| BackgroundAccording to the World Health Organization(WHO)global tuberculosis report 2017:in 2016,the number of new reported cases of tuberculosis(TB)in the world reached 10.4 million,with China taking the third place in the world.There is a close association between diabetes mellitus(DM)and TB.DM increases the risk of active TB,and patients with DM are more likely to occur renal damage than those with TB alone.The treatment in tuberculosis patients with diabetes mellitus(TB-DM)was more complicated.Pyrazinamide(PZA)is one of the most important drugs against mycobacterium tuberculosis.In addition to drug resistance,pyrazinamide was usually included in anti-tuberculotic regimen.However,many adverse reactions were shown during the use of PZA,such as liver injury and elevated serum uric acid(SUA).PZA induced hyperuricemia(PIHU)has a high incidence when patients ungoing PZA treatment,and more likey leads to quit PZA treatment.ObjectiveThe aim of this study was to investigate whether the SUA level could return to their baseline after discontinauation of PZA in a short time in primarily diagnosed TB patients and TB-DM patients.MethodsThe inpatients with primrily diagnosed TB and TB-DM in the department of infectious diseases from Jianshui County people’s Hospital and Chinese people’s Liberation Army Joint Service support Force No.920(former Kunming General Hospital of Chengdu military region)Hospital from January 2014 to December 2017 were included,and their clinical data were used as the study group.The chronic hepatitis B(hepatitis B)patients and the DM patients without TB who were hospitalized during the same period were used as the control group.Demographic data,clinical background and SUA data from baseline(WO)to sixth month(M6)of all patients were collected.Based on their baseline SUA levels,the patients were be classified into the non-HUA(n=351)and the HUA groups(n=80).According to continuation phase protocol with HR or HRE,they were divided into tuberculosis Group 1(2HRZE/HR,n=165)and tuberculosis Group 2(2HRZE/HRE,n=266).The inpatients with chronic hepatitis B were used as the control group during the same period.TB-DM patients(n=30)was divided into two groups according to the levels of fasting blood glucose(FPG)before anti-TB treatment,which included the group with normal FPG(FPG<7.0mmol/L,n = 12)and the group with elevated FPG(FPG≥7.0mmol/L,n = 18).The DM patients without TB(n = 30)and the TB patients without DM(n = 30)were used as the control group during the same period.The levels of SUA were analyzed.1.Statistical methodsAll data in the research process were recorded by EXCEL,and statistical analysis were conducted using IBM SPSS Statistics 19.0(IBM,Armonk,NY,USA),and the figures were drawn using the GraphPad Prism software package(version 5 for Windows;GraphPad software,San Diego,CA).Categorical variables were expressed as n(%)and continuous parameters as mean± standard deviation(Mean± SD)or median(IQR).Pearson χ2 test or Fisher’s exact test were used to compare the categorical variables,while either the Studen’s T test or the Mann-Whitney U test was used for comparison of pairs of continuous variables,and either the one-way ANOVA or Kruskal-Wallis H test were used for comparisons of more than two means.All statistical analyses were based on a two-tailed hypothesis tests,and the criterion for statistical significance was set at P<0.05.ResultsAt the 4th month after discontinuation of PZA(the 6th month of anti-tuberculosis treatment),the mean level of SUA of tuberculosis patients(n=431)was significantly higher than that at the baseline(382.23±133.56 vs.340.31±106.97μmol/L,t=-7.5441,P=0.0000);while in the hepatitis control group,the mean level of SUA were not shown significant difference within 6 months observation(302.78±75.69 vs.308.21±74.19 μmol/L,t=0.5650,P=0.5748).The incidence of HUA in the non-HUA group at the 4th month after discontinuation of PZA was higher than that in the hepatitis control group[18.23%(64/351,95%CI:16.67%-19.79%)vs.4.34%(2/46,95%CI:1.55%-10.23%),χ 2=4.4589,P=0.0347].Both the HR group(384.32±151.27 vs.325.44±106.26 μmol/L,t=-5.9526,P=0.0000)and the HRE group(380.93±121.59 vs.349.54±106.57 μmol/L,t=-4.8153,P=0.0000)showed higher SUA levels than their baseline SUA levels at the 4th month after discontinuation of PZA.When patients with tuberculosis were followed up for 1 year(n=17),the SUA levels both at discontinued PZA for 10 months(341.35±15.11 vs.312.47±18.55 μmol/L,t=-2.3131,P=0.0343)and at discontinued PZA for 4 months(343.06±19.26 vs.312.47±18.55μmol/L,t=-2.6373,P=0.0179)were higher than their baseline levels,but there were no difference between these two time-points(t=0.1611,P = 0.8740).At the 4th month after discontinuation of PZA(M6)in TB-DM patients,the mean level of SUA was significantly higher than that in the baseline(378.57 ±106.57 vs.282.63±63.16 Μmol/L,t=-5.1588,P=0.0000),both groups with normal FPG level(418.25±124.19 vs 294.17±62.68μmol/L,t=-3.3863,P=0.0061)and with elevated FPG level(352.11 ±86.85 vs.274.94±64.07 μmol/L,t,= 4.1120,P=0.0007)showed higher SUA levels than those of their baseline.At the 4th month after discontinuation of PZA,the increased change in SUA levels was higher in patients with normal FPG level group than that of the patients with elevated FPG level group(124.08 ± 126.94 vs.77.17± 79.62 μmol/L),with no statistical difference(t= 1.2478,P = 0.2224).There was no difference on the baseline SUA levels between TB-DM group and the TB control group(282.63±63.16vs.301.80±83.46μmol/L,t=-1.0028,P=0.3210)and the DM control group(282.63±63.16 vs.301.70±101.06 μmol/L,t=-0.8763,P=3851).At the 4th month after PZA discontinuation,the increased chanange in SUA level was higher in the TB-DM group than in the TB group(95.93 ± 101.85 vs 45.45 ± 90.38μmol/L,t=-2.0306,P=0.0449)and than in the DM group(95.93 ±101.85 vs.21.23 ± 64.27 μmol/L,t=-3.3369,P=0.0016).There was no significant difference on the level of SUA between W0 and M6 in the DM group(322.93±116.09 vs.301.70±101.06μmol/L,t=-1.7033,P=0.0992).ConclusionsThe levels of serum uric acid in most TB patients and TB-DM patients couldn’t return to their baseline levels in a short term after discontinuation of PZA,which increased the incidence of hyperuricemia.At the 4th month,the increase in SUA levels was higher in the TB-DM group than in the TB gtoup,was higher in patients with normal FPG level group than the patients with elevated FPG level group. |
