Risk factors of acute kidney injury in pediatric acute lymphoblastic leukemia with hyperleukocytosis

  • Rengganis Ayu Kinanti Department of Pediatric Health, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Central Java
  • Retno Palupi-Baroto Department of Pediatric Health, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Central Java
  • Sutaryo Sutaryo Department of Pediatric Health, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University/Dr. Sardjito General Hospital, Yogyakarta, Central Java
Keywords: risk factor; acute kidney injury; acute lymphoblastic leukemia; children; hyperleukocytosis


Background Acute kidney injury (AKI) can be found in pediatric acute lymphoblastic leukemia (ALL) patients with hyperleukocytosis. Acute kidney Injury (AKI) increases hospital length of stay and mortality. Previous studies have only reported the AKI incidence in ALL patients with hyperleukocytosis, without clarifying risk factors attributed to AKI incidence.

Objective To determine the risk factors of AKI in pediatric ALL patients with hyperleukocytosis.

Methods A case-control study was conducted in children aged 1-18 years  admitted to Dr. Sardjito Hospital (RSUP Dr. Sardjito), Yogyakarta, Central Java Total population sampling of pediatric ALL patients with hyperleukocytosis and AKI was used for the case group, and a simple random sampling ratio of 1:2 was used for the control group. Cut-off values for each independent variable were determined by receiver-operator characteristic (ROC) curves. Bivariate and multivariate analyses were performed on potential risk factors.

Results Fourteen pediatric ALL patients with hyperleukocytosis and AKI were included in the case group and 28 children with ALL and hyperleukocytosis but without AKI were included in the control group. The incidence of AKI in children with ALL and hyperleukocytosis was 15.4%. Multivariate analysis revealed that the significant risk factors of AKI in ALL patients with hyperleukocytosis were phosphate concentration ?5.15 mg/L (OR 10.43; 95%CI 1.38 to 79.04; P=0.02) and uric acid concentration ?9.08 mg/dL (OR 12.39; 95%CI 1.88 to 81.44; P=0.009).

Conclusion Phosphate concentration  ?5.15 mg/L and uric acid  ?9.08 mg/dL were risk factors of AKI in pediatric ALL patients with hyperleukocytosis.


