Gout, Tophi and the Kidneys (PRA 2011 Presentation Part 1)

Gout is the most common inflammatory arthritis, especially among males more than 40 years of age. Philippine data shows that from 1985 to 2003, the over-all prevalence of the disease had increased from 0.5% to 1.6%. This three-fold increase is not unique to our country. World-wide, gout prevalence had increased 3- to 5-fold over the last 2 decades. This trend has been attributed to the following factors:
  • Increase in the number of overweight individuals
  • An aging population
  • Increase in the prevalence of hypertension and kidney failure
  • Widespread use of mini-dose aspirin and thiazide diuretics
  • Consumption of beer and other alcoholic beverages
While kidney disease had contributed to the increased prevalence of gout, it is interesting to note that incident gout and annual flares tend to decrease as renal function progressive declines. This had been attributed to decreased secretion of pro-inflammatory cytokines when patients develop end-stage renal disease. This observation is similar to what is observed in SLE patients who develop End-Stage Renal Disease.
Complicated gout occurs in patients with uncontrolled hyperuricemia who develop such problems as tophi, destructive arthropathy and nephrolithiases. Observational studies suggest that the following disease presentations would predict those who are more likely to develop complications:
  • Serum uric acid levels between 9-13 mg/dl
  • Symptom onset before the age 25 years
  • Annual flares >4
  • Prolonged periods of active untreated disease before initial medical consult
  • Predisposition for upper extremity involvement
  • Polyarticular presentation
  • Prolonged steroid use (i.e. Prednisone 15 mg/day for at least 3 months)
Some may wonder how steroids which are used in the treatment of acute gout can lead to complications. Steroids are probably the most effective agents used for gout that frequent and non-medically supervised use can markedly reduce the dramatic presentation of arthritis. This would then further delay the patient’s decision to seek medical opinion causing a prolonged period of unmanaged hyperuricemia.
Another form of complicated gout that we must be aware of is that of Treatment Failure Gout (TFG). This is a severe outcome of progressive gout when patients are intolerant to available urate lowering agents or are refractory to maximal medically appropriate doses of these urate lowering agents. Patients would usually have multiple complications (tophi, arthropathy and nephrolithiases), suffer from impaired quality of life and chronic disability, and have significant co-morbid conditions such as cardiovascular disease, hypertension, diabetes, kidney disease, dyslipidemia and obesity. This places patients in the setting for drug interactions considering the amount of medications patients should take. In the US, it is estimated that 1% of all gout patients would fall into this category. There is no local data regarding TFG among our patients.
Another closely related condition is that of Conventional Therapy Refractory Gout (CTRG) which so far has been vaguely defined in literature. This category of complicated gout probably includes  TFG but expands the failure to control gout symptoms on maximal medically appropriate doses of other drugs used in treatment such as NSAIDs, colchicine and steroids. But until more precise definitions are made, TFG is used to encompass these conditions.
References:
  1. Edwards NL. Treatment Failure Gout. Arth Rheum 2008; 58 (9): 2587-90.
  2. Iwao O, Kimiyoshi I, Hideaki O, et al. Frequency of Gouty Arthritis in Patient with ESRD in Japan. Int Med 2005; 44 (7): 706-709
  3. Terkeltaub R. Novel therapies for the treatment of gout and hyperuricemia. Arth Res Ther 2009; 11: 236
  4. Schreiner O, Wandel E, Himmelsbasch F, et al. Reduced secretion of proinflammatory cytokines of MSU stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients. Nephro Dial Transp 2000; 15: 644-49.
  5. Raso AA, Sto Nino OV, Li Yu J. Does prolonged systemic glucocorticoid use increase risk of tophus formation among gouty arthritis patients. Int J Rheum Dis 2009; 12 (3): 243-9.
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