Abstract
Objective
We want to know the causes of AKI in oncology patients, including disease-related complications and the nephrotoxicity of chemotherapy drugs, in order to provide more useful clinical information.
Methods
In this review, an electronic search of the English language literature was performed in the database PubMed, with the results enriched by manual searches and citation mining, factors investigated in the selected articles included acute kidney injury, oncology, chemotherapy, anticancer drug, antitumor drug.
Results
According to the searched articles, we summarized the causes (including pre-renal, intrinsic renal, and post-renal lesion) of AKI in cancer patients and the corresponding management measures. Among the pre-renal factors we mainly described hypercalcemia, hematopoietic cell transplantation, post-renal factors we mainly described hemorrhagic cystitis, and intrinsic renal factors we mainly described thrombotic microangiopathy, chemotherapeutics, tumor lysis syndrome, cast nephropathy, in which the emphasis was on chemotherapy drug associated AKI and its treatment.
Conclusions
AKI is not uncommon in cancer patients, and has diverse causes and negative outcomes. Both nephrologists and oncologists need to be aware of the unique reasons of AKI in this population and its optimal management.
Similar content being viewed by others
References
Cheng Y, Nie S, Li L, Li Y, Liu D, Xiong M, et al. Epidemiology and outcomes of acute kidney injury in hospitalized cancer patients in China. Int J Cancer. 2019;144(11):2644–50. https://doi.org/10.1002/ijc.31993.
Fidler MM, Bray F, Soerjomataram I. The global cancer burden and human development: a review. Scand J Public Health. 2018;46(1):27–36. https://doi.org/10.1177/1403494817715400.
Mattiuzzi C, Lippi G. Current cancer epidemiology. J Epidemiol Glob Health. 2019;9(4):217–22. https://doi.org/10.2991/jegh.k.191008.001.
Salahudeen AK, Doshi SM, Pawar T, Nowshad G, Lahoti A, Shah P. Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center. Clin J Am Soc Nephrol. 2013;8(3):347–54. https://doi.org/10.2215/cjn.03530412.
Lam AQ, Humphreys BD. Onco-nephrology: AKI in the cancer patient. Clin J Am Soc Nephrol. 2012;7(10):1692–700. https://doi.org/10.2215/cjn.03140312.
Cosmai L, Porta C, Gallieni M, Perazella MA. Onco-nephrology: a decalogue. Nephrol Dial Transplant. 2016;31(4):515–9. https://doi.org/10.1093/ndt/gfv320.
Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ (Clinical research ed). 2019;364: k4891. https://doi.org/10.1136/bmj.k4891.
Canet E, Zafrani L, Lambert J, Thieblemont C, Galicier L, Schnell D, et al. Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival. PLoS One. 2013;8(2):e55870. https://doi.org/10.1371/journal.pone.0055870.
Rosner MH, Dalkin AC. Onco-nephrology: the pathophysiology and treatment of malignancy-associated hypercalcemia. Clin J Am Soc Nephrol. 2012;7(10):1722–9. https://doi.org/10.2215/cjn.02470312.
Toka HR, Al-Romaih K, Koshy JM, DiBartolo S 3rd, Kos CH, Quinn SJ, et al. Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone-independent hypocalciuria. J Am Soc Nephrol. 2012;23(11):1879–90. https://doi.org/10.1681/asn.2012030323.
Rosner MH, Perazella MA. Acute kidney injury in the patient with cancer. Kidney Res Clin Pract. 2019;38(3):295–308. https://doi.org/10.23876/j.krcp.19.042.
Shingai N, Morito T, Najima Y, Kobayashi T, Doki N, Kakihana K, et al. Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients. Bone Marrow Transplant. 2015;50(12):1557–62. https://doi.org/10.1038/bmt.2015.188.
Kagoya Y, Kataoka K, Nannya Y, Kurokawa M. Pretransplant predictors and posttransplant sequels of acute kidney injury after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(3):394–400. https://doi.org/10.1016/j.bbmt.2010.07.010.
Hosing C, Nash R, McSweeney P, Mineishi S, Seibold J, Griffith LM, et al. Acute kidney injury in patients with systemic sclerosis participating in hematopoietic cell transplantation trials in the United States. Biol Blood Marrow Transplant. 2011;17(5):674–81. https://doi.org/10.1016/j.bbmt.2010.08.003.
Labrador J, López-Corral L, López-Godino O, Vázquez L, Cabrero-Calvo M, Pérez-López R, et al. Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus. Bone Marrow Transplant. 2014;49(5):684–90. https://doi.org/10.1038/bmt.2014.17.
Hingorani S. Renal complications of hematopoietic-cell transplantation. N Engl J Med. 2016;374(23):2256–67. https://doi.org/10.1056/NEJMra1404711.
