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Graft-Versus-Host Disease

GVHD-associated chronic kidney disease after allogeneic haematopoietic cell transplantation

Bone Marrow Transplantation volume 48, pages 1329–1334 (2013)Cite this article

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Abstract

Chronic kidney disease (CKD) has been related to allogeneic haematopoietic cell transplantation (HCT) as a late effect caused by a variety of factors. We retrospectively evaluated the development of CKD in 230 patients, aged 34 (5–65) years, who had undergone allogeneic HCT for haematological disease, using sibling or unrelated donors and myeloablative or reduced conditioning regimens. Pre-HCT glomerular filtration rate (GFR) was within normal limits (108±28 mL/min/1.73 m2) in patients who did not develop CKD and 95±24 mL/min/1.73 m2 in those with CKD postHCT, while the GFR 12 months post transplant declined to 104±26 and 69±19 mL/min/1.73 m2, respectively. CKD incidence was 20.4%, with a median time of development of 6 (3–18) months post transplant. On multivariate analysis, risk factors for CKD were the presence of chronic GVHD (cGVHD; P=0.001), unrelated donor transplantation (P=0.008), post-transplant event of acute kidney injury (AKI) (P=0.002) and older age (P=0.002). In long-term survivors stable significant predictors for CKD were older age at transplantation, cGVHD and AKI. CKD did not influence non-relapse mortality. In our study, cGVHD emerges as an important cause of kidney injury in HCT survivors, regardless of administration of nephrotoxic agents.

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References

  1. Gratwohl A, Baldomero H, Frauendorfer K, Rocha V, Apperley J, Niederwieser D . The EBMT activity survey 2006 on hematopoietic stem cell transplantation: focus on the use of cord blood products. Bone Marrow Transplant 2008; 41: 687–705.

    Article  CAS  Google Scholar 

  2. Tichelli A, Rovo A, Gratwohl A . Late pulmonary, cardiovascular, and renal complications after hematopoietic stem cell transplantation and recommended screening practices. Hematology Am Soc Hematol Educ Program 2008, 125–133.

    Article  Google Scholar 

  3. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31.

    Article  Google Scholar 

  4. Ellis MJ, Parikh CR, Inrig JK, Kanbay M, Patel UD . Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 2008; 8: 2378–2390.

    Article  CAS  Google Scholar 

  5. Abboud I, Peraldi MN, Hingorani S . Chronic kidney diseases in long-term survivors after allogeneic hematopoietic stem cell transplantation: monitoring and management guidelines. Semin Hematol 2012; 49: 73–82.

    Article  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. Kersting S, Hene RJ, Koomans HA, Verdonck LF . Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 1169–1175.

    Article  Google Scholar 

  8. Al-Hazzouri A, Cao Q, Burns LJ, Weisdorf DJ, Majhail NS . Similar risks for chronic kidney disease in long-term survivors of myeloablative and reduced-intensity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2008; 14: 658–663.

    Article  Google Scholar 

  9. Darmon M, Ciroldi M, Thiery G, Schlemmer B, Azoulay E . Clinical review: specific aspects of acute renal failure in cancer patients. Crit Care 2006; 10: 211.

    Article  Google Scholar 

  10. Ando M, Ohashi K, Akiyama H, Sakamaki H, Morito T, Tsuchiya K et al. Chronic kidney disease in long-term survivors of myeloablative allogeneic haematopoietic cell transplantation: prevalence and risk factors. Nephrol Dial Transplant 2010; 25: 278–282.

    Article  Google Scholar 

  11. Ishani A, Xue JL, Himmelfarb J, Eggers PW, Kimmel PL, Molitoris BA et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 2009; 20: 223–228.

    Article  Google Scholar 

  12. Touzot M, Elie C, van Massenhove J, Maillard N, Buzyn A, Fakhouri F . Long-term renal function after allogenic haematopoietic stem cell transplantation in adult patients: a single-center study. Nephrol Dial Transplant 2010; 25: 624–627.

