Acute kidney injury (AKI) increases early mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients and may accelerate chronic kidney disease (CKD) development. We analyzed prospective variables related to AKI and CKD in 422 allo-HCT recipients to establish risk factors of severe acute renal failure and CKD. Renal function and creatinine were periodically assessed from baseline till the last follow-up. Sixty-three patients (14%) developed severe AKI (AKI-3) at 100 days post transplant and 15% at 12 months. Variables associated with AKI-3 were age above 55 years [hazard ratio (HR): 2.4; p = 0.019], total body irradiation (TBI) (HR: 1.8; p = 0.044), high-risk cytomegalovirus reactivation (HR: 1.8; p = 0.041), and methotrexate as GVHD prophylaxis (HR: 2.1; p = 0.024). AKI-3 increased the mortality risk (HR: 2.5, 95% confidence interval: 1.9–3.4). The CKD prevalence in 161 living patients was 10.2% at the last follow-up and in most, CKD developed 1 year post HCT, independent of AKI. The CKD at 1 year post HCT was associated with increased mortality (HR: 3.54; p < 0.001). Interestingly, pretransplant CKD was associated with early mortality (HR: 5.6; p < 0.001). In fact, pre- and posttransplant CKD had independent unfavorable long-term outcomes. These pretransplant factors can potentially be targeted to improve allo-HCT outcomes.
Subscribe to Journal
Get full journal access for 1 year
only $89.17 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Hahn T, Rondeau C, Shaukat A, Jupudy V, Miller A, Alam AR, et al. Acute renal failure requiring dialysis after allogeneic blood and marrow transplantation identifies very poor prognosis patients. Bone Marrow Transpl. 2003;32:405–10. https://doi.org/10.1038/sj.bmt.1704144.
Pinana JL, Valcarcel D, Martino R, Barba P, Moreno E, Sureda A, et al. Study of kidney function impairment after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. A single-center experience. Biol Blood Marrow Transpl. 2009;15:21–29. https://doi.org/10.1016/j.bbmt.2008.10.011.
Hingorani S. Renal complications of hematopoietic-cell transplantation. N Engl J Med. 2016;374:2256–67. https://doi.org/10.1056/NEJMra1404711.
Liu H, Li YF, Liu BC, Ding JH, Chen BA, Xu WL, et al. A multicenter, retrospective study of acute kidney injury in adult patients with nonmyeloablative hematopoietic SCT. Bone Marrow Transpl. 2010;45:153–8. https://doi.org/10.1038/bmt.2009.99.
Ellis MJ, Parikh CR, Inrig JK, Kanbay M, Patel UD. Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transpl. 2008;8:2378–90. https://doi.org/10.1111/j.1600-6143.2008.02408.x.
Lopes JA, Goncalves S, Jorge S, Raimundo M, Resende L, Lourenco F, et al. Contemporary analysis of the influence of acute kidney injury after reduced intensity conditioning haematopoietic cell transplantation on long-term survival. Bone Marrow Transpl. 2008;42:619–26. https://doi.org/10.1038/bmt.2008.207.
Parikh CR, McSweeney PA, Korular D, Ecder T, Merouani A, Taylor J, et al. Renal dysfunction in allogeneic hematopoietic cell transplantation. Kidney Int. 2002;62:566–73. https://doi.org/10.1046/j.1523-1755.2002.00455.x.
Parikh CR, Schrier RW, Storer B, Diaconescu R, Sorror ML, Maris MB, et al. Comparison of ARF after myeloablative and nonmyeloablative hematopoietic cell transplantation. Am J Kidney Dis. 2005;45:502–9. https://doi.org/10.1053/j.ajkd.2004.11.013.
Kersting S, Koomans HA, Hene RJ, Verdonck LF. Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival. Bone Marrow Transpl. 2007;39:359–65. https://doi.org/10.1038/sj.bmt.1705599.
Parikh CR, McSweeney P, Schrier RW. Acute renal failure independently predicts mortality after myeloablative allogeneic hematopoietic cell transplant. Kidney Int. 2005;67:1999–2005. https://doi.org/10.1111/j.1523-1755.2005.00301.x.
Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101. https://doi.org/10.1056/NEJMoa1004383.
Hingorani S. Chronic kidney disease in long-term survivors of hematopoietic cell transplantation: epidemiology, pathogenesis, and treatment. J Am Soc Nephrol. 2006;17:1995–2005. https://doi.org/10.1681/ASN.2006020118.