Satwani P, Bavishi S, Jin Z, Jacobson JS, Baker C, Duffy D, et al. Risk factors associated with kidney injury and the impact of kidney injury on overall survival in pediatric recipients following allogeneic stem cell transplant. Biol Blood and Marrow Transplant. 2011;17(10):1472–80. https://doi.org/10.1016/j.bbmt.2011.02.006.
Gaziev J, Paba P, Miano R, Germani S, Sodani P, Bove P, et al. Late-onset hemorrhagic cystitis in children after hematopoietic stem cell transplantation for thalassemia and sickle cell anemia: a prospective evaluation of polyoma (BK) virus infection and treatment with cidofovir. Biol Blood Marrow Transplant. 2010;16(5):662–71. https://doi.org/10.1016/j.bbmt.2009.12.009.
Parikh CR, Yarlagadda SG, Storer B, Sorror M, Storb R, Sandmaier B. Impact of acute kidney injury on long-term mortality after nonmyeloablative hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2008;14(3):309–15. https://doi.org/10.1016/j.bbmt.2007.12.492.
Lopes JA, Jorge S, Neves M. Acute kidney injury in HCT: an update. Bone Marrow Transplant. 2016;51(6):755–62. https://doi.org/10.1038/bmt.2015.357.
Yang WC, Chen YT, Chang WW, Chang CH, Fan PC, Lee SY, et al. Outcome predictors of allogeneic hematopoietic stem cell transplant. Am J Med Sci. 2013;345(1):33–8. https://doi.org/10.1097/MAJ.0b013e31824c6f29.
Mori J, Ohashi K, Yamaguchi T, Ando M, Hirashima Y, Kobayashi T, et al. Risk assessment for acute kidney injury after allogeneic hematopoietic stem cell transplantation based on Acute Kidney Injury Network criteria. Intern Med (Tokyo, Japan). 2012;51(16):2105–10. https://doi.org/10.2169/internalmedicine.51.7418.
Petri CR, O’Donnell PH, Cao H, Artz AS, Stock W, Wickrema A, et al. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant. Leuk Lymphoma. 2014;55(12):2866–73. https://doi.org/10.3109/10428194.2014.897701.
Siddall E, Khatri M, Radhakrishnan J. Capillary leak syndrome: etiologies, pathophysiology, and management. Kidney Int. 2017;92(1):37–46. https://doi.org/10.1016/j.kint.2016.11.029.
Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157–68. https://doi.org/10.1016/j.bbmt.2009.08.024.
Kersting S, Koomans HA, Hené RJ, Verdonck LF. Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival. Bone Marrow Transplant. 2007;39(6):359–65. https://doi.org/10.1038/sj.bmt.1705599.
Spitzer TR. Engraftment syndrome: double-edged sword of hematopoietic cell transplants. Bone Marrow Transplant. 2015;50(4):469–75. https://doi.org/10.1038/bmt.2014.296.
Wanchoo R, Stotter BR, Bayer RL, Jhaveri KD. Acute kidney injury in hematopoietic stem cell transplantation. Curr Opin Crit Care. 2019;25(6):531–8. https://doi.org/10.1097/mcc.0000000000000657.
Carreras E, Fernández-Avilés F, Silva L, Guerrero M, Fernández de Larrea C, Martínez C, et al. Engraftment syndrome after auto-SCT: analysis of diagnostic criteria and risk factors in a large series from a single center. Bone Marrow Transplant. 2010;45(9):1417–22. https://doi.org/10.1038/bmt.2009.363.
Dejana E, Orsenigo F, Lampugnani MG. The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci. 2008;121(Pt 13):2115–22. https://doi.org/10.1242/jcs.017897.
Casadei Gardini A, Aquilina M, Oboldi D, Lucchesi A, Carloni S, Tenti E, et al. Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease. BMC Cancer. 2013;13:542. https://doi.org/10.1186/1471-2407-13-542.
Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4(2):481–508. https://doi.org/10.2215/cjn.04800908.
Coomes EA, Wolfe Jacques A, Michelis FV, Kim DDH, Thyagu S, Viswabandya A, et al. Efficacy of cidofovir in treatment of BK virus-induced hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2018;24(9):1901–5. https://doi.org/10.1016/j.bbmt.2018.04.009.
Höller K, Fabeni L, Herling M, Holtick U, Scheid C, Knops E, et al. Dynamics of BKPyV reactivation and risk of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Eur J Haematol. 2017;99(2):133–40. https://doi.org/10.1111/ejh.12895.
Beck LH Jr. Membranous nephropathy and malignancy. Semin Nephrol. 2010;30(6):635–44. https://doi.org/10.1016/j.semnephrol.2010.09.011.
Wanchoo R, Bernabe Ramirez C, Barrientos J, Jhaveri KD. Renal involvement in chronic lymphocytic leukemia. Clin Kidney J. 2018;11(5):670–80. https://doi.org/10.1093/ckj/sfy026.
