The Risk Factors Of Impaired Liver And Renal Function In Patients With Gout And The Effect Of Dapagliflozin In Patients With Gout And T2DM

Objective To analyze the risk factors of impaired liver and renal function in patients with gout and the effect of Dapagliflozin in patients with gout and T2 DM.Methods A total of 494 hospitalized patients with confirmed primary gout were selected and divided into four groups according liver and renal function,control(CON),impaired liver function(ILF),impaired renal function(IRF)and both function impaired(ILRF)group.Multivariate logistic regression was used to analyze the risk factors related with impaired liver and renal function.Then,A total of 107 gout with T2 DM patients who first visited the gout clinic of the Affiliated Hospital of Qingdao University,Qingdao,China from January 2021 to March 2022 were consecutively enrolled for a 6-month prospective observational study,divided into dapagliflozin group and control group according to whether or not received dapagliflozin treatment,observed for 6 months,and compared the number of gout attacks,body mass index(BMI),waist circumference(WC),visceral fat index(VAI),and blood uric acid(SUA),fasting blood glucose(FPG),liver and kidney function,blood lipid changes between the two groups.Results The first sectionA total of 494 gout inpatients were included,463 were males(93.72%)and 31females(6.28%).complicated with liver impairment was 50.35% and renal impairment was 32.79%.The mean age was(51.71±16.36)years,the median course of gout was7(3,13)years.Compared to control group,impaired liver function group were younger,with shorter duration,higher body mass index,waist circumference,homeostasis model assessment for insulin resistance(HOMA-IR)and serum uric acid,low density lipoprotein-cholesterol(LDL-C),total cholesterol,triglycerides,higher prevalence of obesity,fatty liver,dyslipidemia and monosodium urate crystal(MSU)deposition(P<0.05).impaired renal function group were older and with higher serum uric acid,C reactive protein,and hypertension,MSU prevalence(P<0.05).Compared to impaired renal function group,impaired liver function group were younger,with shorter duration,higher level of body mass index,waist circumference,LDL-C,total cholesterol,triglycerides,HOMA-IR,higher prevalence of fatty liver,obesity and lower prevalence of hypertension and type 2 diabetes(P<0.05).The univariate logistic regression analysis showed that age(OR=0.941,95%CI 0.906-0.977,P<0.001),serum uric acid(OR=1.002,95%CI 1.000-1.005,P=0.043),HOMA-IR(OR=1.147,95%CI 1.024-1.285,P=0.018)and MSU(OR=1.959,95%CI 1.154-3.326,P=0.013)were the independent risk factors of impaired liver function,while the independent risk factors of impaired renal function were age(OR=1.104,95%CI 1.048-1.162,P < 0.001),serum uric acid(OR=1.007,95%CI 1.004-1.010,P<0.001)and MSU(OR=2.393,95%CI 1.191-4.805,P=0.014).The second sectionA total of 107 patients with gout and T2 DM were finally selected,including 45 patients in dapagliflozin group and 62 patients in control group.The average observation time was 6 months.Analyzed the baseline data of the two groups,the results showed that the dapagliflozin group with higher waist circumference,body mass index,triglyceride(TG),visceral fat index(VAI)and the proportion of combined obesity than the control group(all P<0.05).There were no significant differences in the age,gender,duration of gout,the number of gout attacks within 6 months,and the level of systolic blood pressure,diastolic blood pressure,serum uric acid(SUA),estimated glomerular filtration rate(e GFR),creatinine,aspartate aminotransferase(AST),alanine aminotransferase(ALT),total cholesterol,high density lipoprotein cholesterol(HDL-c),low density lipoprotein cholesterol(LDL-C),fasting blood glucose and the proportion of smoking history,drinking history,hypertension,and lipid metabolism disorder between the two groups(P > 0.05).In order to exclude the influence of drugs,the related drugs used in the two groups were analyzed at baseline and 6 months after treatment,the results showed that there was no significant difference between two groups in uric-lowering treating(44.4%vs32.3%,95.6%vs98.4%),non-steroidal anti-inflammatory drugs(37.8%vs54.8 %,6.7%vs11.3%),and colchicine(42.2% vs 53.2%,46.7% vs58.1%),glucocorticoids(4.4%%vs3.2%,2.2%vs3.2%),oral hypoglycemic drugs(75.6%vs58.1%,97.8%vs100%),insulin(2.2%vs0,2.2%vs0),lipid-lowering(38.6%vs35.5%,53.3%vs35.5%),antihypertensive drugs(46.7%vs35.5%,53.3%vs37.1%)and hepatoprotective drugs(6.7%vs1.6%,13.3%vs11.5%)within 6 months before and after baseline(all P > 0.05).The dose of febuxostat was further compared between the two groups during the follow-up period.The results showed that the average daily dose of febuxostat in the dapagliflozin group was less than control group(20.89±10.78mg/d vs27.17±12.79mg/d,P < 0.05).Compared the data before the baseline and 6 months after treatment,the results showed that after treatment for 6 month,in both of two groups the waist circumference,serum uric acid and the number of gout flare within 6 months all decreased(all P < 0.05).Body mass index(BMI),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-c),fasting blood glucose(FBG)and visceral fat index(VAI)decreased in the dapagliflozin group(all P< 0.05),but in the control group VAI increased(P < 0.05),although body mass index,ALT,AST,total cholesterol,LDL-c and fasting blood glucose decreased,the difference was not statistically significant(P > 0.05).The TG level in the control group was higher than baseline(P < 0.05),in the dapagliflozin group which was lower than baseline,but the difference was not statistically significant(P > 0.05).The change of creatinine,e GFR,and HDL-c in the two groups were not statistically significant(all P>0.05).The indicators existing significant difference between baseline and 6 months after treated,whose difference value was calculated and further compared and analyzed between the two groups,the results showed that in the dapagliflozin group with the higher changes in waist circumference,VAI and the number of gout flare than control group(p < 0.05),while the change of SUA between the two groups have not statistically significant(P > 0.05).Finally,the rate of target serum uric acid were compared between the two groups.The results showed that the rate of target serum uric acid in the dapagliflozin group and control group were increased compared before treatment(24.4%vs60.0%,29.0%vs51.6% p < 0.05).Although the rate of target serum uric acid in dapagliflozin group was higher after treatment,however,the difference between the two groups was not statistically significant(60%vs51.6% P > 0.05).Conclusion1.The proportion of inpatient gout with impaired liver and renal are high,was50.35% and 32.79%,respectively,and there is a great difference between the two groups.2.Younger patients with insulin resistance,obesity,and fatty liver are susceptible to impaired liver function,Older with hypertension and diabetes are susceptible to impaired renal function.Serum uric acid and MSU are the common independent risk factors for impaired liver and renal function in patients with primary gout.3.Dapagliflozin has a good effect on decreasing the frequency of gout and visceral fat index in gout complicated with T2 DM.