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14.05.2024 | Original Article

Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

verfasst von: Raagul Shankar, Abhijeet Saha, Rachita Singh Dhull, Rukshana Shroff, Anita Nangia, Sunita Sharma

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Abstract

Background

Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD.

Methods

A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant.

Results

The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001).

Conclusions

Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Graphical abstract

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Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group (2017) KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 7:1–59CrossRef

Mitsnefes MM, Betoko A, Schneider MF et al (2018) FGF23 and Left Ventricular Hypertrophy in Children with CKD. Clin J Am Soc Nephrol 13:45–52. https://doi.org/10.2215/CJN.02110217CrossRefPubMed

Perry WK (2013) Bone disease in Pediatric Chronic Kidney Disease. Pediatr Nephrol 28:569–576. https://doi.org/10.1007/s00467-012-2324-4CrossRef

Kocełak P, Olszanecka-Glinianowicz M, Chudek J (2012) Fibroblast growth factor 23 structure, function and role in kidney diseases. Adv Clin Exp Med 21:391–401PubMed

Hruska KA, Sugatani T, Agapova O, Fang Y (2017) The chronic kidney disease - Mineral bone disorder (CKD-MBD): Advances in pathophysiology. Bone 100:80–86. https://doi.org/10.1016/j.bone.2017.01.023CrossRefPubMedPubMedCentral

Sugatani T (2018) Systemic activation of activin a signaling causes chronic kidney disease-mineral bone disorder. Int J Mol Sci 19:2490. https://doi.org/10.3390/ijms19092490CrossRefPubMedPubMedCentral

Cianciolo G, La Manna G, Capelli I et al (2021) The role of activin: the other side of chronic kidney disease-mineral bone disorder? Nephrol Dial Transplant 36:966–974. https://doi.org/10.1093/ndt/gfaa203CrossRefPubMed

Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV (2016) Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 20:846–852. https://doi.org/10.4103/2230-8210.192914CrossRefPubMedPubMedCentral

Agapova OA, Fang Y, Sugatani T, Seifert ME, Hruska KA (2016) Ligand trap for the activin type IIA receptor protects against vascular disease and renal fibrosis in mice with chronic kidney disease. Kidney Int 89:1231–1243. https://doi.org/10.1016/j.kint.2016.02.002CrossRefPubMedPubMedCentral

10.

Lima F, Mawad H, El-Husseini AA, Davenport DL, Malluche HH (2016) Serum bone markers in ROD patients across the spectrum of decreases in GFR: Activin A increases before all other markers. Clin Nephrol 91:222–230. https://doi.org/10.5414/CN109650CrossRef

11.

Nordholm A, Sørensen IMH, Bjergfelt SS et al (2023) Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease. Clin Kidney J 6:2712–2720. https://doi.org/10.1093/ckj/sfad238CrossRef

12.

Iriuchishima H, Maeshima A, Takahashi S et al (2019) Activin A: a novel urinary biomarker of renal impairment in multiple myeloma. Biosci Rep 39:7. https://doi.org/10.1042/BSR20190206CrossRef

13.

Harada K, Shintani Y, Sakamoto Y, Wakatsuki M, Shitsukawa K, Saito S (1996) Serum immunoreactiveactivin A levels in normal subjects and patients with various diseases. J Clin Endocrinol Metab 81:2125–2130. https://doi.org/10.1210/jcem.81.6.8964839CrossRefPubMed

14.

Anastasilakis AD, Polyzos SA, Makras P et al (2013) Circulating activin-A is elevated in postmenopausal women with low bone mass: the three-month effect of zoledronic acid treatment. Osteoporos Int 24:2127–2132. https://doi.org/10.1007/s00198-012-2198-0CrossRefPubMed

15.

Inoue S, Orimo A, Hosoi T et al (1994) Demonstration of activin-A in arteriosclerotic lesions. Biochem Biophys Res Commun 205:441–448. https://doi.org/10.1006/bbrc.1994.2685CrossRefPubMed

16.

Yamashita S, Maeshima A, Kojima I et al (2004) Activin A is a potent activator of renal interstitial fibroblasts. J Am Soc Nephrol 15:91–101. https://doi.org/10.1097/01.asn.0000103225.68136.e6CrossRefPubMed

17.

van Husen M, Fischer A-K, Lehnhardt A et al (2010) Fibroblast growth factor 23 and bone metabolism in children with chronic kidney disease. Kidney Int 78:200–206. https://doi.org/10.1038/ki.2010.107CrossRefPubMed

18.

Siomou E, Challa A, Printza N et al (2011) Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease. Pediatr Nephrol 26:1105–1114. https://doi.org/10.1007/s00467-011-1870-5CrossRefPubMed

19.

Troen BR (2004) The role of cathepsin K in normal bone resorption. Drug News Perspect 17:19–28. https://doi.org/10.1358/dnp.2004.17.1.829022CrossRefPubMed

20.

Holzer G, Noske H, Lang T, Holzer L, Willinger U (2005) Soluble cathepsin K: a novel marker for the prediction of nontraumatic fractures? J Lab Clin Med 146:13–17. https://doi.org/10.1016/j.lab.2005.03.016CrossRefPubMed

21.

Adolf D, Wex T, Jahn O et al (2012) Serum cathepsin K levels are not suitable to differentiate women with chronic bone disorders such as osteopenia and osteoporosis from healthy pre- and postmenopausal women. Maturitas 71:169–172. https://doi.org/10.1016/j.maturitas.2011.11.024CrossRefPubMed

22.

Piatek S, Adolf D, Wex T et al (2013) Multiparameter analysis of serum levels of C-telopeptide crosslaps, bone-specific alkaline phosphatase, cathepsin K, osteoprotegerin and receptor activator of nuclear factor κB ligand in the diagnosis of osteoporosis. Maturitas 74:363–368. https://doi.org/10.1016/j.maturitas.2013.01.005CrossRefPubMed

23.

Kerschan-Schindl K, Hawa G, Kudlacek S, Woloszczuk W, Pietschmann P (2005) Serum levels of cathepsin K decrease with age in both women and men. Exp Gerontol 40:532–535. https://doi.org/10.1016/j.exger.2005.04.001CrossRefPubMed

Titel: Activin A: a marker of mineral bone disorder in children with chronic kidney disease?
verfasst von: Raagul Shankar
Abhijeet Saha
Rachita Singh Dhull
Rukshana Shroff
Anita Nangia
Sunita Sharma
Publikationsdatum: 14.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-024-06400-x

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Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

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Ähnliche Überlebensraten nach Reanimation während des Transports bzw. vor Ort

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