Jhaveri KD, Shah HH, Calderon K, Campenot ES, Radhakrishnan J. Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney Int. 2013;84(1):34–44. https://doi.org/10.1038/ki.2012.484.
Campbell GA, Hu D, Okusa MD. Acute kidney injury in the cancer patient. Adv Chronic Kidney Dis. 2014;21(1):64–71. https://doi.org/10.1053/j.ackd.2013.08.002.
Rosner MH, Perazella MA. Acute kidney injury in patients with cancer. N Engl J Med. 2017;376(18):1770–81. https://doi.org/10.1056/NEJMra1613984.
Izzedine H, Perazella MA. Thrombotic microangiopathy, cancer, and cancer drugs. Am J Kidney Dis. 2015;66(5):857–68. https://doi.org/10.1053/j.ajkd.2015.02.340.
Robier C, Neubauer M, Beham-Schmid C, Sill H. Thrombotic microangiopathy and disseminated intravascular coagulation associated with carcinocythemia in a patient with breast cancer. J Clin Oncol. 2011;29(34):e825–6. https://doi.org/10.1200/jco.2011.36.7433.
Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011;118(6):1452–62. https://doi.org/10.1182/blood-2011-02-321315.
Laskin BL, Goebel J, Davies SM, Khoury JC, Bleesing JJ, Mehta PA, et al. Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT. Bone Marrow Transplant. 2011;46(5):682–9. https://doi.org/10.1038/bmt.2010.182.
Derungs A. Drug-induced acute kidney injury. Ther Umsch. 2015;72(11–12):717–27. https://doi.org/10.1024/0040-5930/a000742.
El-Ghazal R, Podoltsev N, Marks P, Chu E, Saif MW. Mitomycin–C-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: cumulative toxicity of an old drug in a new era. Clin Colorectal Cancer. 2011;10(2):142–5. https://doi.org/10.1016/j.clcc.2011.03.012.
Garcia G, Atallah JP. Antineoplastic agents and thrombotic microangiopathy. J Oncol Pharm Pract. 2017;23(2):135–42. https://doi.org/10.1177/1078155216628324.
Glezerman I, Kris MG, Miller V, Seshan S, Flombaum CD. Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution. Clin Nephrol. 2009;71(2):130–9. https://doi.org/10.5414/cnp71130.
Markowitz GS, Bomback AS, Perazella MA. Drug-induced glomerular disease: direct cellular injury. Clin J Am Soc Nephrol. 2015;10(7):1291–9. https://doi.org/10.2215/cjn.00860115.
Izzedine H, Escudier B, Lhomme C, Pautier P, Rouvier P, Gueutin V, et al. Kidney diseases associated with anti-vascular endothelial growth factor (VEGF): an 8-year observational study at a single center. Medicine. 2014;93(24):333–9. https://doi.org/10.1097/md.0000000000000207.
Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thrombotic microangiopathy with targeted cancer agents. Clin Cancer Res. 2011;17(18):5858–66. https://doi.org/10.1158/1078-0432.Ccr-11-0804.
den Deurwaarder ES, Desar IM, Steenbergen EJ, Mulders PF, Wetzels JF, van Herpen CM. Kidney injury during VEGF inhibitor therapy. Neth J Med. 2012;70(6):267–71.
Gurevich F, Perazella MA. Renal effects of anti-angiogenesis therapy: update for the internist. Am J Med. 2009;122(4):322–8. https://doi.org/10.1016/j.amjmed.2008.11.025.
Bollée G, Patey N, Cazajous G, Robert C, Goujon JM, Fakhouri F, et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant. 2009;24(2):682–5. https://doi.org/10.1093/ndt/gfn657.
Markowitz GS, Nasr SH, Stokes MB, D’Agati VD. Treatment with IFN-{alpha}, -{beta}, or -{gamma} is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010;5(4):607–15. https://doi.org/10.2215/cjn.07311009.
Xu XJ, Zhao HZ, Tang YM. Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials. Leuk Lymphoma. 2013;54(2):255–60. https://doi.org/10.3109/10428194.2012.715350.
Perazella MA, Shirali AC. Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do? Kidney Int. 2020;97(1):62–74. https://doi.org/10.1016/j.kint.2019.07.022.
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–68. https://doi.org/10.1056/NEJMra1703481.
Cortazar FB, Marrone KA, Troxell ML, Ralto KM, Hoenig MP, Brahmer JR, et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int. 2016;90(3):638–47. https://doi.org/10.1016/j.kint.2016.04.008.
Kitchlu A, Fingrut W, Avila-Casado C, Chan CT, Crump M, Hogg D, et al. Nephrotic syndrome with cancer immunotherapies: a report of 2 cases. Am J Kidney Dis. 2017;70(4):581–5. https://doi.org/10.1053/j.ajkd.2017.04.026.
