Publikation

Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria

Wissenschaftlicher Artikel/Review - 01.11.2023

Bereiche
Schlagwörter (Tags)
calcium, FGF23, hypercalciuria, nephrolithiasis, phosphate, urolithiasis
DOI
Link

Zitation
Rodríguez D, Gurevich E, Mohammadi Jouabadi, Pastor Arroyo E, Ritter A, Estoppey Younes S, Wagner C, Imenez Silva P, Seeger H, Mohebbi N. Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria. Clinical Kidney Journal 2023
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Clinical Kidney Journal 2023
Veröffentlichungsdatum
01.11.2023
Verlag
Oxford University Press
Kurzbeschreibung/Zielsetzung

ABSTRACT
Background
Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis.

Methods
We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort.

Results
Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors.

Conclusion
This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.