    Article  Google Scholar 

  13. Gruss E, Bernis C, Tomas JF, Garcia-Canton C, Figuera A, Motellon JL et al. Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome. Am J Nephrol 1995; 15: 473–479.

    Article  CAS  Google Scholar 

  14. Hingorani SR, Guthrie K, Batchelder A, Schoch G, Aboulhosn N, Manchion J et al. Acute renal failure after myeloablative hematopoietic cell transplant: incidence and risk factors. Kidney Int 2005; 67: 272–277.

    Article  Google Scholar 

  15. Lamas S . Cellular mechanisms of vascular injury mediated by calcineurin inhibitors. Kidney Int 2005; 68: 898–907.

    Article  CAS  Google Scholar 

  16. Kersting S, Dorp SV, Theobald M, Verdonck LF . Acute renal failure after nonmyeloablative stem cell transplantation in adults. Biol Blood Marrow Transplant 2008; 14: 125–131.

    Article  CAS  Google Scholar 

  17. 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 Transplant 2009; 15: 21–29.

    Article  CAS  Google Scholar 

  18. 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: 579–585.

    Article  CAS  Google Scholar 

  19. Weiss AS, Sandmaier BM, Storer B, Storb R, McSweeney PA, Parikh CR . Chronic kidney disease following non-myeloablative hematopoietic cell transplantation. Am J Transplant 2006; 6: 89–94.

    Article  CAS  Google Scholar 

  20. Abboud I, Porcher R, Robin M, de Latour RP, Glotz D, Socie G et al. Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15: 1251–1257.

    Article  CAS  Google Scholar 

  21. Nieder ML, McDonald GB, Kida A, Hingorani S, Armenian SH, Cooke KR et al. National Cancer Institute-National Heart, Lung and Blood Institute/pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: long-term organ damage and dysfunction. Biol Blood Marrow Transplant 2011; 17: 1573–1584.

    Article  Google Scholar 

  22. Kansu E . The pathophysiology of chronic graft-versus-host disease. Int J Hematol 2004; 79: 209–215.

    Article  Google Scholar 

  23. Kitamura M, Suto TS . TGF-beta and glomerulonephritis: anti-inflammatory versus prosclerotic actions. Nephrol Dial Transplant 1997; 12: 669–679.

    Article  CAS  Google Scholar 

  24. Negri AL . Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents. J Nephrol 2004; 17: 496–503.

    CAS  PubMed  Google Scholar 

  25. Seconi J, Watt V, Ritchie DS . Nephrotic syndrome following allogeneic stem cell transplantation associated with increased production of TNF-alpha and interferon-gamma by donor T cells. Bone Marrow Transplant 2003; 32: 447–450.

    Article  CAS  Google Scholar 

  26. Takatsuka H, Takemoto Y, Yamada S, Wada H, Tamura S, Fujimori Y et al. Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome. Bone Marrow Transplant 2000; 26: 419–426.

    Article  CAS  Google Scholar 

  27. Biedermann BC, Sahner S, Gregor M, Tsakiris DA, Jeanneret C, Pober JS et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet 2002; 359: 2078–2083.

    Article  Google Scholar 

  28. Disel U, Paydas S, Dogan A, Gulfiliz G, Yavuz S . Effect of colchicine on cyclosporine nephrotoxicity, reduction of TGF-beta overexpression, apoptosis, and oxidative damage: an experimental animal study. Transplant Proc 2004; 36: 1372–1376.

    Article  CAS  Google Scholar 

  29. Cohen EP . Radiation nephropathy after bone marrow transplantation. Kidney Int 2000; 58: 903–918.

    Article  CAS  Google Scholar 

  30. Lonnerholm G, Carlson K, Bratteby LE, Backlund L, Hagberg H, Rikner G et al. Renal function after autologous bone marrow transplantation. Bone Marrow Transplant 1991; 8: 129–134.

