Abstract
Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use.
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Stamp L, Ha L, Searle M, et al. Gout in renal transplant recipients. Nephrology. 2006;11:367–71.
Stamp L, Searle M, O’Donnell J, Chapman P. Gout in solid organ transplantation: a challenging clinical problem. Drugs. 2005;65:2593–611.
Cea-Soriano L, Rothenbache D, Choi H, García Rodríguez L. Contemporary epidemiology of gout in the UK general population. Arthritis Res Ther. 2011;13:R39.
•• Singh J, Reddy S, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheum. 2011;23:192–202. This review highlights the evidence for key risk factors for gout, including dietary factors, alcohol, and medications.
• Zawiasa A, Szklarek-Kubicka M, Fijałkowska-Morawska J, et al. Effect of oral fructose load on serum uric acid and lipids in kidney transplant recipients treated with cyclosporine or tacrolimus. Transplant Proc. 2009;41:188–91. Dietary fructose recently has been recognized as having important effects on SU. This is the only study examining the effects of oral fructose on patients with kidney transplants. It clearly documents a rise in SU with an oral fructose load, with no difference between patients on tacrolimus or cyclosporine.
Barrera Pulido L, Álamo Martínez J, Pareja Ciuró F, et al. Efficacy and safety of mycophenolate mofetil monotherapy in liver transplant patients with renal failure induced by calcineurin inhibitors. Transplant Proc. 2008;40:2985–7.
Urbizu J, Zarraga S, Gomez-Ullate P, et al. Safety and efficacy of tacrolimus rescue therapy in 55 kidney transplant recipients treated with cyclosporin. Transplant Proc. 2003;35:1704–5.
Trück, Laube G, von Vigier R, Goetschel P. Gout in pediatric renal transplant recipients. Pediatr Nephrol. 2010;25:2535–8.
Cohen M, Cohen E. Enthesopathy and atypical gouty arthritis following renal transplantation: a case controlled study. Revue du Rheumatisme (English edition). 1995;62:86–90.
Peeters P, Sennesael J. Low-back pain caused by spinal tophus—a complication of gout in a kidney transplant recipient. Nephrol Dial Transplant. 1998;13:3245–7.
Chan P, Seeger L, Motamedi K, Chan J. Tophaceous gout of the first costochondral junction in a heart transplant patient. Skeletal Radiol. 2006;35:684–6.
Weng C, Liu M, Lin L, et al. Rare coexistence of gouty and septic arthritis; a report of 14 cases. Clin Exp Rheumatol. 2009;27:902–6.
Baker J, Stonecypher M. Coexistence of oligo-articular gout and Mycobacterium kansasii joint and bursal infection in a patient with an orthotopic heart transplant. Clin Exp Rheumatol. 2009;27:843–5.
Gambaro G, Perazella M. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J Int Med. 2003;253:643–52.
Naesens M, Kuypers D, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4:481–508.
Terkeltaub R, Furst D, Bennett K, et al. Colchicine efficacy assessed by time to reduction of pain is comparable in low dose and high dose regimens: secondary analyses of the AGREE trial. Arthritis Rheum. 2010;62:1060–8.
Wallace S, Singer J, Duncan G, et al. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol. 1991;18:264–9.
Wluka A, Ryan P, Miller A, et al. Post-cardiac transplantation gout: incidence and therapeutic complications. J Heart Lung Transplant. 2000;19:951–6.
Ducloux D, Schuller V, Bresson-Vautrin, Chalopin J. Colchicine myopathy in renal transplant recipients on cyclosporin. Nephrol Dial Transplant. 1997;12:2389–92.
Pope R, Tschopp J. The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheum. 2007;56:3183–8.
So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis. Results of a multicenter, phase II, dose ranging study. Arthritis Rheum. 2010;62:3064–76.
• Wanderer A. Rationale and timeliness for IL-1beta-targeted therapy to reduce allogenic organ injury at procurement and to diminish risk of rejection after transplantation. Clin Transplant. 2010;24:301–11. This review examines the evidence for IL-1 inhibition in patients with kidney transplants and highlights the potential role for IL-1 inhibition in preventing transplant rejection. Although this paper has no reference to gout, it provides background evidence for considering further studies of IL-1 inhibition in transplant recipients with gout.
Li-Yu J, Clayburne G, Sieck M, et al. Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? J Rheumatol. 2001;28:577–80.
Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricaemic therapy. Arthritis Care Res. 2004;51:321–5.
Navascues R, Gomez E, Rodriguez M, et al. Safety of the allopurinol-mycophenolate mofetil combination in the treatment of hyperuricaemia of kidney transplant recipients. Nephron. 2002;91:173–4.
Stevens S, Goldman M. Cyclosporin toxicity associated with allopurinol. South Med J. 1992;85:1265–6.
