. This case underscores the critical role of genetic testing in differentiating etiologies of cystic kidney disease, for personalized management strategies that minimize risk and expense.
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BibTeX
@article{ellabbad2026role,
title = {{The Role of Genetic Testing in Tolvaptan Decision Making: A Case of Atypical Cystic Kidney Disease Associated With CYP24A1}},
author = {Mohamed M. Ellabbad and Usama Qamar and Zeeshan Imtiaz and Fouad T. Chebib and Christian Hanna and Navin R. Gupta},
journal = {Kidney Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xkme.2026.101534},
url = {https://doi.org/10.1016/j.xkme.2026.101534},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - The Role of Genetic Testing in Tolvaptan Decision Making: A Case of Atypical Cystic Kidney Disease Associated With CYP24A1
AU - Mohamed M. Ellabbad
AU - Usama Qamar
AU - Zeeshan Imtiaz
AU - Fouad T. Chebib
AU - Christian Hanna
AU - Navin R. Gupta
PY - 2026
DA - 2026/09/16
JO - Kidney Medicine
DO - 10.1016/j.xkme.2026.101534
UR - https://doi.org/10.1016/j.xkme.2026.101534
AB - Autosomal dominant polycystic kidney disease (PKD) is a genetically heterogenous group of disorders, most often caused by mutations in polycystin-1 ( PKD1 ) or polycystin-2 ( PKD2 ), for which tolvaptan is the only Food and Drug Administration--approved therapy to slow disease progression in rapidly progressive cases. However, atypical genetic causes of cystic kidney disease present unique diagnostic and therapeutic challenges, as these patients may have recessive forms of PKD that are poorly represented in clinical trials and not approved for tolvaptan. We present the case of a 45-year-old man with bilateral kidney cysts initially diagnosed with autosomal dominant PKD and referred for a second opinion regarding tolvaptan initiation. Comprehensive genetic testing revealed homozygous CYP24A1 missense mutations (c.1147G>C, p.Glu383Gln). Although traditionally associated with infantile hypercalcermia, CYP24A1 deficiency has been recently described in a case series of patients with cystic kidney disease. Laboratory findings confirmed elevated 1,25-dihydroxyvitamin D levels associated with suppressed parathyroid hormone and hypercalciuria. Given the absence of evidence supporting tolvaptan efficacy in this patient's recessive form of PKD, combined with the side effects and cost of the drug, therapy was not recommended. This case underscores the critical role of genetic testing in differentiating etiologies of cystic kidney disease, for personalized management strategies that minimize risk and expense.
SN - 2590-0595
ER -