Mamlouk O, Selamet U, Machado S, Abdelrahim M, Glass WF, Tchakarov A, et al. Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience. J Immunother Cancer. 2019;7(1):2. https://doi.org/10.1186/s40425-018-0478-8.
Finkel KW, Cohen EP, Shirali A, Abudayyeh A. Paraprotein-related kidney disease: evaluation and treatment of myeloma cast nephropathy. Clin J Am Soc Nephrol. 2016;11(12):2273–9. https://doi.org/10.2215/cjn.01640216.
Basnayake K, Ying WZ, Wang PX, Sanders PW. Immunoglobulin light chains activate tubular epithelial cells through redox signaling. J Am Soc Nephrol. 2010;21(7):1165–73. https://doi.org/10.1681/asn.2009101089.
Scheid C, Sonneveld P, Schmidt-Wolf IG, van der Holt B, el Jarari L, Bertsch U, et al. Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial. Haematologica. 2014;99(1):148–54. https://doi.org/10.3324/haematol.2013.087585.
Burnette BL, Leung N, Rajkumar SV. Renal improvement in myeloma with bortezomib plus plasma exchange. N Engl J Med. 2011;364(24):2365–6. https://doi.org/10.1056/NEJMc1101834.
Bridoux F, Fermand JP. Optimizing treatment strategies in myeloma cast nephropathy: rationale for a randomized prospective trial. Adv Chronic Kidney Dis. 2012;19(5):333–41. https://doi.org/10.1053/j.ackd.2012.07.003.
Mirrakhimov AE, Voore P, Khan M, Ali AM. Tumor lysis syndrome: a clinical review. World J Crit Care Med. 2015;4(2):130–8. https://doi.org/10.5492/wjccm.v4.i2.130.
Wilson FP, Berns JS. Tumor lysis syndrome: new challenges and recent advances. Adv Chronic Kidney Dis. 2014;21(1):18–26. https://doi.org/10.1053/j.ackd.2013.07.001.
Sherwood GB, Paschal RD, Adamski J. Rasburicase-induced methemoglobinemia: case report, literature review, and proposed treatment algorithm. Clin Case Rep. 2016;4(4):315–9. https://doi.org/10.1002/ccr3.495.
Perazella MA. Onco-nephrology: renal toxicities of chemotherapeutic agents. Clin J Am Soc Nephrol. 2012;7(10):1713–21. https://doi.org/10.2215/cjn.02780312.
Hamroun A, Lenain R, Bigna JJ, Speyer E, Bui L, Chamley P, et al. Prevention of cisplatin-induced acute kidney injury: a systematic review and meta-analysis. Drugs. 2019;79(14):1567–82. https://doi.org/10.1007/s40265-019-01182-1.
Canet E, Vincent F, Darmon M, Soares M. Acute kidney injury in hematological patients. Curr Opin Crit Care. 2015;21(6):549–58. https://doi.org/10.1097/mcc.0000000000000253.
Howard SC, Mccormick J, Pui CH, Buddington RK, Harvey RDJO. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21:1471–82.
Asati V, Bharti SK, Mahapatra DK. Mutant B-raf kinase inhibitors as anticancer agents. Anticancer Agents Med Chem. 2016;16(12):1558–75. https://doi.org/10.2174/1871520616666160606101848.
Holderfield M, Deuker MM, McCormick F, McMahon M. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer. 2014;14(7):455–67. https://doi.org/10.1038/nrc3760.
Jhaveri KD, Sakhiya V, Fishbane S. Nephrotoxicity of the BRAF inhibitors vemurafenib and dabrafenib. JAMA Oncol. 2015;1(8):1133–4. https://doi.org/10.1001/jamaoncol.2015.1713.
Franzin R, Netti GS, Spadaccino F, Porta C, Gesualdo L, Stallone G, et al. The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: where do we stand? Front Immunol. 2020;11:574271. https://doi.org/10.3389/fimmu.2020.574271.
Cortazar FB, Kibbelaar ZA, Glezerman IG, Abudayyeh A, Mamlouk O, Motwani SS, et al. Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: a multicenter study. J Am Soc Nephrol. 2020;31(2):435–46. https://doi.org/10.1681/asn.2019070676.
Shirali AC, Perazella MA, Gettinger S. Association of acute interstitial nephritis with programmed cell Death 1 inhibitor therapy in lung cancer patients. Am J Kidney Dis. 2016;68(2):287–91. https://doi.org/10.1053/j.ajkd.2016.02.057.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No potential conflict of interest was reported by the author(s).
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
Liu, S., Zhao, J. & Wang, F. Acute kidney injury in cancer patients. Clin Exp Nephrol 26, 103–112 (2022). https://doi.org/10.1007/s10157-021-02131-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10157-021-02131-7