Advertisement
American Journal of Kidney Diseases

Tumor Lysis Syndrome and Acute Kidney Injury: Evaluation, Prevention, and Management

      Tumor lysis syndrome (TLS) describes a constellation of biochemical and clinical abnormalities resulting from rapid and massive tumor cell death. TLS is frequently associated with hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia that may lead to serious clinical complications, including acute kidney injury and cardiac arrest. Identification of tumor- and patient-specific risk factors for TLS and early recognition of laboratory and clinical TLS based on established criteria are essential for preventing TLS and forestalling acute kidney injury. Early collaboration between oncologists and nephrologists will help improve assessment of patients' kidney function and risk factors, paving the way for timely and efficacious interventions.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mehta R.L.
        • Kellum J.A.
        • Shah S.V.
        • et al.
        Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.
        Crit Care. 2007; 11: R31
        • National Kidney Foundation
        Definition and classification of stages of chronic kidney disease.
        Am J Kidney Dis. 2002; 39: S46-S75
        • Hande K.R.
        • Garrow G.C.
        Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.
        Am J Med. 1993; 94: 133-139
        • Cairo M.S.
        • Bishop M.
        Tumour lysis syndrome: new therapeutic strategies and classification.
        Br J Haematol. 2004; 127: 3-11
        • Bessmertny O.
        • Robitaille L.M.
        • Cairo M.S.
        Rasburicase: a new approach for preventing and/or treating tumor lysis syndrome.
        Curr Pharm Des. 2005; 11: 4177-4185
        • Coiffier B.
        • Altman A.
        • Pui C.-H.
        • Younes A.
        • Cairo M.S.
        Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.
        J Clin Oncol. 2008; 26: 2767-2778
        • Leblanc M.
        • Kellum J.A.
        • Gibney R.T.
        • Lieberthal W.
        • Tumlin J.
        • Mehta R.
        Risk factors for acute renal failure: inherent and modifiable risks.
        Curr Opin Crit Care. 2005; 11: 533-536
        • Hsu C.Y.
        • Ordoñez J.D.
        • Chertow G.M.
        • Fan D.
        • McCulloch C.E.
        • Go A.S.
        The risk of acute renal failure in patients with chronic kidney disease.
        Kidney Int. 2008; 74: 101-107
        • Montesinos P.
        • Lorenzo I.
        • Martin G.
        • et al.
        Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model.
        Haematologica. 2008; 93: 67-74
        • Mato A.R.
        • Riccio B.E.
        • Qin L.
        • et al.
        A predictive model for the detection of tumor lysis syndrome during AML induction therapy.
        Leuk Lymphoma. 2006; 47: 877-883
        • Seidemann K.
        • Meyer U.
        • Jansen P.
        • et al.
        • BFM-Study Group
        Impaired renal function and tumor lysis syndrome in pediatric patients with non-Hodgkin's lymphoma and B-ALL.
        Klin Pädiatr. 1998; 210: 279-284
        • Annemans L.
        • Moeremans K.
        • Lamotte M.
        • et al.
        Incidence, medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin's lymphoma in four European countries.
        Leuk Lymphoma. 2003; 44: 77-83
        • Cairo M.S.
        • Gerrard M.
        • Sposto R.
        • et al.
        • FAB LMB96 International Study Committee
        Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents.
        Blood. 2007; 109: 2736-2743
        • Jeha S.
        • Kantarjian H.
        • Irwin D.
        • et al.
        Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial.
        Leukemia. 2005; 19: 34-38
        • Coiffier B.
        • Mounier N.
        • Bologna S.
        • et al.
        • Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma
        Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study.
        J Clin Oncol. 2003; 21: 4402-4406
        • Hochberg J.
        • Cairo M.S.
        Tumor lysis syndrome: current perspective.
        Haematologica. 2008; 93: 9-13
        • Potter J.L.
        • Silvidi A.A.
        Xanthine lithiasis, nephrocalcinosis, and renal failure in a leukemia patient treated with allopurinol.
        Clin Chem. 1987; 33: 2314-2316
        • Pumo V.
        • Sciacca D.
        • Malaguarnera M.
        Tumor lysis syndrome in elderly.
        Crit Rev Oncol Hematol. 2007; 64: 31-42
        • Roncal C.A.
        • Mu W.
        • Croker B.
        • et al.
        Effect of elevated serum uric acid on cisplatin-induced acute renal failure.
        Am J Physiol Renal Physiol. 2007; 292: F116-F122
        • Shimada M.
        • Johnson R.J.
        • May Jr, W.S.
        • et al.
        A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome.
        Nephrol Dial Transplant. 2009; 24: 2960-2964
        • Kanfer A.
        • Richet G.
        • Roland J.
        • Chatelet F.
        Extreme hyperphosphataemia causing acute anuric nephrocalcinosis in lymphosarcoma.
        Br Med J. 1979; 1: 1320-1321
        • Boles J.M.
        • Dutel J.L.
        • Briere J.
        • et al.
        Acute renal failure caused by extreme hyperphosphatemia after chemotherapy of an acute lymphoblastic leukemia.
        Cancer. 1984; 53: 2425-2429
        • Markowitz G.S.
        • Stokes M.B.
        • Radhakrishnan J.
        • D'Agati V.D.
        Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure.
        J Am Soc Nephrol. 2005; 16: 3389-3396
        • Hebert L.A.
        • Lemann Jr, J.
        • Petersen J.R.
        • Lennon E.J.
        Studies of the mechanism by which phosphate infusion lowers serum calcium concentration.
        J Clin Invest. 1966; 45: 1886-1894
        • Schmitt R.
        • Coca S.
        • Kanbay M.
        • Tinetti M.E.
        • Cantley L.G.
        • Parikh C.R.
        Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis.
        Am J Kidney Dis. 2008; 52: 262-271
        • Coresh J.
        • Astor B.C.
        • Greene T.
        • Eknoyan G.
        • Levey A.S.
        Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.
        Am J Kidney Dis. 2003; 41: 1-12
        • Chonchol M.
        • Shlipak M.G.
        • Katz R.
        • et al.
        Relationship of uric acid with progression of kidney disease.
        Am J Kidney Dis. 2007; 50: 239-247
        • Candrilli S.
        • Bell T.
        • Irish W.
        • Morris E.
        • Goldman S.
        • Cairo M.S.
        A comparison of inpatient length of stay and costs among patients with hematologic malignancies (excluding Hodgkin disease) associated with and without acute renal failure.
        Clin Lymphoma Myeloma. 2008; 8: 44-51
        • Conger J.D.
        • Falk S.A.
        Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.
        J Clin Invest. 1977; 59: 786-793
        • Jones D.P.
        • Mahmoud H.
        • Chesney R.W.
        Tumor lysis syndrome: pathogenesis and management.
        Pediatr Nephrol. 1995; 9: 206-212
        • Andreoli S.P.
        • Clark J.H.
        • McGuire W.A.
        • Bergstein J.M.
        Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: relationship to acute renal failure.
        J Pediatr. 1986; 109: 292-298
        • Silverman P.
        • Distelhorst C.W.
        Metabolic emergencies in clinical oncology.
        Semin Oncol. 1989; 16: 504-515
        • Weisberg L.S.
        Management of severe hyperkalemia.
        Crit Care Med. 2008; 36: 3246-3251
        • Smalley R.V.
        • Guaspari A.
        • Haase-Statz S.
        • Anderson S.A.
        • Cederberg D.
        • Hohneker J.A.
        Allopurinol: intravenous use for prevention and treatment of hyperuricemia.
        J Clin Oncol. 2000; 18: 1758-1763
      1. Elitek [package insert].
        Sanofi-Aventis US LLC, Bridgewater, NJ2009
        • Pui C.-H.
        • Mahmoud H.H.
        • Wiley J.M.
        • et al.
        Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma.
        J Clin Oncol. 2001; 19: 697-704
        • Goldman S.C.
        • Holcenberg J.S.
        • Finklestein J.Z.
        • et al.
        A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis.
        Blood. 2001; 97: 2998-3003
      2. Cortes J, Seiter K, Maziarz RT, et al. Superiority of rasburicase versus allopurinol on serum uric acid control in adult patients with hematological malignancies at risk of developing tumor lysis syndrome: results of a randomized comparative phase III study. Program and abstracts of the 50th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2008; San Francisco, CA. Abstract 919.

