Acute kidney injury and tubular biomarkers after hematopoietic stem cell transplantation

Cite item


Aim. To determine the value of molecular biomarkers (BMs) associated with tubular epithelial damage in developing and predicting acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT). Subjects and methods. The open-label observational prospective study enrolled 90 patients (46 males and 44 females) who had undergone HSCT. The concentrations of BMs (calbindin, clusterin, interleukin-18 (IL-18), kidney injury molecules-1 (KIM-1), glutathione S-transferase-π (GST-π), and monocyte chemoattractant protein-1 (MCP-1) were measured in urinary samples 7 days before HSCT (week 0) and at weeks 1, 2, 3, 4, and 5. Main clinical parameters were simultaneously monitored. AKI was diagnosed and stratified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Results. At weeks 1, 2, 3, 4, and 5 after HSCT, the proportion of AKI cases was 7.8, 8.9, 12.5, 27.3, and 35.9%, respectively. The elevated urinary levels of BMs (above the median) were found to be substantially more common than AKI cases. The urinary excretion of the majority of BMs dramatically increased in the early HSCT period. The median number of simultaneously elevated BMs was 3 (2; 5) during the entire follow-up period. Clusterin, MCP-1 and KIM-1 positively and significantly correlated with serum creatinine at the week following the determination of BMs in the multivariate linear regression models adjusted for other confounders. The higher urinary KIM-1 and/or MCP-1 excretion regardless of other clinical indicators was associated with the higher relative risk (RR) of AKI, which increased by 2.3 times with a rise in one of these indicators and by 3.4 times with a rise in both indicators. Conclusion. Multiple renal toxic effects after HSCT result in a substantial and simultaneous elevation of urinary excretion of BMs for tubular damage. Among the BMs studied, KIM-1 and MCP-1 seem to be the most suitable molecules for assessing the risk of AKI in this cohort of patient within the predictive diagnostic approach.


  1. Zeng X, McMahon GM, Brunelli SM et al. Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals. Clin J Am Soc Nephrol. 2014;9(1):12-20. doi: 10.2215/CJN.02730313.
  2. Haase M, Kellum JA, Ronco C. Subclinical AKI-an emerging syndrome with important consequences. Nat Rev Nephrol. 2012;8 (12):735-739. doi: 10.1038/nrneph.2012.197.
  3. Bellomo R, Kellum JA, Ronco C. Defining acute renal failure: physiological principles. Intensive Care Med. 2004;30(1):33-37. doi: 10.1007/s00134-003-2078-3.
  4. Смирнов А.В., Добронравов В.А., Румянцев А.Ш., Шилов Е.М., Ватазин А.В. и др. Национальные рекомендации. Острое повреждение почек: основные принципы диагностики, профилактики и терапии. Часть 1. Нефрология. 2016; 20(1):79-104.
  5. Kellum JA, Aspelin P, Barsoum RS et al. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements. 2012;(2):1. doi: 10.1038/kisup.2012.1.
  6. Hjortrup PB, Haase N et al. Clinical review: Predictive value of neutrophil gelatinase-associated lipocalin for acute kidney injury in intensive care patients. Critical Care. 2013;17(2):211. doi: 10.1186/cc11855.
  7. Martensson J, Martling CR, Bell M Novel Biomarkers of acute kidney injury and failure: clinical applicability. Br J Anaesth. 2012;109(6):843-850. doi: 10.1093/bja/aes357.
  8. Coca SG, Parikh CR Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol. 2008;3(2):481-490. doi: 10.2215/CJN.03520807.
  9. Basile DP, Anderson MD, Sutton TA. Pathophysiology of Acute Kidney Injury. Compr Physiol. 2012;2(2):1303-1353. doi: 10.1002/cphy.c110041.
  10. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of Acute Kidney Injury. Annu Rev Pharmacol Toxicol. 2008;48:463-493. doi:10.11.46/annurev.pharmtox.48.113006.094615.
  11. Смирнов А.В., Добронравов В.А., Румянцев А.Ш., Каюков И.Г. Острое повреждение почек. М.: Медицинское информационное агентство; 2015.
  12. Смирнов А.В., Каюков И.Г., Добронравов В.А., Кучер А.Г. Острое повреждение почек и острая почечная недостаточность: некоторые уроки международных инициатив. Нефрология. 2008;12(3):7-12.
  13. Soni SS, Cruz D, Bobek I NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol. 2010; 42(1):141-150. doi: 10.1007/s11255-009-9608-z.
  14. Ghatanatti R, Teli A, Tirkey SS et al. Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery. Asian Cardiovasc Thorac Ann. 2014;22(2):234-241. doi: 10.1177/0218492313502028.
  15. Field M, Dronovalli V, Mistry P et al. Urinary biomarkers of acute kidney injury in deceased organ donors-kidney injury molecule-1 as an adjunct to predicting outcome. Clin Transplant. 2014;28(7): 808-815. doi: 10.1111/ctr.12383.
  16. Мензоров М.В., Шутов А.М., Макеева Е.Р., Михайлова Е.В., Парфенова Е.А. Роль липокалина, ассоциированного с желатиназой нейтрофилов в раннем прогнозировании острого повреждения почек у больных с острым коронарным синдромом. Фундаментальные исследования. 2013;9(4):698-702.
  17. Shingai N, Morito T. Urinary Liver-Type Fatty Acid-binding Protein Linked with Increased Risk of Acute Kidney Injury after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2014;20(12):2010-2014. doi: 10.1016/j.bbmt.2014.08.022.
  18. Lopes JA, Jorge S. Acute kidney injury following HCT: incidence, risk factors and outcome. Bone Marrow Transplantation. 2011; 46(11):1399-1408. doi: 10.1038/bmt.2011.46.
  19. Sawinski D. The Kidney Effects of Hematopoietic stem Cell Transplantation. Advances in ChronicKidney Disease. 2014;21(1): 96-105. doi: 10.1053/j.ackd.2013.08.007.
  20. Metzger J, Kirsch T, Schiffer E et al. Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury. Kidney Int. 2010;78(12):1252-1262. doi: 10.1038/ki.2010.322.
  21. Kuwata K, Nakamura I, Ide M, Sato H, Nishikawa S, Tanaka M. Comparison of changes in urinary and blood levels of biomarkers associated with proximal tubular injury in rat models. J Toxicol Pathol. 2015;28(3):151-164. doi: 10.1293/tox.2014-0039.
  22. Alnasser HA, Guan Q, Zhang F, Gleave ME, Nguan CY, Du C. Requirment of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells. Am J Physiol Renal Physiol. 2016;310(2):F160-F173. doi: 10.1152/ajprenal.00304.2015.

Copyright (c) 2016 Dobronravov V.A., Smirnov K.A., Afanasiev B.V., Galkina O.V., Smirnov A.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail:


© 2018-2021 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies