| Objective We aim to explore the trend of early-onset gout and related risk factors in mainland China,and provide decision-making information to prevent the early-onset gout.The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion,yet the standard urate-lowering therapy(ULT)recommendation is first line xanthine oxidase inhibition(XOI)irrespective of the cause of hyperuricemia.Here,we conducted a comparative effectiveness clinical trial of first line un-titrated,benzbromarone uricosuric therapy vs.XOI ULT with febuxostat in gout with renal uric acid underexcretion.Methods We collected data through electronic medical records combined with face-to-face communication with 8393 gout patients who first visited the gout clinic of the Affiliated Hospital of Qingdao University from September 2016 to December 2021.Data included the baseline data,comorbidity and biochemical examinations.The dynamic changes of onset age from 2002 to 2021 were statistically analyzed by SPSS 25.0 and Graph Pad prism 9.0 software.The clinical characteristics and related risk factors of patients with early-onset and late-onset gout were statistically analyzed.A prospective,randomized,single-center,open-labeled trial of men with gout and renal uric acid underexcretion(defined as fractional excretion of urate <5.5% and uric acid excretion≤600 mg/day/1.73m2).We randomly assigned 196 participants to benzbromarone 25 mg daily or low-dose febuxostat 20 mg daily for 12 weeks.All participants received daily urine alkalization with oral sodium bicarbonate.The primary endpoint was serum urate.Results The age of onset of gout decreased significantly from 2002 to 2021.Compared with 2002,the average age of onset in 2021 decreased by 2.3 years(41.9 ± 10.6 vs 39.6 ±14.0 years,P =0.042).The median age of onset decreased by 3 years in 2012-2021 compared with 2002-2011(37 years vs 40 years,P < 0.001).The proportion of gout patients with onset age < 40 years old increased significantly,from 45.1% in 2002 to57.8%,and increased by 12.7% in 20 years(P < 0.001).The constituent ratios of 20-29 years old group and ≤ 19 years old group increased year by year(P < 0.001),increased by9.3%(P < 0.001).and 4.2% respectively during 20 years(P = 0.002),which was the highest increase in all age groups with onset age < 40 years old.Multiple stepwise linear regression analysis showed that positive family history,blood uric acid level,metabolic syndrome and smoking were independent risk factors for early onset of gout.As for the prospective trial,at week 12,the mean(SD)level of SU decreased from 515.23 ± 42.46μmol/L to 348.25 ± 71.32 μmol/L in the LDBen group and from 523.65 ± 43.62 μmol/L to383.75 ± 56.45 μmol/L in the LDFeb group,respectively(P<0.001).Adverse events,including gout flares and e GFR did not differ between groups,with the exception of higher AST and ALT in the LDFeb group.Conclusion The age of gout onset tends to be younger.The increase of the proportion of patients younger than 30 years old is probably the key factor leading to the early-onset gout in China.Early and effective intervention on the risk factors related to early-onset gout is the key measure to prevent the early-onset gout as well as to reduce the prevalence of gout and its related complications. |
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