        • Hummel M.
        • Reiter S.
        • Adam K.
        • Hehlmann R.
        • Buchheidt D.
        Effective treatment and prophylaxis of hyperuricemia and impaired renal function in tumor lysis syndrome with low doses of rasburicase.
        Eur J Haematol. 2008; 80: 331-336
        • Hershfield M.S.
        Reassessing serum urate targets in the management of refractory gout: can you go too low?.
        Curr Opin Rheumatol. 2009; 21: 138-142
        • Seegmiller J.E.
        Xanthine stone formation.
        Am J Med. 1968; 45 (780-773)
        • Browning L.A.
        • Kruse J.A.
        Hemolysis and methemoglobinemia secondary to rasburicase administration.
        Ann Pharmacother. 2005; 39: 1932-1935
        • Borinstein S.C.
        • Xu M.
        • Hawkins D.S.
        Methemoglobinemia and hemolytic anemia caused by rasburicase administration in a newly diagnosed child with Burkitt lymphoma/leukemia [letter].
        Pediatr Blood Cancer. 2008; 50: 189
        • Góth L.
        • Bigler N.W.
        Catalase deficiency may complicate urate oxidase (rasburicase) therapy.
        Free Radic Res. 2007; 41: 953-955
        • Howard S.C.
        • Ribeiro R.C.
        • Pui C.-H.
        Acute complications.
        in: Pui C.-H. Childhood Leukemias. 2nd ed. Cambridge University Press, New York2006: 709-738
        • Ten Harkel A.D.J.
        • Kist-Van Holthe J.E.
        • Van Weel M.
        • Van der Vorst M.M.
        Alkalinization and the tumor lysis syndrome.
        Med Pediatr Oncol. 1998; 31: 27-28
        • Prince M.R.
        • Zhang H.
        • Morris M.
        • et al.
        Incidence of nephrogenic systemic fibrosis at two large medical centers.
        Radiology. 2008; 248: 807-816
        • Kjellstrand C.M.
        • Campbell II, D.C.
        • von Hartitzsch B.
        • Buselmeier T.J.
        Hyperuricemic acute renal failure.
        Arch Intern Med. 1974; 133: 349-359
        • Saccente S.L.
        • Kohaut E.C.
        • Berkow R.L.
        Prevention of tumor lysis syndrome using continuous veno-venous hemofiltration.
        Pediatr Nephrol. 1995; 9: 569-573
        • Agha-Razii M.
        • Amyot S.L.
        • Pichette V.
        • Cardinal J.
        • Ouimet D.
        • Leblanc M.
        Continuous veno-venous hemodiafiltration for the treatment of spontaneous tumor lysis syndrome complicated by acute renal failure and severe hyperuricemia.
        Clin Nephrol. 2000; 54: 59-63
        • Choi K.A.
        • Lee J.E.
        • Kim Y.-G.
        • et al.
        Efficacy of continuous venovenous hemofiltration with chemotherapy in patients with Burkitt lymphoma and leukemia at high risk of tumor lysis syndrome.
        Ann Hematol. 2009; 88: 639-645
        • Coca S.G.
        • Peixoto A.J.
        • Garg A.X.
        • Krumholz H.M.
        • Parikh C.R.
        The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis.
        Am J Kidney Dis. 2007; 50: 712-720
        • Schiffl H.
        Renal recovery from acute tubular necrosis requiring renal replacement therapy: a prospective study in critically ill patients.
        Nephrol Dial Transplant. 2006; 21: 1248-1252
        • Ponte B.
        • Felipe C.
        • Muriel A.
        • Tenorio M.T.
        • Liaño F.
        Long-term functional evolution after an acute kidney injury: a 10-year study.
        Nephrol Dial Transplant. 2008; 23: 3859-3866
        • Hsu C.Y.
        • Chertow G.M.
        • McCulloch C.E.
        • Fan D.
        • Ordoñez J.D.
        • Go A.S.
        Nonrecovery of kidney function and death after acute on chronic renal failure.
        Clin J Am Soc Nephrol. 2009; 4: 891-898