TY - JOUR
T1 - Kidney Cysts in Hypophosphatemic Rickets With Hypercalciuria
T2 - A Case Series
AU - Hanna, Christian
AU - Potretzke, Theodora A.
AU - Chedid, Maroun
AU - Rangel, Laureano J.
AU - Arroyo, Jennifer
AU - Zubidat, Dalia
AU - Tebben, Peter J.
AU - Cogal, Andrea G.
AU - Torres, Vicente E.
AU - Harris, Peter C.
AU - Sas, David J.
AU - Lieske, John C.
AU - Milliner, Dawn S.
AU - Chebib, Fouad T.
N1 - Funding Information:
Christian Hanna, MD, MS, Theodora A. Potretzke, MD, Maroun Chedid, MD, Laureano J. Rangel, MS, Jennifer Arroyo, PhD, Dalia Zubidat, MD, Peter J. Tebben, MD, Andrea G. Cogal, BS, Vicente E. Torres, MD, PhD, Peter C. Harris, PhD, David J. Sas, DO, John C. Lieske, MD, Dawn S. Milliner, MD, and Fouad T. Chebib, MD, Research idea and study design: CH, TAP, FTC, DSM; data acquisition: CH, TAP, FTC, JA, AGC; genetic analysis: AGC, JA, JCL, PCH; data analysis and interpretation: CH, LJR, TAP, MC, DZ, FTC; statistical analysis: CH, LJR; supervision and mentorship: DSM, PCH, JCL, VET, DJS, PJT. CH and TAP contributed equally to this work. DSM and FTC contributed equally to this work. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This work was funded by the Rare Kidney Stone Consortium (U54DK83908), which is part of Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences and R21TR003174. The Rare Kidney Stone Consortium was funded through collaboration between National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors declare that they have no relevant financial interests. We thank the staff of the Mayo Clinic and the Rare Kidney Stone Consortium (RKSC), referring physician Dr. David S. Goldfarb, and the many physicians and patients who have contributed to the study. Received August 12, 2021. Evaluated by 2 external peer reviewers, with direct editorial input by an Associate Editor and the Editor-in-Chief. Accepted in revised form December 2, 2021.
Funding Information:
This work was funded by the Rare Kidney Stone Consortium (U54DK83908), which is part of Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences and R21TR003174. The Rare Kidney Stone Consortium was funded through collaboration between National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases.
Publisher Copyright:
© 2022 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - Rationale & Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts’ presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease. Study Design: Case series. Setting & Participants: Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded. Results: Twelve patients with SLC34A3 pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease. Limitations: Retrospective study, possible selection bias, single-center experience. Conclusions: A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in SLC34A3 favor cyst formation.
AB - Rationale & Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts’ presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease. Study Design: Case series. Setting & Participants: Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded. Results: Twelve patients with SLC34A3 pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease. Limitations: Retrospective study, possible selection bias, single-center experience. Conclusions: A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in SLC34A3 favor cyst formation.
KW - Case series
KW - HHRH
KW - SLC34A3 gene
KW - hypercalciuria
KW - hypophosphatemic rickets with hypercalciuria
KW - kidney cyst
KW - nephrocalcinosis
KW - urinary stone disease
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U2 - 10.1016/j.xkme.2022.100419
DO - 10.1016/j.xkme.2022.100419
M3 - Article
AN - SCOPUS:85124515634
VL - 4
JO - Kidney Medicine
JF - Kidney Medicine
SN - 2590-0595
IS - 3
M1 - 100419
ER -