    CAS  PubMed  Google Scholar 

  31. Molteni A, Moulder JE, Cohen EP, Fish BL, Taylor JM, Veno PA et al. Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker. Exp Biol Med (Maywood) 2001; 226: 1016–1023.

    Article  CAS  Google Scholar 

  32. Van Why SK, Friedman AL, Wei LJ, Hong R . Renal insufficiency after bone marrow transplantation in children. Bone Marrow Transplant 1991; 7: 383–388.

    CAS  PubMed  Google Scholar 

  33. Delgado JF, Crespo-Leiro MG, Gomez-Sanchez MA, Paniagua MJ, Gonzalez-Vilchez F, Vazquez de Prada JA et al. Risk factors associated with moderate-to-severe renal dysfunction among heart transplant patients: results from the CAPRI study. Clin Transplant 2010; 24: E194–E200.

    Article  Google Scholar 

  34. Frisk P, Arvidson J, Neveus T . Glomerular and tubular function in young adults treated with stem-cell transplantation in childhood. Pediatr Nephrol 2010; 25: 1337–1342.

    Article  Google Scholar 

  35. Gronroos MH, Bolme P, Winiarski J, Berg UB . Long-term renal function following bone marrow transplantation. Bone Marrow Transplant 2007; 39: 717–723.

    Article  CAS  Google Scholar 

  36. Choi M, Sun CL, Kurian S, Carter A, Francisco L, Forman SJ et al. Incidence and predictors of delayed chronic kidney disease in long-term survivors of hematopoietic cell transplantation. Cancer 2008; 113: 1580–1587.

    Article  Google Scholar 

  37. Glezerman IG, Jhaveri KD, Watson TH, Edwards AM, Papadopoulos EB, Young JW et al. Chronic kidney disease, thrombotic microangiopathy, and hypertension following T cell-depleted hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2010; 16: 976–984.

    Article  Google Scholar 

  38. Kist-van Holthe JE, Bresters D, Ahmed-Ousenkova YM, Goedvolk CA, Abbink FC, Wolterbeek R et al. Long-term renal function after hemopoietic stem cell transplantation in children. Bone Marrow Transplant 2005; 36: 605–610.

    Article  CAS  Google Scholar 

  39. Leung JC, Chan LY, Tang SC, Lam MF, Chow CW, Lim AI et al. Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone. J Transl Med 2011; 9: 169.

    Article  CAS  Google Scholar 

  40. Miralbell R, Sancho G, Bieri S, Carrio I, Helg C, Brunet S et al. Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment. Int J Radiat Oncol Biol Phys 2004; 58: 809–816.

    Article  Google Scholar 

  41. Koenecke C, Hertenstein B, Schetelig J, van Biezen A, Dammann E, Gratwohl A et al. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT. Am J Transplant 2010; 10: 1897–1906.

    Article  CAS  Google Scholar 

  42. Hingorani SR, Seidel K, Lindner A, Aneja T, Schoch G, McDonald G . Albuminuria in hematopoietic cell transplantation patients: prevalence, clinical associations, and impact on survival. Biol Blood Marrow Transplant 2008; 14: 1365–1372.

    Article  Google Scholar 

  43. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 2003; 139: 244–252.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Haematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece

    I Sakellari, A Barbouti, D Mallouri, P Kaloyannidis, I Batsis, C Apostolou, A Karpouza, E Yannaki, C Smias & A Anagnostopoulos

  2. Nephrology Department, George Papanicolaou Hospital, Thessaloniki, Greece

    G Bamichas, S Fragidis & K Sombolos

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  1. I Sakellari
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Sakellari, I., Barbouti, A., Bamichas, G. et al. GVHD-associated chronic kidney disease after allogeneic haematopoietic cell transplantation. Bone Marrow Transplant 48, 1329–1334 (2013). https://doi.org/10.1038/bmt.2013.55

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