Acute kidney injury associated with anticancer drugs: A narrative review
Main Article Content
Abstract
Acute kidney injury (AKI) is a common complication in patients with cancer and may lead to treatment interruption, increased hospitalization, and higher mortality. This narrative review aims to summarize the epidemiology, mechanisms, injury patterns, risk factors, prevention, and management of AKI associated with systemic anticancer therapies. Nephrotoxicity varies across drug classes: cisplatin predominantly causes dose-dependent tubular injury; high-dose methotrexate is associated with crystal nephropathy; and ifosfamide is linked to proximal tubular toxicity and Fanconi syndrome. Targeted therapies may induce proteinuria, thrombotic microangiopathy, or pseudo-elevation of serum creatinine, whereas immunotherapy is more commonly associated with acute interstitial nephritis. Key preventive strategies include risk stratification, optimization of fluid and electrolyte balance, avoidance of unnecessary nephrotoxic agents, and early monitoring of kidney function. Early recognition of the underlying mechanisms and AKI phenotypes may support individualized management, facilitate treatment continuation, and improve clinical outcomes.
Article Details
Keywords
Acute kidney injury, nephrotoxicity, anticancer drugs, prevention, management
References
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22. Glezerman IG, Pietanza MC, Miller V, Seshan SV. Kidney tubular toxicity of maintenance pemetrexed therapy. Am J Kidney Dis. Nov 2011;58(5):817-20. doi:10.1053/j.ajkd.2011.04.030
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26. Ensergueix G, Pallet N, Joly D, et al. Ifosfamide nephrotoxicity in adult patients. Clin Kidney J. Aug 2020;13(4):660-665. doi:10.1093/ckj/sfz183
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28. Halka J, Spaleniak S, Kade G, Antosiewicz S, Sigorski D. The Nephrotoxicity of Drugs Used in Causal Oncological Therapies. Curr Oncol. Dec 8 2022;29(12):9681-9694. doi:10.3390/curroncol29120760
29. Aklilu AM, Shirali AC. Chemotherapy-Associated Thrombotic Microangiopathy. Kidney360. Mar 1 2023;4(3):409-422. doi:10.34067/KID.0000000000000061
30. van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers (Basel). Jan 26 2022;14(3)doi:10.3390/cancers14030627
31. Mazzierli T, Allegretta F, Maffini E, Allinovi M. Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management. Front Pharmacol. 2022;13:1088031. doi:10.3389/fphar.2022.1088031
32. Van Wynsberghe M, Flejeo J, Sakhi H, et al. Nephrotoxicity of Anti-Angiogenic Therapies. Diagnostics (Basel). Apr 1 2021;11(4)doi:10.3390/diagnostics11040640
33. Izzedine H, Perazella MA. Anticancer Drug-Induced Acute Kidney Injury. Kidney Int Rep. Jul 2017;2(4):504-514. doi:10.1016/j.ekir.2017.02.008
34. Lafayette RA, McCall B, Li N, et al. Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled analysis from randomized controlled trials. Am J Nephrol. 2014;40(1):75-83. doi:10.1159/000365156
35. Zhang ZF, Wang T, Liu LH, Guo HQ. Risks of proteinuria associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis. PLoS One. 2014;9(3):e90135. doi:10.1371/journal.pone.0090135
36. Rashidi A, Wanchoo R, Izzedine H. How I Manage Hypertension and Proteinuria Associated with VEGF Inhibitor. Clin J Am Soc Nephrol. Jan 1 2023;18(1):121-123. doi:10.2215/CJN.05610522
37. Kala J, Joseph T, Pirovano M, Fenoglio R, Cosmai L. Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies. Kidney360. Nov 1 2024;5(11):1750-1762. doi:10.34067/KID.0000000566
