Gout: Stamp L

Dalbeth N, Stamp L. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Semin Dial. · Pubmed #17897242 No free full text.

Abstract: Allopurinol is the mainstay of urate-lowering therapy for patients with gout and impaired renal function. Although rare, a life-threatening hypersensitivity syndrome may occur with this drug. The risk of this allopurinol hypersensitivity syndrome (AHS) is increased in renal impairment. The recognition that AHS may be because of delayed-type hypersensitivity to oxypurinol, the main metabolite of allopurinol, and that oxypurinol concentrations are frequently elevated in patients with renal impairment prescribed standard doses of allopurinol has led to the widespread adoption of allopurinol-dosing guidelines. These guidelines advocate allopurinol dose reduction according to creatinine clearance in patients with renal impairment. However, recent studies have challenged the role of these guidelines, suggesting that AHS may occur even at low doses of allopurinol, and that these guidelines lead to under-treatment of hyperuricemia, a key therapeutic target in gout. Based on current data, we advocate gradual introduction of allopurinol according to current treatment guidelines, with close monitoring of serum uric acid concentrations. In patients with severe disease and persistent hyperuricemia, allopurinol dose escalation above those recommended by the guidelines should be considered, with careful evaluation of the benefits and risks of therapy. Further work is needed to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.

Stamp L, Searle M, O'Donnell J, Chapman P. · Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand. · Drugs. · Pubmed #16392875 No free full text.

Abstract: Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor.Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined.Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone.Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function.Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.

Taylor WJ, Schumacher HR, Baraf HS, Chapman P, Stamp L, Doherty M, McQueen F, Dalbeth N, Schlesinger N, Furst DE, Vazquez-Mellado J, Mellado JV, Becker MA, Kavanaugh A, Louthrenoo W, Bardin T, Khanna D, Simon LS, Yamanaka H, Choi HK, Zeng X, Strand V, Grainger R, Clegg D, Singh JA, Diaz-Torne C, Boers M, Gow P, Barskova VG. · Department of Medicine, University of Otago, Wellington 6242, New Zealand. · Ann Rheum Dis. · Pubmed #18055475 No free full text.

Abstract: OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). METHODS: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except "total body urate pool". Additional domains were suggested and clarification sought for defining "joint inflammation" and "musculoskeletal function". Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1-2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. CONCLUSIONS: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

Stamp L, Ha L, Searle M, O'Donnell J, Frampton C, Chapman P. · Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. · Nephrology (Carlton). · Pubmed #16889578 No free full text.

Abstract: AIMS: The aims of the present audit were to determine the prevalence of gout in renal transplant recipients in Canterbury, New Zealand, to identify risk factors for gout, and to assess the range of treatments used, their efficacy and complications. In addition, the authors wished to assess the impact of post-renal transplant gout on the patient. METHODS: Patients with post-transplantation gout were identified from the Christchurch Hospital Nephrology database. For each patient with gout a post-renal transplantation recipient without gout post transplant was found matched for age, sex and date of transplant. Case notes were audited and patients interviewed. RESULTS: In total, 47/202 (23%) living renal transplant recipients had gout post transplant. Those patients with gout were more likely to be taking a loop diuretic (68%vs 34%, P < 0.001), to have a higher serum urate and impaired renal function and to have had gout prior to the transplant. Of those patients who developed gout post transplant 70% had an attack at least every 3 months. Of those who returned to work post transplant 48% required time off work because of gout. CONCLUSION: out is an important problem in the post-transplant population causing significant morbidity and time off work. Diuretics, impaired renal function, gout prior to transplantation and hyperuricaemia are important risk factors. The need for diuretic therapy should be kept under review in these patients. Hypouricaemic therapy should be considered early in those who develop gout post renal transplantation. Further studies are required to determine whether treatment for asymptomatic hyperuricaemia is justified.

Dalbeth N, Kumar S, Stamp L, Gow P. · Department of Medicine, University of Auckland, Auckland, New Zealand. · J Rheumatol. · Pubmed #16783857 No free full text.

Abstract: OBJECTIVE: Published guidelines state that allopurinol doses should be adjusted according to creatinine clearance. We investigated whether such dosing provides adequate control of hyperuricemia. METHODS: We studied 250 patients with gout attending rheumatology clinics in South Auckland from 2001 to 2004. Allopurinol dose, creatinine clearance, and serum uric acid (SUA) level were recorded. We analyzed the relationship between recommended allopurinol dose and SUA lowering to <or= 0.36 mmol/l. RESULTS: For patients taking allopurinol, 70.9% were taking recommended doses, based on published allopurinol dosing guidelines. There were 4 (1.6%) patients with cutaneous hypersensitivity reactions to allopurinol, but none of these patients were taking higher than recommended allopurinol doses. The proportion of patients achieving SUA <or= 0.36 mmol/l was lower in those taking recommended doses, compared with those taking higher than recommended doses (19% vs 38.1%; p < 0.01). CONCLUSION: Adherence to published allopurinol dosing guidelines led to suboptimal control of hyperuricemia in this population of patients with gout. Further work is required to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.

Stamp L, Gow P, Sharples K, Raill B. · Middlemore Hospital, South Auckland, New Zealand. · Aust N Z J Med. · Pubmed #11108066 No free full text.

Abstract: BACKGROUND: Gout is a common and challenging problem in South Auckland, New Zealand. Allopurinol is widely used but urate reduction remains unsatisfactory. Allopurinol dosing guidelines and a therapeutic range for plasma oxypurinol levels have been published. AIMS: We aimed to determine the appropriateness of allopurinol dosing according to current guidelines and to assess the relationship between plasma creatinine, oxypurinol and urate. In addition, we assessed the clinical usefulness of the oxypurinol level. METHODS: Thirty-one patients, on a stable dose of allopurinol for at least three weeks, had plasma creatinine, urate and oxypurinol measured as part of routine clinical assessment. Relationships between the various methods were examined using regression analysis. Fisher's exact test was used to test associations with categorical variables. RESULTS: Fifty-five per cent of patients were on higher than recommended doses of allopurinol. There was a statistically significant relationship between calculated creatinine clearance and plasma oxypurinol level. Only 50% of patients with a plasma oxypurinol within the therapeutic range (30-100 micromol/L) had a plasma urate < 0.42 mmol/L and this did not increase significantly in the patients with an oxypurinol level > 100 micromol/L. CONCLUSIONS: There is poor adherence to the current recommended dosing guidelines for allopurinol. Creatinine clearance rather than plasma creatinine needs to be used to predict the dose of allopurinol. The current role of the oxypurinol level is to identify non-compliers with allopurinol therapy. We need further research to clarify whether increasing the dose of allopurinol outside the recommended dose range to reach an oxypurinol level of close to 100 micromol/L may be of benefit in those who have not had sufficient urate reduction.