1. Rakhmawati U, Murni IK, Rusmawatiningtyas D. Predictors of mortality in children with acute kidney injury in intensive care unit. Pediatr Indones. 2019;59:92-7. DOI: https://doi.org/10.14238/pi59.2.2019.92-7.
2. Xiong M, Wang L, Su L, Luo W, Li Y, Li L, et al. Acute kidney injury among hospitalized children with cancer. Pediatr Nephrol. 2021;36:171–9. DOI: https://doi.org/10.1007/s00467-020-04678-1
3. Park PG, Hong CR, Kang E, Park M, Lee H, Kang HJ, et al. Acute kidney injury in pediatric cancer patients. J Pediatr. 2019;208:243-250.e3. DOI: https://doi.org/10.1016/j.jpeds.2018.12.023
4. Kanwar VS. Pediatric acute lymphoblastic leukemia. In: Willert JR, editor. Medscape. 2021. [cited 2021 December 20]. Available from: https://emedicine.medscape.com/article/ 990113-overview.
5. Supriyadi E, Widjajanto P, Purwanto I, Cloos J, Veerman AJ., Sutaryo S. Incidence of Childhood Leukemia in Yogyakarta, Indonesia 1998-2009. Pediatr Blood Cancer. 2011;57:588–93. DOI: https://doi.org/10.1002/pbc.23109
6. Alfina D, Widjajanto H, Patria S. The outcomes of childhood acute lymphoblastic leukemia with hyperleukocytosis Din. Paediatr Indones. 2018;58:186–91. DOI: http://doi.org/10.14238/pi58.4
7. Schiffer CA. Hyperleukocytosis and leukostasis in hematologic malignancies. Uptodate. In: Larson RA, Rosmarin AG, editors. 2021. [cited 2021 July 24]. Available from: https://www.uptodate.com/contents/hyperleukocytosis-and-leukostasis-in-hematologic-malignancies
8. Zhang D, Zhu Y, Jin Y, Kaweme NM, Dong Y. Leukapheresis and hyperleukocytosis, past and future. Int J Gen Med. 2021;14:3457–67. https://doi.org/10.2147/IJGM.S321787
9. Cosmai L, Porta C, Ronco C, Gallieni M. Acute Kidney Injury in Oncology and Tumor Lysis Syndrome. In: Ronco C, Bellomo R, Kellum J, Ricci Z, editors. Critical care nephrology. 3rd ed. Philadelphia: Elsevier; 2019. p. 234-250.e1. DOI: https://doi.org/10.1016/B978-0-323-44942-7.00041-8
10. Larson RA, Pui C-H. Tumor lysis syndrome: prevention and treatment. In: Drews RE, Freedman AS, Poplack DG, Savarese DMF, editors. Uptodate; 2021. [cited 2022 January 18]. Available from: https://www.uptodate.com/contents/tumor-lysis-syndrome-prevention-and-treatment/print
11. Lowe EJ, Pui CH, Hancock ML, Geiger TL, Khan RB, Sandlund JT. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005;45:10–5. DOI: https://onlinelibrary.wiley.com/doi/10.1002/pbc.20178
12. Rustagi RS, Arora K, Das RR, Pooni PA, Singh D. Incidence, risk factors and outcome of acute kidney injury in critically ill children–a developing country perspective. Paediatr Int Child Health. 2017;37:35–41.DOI: https://doi.org/10.1080/20469047.2015.1120409
13. de Rovetto R, Consuelo, Mora A, Sergio AC, Marmolejo AF, Paz JF, et al. Acute kidney injury applying pRifle scale in Children of Hospital Universitario del Valle in Cali, Colombia: clinical features, management and evolution. Colomb Med. 2012;(July 2012):200–5. DOI: https://doi.org/10.25100/cm.v43i3.797
14. Li Y, Chen X, Wang Y, Hu J, Xu J, Jiang W, et al. Epidemiology of Acute Kidney Injury and Associated Factors Among Patients with Malignancy?: Analysis of Hospital Inpatient Database in Shanghai , China. J Onco-Nephrology. 2019;3(1):39–48..DOI: https://doi.org/10.1177/2399369319830096
15. Nada A, Askenazi D, Boohaker LJ, Li L, Mahan JD, Charlton J, et al. Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group. Pediatr Res. 2021;89:922–31. DOI: https://doi.org/10.1038/s41390-020-0963-x
16. Mansoor AER, Zahid MF, Mubashir M, Fadoo Z, Ul Haq A, Rahman AJ. Outcome of tumor lysis syndrome in pediatric patients with hematologic malignancies - A single-center experience from Pakistan. J Community Support Oncol. 2016;14:457–65. DOI: https://doi.org/10.12788/jcso.0300.