38. Cellier M, Bourneau-Martin D, Abbara C, et al. Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase((R)), the WHO Pharmacovigilance Database. Cancers (Basel). Mar 29 2023;15(7)doi:10.3390/cancers15072041
39. Arakawa H, Omote S, Tamai I. Inhibitory Effect of Crizotinib on Creatinine Uptake by Renal Secretory Transporter OCT2. J Pharm Sci. Sep 2017;106(9):2899-2903. doi:10.1016/j.xphs.2017.03.013
40. Muller-Krebs S, Weber L, Tsobaneli J, et al. Cellular effects of everolimus and sirolimus on podocytes. PLoS One. 2013;8(11):e80340. doi:10.1371/journal.pone.0080340
41. Axelsson J, Rippe A, Rippe B. mTOR inhibition with temsirolimus causes acute increases in glomerular permeability, but inhibits the dynamic permeability actions of puromycin aminonucleoside. Am J Physiol Renal Physiol. May 15 2015;308(10):F1056-64. doi:10.1152/ajprenal.00632.2014
42. Ha SH, Park JH, Jang HR, et al. Increased risk of everolimus-associated acute kidney injury in cancer patients with impaired kidney function. BMC Cancer. Dec 3 2014;14:906. doi:10.1186/1471-2407-14-906
43. Zhou P, Gao Y, Kong Z, et al. Immune checkpoint inhibitors and acute kidney injury. Front Immunol. 2024;15:1353339. doi:10.3389/fimmu.2024.1353339
44. Meraz-Munoz A, Amir E, Ng P, et al. Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes. J Immunother Cancer. Jun 2020;8(1)doi:10.1136/jitc-2019-000467
45. Kitchlu A, Silva V, Anand S, et al. Assessment of GFR in Patients with Cancer Part 2: Anticancer Therapies-Perspectives from the American Society of Onco-Nephrology (ASON). Clin J Am Soc Nephrol. Aug 1 2024;19(8):1073-1077. doi:10.2215/CJN.0000000000000509
46. Yarandi N, Shirali AC. Onconephrology: Core Curriculum 2023. Am J Kidney Dis. Dec 2023;82(6):743-761. doi:10.1053/j.ajkd.2023.04.014
47. Chiruvella V, Annamaraju P, Guddati AK. Management of nephrotoxicity of chemotherapy and targeted agents: 2020. Am J Cancer Res. 2020;10(12):4151-4164.
48. Garcia-Carro C, Draibe J, Soler MJ. Onconephrology: Update in Anticancer Drug-Related Nephrotoxicity. Nephron. 2023;147(2):65-77. doi:10.1159/000525029
2. Rosner MH, Perazella MA. Acute kidney injury in the patient with cancer. Kidney Res Clin Pract. Sep 30 2019;38(3):295-308. doi:10.23876/j.krcp.19.042
3. Renaghan AD, Ostermann M, Ronco C, et al. The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol. Apr 2026;22(4):283-300. doi:10.1038/s41581-025-01031-3
4. Sikking C, Niggebrugge-Mentink KL, van der Sman ASE, et al. Hydration Methods for Cisplatin Containing Chemotherapy: A Systematic Review. Oncologist. Feb 2 2024;29(2):e173-e186. doi:10.1093/oncolo/oyad297
5. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist. Dec 2016;21(12):1471-1482. doi:10.1634/theoncologist.2015-0164
6. Chen JJ, Lee TH, Kuo G, et al. All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality. Clin Kidney J. Jan 2024;17(1):sfad292. doi:10.1093/ckj/sfad292
7. Vanhoutte T, Sprangers B. Pseudo-AKI associated with targeted anti-cancer agents-the truth is in the eye of the filtration marker. Clin Kidney J. Apr 2023;16(4):603-610. doi:10.1093/ckj/sfad011
8. Christiansen CF, Johansen MB, Langeberg WJ, Fryzek JP, Sorensen HT. Incidence of acute kidney injury in cancer patients: a Danish population-based cohort study. Eur J Intern Med. Aug 2011;22(4):399-406. doi:10.1016/j.ejim.2011.05.005
9. Kitchlu A, McArthur E, Amir E, et al. Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study. J Natl Cancer Inst. Jul 1 2019;111(7):727-736. doi:10.1093/jnci/djy167
10. Zhu J, Ding X, Zhang J, et al. Acute kidney injury in cancer patients receiving anti-vascular endothelial growth factor monoclonal antibody vs. immune checkpoint inhibitors: a retrospective real-world study. BMC Cancer. Jun 24 2024;24(1):756. doi:10.1186/s12885-024-12540-y
