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Acute kidney injury during autologous stem cell transplantation in light chain amyloidosis with kidney involvement and their impact on prognosis

Abstract

Acute kidney injury (AKI) is a complication related to important organ dysfunction during autologous stem cell transplantation (ASCT) in light chain (AL) amyloidosis. This study aims to validate the risk factors of AKI during different periods of ASCT and the impact of AKI on long-term outcomes. 302 patients with AL amyloidosis and kidney involvement who underwent ASCT were included. The procedures from stem cell mobilization to 30 days after transplantation were categorized into four periods: Period 0 (stem cell mobilization and harvest), Period 1 (preparation), Period 2 (conditioning and transplantation), and Period 3 (engraftment). The incidence of AKI during ASCT was 27.15% (0.66% in Period 0, 6.62% in Period 1, 15.23% in Period 2, and 6.95% in Period 3). The major causes of AKI were capillary leak syndrome in Period 0, ganciclovir or sulfamethoxazole/trimethoprim in Period 1, high-dose melphalan in Period 2, and engraftment syndrome in Period 3. AKI in different periods had distinct risk factors and predictive models. AKI was a risk factor for both kidney survival and overall survival (OS). Even recovered AKI reduced 10-year kidney survival from 91.7% to 68.4% (pā€‰=ā€‰0.002) and 10-year OS from 91.1% to 77.7% (pā€‰=ā€‰0.005).

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Fig. 1: An overview of different periods of ASCT and AKI.
Fig. 2: Long-term survival outcomes in different groups of patients.
Fig. 3: Multivariate Cox regression with stepwise forward elimination of risk factors for long-term survival.

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Data availability

The datasets are available in deidentified form from the corresponding author on reasonable request considering about the patient privacy.

References

  1. Miao F, Ren G, Guo J, Zhao L, Xu W, Huang X. Characteristics of engraftment syndrome following autologous stem cell transplantation in light chain amyloidosis with renal involvement. Transplant Cell Ther. 2023;29:110.e1ā€“110.e8.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  2. Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004;140:85ā€“93.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  3. Gatt ME, Palladini G. Light chain amyloidosis 2012: a new era. Br J Haematol. 2013;160:582ā€“98.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  4. Dā€™Souza A, Dispenzieri A, Wirk B, Zhang MJ, Huang J, Gertz MA, et al. Improved outcomes after autologous hematopoietic cell transplantation for light chain amyloidosis: a center for international blood and marrow transplant research study. J Clin Oncol. 2015;33:3741ā€“9.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  5. Leung N, Slezak JM, Bergstralh EJ, Dispenzieri A, Lacy MQ, Wolf RC, et al. Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am J Kidney Dis. 2005;45:102ā€“11.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  6. Nader R, Zhen A, Angel-Korman A, Pavlovich SS, Pogrebinsky A, Doros G, et al. Predictors and outcomes of acute kidney injury during autologous stem cell transplantation in AL amyloidosis. Nephrol Dial Transplant. 2022;37:1281ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  7. Leung N, Kumar SK, Glavey SV, Dispenzieri A, Lacy MQ, Buadi FK, et al. The impact of dialysis on the survival of patients with immunoglobulin light chain (AL) amyloidosis undergoing autologous stem cell transplantation. Nephrol Dial Transplant. 2016;31:1284ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  8. Bleeker JS, Gertz MA, Pellikka PA, Larson DR, Buadi F, Dingli D, et al. Evaluation of pretransplant factors predicting cardiac dysfunction following high-dose melphalan conditioning and autologous peripheral blood stem cell transplantation. Eur J Haematol. 2012;89:228ā€“35.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  9. Havasi A, Stern L, Lo S, Sun F, Sanchorawala V. Validation of new renal staging system in AL amyloidosis treated with high dose melphalan and stem cell transplantation. Am J Hematol. 2016;91:E458ā€“60.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  10. Obici L, Perfetti V, Palladini G, Moratti R, Merlini G. Clinical aspects of systemic amyloid diseases. Biochim Biophys Acta. 2005;1753:11ā€“22.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  11. Gertz MA, Leung N, Lacy MQ, Dispenzieri A, Zeldenrust SR, Hayman SR, et al. Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney. Nephrol Dial Transplant. 2009;24:3132ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  12. Li T, Huang X, Wang Q, Zhao L, Ren G, Chen W, et al. A risk stratification for systemic immunoglobulin light-chain amyloidosis with renal involvement. Br J Haematol. 2019;187:459ā€“69.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  13. Huang X, Ren G, Chen W, Guo J, Zhao L, Zeng C, et al. The role of induction therapy before autologous stem cell transplantation in low disease burden AL amyloidosis patients. Amyloid. 2021;28:75ā€“83.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  14. Andronesi AG, Tanase AD, Sorohan BM, Craciun OG, Stefan L, Varady Z, et al. Incidence and risk factors for acute kidney injury following autologous stem cell transplantation for multiple myeloma. Cancer Med. 2019;8:3278ā€“85.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  15. Fadia A, Casserly LF, Sanchorawala V, Seldin DC, Wright DG, Skinner M, et al. Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL amyloidosis. Kidney Int. 2003;63:1868ā€“73.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  16. Irazabal MV, Eirin A, Gertz MA, Dispenzieri A, Kumar S, Buadi FK, et al. Acute kidney injury during leukocyte engraftment after autologous stem cell transplantation in patients with light-chain amyloidosis. Am J Hematol. 2012;87:51ā€“4.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  17. Tamaki M, Nakasone H, Gomyo A, Hayakawa J, Akahoshi Y, Harada N, et al. Lower glomerular filtration rate predicts increased hepatic and mucosal toxicity in myeloma patients treated with high-dose melphalan. Int J Hematol. 2018;108:423ā€“31.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  18. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005;79:319ā€“28.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  19. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120:c179ā€“84.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  20. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30:4541ā€“9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  21. Palladini G, Hegenbart U, Milani P, Kimmich C, Foli A, Ho AD, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124:2325ā€“32.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  22. Huang X, Fu C, Chen L, Chen W, Ren G, Guo J, et al. Combination of bortezomib in the induction, conditioning and consolidation with autologous hematopoietic stem cell transplantation in patients with immunoglobulin light chain amyloidosis. Am J Hematol. 2019;94:E101ā€“e4.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  23. Shimizu Y, Hirai T, Ogawa Y, Yamada C, Kobayashi E. Characteristics of risk factors for acute kidney injury among inpatients administered sulfamethoxazole/trimethoprim: a retrospective observational study. J Pharm Health Care Sci. 2022;8:20.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  24. Slater MB, Gruneir A, Rochon PA, Howard AW, Koren G, Parshuram CS. Identifying High-Risk Medications Associated with Acute Kidney Injury in Critically Ill Patients: A Pharmacoepidemiologic Evaluation. Paediatr Drugs. 2017;19:59ā€“67.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  25. Zavras P, Su Y, Fang J, Stern A, Gupta N, Tang Y, et al. Impact of Preemptive Therapy for Cytomegalovirus on Toxicities after Allogeneic Hematopoietic Cell Transplantation in Clinical Practice: A Retrospective Single-Center Cohort Study. Biol Blood Marrow Transplant. 2020;26:1482ā€“91.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  26. Lilly CM, Welch VL, Mayer T, Ranauro P, Meisner J, Luke DR. Evaluation of intravenous voriconazole in patients with compromised renal function. BMC Infect Dis. 2013;13:14.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  27. Melphalan. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