Perez-Ruiz F, Gomez-Ullate P, Amenabar J, et al. Long-term efficacy of hyperuricaemia treatment in renal transplant recipients. Nephrol Dial Transplant. 2003;18:603–6.
Hande K, Noone R, Stone W. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76:47–56.
Dalbeth N, Kumar S, Stamp LK, Gow P. Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricaemia in patients with gout. J Rheumatol. 2006;33:1646–50.
•• Stamp L, O’Donnell J, Zhang M, et al. Using allopurinol above the dose based on creatinine clearance is effective and safe in chronic gout, including in those with renal impairment. Arthritis Rheum. 2011;63:412–21. This study reports the efficacy and safety of treating to target SU in patients with gout. Although transplant recipients were not included, patients with renal impairment were successfully treated with higher-than-CrCL-based doses of allopurinol. Although specific studies in transplant recipients are required, this paper provides evidence for such an approach in this difficult-to-treat group.
Zurcher R, Bock H, Thiel G. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A treated renal transplant patients: a prospective study. Nephrol Dial Transplant. 1994;9:548–51.
Masbernard A, Giudicelli C. Ten years experience with benzbromarone in then management of gout and hyperuricaemia. South African Med J. 1981;59:701–6.
Lee M-H, Graham G, Williams K, Day R. A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interests of patients? Drug Safety. 2008;31:643–65.
Baraf H, Matsumoto A, Maroli A, Waltrip R. Resolution of gouty tophi after 12 weeks of pegloticase treatment. Arthritis Rheum. 2008;58:3632–4.
Becker M, Treadwell E, Baraf H, et al. Immunoreactivity and clinical response to pegloticase (PGL): pooled data from GOUT1 and GOUT2, PGL phase 3 randomised, doubleblind, placebo controlled trials. Arthritis Rheum. 2008;58:S880.
Rozenberg S, Koeger A, Bourgeois P. Urate oxidase for gouty arthritis in cardiac transplant recipients. J Rheumatol. 1993;20:2171.
Ippoliti G, Negri M, Campana C, Vigano M. Urate oxidase in hyperuricaemic heart transplant recipients treated with azathioprine. Transplantation. 1997;63:1370–1.
Burnier M, Rutschmann B, Nussberger J, et al. Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects. Hypertension. 1993;22:339–47.
Milionis H, Kakafika A, Tsouli S, et al. Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia. Am Heart J. 2004;148:635–40.
Melenovsky V, Malik J, Wichterle D, et al. Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. Am Heart J. 2002;144:e6.
Yamamoto T, Moriwaki Y, Takahashi S, et al. Effect of fenofibrate on plasma concentration and urinary excretion of purine bases and oxypurinol. J Rheumatol. 2001;28:2294–7.
Takahashi S, Moriwaki Y, Yamamoto T, et al. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis. 2003;62:572–5.
Broeders N, Knoop C, Antoine M, et al. Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent? Nephrol Dial Transplant. 2000;15:1993–9.
Sugioka N, Takai M, Yoshida K, et al. Effects of plasma uric acid on pharmacokinetics of cyclosporine A in living-related renal transplant recipients and pharmacokinetic study in rats with experimental hyperuricaemia. J Clin Pharm Ther. 2010;35:323–32.
•• Bandukwala F, Huang M, Zaltzman J, et al. Association of uric acid with inflammation, progressive allograft dysfunction and post-transplant cardiovascular risk. Am J Cardiol. 2009;103:867–71. This study examines the relationship among SU, renal transplant function, and cardiovascular disease in 405 patients. Hyperuricemia (SU >6.1 mg/dL) was negatively correlated with glomerular filtration rate (P<0.0001) and positively associated with diuretic use (P=0.013) and time since transplantation. Importantly, those with hyperuricemia had significantly more cardiovascular events than those with normouricemia (P<0.001).
Siu Y-P, Leung K-T, Tong M, Kwan T-H. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kid Dis. 2006;47:51–9.
Goicoechea M, de Vinuesa S, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5:1388–93.
Neal D, Tom B, Gimson A, et al. Hyperuricaemia, gout and renal function after liver transplantation. Transplantation. 2001;72:1689–91.
• Krishnan E, Sokolove J. Uric acid in heart disease: a new C-reactive protein. Curr Opin Rheum. 2011;23:174–77. This review highlights the evidence linking uric acid and cardiovascular disease in the general population.
Luk AJ, Levin GP, Moore EE, et al. Allopurinol and mortality in hyperuricaemic patients. Rheumatology. 2009;48:804–6.
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Stamp, L.K., Chapman, P.T. Gout and Organ Transplantation. Curr Rheumatol Rep 14, 165–172 (2012). https://doi.org/10.1007/s11926-012-0235-9
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DOI: https://doi.org/10.1007/s11926-012-0235-9