Hyperuricemia and gout in renal transplant recipients
- Michael A Becker, MD
Michael A Becker, MD
- Section Editor — Crystal Diseases
- Professor Emeritus of Medicine
- University of Chicago Pritzker School of Medicine
- Section Editor
- Daniel C Brennan, MD, FACP
Daniel C Brennan, MD, FACP
- Editor-in-Chief — Nephrology
- Section Editor — Renal Transplantation
- Professor of Medicine
- Medical Director and Co-Director of the Comprehensive Transplant Center, Department of Internal Medicine, Division of Nephrology
- Johns Hopkins Medical School
●The incidence of hyperuricemia in one study of renal transplant recipients was 84 percent in those treated with cyclosporine versus 30 percent in patients treated with azathioprine and prednisone .
●In a retrospective cohort study, there was an increased relative risk of new-onset gout with Neoral compared with tacrolimus (adjusted hazard ratio [HR] 1.25, 95% CI 1.07-1.47) .
The lower glomerular filtration rate (GFR) induced by cyclosporine probably contributes to uric acid retention , but tubular damage may also be important by impairing urate secretion . Concurrent diuretic use and renal insufficiency due to rejection are other risk factors for hyperuricemia . (See "Diuretic-induced hyperuricemia and gout".)
Renal insufficiency predisposes to hyperuricemia and gout . Patients with end-stage renal disease (ESRD) treated with maintenance dialysis, however, may be at lesser risk for symptomatic gout. Despite persistent hyperuricemia, patients with previous gouty arthritis note a marked reduction in symptomatic episodes, and de novo gout is a rare event . Why this occurs and whether it is applicable to transplant recipients are not clear; it is possible that the anti-inflammatory effect of persistent uremia is an important protective factor [7,8].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Lin HY, Rocher LL, McQuillan MA, et al. Cyclosporine-induced hyperuricemia and gout. N Engl J Med 1989; 321:287.
- Noordzij TC, Leunissen KM, Van Hooff JP. Renal handling of urate and the incidence of gouty arthritis during cyclosporine and diuretic use. Transplantation 1991; 52:64.
- Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol 2000; 11:974.
- Deray G, Benhmida M, Le Hoang P, et al. Renal function and blood pressure in patients receiving long-term, low-dose cyclosporine therapy for idiopathic autoimmune uveitis. Ann Intern Med 1992; 117:578.
- Abbott KC, Kimmel PL, Dharnidharka V, et al. New-onset gout after kidney transplantation: incidence, risk factors and implications. Transplantation 2005; 80:1383.
- Krishnan E. Reduced glomerular function and prevalence of gout: NHANES 2009-10. PLoS One 2012; 7:e50046.
- Ifudu O, Tan CC, Dulin AL, et al. Gouty arthritis in end-stage renal disease: clinical course and rarity of new cases. Am J Kidney Dis 1994; 23:347.
- Schreiner O, Wandel E, Himmelsbach F, et al. Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients? Nephrol Dial Transplant 2000; 15:644.
- Burack DA, Griffith BP, Thompson ME, Kahl LE. Hyperuricemia and gout among heart transplant recipients receiving cyclosporine. Am J Med 1992; 92:141.
- Simkin PA, Gardner GC. Colchicine use in cyclosporine treated transplant recipients: how little is too much? J Rheumatol 2000; 27:1334.
- Rana SS, Giuliani MJ, Oddis CV, Lacomis D. Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients. Clin Neurol Neurosurg 1997; 99:266.
- Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken) 2012; 64:1447.
- Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353:2450.
- Febuxostat [Package Insert]. Deerfield, IL: Takeda Pharmaceuticals North America, Inc. 2009.
- Elion GB, Callahan S, Nathan H. Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem Pharmacol 1963; 12:85.
- Ragab AH, Gilkerson E, Myers M. The effect of 6-mercaptopurine and allopurinol on granulopoiesis. Cancer Res 1974; 34:2246.
- Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2006; 65:1312.
- Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 2012; 64:1431.
- Fam AG. Xanthine oxidase inhibitors. In: Crystal-Induced Arthropathies. Gout, Psuedogout and Apatite-Associated Sydnromes, Wortmann RL. Schumacher HR Jr, Becker MA, Ryan LM (Eds), Taylor & Francis, New York 2006. p.381.
- Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76:47.
- Dalbeth N, Kumar S, Stamp L, Gow P. Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout. J Rheumatol 2006; 33:1646.
- Vázquez-Mellado J, Morales EM, Pacheco-Tena C, Burgos-Vargas R. Relation between adverse events associated with allopurinol and renal function in patients with gout. Ann Rheum Dis 2001; 60:981.
- Stamp L, O'Donnell JL, Zhang M, et al. Increasing allopurinol dose above the recommended range is effective and safe in chronic gout, including those with renal impairment. Arthritis Rheum 2009; 60:1950.
- Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA 2011; 306:711.
- Lipsky PE, Calabrese LH, Kavanaugh A, et al. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res Ther 2014; 16:R60.
- Enomoto A, Kimura H, Chairoungdua A, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 2002; 417:447.
- Minghelli G, Seydoux C, Goy JJ, Burnier M. Uricosuric effect of the angiotensin II receptor antagonist losartan in heart transplant recipients. Transplantation 1998; 66:268.
- Kamper AL, Nielsen AH. Uricosuric effect of losartan in patients with renal transplants. Transplantation 2001; 72:671.
- Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005; 102:4134.
- Zürcher RM, Bock HA, Thiel G. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study. Nephrol Dial Transplant 1994; 9:548.
- Perez-Ruiz F, Calabozo M, Fernandez-Lopez MJ, et al. Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. J Clin Rheumatol 1999; 5:49.
- Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237.
- So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007; 9:R28.
- Schumacher HR Jr, Sundy JS, Terkeltaub R, et al. Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2012; 64:876.
- Schumacher HR Jr, Evans RR, Saag KG, et al. Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study. Arthritis Care Res (Hoboken) 2012; 64:1462.
- Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012; 71:1839.
- Acute gouty arthritis and gout flare prophylaxis
- - Colchicine
- - Nonsteroidal anti-inflammatory agents
- - Increased glucocorticoid dose
- Urate-lowering therapy
- - Xanthine oxidase inhibitors
- Modified mammalian recombinant uricase
- - Pegloticase
- Uricosuric agents
- - Probenecid or sulfinpyrazone
- - Losartan
- - Benzbromarone
- Investigational agents