Abstract
A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr–Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Moreover, the serum creatinine level increased mildly during this period. The urinary protein level reached 2.18 g/gCr; hence, a renal biopsy was conducted. Light microscopy revealed mild proliferation of mesangial cells, and immunofluorescence analysis revealed IgG and C3 depositions in the mesangial area. Electron microscopy revealed electron-dense deposition in the paramesangial area, partial podocyte foot process effacement, and segmental endothelial cell swelling with a slight expansion of the subendothelial space. Dasatinib was discontinued, and within 3 weeks, the proteinuria disappeared, with improvements in her renal function. After switching to bosutinib, a new second-generation of tyrosine kinase inhibitor, the proteinuria remained negative. The rapid cessation of proteinuria following dasatinib discontinuation indicated that proteinuria was induced by the long-term administration of dasatinib. Proteinuria and renal function should be regularly monitored during dasatinib therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, Wang J, Ipina JJ, Kim DW, Ogura M, Pavlovsky C, Junghanss C, Milone JH, Nicolini FE, Robak T, Van Droogenbroeck J, Vellenga E, Bradley-Garelik MB, Zhu C, Hochhaus A. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119:1123–9.
Saglio G, Hochhaus A, Goh YT, Masszi T, Pasquini R, Maloisel F, Erben P, Cortes J, Paquette R, Bradley-Garelik MB, Zhu C, Dombret H. Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. Cancer. 2010;116:3852–61.
Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M, Party GALW. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011;118:6521–8.
Wallace E, Lyndon W, Chumley P, Jaimes EA, Fatima H. Dasatinib-induced nephrotic-range proteinuria. Am J Kidney Dis. 2013;61:1026–31.
Ruebner RL, Copelovitch L, Evageliou NF, Denburg MR, Belasco JB, Kaplan BS. Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric malignancy: case series and review of the literature. Pediatr Nephrol. 2014;29:863–9.
Hirano T, Hashimoto M, Korogi Y, Tsuji T, Miyanaka K, Yamasaki H, Tsuda H. Dasatinib-induced nephrotic syndrome. Leuk Lymphoma. 2016;57:726–7.
Lim YT, Kim YJ, Park YH, Hah JO, Lee JM. A case of dasatinib-induced nephrotic syndrome in a child with philadelphia chromosome positive acute lymphoblastic leukemia. Yonsei Med J. 2016;57:532–3.
Ochiai S, Sato Y, Minakawa A, Fukuda A, Fujimoto S. Dasatinib-induced nephrotic syndrome in a patient with chronic myelogenous leukemia: a case report. BMC Nephrol. 2019;20:87.
De Luca M, Carmosino I, Stefanizz C, Campanelli M, De Angelis F, Cesini L, Latagliata R, Alimena G. Nephrotic proteinuria developed under dasatinib treatment in a patient with chronic myeloid leukemia: a case report and review of the literature. Ann Hematol Oncol. 2016;36:1106.
Mandac Rogulj I, Matisic V, Arsov B, Boban L, Juginovic A, Molnar V, Primorac D. Dasatinib-induced nephrotic syndrome: a case of phenoconversion. Croat Med J. 2019;60:250–4.
Cuellar S, Vozniak M, Rhodes J, Forcello N, Olszta D. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia. J Oncol Pharm Pract. 2018;24:433–52.
Rix U, Hantschel O, Durnberger G, Remsing Rix LL, Planyavsky M, Fernbach NV, Kaupe I, Bennett KL, Valent P, Colinge J, Kocher T, Superti-Furga G. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood. 2007;110:4055–63.
Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boque C, Chuah C, Pavlovsky C, Mayer J, Cortes J, Baccarani M, Kim DW, Bradley-Garelik MB, Mohamed H, Wildgust M, Hochhaus A. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.
Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boque C, Shah NP, Chuah C, Casanova L, Bradley-Garelik B, Manos G, Hochhaus A. Final 5-year study results of DASISION: the Dasatinib versus imatinib study in treatment-naive chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–400.
Demetri GD, Lo Russo P, MacPherson IR, Wang D, Morgan JA, Brunton VG, Paliwal P, Agrawal S, Voi M, Evans TR. Phase I dose-escalation and pharmacokinetic study of dasatinib in patients with advanced solid tumors. Clin Cancer Res. 2009;15:6232–40.
Muller-Hansma AHG, van der Lugt J, Zwaan CM. Nephrotic syndrome under treatment with dasatinib: be aware of a possible adverse drug reaction. Neth J Med. 2017;75:428–31.
Shah NP, Guilhot F, Cortes JE, Schiffer CA, le Coutre P, Brummendorf TH, Kantarjian HM, Hochhaus A, Rousselot P, Mohamed H, Healey D, Cunningham M, Saglio G. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014;123:2317–24.
Hughes TP, Laneuville P, Rousselot P, Snyder DS, Rea D, Shah NP, Paar D, Abruzzese E, Hochhaus A, Lipton JH, Cortes JE. Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia. Haematologica. 2019;104:93–101.
Ollero M, Sahali D. Inhibition of the VEGF signalling pathway and glomerular disorders. Nephrol Dial Transplant. 2015;30:1449–555.
Liang W, Kujawski M, Wu J, Lu J, Herrmann A, Loera S, Yen Y, Lee F, Yu H, Wen W, Jove R. Antitumor activity of targeting SRC kinases in endothelial and myeloid cell compartments of the tumor microenvironment. Clin Cancer Res. 2010;16:924–35.
Calizo RC, Bhattacharya S, van Hasselt JGC, Wei C, Wong JS, Wiener RJ, Ge X, Wong NJ, Lee JJ, Cuttitta CM, Jayaraman G, Au VH, Janssen W, Liu T, Li H, Salem F, Jaimes EA, Murphy B, Campbell KN, Azeloglu EU. Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity. Nat Commun. 2019;10:2061.
Ma TK, McAdoo SP, Tam FW. Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond. Nephrol Dial Transplant. 2017;32:i129–i138138.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Informed consent
Informed consent was obtained from the patient for publication of this case report.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Koinuma, K., Sakairi, T., Watanabe, Y. et al. A case of long-term dasatinib-induced proteinuria and glomerular injury. CEN Case Rep 9, 359–364 (2020). https://doi.org/10.1007/s13730-020-00484-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13730-020-00484-8