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High serum cystatin C levels in juvenile myelomonocytic leukemia patients without abnormal kidney function

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Abstract

Background

In pediatric cancer patients, the estimated glomerular filtration rate based on serum cystatin C (CysC) was reported to be suitable for estimating kidney function because of low serum creatinine (Cr) and high serum β2-microglobulin. Recently, however, serum CysC levels have been reported to be elevated in some cancer patients other than those with juvenile myelomonocytic leukemia (JMML), regardless of normal kidney function.

Case reports

We describe two pediatric cases of JMML with an elevated serum CysC level. Urinalysis tests showed no abnormalities and no evidence of nephritis or nephropathy, and there were no findings indicating abnormal kidney function, such as Cr clearance in one case or the estimated glomerular filtration rate based on serum Cr in both cases, except for the serum CysC levels. There were no other causes of a high serum CysC level, including hyperthyroidism and steroid administration. The patients were treated with a conventional dosage of drugs, and their serum CysC levels decreased to the normal range when they were in complete remission after treatment.

Conclusion

An elevated serum CysC level may reflect tumor burden independent of kidney function in JMML patients. Therefore, creatinine or inulin clearance should be determined to more accurately estimate kidney function for administering an optimal dose of anticancer drugs. In addition, a high serum CysC level may be a potential biomarker of cancer progression.

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References

  1. Nomura T, Huang WC, Zhau HE, Josson S, Mimata H, Kaur M (2014) β2-Microglobulin-mediated signaling as a target for cancer therapy. Anticancer Agents Med Chem 14:343–352. https://doi.org/10.2174/18715206113139990092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bárdi E, Bobok I, Oláh AV, Oláh E, Kappelmayer J, Kiss C (2004) Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatr Nephrol 19:1145–1147. https://doi.org/10.1007/s00467-004-1548-3

    Article  PubMed  Google Scholar 

  3. Lankisch P, Wessalowski R, Maisonneuve P, Haghgu M, Hermsen D, Kramm CM (2006) Serum cystatin C is a suitable marker for routine monitoring of renal function in pediatric cancer patients, especially of very young age. Pediatr Blood Cancer 46:767–772. https://doi.org/10.1002/pbc.20581

    Article  CAS  PubMed  Google Scholar 

  4. Blufpand HN, Tromp J, Abbink FC, Stoffel-Wagner B, Bouman AA, Schouten-van Meeteren AY, van Wijk JA, Kaspers GJ, Bökenkamp A (2011) Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 57:262–267. https://doi.org/10.1002/pbc.23119

    Article  PubMed  Google Scholar 

  5. Leto G, Crescimanno M, Flandina C (2018) On the role of cystatin C in cancer progression. Life Sci 202:152–160. https://doi.org/10.1016/j.lfs.2018.04.013

    Article  CAS  PubMed  Google Scholar 

  6. Hasle H, Wadsworth LD, Massing BG, McBride M, Schultz KR (1999) A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada. Br J Haematol 106:1027–1032. https://doi.org/10.1046/j.1365-2141.1999.01645.x

    Article  CAS  PubMed  Google Scholar 

  7. Passmore SJ, Chessells JM, Kempski H, Hann IM, Brownbill PA, Stiller CA (2003) Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival. Br J Haematol 121:758–767. https://doi.org/10.1046/j.1365-2141.2003.04361.x

    Article  PubMed  Google Scholar 

  8. Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2014) Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol 18:626–633. https://doi.org/10.1007/s10157-013-0856-y

    Article  CAS  PubMed  Google Scholar 

  9. Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2014) Cystatin C-based equation for estimating glomerular filtration rate in Japanese children and adolescents. Clin Exp Nephrol 18:718–725. https://doi.org/10.1007/s10157-013-0910-9

    Article  CAS  PubMed  Google Scholar 

  10. Ikezumi Y, Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Fujita N, Akioka Y, Kaneko T, Iijima K, Honda M (2015) Beta-2 microglobulin-based equation for estimating glomerular filtration rates in Japanese children and adolescents. Clin Exp Nephrol 19:450–457. https://doi.org/10.1007/s10157-014-1015-9

    Article  CAS  PubMed  Google Scholar 

  11. Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C (2003) Impact of thyroid dysfunction on serum cystatin C. Kidney Int 63:1944–1947. https://doi.org/10.1046/j.1523-1755.2003.00925.x

    Article  CAS  PubMed  Google Scholar 

  12. Cimerman N, Brguljan PM, Krašovec M, Šuškovič S, Kos J (2000) Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta 300:83–95. https://doi.org/10.1016/S0009-8981(00)00298-9

