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
●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].
- 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