| Background:Allopurinol, a kind of xanthine oxidase inhibitors, can decrease blood uric acid concentration by inhibiting production of uric acid, which is a first-line drug used for treating hyperuricemia and chronic gout for a long time. Many studies have shown that allopurinol can help to resist oxidative stress and improve the function of endothelial cells as well, which plays a protective role for multisystem and organs in our body. However, many severe cutaneous adverse drug reactions of allopurinol related with HLA-B*5801 gene have been reported, which lead many clinicians have concerns on the use of it and tend to use a new medicine called Febuxostat. But allopurinol has low price, good uric acid reduction effect as well as being the best choice for patients who are renal insufficient or not sensitive to the treatment of excreting uric acid. Whether should we reduce allopurinol use remains unclear. So we carry on this research in order to discuss this problem.Object:By analysing safety and efficacy of allopurinol used in patient of chronic kidney disease, the relationship between allopurinol hypersensitivity and HLA-B*5801 gene, as well as cost-effectiveness of allopurinol and febuxostat in order to comprehensive evaluate the value of allopurinol using in the clinic.Method:1. Screening patiets who came to the outpatient clinic of nephrology in PUMCH between December 2012 and November 2014, prescribed allopurinol for at least twice as well as having created medical profiles in PUMCH. Reviewing their medical profiles and collecting datas in order to evaluate the safety and efficacy of allopurinol. At the same time exploring the factors which may influence the efficacy of allopurinol by comparing subgroups and single or multiple factor analysis.2. Gout group has been set up based on gout patients from gout clinic and inpatients of general medicine department of PUMCH, and normal control group have been set up with staff of PUMCH participating physical examinations. We detect HLA-B*5801 gene by DNA extraction and fluorescence PCR and then try to find positive rate of HLA-B*5801 gene in different populations and the relationship between HLA-B*5801 positive and allopurinol-associated cutaneous adverse reaction.3. We use the data of a clinical research named "A 28-week, multicentre, randomized, double-blind, parallel controll study of febuxostat in treating gout accompanied by hyperuricemia", which was hosted by PUMCH, in order to compare the cost-effectiveness of allopurinol and febuxostat by building Decision Tree Model.Results:1. The uric acid (UA) values of 100 cases patients with CKD decrease significantly at 2 months after taking allopurinol compared with baseline values and then keep the value at about 400 μ mol/L for a long time. Single factor correlation analysis shows that age, gender, baseline levels of uric acid have P values<0.05. Multiple factors regression analysis shows that β value of age and baseline levels of uric acid are 0.017 and -0.817 respectively.Using Kaplan-Meier analysis to explore the relationship between age, baseline levels of UA and the success rate of lowering UA to normal levels, we find that patients aging less than 50 years have better success rate of lowering UA levels (P=0.017). Furthermore, patients who’s UA<500 μ mol/L also have better success rate of lowering UA levels (P=0.000).2. At the 2nd,4th,6th,12th,24th,36th,48th,60th month after taking allopurinol, there is no significant change in eGFR of CKD patients compared with baseline eGFR values (P>0.05). Dosage of allopurinol and the stage of CKD have no significant influence on eGFR changing.3. There are 6 cases whose white blood cell decrease,8 cases whose liver function is injured and 1 case who have skin rash in these 100 cases of CKD patients.4. The positive rate of HLA-B*5801 in general population, allopurinol-tolerant patients and allopurinol-hypersensitive patients are 14.3%,13.9% and 0% respectively.5. In China, the cost of treating with allopurinol 300mg qd followed by febuxostat 40mg or 80mg qd is 8745(?) and the QALY is 1.64. The cost of treating with febuxostat 40mg followed by 80mg qd is 20590(?) and the QALY is 1.62.Conclusion:1. The uric acid reduction effect of allopurinol using in CKD patients of our research is good. Age is a favorable factor to reduce uric acid levels to normal, while the baseline value of uric acid is an unfavorable factor. We don’t find out that allopurinol dosage and CKD stage have influence on success rate of reducing uric acid to normal.2. Long-term using of allopurinol in CKD patients have no significance damage on renal function, and we don’t observe that renal function is affected by allopurinol dosage and CKD stages.3. Using allopurinol in CKD patients of our research has low incidence of adverse events and good safety.4. There is no significant difference of positive rate of HLA-B*5801 gene between general population and gout patients.5. We don’t confirm that HLA-B*5801 positive is in relationship with allopurinol-related cutaneous adverse reactions.6. Treating gout or hyperuricemia with allopurinol 300mg qd followed by febuxostat 40mg or 80mg qd has better cost-effectiveness.
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