    Article  CAS  PubMed  Google Scholar 

  13. Olson OC, Joyce JA (2015) Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat Rev Cancer 15:712–729. https://doi.org/10.1038/nrc4027

    Article  CAS  PubMed  Google Scholar 

  14. Zi M, Xu Y (2018) Involvement of cystatin C in immunity and apoptosis. Immunol Lett 196:80–90. https://doi.org/10.1016/j.imlet.2018.01.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Meynier S, Rieux-Laucat F (2020) After 95 years, it’s time to eRASe JMML. Blood Rev 43:100652. https://doi.org/10.1016/j.blre.2020.100652

    Article  CAS  PubMed  Google Scholar 

  16. Ziegelasch N, Vogel M, Müller E, Tremel N, Jurkutat A, Löffler M, Terliesner N, Thiery J, Willenberg A, Kiess W, Dittrich K (2019) Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage. Pediatr Nephrol 34:449–457. https://doi.org/10.1007/s00467-018-4087-z

    Article  PubMed  Google Scholar 

  17. Nakamura N, Watanabe H, Okamura K, Kagami S (2018) Assessment of renal function in Japanese children with malignancies using serum cystatin C. J Med Invest 65:231–235. https://doi.org/10.2152/jmi.65.231

    Article  PubMed  Google Scholar 

  18. Hammouda NE, Salah El-Din MA, El-Shishtawy MM, El-Gayar AM (2017) Serum cystatin C as a biomarker in diffuse large B-cell lymphoma. Sci Pharm 85:9. https://doi.org/10.3390/scipharm85010009

    Article  CAS  PubMed Central  Google Scholar 

  19. Jiang Y, Zhang J, Zhang C, Hong L, Jiang Y, Lu L, Huang H, Guo D (2020) The role of cystatin C as a proteasome inhibitor in multiple myeloma. Hematol 25:457–463. https://doi.org/10.1080/16078454.2020.1850973

    Article  CAS  Google Scholar 

  20. Barnfield MC, Burniston MT, Reid U, Graham AM, Henderson M, Picton SV (2013) Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer. Nucl Med Commun 34:609–614. https://doi.org/10.1097/MNM.0b013e328360d929

    Article  CAS  PubMed  Google Scholar 

  21. Jones M, Denieffe S, Griffin C, Tinago W, Fitzgibbon MC (2017) Evaluation of cystatin C in malignancy and comparability of estimates of GFR in oncology patients. Pract Lab Med 8:95–104. https://doi.org/10.1016/j.plabm.2017.05.005

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lambert M, White-Koning M, Alonso M, Garnier A, Alphonsa G, Puiseux C, Munzer C, Berthier J, Malard L, Pasquet M, Chatelut E (2021) Plasma cystatin C is a marker of renal glomerular injury in children treated with cisplatin or ifosfamide. Pediatr Blood Cancer 68:e28747. https://doi.org/10.1002/pbc.28747

    Article  CAS  PubMed  Google Scholar 

  23. Xu Y, Ding Y, Li X, Wu X (2015) Cystatin C is a disease-associated protein subject to multiple regulation. Immunol Cell Biol 93:442–451. https://doi.org/10.1038/icb.2014.121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Dr. Kazuya Hamada and Dr. Noriko Kinjo for the treatment of the patients in this report, and Robert Blakytny, DPhil, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Child Health and Welfare, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa, 903-0215, Japan

    Wataru Shimabukuro, Satoru Hamada, Tokiko Oshiro, Shougo Nakada, Nobuyuki Hyakuna & Koichi Nakanishi

  2. Department of Pediatrics, University of the Ryukyus Hospital, Nishihara, Okinawa, Japan

    Wataru Shimabukuro, Satoru Hamada, Tokiko Oshiro, Nobuyuki Hyakuna & Koichi Nakanishi

Authors
  1. Wataru Shimabukuro
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  2. Satoru Hamada
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  3. Tokiko Oshiro
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  4. Shougo Nakada
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  5. Nobuyuki Hyakuna
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  6. Koichi Nakanishi
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Contributions

All authors were physicians treating the patients in this report. Wataru Shimabukuro prepared the manuscript; Satoru Hamada and Nobuyuki Hyakuna reviewed and revised the manuscript; Koichi Nakanishi oversaw the work as the corresponding author and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Koichi Nakanishi.

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Informed consent was obtained from both patients’ parents included in the study.

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Shimabukuro, W., Hamada, S., Oshiro, T. et al. High serum cystatin C levels in juvenile myelomonocytic leukemia patients without abnormal kidney function. Pediatr Nephrol 37, 1687–1691 (2022). https://doi.org/10.1007/s00467-021-05418-9

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  • DOI: https://doi.org/10.1007/s00467-021-05418-9

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