11. Xiong Y, Wang Q, Liu Y, Wei J, Chen X. Renal adverse reactions of tyrosine kinase inhibitors in the treatment of tumours: A Bayesian network meta-analysis. Front Pharmacol. 2022;13:1023660. doi:10.3389/fphar.2022.1023660
12. Lyrio R, Rocha BRA, Correa A, et al. Chemotherapy-induced acute kidney injury: epidemiology, pathophysiology, and therapeutic approaches. Front Nephrol. 2024;4:1436896. doi:10.3389/fneph.2024.1436896
13. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel). Nov 2010;2(11):2490-518. doi:10.3390/toxins2112490
14. McSweeney KR, Gadanec LK, Qaradakhi T, Ali BA, Zulli A, Apostolopoulos V. Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations. Cancers (Basel). Mar 29 2021;13(7)doi:10.3390/cancers13071572
15. Ozkok A, Edelstein CL. Pathophysiology of cisplatin-induced acute kidney injury. Biomed Res Int. 2014;2014:967826. doi:10.1155/2014/967826
16. Chen HC, Hou HY, Sung JM, Shieh CC. Deletion of NADPH oxidase 2 attenuates cisplatin-induced acute kidney injury through reducing ROS-induced proximal tubular cell injury and inflammation. Front Med (Lausanne). 2023;10:1097671. doi:10.3389/fmed.2023.1097671
17. Li J, Wu Y, Chen C, Zhang W, Yue L, Liu T. A systematic review for prevention of cisplatin-induced nephrotoxicity using different hydration protocols and meta-analysis for magnesium hydrate supplementation. Clinical and experimental nephrology. 08/02 2023;28doi:10.1007/s10157-023-02386-2
18. Bielack S, Fox CP, Hoang-Xuan K, Giro-Perafita A, Rizzari C. A Delphi study to determine the epidemiology and clinical management of patients treated with HDMTX who develop methotrexate (MTX) delayed elimination in France, Germany, Italy, and the UK. Health Sci Rep. Jan 2024;7(1):e1749. doi:10.1002/hsr2.1749
19. Ramsey LB, Balis FM, O’Brien MM, et al. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. Jan 2018;23(1):52-61. doi:10.1634/theoncologist.2017-0243
20. Bielack SS, Soussain C, Fox CP, et al. A European consensus recommendation on the management of delayed methotrexate elimination: supportive measures, leucovorin rescue and glucarpidase treatment. J Cancer Res Clin Oncol. Oct 2 2024;150(10):441. doi:10.1007/s00432-024-05945-6
21. de Rouw N, Boosman RJ, van de Bruinhorst H, et al. Cumulative pemetrexed dose increases the risk of nephrotoxicity. Lung Cancer. Aug 2020;146:30-35. doi:10.1016/j.lungcan.2020.05.022
22. Glezerman IG, Pietanza MC, Miller V, Seshan SV. Kidney tubular toxicity of maintenance pemetrexed therapy. Am J Kidney Dis. Nov 2011;58(5):817-20. doi:10.1053/j.ajkd.2011.04.030
23. Kurata T, Iwamoto T, Kawahara Y, Okuda M. Characteristics of pemetrexed transport by renal basolateral organic anion transporter hOAT3. Drug Metab Pharmacokinet. 2014;29(2):148-53. doi:10.2133/dmpk.dmpk-13-rg-042
24. Agency EM. Pemetrexed medac: EPAR – Product information. 2025. https://www.ema.europa.eu/en/documents/product-information/pemetrexed-medac-epar-product-information_en.pdf
25. Gupta S, Portales-Castillo I, Daher A, Kitchlu A. Conventional Chemotherapy Nephrotoxicity. Adv Chronic Kidney Dis. Sep 2021;28(5):402-414 e1. doi:10.1053/j.ackd.2021.08.001
26. Ensergueix G, Pallet N, Joly D, et al. Ifosfamide nephrotoxicity in adult patients. Clin Kidney J. Aug 2020;13(4):660-665. doi:10.1093/ckj/sfz183
27. Leem AY, Kim HS, Yoo BW, et al. Ifosfamide-induced Fanconi syndrome with diabetes insipidus. Korean J Intern Med. Mar 2014;29(2):246-9. doi:10.3904/kjim.2014.29.2.246
28. Halka J, Spaleniak S, Kade G, Antosiewicz S, Sigorski D. The Nephrotoxicity of Drugs Used in Causal Oncological Therapies. Curr Oncol. Dec 8 2022;29(12):9681-9694. doi:10.3390/curroncol29120760
