Plasma oxypurinol concentration versus alterations of serum urate level and glomerular filtration rate in gouty patients with renal insufficiency

Abstract

The purpose was to study the renal effect after standard dose of allopurinol 300 mg daily and to examine the relationship between plasma oxypurinol concentrations and the change in renal function and scrum urate levels in gout patients with renal insufficiency. The study was conducted in twenty-seven gout patients with renal insufficiency in rheumatology clinic at Rajavithi Hospital. Both new cases or old cases of gout who were already discontinued allopurinol completely for 4 weeks, were treated with allopurinol 300 mg daily for 6 weeks. The renal functions and serum urate level were monitored at before and after allopurinol treatment. The results of this study showed that there were no significantly different in CrCI, serum creatininc, 24 hour urine volume, excretion of crcatinine and protein between before and after allopurinol treatment. However, there were tendency that the proportion of patients with decrement of CrCl more than 4 ml/min would increase with higher oxypurinol concentration of either trough or peak. Most patients had plasma oxypurinol concentration which were higher than the proposed therapeutic range. There were significant relationship between changes of scrum urate levels with both trough and peak oxypurinol concentrations (R²=0.42, p=0.002 and R²=0.27, p=0.007, respectively). Mean serum urate was 5.8 mg/dl after treatment which was lower than the general target level of serum urate for chronic gout. Seventy percent of the patients with no tophi met the therapeutic goal, however, only one case (10%) with evidence of tophi had serum urate less than 5 mg/dl which was the recommended serum urate level in patient with tophi. None of the patients developed any skin rash or serious adverse events after allopurinol treatment. In conclusion, Allopurinol 300 mg daily for 6 weeks were effective in reducing serum urate in patient with no tophi, but patients with evidence of tophi might require doses of allopurinol which were higher than 300 mg daily. Although, the relationship between oxypurinol concentration and change in CrCl was not statistically significant different, standard dose allopurinol should be used with caution especially when use for long term period in patient with renal insufficiency.