Jo T, Arai Y, Kondo T, Kitano T, Hishizawa M, Yamashita K, et al. Chronic kidney disease in long-term survivors after allogeneic hematopoietic stem cell transplantation: retrospective analysis at a single institute. Biol Blood Marrow Transpl. 2017;23:2159–65. https://doi.org/10.1016/j.bbmt.2017.08.016.
Ikegawa S, Matsuoka KI, Inomata T, Ikeda N, Sugiura H, Kuroi T, et al. Mild renal dysfunction defined by creatinine clearance rate has limited impact on clinical outcomes after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2018;107:568–77. https://doi.org/10.1007/s12185-017-2398-7.
Sakellari I, Barbouti A, Bamichas G, Mallouri D, Kaloyannidis P, Fragidis S, et al. GVHD-associated chronic kidney disease after allogeneic haematopoietic cell transplantation. Bone Marrow Transpl. 2013;48:1329–34. https://doi.org/10.1038/bmt.2013.55.
Shimoi T, Ando M, Munakata W, Kobayashi T, Kakihana K, Ohashi K, et al. The significant impact of acute kidney injury on CKD in patients who survived over 10 years after myeloablative allogeneic SCT. Bone Marrow Transpl. 2013;48:80–84. https://doi.org/10.1038/bmt.2012.85.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9. https://doi.org/10.1182/blood-2005-05-2004.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. modification of diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70.
Kopple JD, Greene T, Chumlea WC, Hollinger D, Maroni BJ, Merrill D, et al. Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study. Kidney Int. 2000;57:1688–703. https://doi.org/10.1046/j.1523-1755.2000.00014.x.
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012;2:1–138. https://doi.org/10.1038/kisup.2012.6.
Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transpl. 2007;40:381–7. https://doi.org/10.1038/sj.bmt.1705727.
Scrucca L, Santucci A, Aversa F. Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transpl. 2010;45:1388–95. https://doi.org/10.1038/bmt.2009.359.
Iacobelli S, Committee ES. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transpl. 2013;48:S1–37. https://doi.org/10.1038/bmt.2012.282.
Schultz LR, Peterson EL, Breslau N. Graphing survival curve estimates for time-dependent covariates. Int J Methods Psychiatr Res. 2002;11:68–74.
Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433–44. https://doi.org/10.1056/NEJMoa1706640.
Shingai N, Morito T, Najima Y, Igarashi A, Kobayashi T, Doki N, et al. Urinary liver-type fatty acid-binding protein linked with increased risk of acute kidney injury after allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:2010–4. https://doi.org/10.1016/j.bbmt.2014.08.022.
Otero A, de Francisco A, Gayoso P, Garcia F, Group ES. Prevalence of chronic renal disease in Spain: results of the EPIRCE study. Nefrologia. 2010;30:78–86. https://doi.org/10.3265/Nefrologia.pre2009.Dic.5732.
Miralbell R, Bieri S, Mermillod B, Helg C, Sancho G, Pastoors B, et al. Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. J Clin Oncol. 1996;14:579–85. https://doi.org/10.1200/JCO.1918.104.22.1689.
Stevenson WS, Nankivell BJ, Hertzberg MS. Nephrotic syndrome after stem cell transplantation. Clin Transpl. 2005;19:141–4. https://doi.org/10.1111/j.1399-0012.2004.00294.x.
Brukamp K, Doyle AM, Bloom RD, Bunin N, Tomaszewski JE, Cizman B. Nephrotic syndrome after hematopoietic cell transplantation: do glomerular lesions represent renal graft-versus-host disease? Clin J Am Soc Nephrol. 2006;1:685–94. https://doi.org/10.2215/CJN.00380705.
Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40 https://doi.org/10.1186/s13045-018-0586-4.
Naesens M, Lerut E. Calcineurin inhibitor nephrotoxicity in the era of antibody-mediated rejection. Transplantation. 2016;100:1599–600. https://doi.org/10.1097/TP.0000000000001244.
Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE. The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int. 2011;79:1361–9. https://doi.org/10.1038/ki.2011.42.
Conflict of interest
GG-G: Honoraria from Takeda and honoraria and grant from Jazz Pharmaceutical. LR: Honoraria from Janssen, Celgene, Amgen, and Takeda. The other authors do not have any conflict of interest to declare.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Gutiérrez-García, G., Villarreal, J., Garrote, M. et al. Impact of severe acute kidney injury and chronic kidney disease on allogeneic hematopoietic cell transplant recipients: a retrospective single center analysis. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-0843-3