29. Aklilu AM, Shirali AC. Chemotherapy-Associated Thrombotic Microangiopathy. Kidney360. Mar 1 2023;4(3):409-422. doi:10.34067/KID.0000000000000061
30. van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers (Basel). Jan 26 2022;14(3)doi:10.3390/cancers14030627
31. Mazzierli T, Allegretta F, Maffini E, Allinovi M. Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management. Front Pharmacol. 2022;13:1088031. doi:10.3389/fphar.2022.1088031
32. Van Wynsberghe M, Flejeo J, Sakhi H, et al. Nephrotoxicity of Anti-Angiogenic Therapies. Diagnostics (Basel). Apr 1 2021;11(4)doi:10.3390/diagnostics11040640
33. Izzedine H, Perazella MA. Anticancer Drug-Induced Acute Kidney Injury. Kidney Int Rep. Jul 2017;2(4):504-514. doi:10.1016/j.ekir.2017.02.008
34. Lafayette RA, McCall B, Li N, et al. Incidence and relevance of proteinuria in bevacizumab-treated patients: pooled analysis from randomized controlled trials. Am J Nephrol. 2014;40(1):75-83. doi:10.1159/000365156
35. Zhang ZF, Wang T, Liu LH, Guo HQ. Risks of proteinuria associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis. PLoS One. 2014;9(3):e90135. doi:10.1371/journal.pone.0090135
36. Rashidi A, Wanchoo R, Izzedine H. How I Manage Hypertension and Proteinuria Associated with VEGF Inhibitor. Clin J Am Soc Nephrol. Jan 1 2023;18(1):121-123. doi:10.2215/CJN.05610522
37. Kala J, Joseph T, Pirovano M, Fenoglio R, Cosmai L. Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies. Kidney360. Nov 1 2024;5(11):1750-1762. doi:10.34067/KID.0000000566
38. Cellier M, Bourneau-Martin D, Abbara C, et al. Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase((R)), the WHO Pharmacovigilance Database. Cancers (Basel). Mar 29 2023;15(7)doi:10.3390/cancers15072041
39. Arakawa H, Omote S, Tamai I. Inhibitory Effect of Crizotinib on Creatinine Uptake by Renal Secretory Transporter OCT2. J Pharm Sci. Sep 2017;106(9):2899-2903. doi:10.1016/j.xphs.2017.03.013
40. Muller-Krebs S, Weber L, Tsobaneli J, et al. Cellular effects of everolimus and sirolimus on podocytes. PLoS One. 2013;8(11):e80340. doi:10.1371/journal.pone.0080340
41. Axelsson J, Rippe A, Rippe B. mTOR inhibition with temsirolimus causes acute increases in glomerular permeability, but inhibits the dynamic permeability actions of puromycin aminonucleoside. Am J Physiol Renal Physiol. May 15 2015;308(10):F1056-64. doi:10.1152/ajprenal.00632.2014
42. Ha SH, Park JH, Jang HR, et al. Increased risk of everolimus-associated acute kidney injury in cancer patients with impaired kidney function. BMC Cancer. Dec 3 2014;14:906. doi:10.1186/1471-2407-14-906
43. Zhou P, Gao Y, Kong Z, et al. Immune checkpoint inhibitors and acute kidney injury. Front Immunol. 2024;15:1353339. doi:10.3389/fimmu.2024.1353339
44. Meraz-Munoz A, Amir E, Ng P, et al. Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes. J Immunother Cancer. Jun 2020;8(1)doi:10.1136/jitc-2019-000467
45. Kitchlu A, Silva V, Anand S, et al. Assessment of GFR in Patients with Cancer Part 2: Anticancer Therapies-Perspectives from the American Society of Onco-Nephrology (ASON). Clin J Am Soc Nephrol. Aug 1 2024;19(8):1073-1077. doi:10.2215/CJN.0000000000000509
46. Yarandi N, Shirali AC. Onconephrology: Core Curriculum 2023. Am J Kidney Dis. Dec 2023;82(6):743-761. doi:10.1053/j.ajkd.2023.04.014
47. Chiruvella V, Annamaraju P, Guddati AK. Management of nephrotoxicity of chemotherapy and targeted agents: 2020. Am J Cancer Res. 2020;10(12):4151-4164.
48. Garcia-Carro C, Draibe J, Soler MJ. Onconephrology: Update in Anticancer Drug-Related Nephrotoxicity. Nephron. 2023;147(2):65-77. doi:10.1159/000525029