17. Moon H, Chin HJ, Na KY, Joo KW, Kim YS, Kim S. Hyperphosphatemia and Risks of Acute Kidney Injury, End-stage Renal Disease, and Mortality in Hospitalized Patients. BMC Nephrol. 2019;20(362):1–7.DOI: https://doi.org/10.1186/s12882-019-1556-y
18. Naeem B, Moorani KN, Anjum M, Imam U. Tumor lysis syndrome in pediatric acute lymphoblastic leukemia at tertiary care center. Pakistan J Med Sci. 2019;35(4):899–904. DOI: https://doi.org/10.12788/jcso.0300
19. Abu-Alfa A, Younes A. Tumor lysis syndrome and acute kidney injury: evaluation, prevention, and management. Am J Kidney Dis. 2010;55:S1–13. DOI: http://dx.doi.org/10.1053/j.ajkd.2009.10.056
20. Ruggiero A, Rizzo D, Amato M, Riccardi R. Management of hyperleukocytosis. Curr Treat Options Oncol. 2016;17:7 DOI: https://doi.org/10.1007/s11864-015-0387-8
21. Budiyanto W, Mulatsih S, Sutaryo. Luaran terapi pasien leukemia limfoblastik akut dengan leukosit ? 50.000/?L di RSUP DR. Sardjito Februari 1999 - Februari 2009. Sari Pediatr. 2009;10:410.DOI: https://doi.org/10.14238/sp10.6.2009.410-6
22. Abla O, Angelini P, Di Giuseppe G, Kanani MF, Lau W, Hitzler J, et al. Early complications of hyperleukocytosis and leukapheresis in childhood acute leukemias. J Pediatr Hematol Oncol. 2016;38:111–7. DOI: https://doi.org/10.1097/MPH.0000000000000490
23. Sethi SK, Bunchman T, Chakraborty R, Raina R. Pediatric acute kidney injury: new advances in the last decade. Kidney Reasearch Clin Pract. 2021;40:40–51.DOI: https://doi.org/10.23876/j.krcp.20.074
24. Aygun F. Prognosis and early prediction of acute kidney injury in critically ill children. Nephro-Urol Mon. 2018;10.DOI: https://doi.org/10.5812/numonthly.83423.
25. Singh SK, Lupo PJ, Scheurer ME, Saxena A, Kennedy AE, Ibrahimou B, et al. A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants. Med (United States). 2016;95(46).DOI: https://doi.org/10.1097/MD.0000000000005300
26. Howard SC, Jones DP, Pui Ch-H. The tumor lysis syndrome. N Engl J Med. 2011; 2011;364:1844-54.
27. Sury K. Update on the prevention and treatment of tumor lysis syndrome. J Onco-Nephrology. 2019;3(1):19–30. DOI: https://doi.org/10.14238/pi59.4.2019.169-74
28. Rozmus J, Flood K, Mammen C, Skippen P, Matsell DG. Fluid overload and acute kidney injury in children with tumor lysis syndrome. Pediatr Blood Cancer. 2021;e29255(June):1–9.DOI: https://doi.org/10.1002/pbc.29255
29. Ding X, Cheng Z, Qian Q. Intravenous Fluids and Acute Kidney Injury. Blood Purif. 2017;43(1–3):163–72. DOI: https://doi.org/10.1159/000452702
30. Baqari SA, Haque A, Ashraf MS, Alam MM, Fadoo Z. Clinical profile and short-term outcome of pediatric hyperleukocytic acute leukemia from a developing country. J Coll Physicians Surg Pakistan. 2017;27(7):450–4.
31. Han SS, Baek SH, Ahn SY, Chin HJ, Na KY, Chae D, et al. Anemia is a risk factor for acute kidney injury and long-term mortality in critically ill patients. Tohoku J Exp Med. 2015;237:287–95.DOI: https://doi.org/ 10.1620/tjem.237.287
32. Abdel-Nabey M, Chaba A, Serre J, Lengliné E, Azoulay E, Darmon M, et al. Tumor lysis syndrome, acute kidney injury and disease-free survival in critically ill patients requiring urgent chemotherapy. Ann Intensive Care. 2022;12(1):1–12. DOI: https://doi.org/10.1186/s13613-022-00990-1
33. Nie S, Feng Z, Tang L, Wang X, He Y, Fang J, et al. Risk factor analysis for AKI including laboratory indicators: A nationwide multicenter study of hospitalized patients. Kidney Blood Press Res. 2018;42(5):761–73.DOI: https://doi.org/10.1159/000484234
How to Cite
Kinanti R, Palupi-Baroto R, Sutaryo S. Risk factors of acute kidney injury in pediatric acute lymphoblastic leukemia with hyperleukocytosis. PI [Internet]. 20Nov.2023 [cited 19Jul.2024];63(6):433-2. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3116
Pediatric Nephrology
Received 2022-09-07
Accepted 2023-11-20
Published 2023-11-20