  28. Alix JL, Swiercz P, Schaerer R, Mousseau M, Cordonnier D, Couderc P.et al. [Nephrotoxicity of high-dose melphalan]. Presse Med. 1983;12:575ā€“6.

  29. Spencer A, Horvath N, Gibson J, Prince HM, Herrmann R, Bashford J, et al. Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant. 2005;35:971ā€“7.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  30. Abidi MH, Agarwal R, Tageja N, Ayash L, Deol A, Al-Kadhimi Z, et al. A phase I dose-escalation trial of high-dose melphalan with palifermin for cytoprotection followed by autologous stem cell transplantation for patients with multiple myeloma with normal renal function. Biol Blood Marrow Transplant. 2013;19:56ā€“61.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  31. GutiĆ©rrez-GarcĆ­a G, Rovira M, Magnano L, RosiƱol L, Bataller A, SuĆ”rez-LledĆ³ M, et al. Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018;53:1541ā€“7.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  32. Liu Z, Zhang S, Horn B, Moreb JS. Postautologous stem cell transplantation engraftment syndrome: Improved treatment and outcomes. Clin Transplant. 2020;34:e13797.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  33. McCoy IE, Chertow GM. AKI-A Relevant Safety End Point? Am J Kidney Dis. 2020;75:508ā€“12.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  34. Meyrier A, Niaudet P. Acute kidney injury complicating nephrotic syndrome of minimal change disease. Kidney Int. 2018;94:861ā€“9.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  35. Parikh CR, Coca SG. Acute kidney injury: defining prerenal azotemia in clinical practice and research. Nat Rev Nephrol. 2010;6:641ā€“2.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  36. Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021;7:52.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  37. Romagnani P, Remuzzi G, Glassock R, Levin A, Jager KJ, Tonelli M, et al. Chronic kidney disease. Nat Rev Dis Primers. 2017;3:17088.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  38. Joslin J, Wilson H, Zubli D, Gauge N, Kinirons M, Hopper A, et al. Recognition and management of acute kidney injury in hospitalised patients can be partially improved with the use of a care bundle. Clin Med (Lond). 2015;15:431ā€“6.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  39. Mehta RL, Cerda J, Burdmann EA, Tonelli M, Garcia-Garcia G, Jha V, et al. International Society of Nephrologyā€™s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet. 2015;385:2616ā€“43.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  40. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery. Ann Thorac Surg. 2010;90:1142ā€“8.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  41. Coca SG, King JT Jr., Rosenthal RA, Perkal MF, Parikh CR. The duration of postoperative acute kidney injury is an additional parameter predicting long-term survival in diabetic veterans. Kidney Int. 2010;78:926ā€“33.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

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WWX was responsible for designing the study, extracting and analyzing data, interpreting results and writing the manuscript. WCC, JZG, LZ, GSR collected the data of the subjects. XHH was responsible for designing the protocol, interpreting results, and helped perform the analysis with constructive discussions.

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Correspondence to Xianghua Huang.

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Xu, W., Chen, W., Guo, J. et al. Acute kidney injury during autologous stem cell transplantation in light chain amyloidosis with kidney involvement and their impact on prognosis. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02292-5

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