| Background and objective: In recent years,the increasing prevalence of diabetes mellitus has resulted in an increasing prevalence of diabetic nephropathy worldwide.The pathogenesis of diabetic nephropathy is still not completely clarified,and there are many risk factors for diabetic nephropathy.Even if the traditional risk factors such as smoking,obesity,hypertension,hyperglycemia and dyslipidemia are intensively controlled,the new incidence of end stage renal disease caused by diabetic nephropathy is not reduced yet.Therefore,it is significant to find other risk factors affecting the progression of diabetic nephropathy.Existing studies have shown that serum uric acid(SUA)is involved in promoting the development of diabetic nephropathy.However,this relationship is still controversial.The purpose of this study was to determine the prevalence of hyperuricemia(HUA),analyze the relationship between SUA level and albuminuria and renal function,investigate the effect of SUA level on renal prognosis,and evaluate the predictive value of SUA level for for poor renal prognosis in patients with type 2 diabetic nephropathy(T2DN),thus provide theoretical basis for the clinical prevention and treatment of diabetic nephropathy.Methods: The clinical data of 3199 patients with T2 DN were collected and analyzed,including follow-up data of 1004 patients.The prevalence of HUA in patients with T2 DN was calculated.Grouping was performed based on whether suffering HUA and quartiles of SUA level,and baseline clinical characteristics were compared between the groups.Spearman analysis was applied to explore the correlation between SUA and other major clinical parameters such as albuminuria and renal function.A logistic regression model was established to assess the relationship between SUA and macroalbuminuria and decreased renal function in patients with T2 DN.Renal outcome events were defined as progression to ESRD or initiation ofrenal replacement therapy,doubling of creatinine,and reduction of eGFR more than50% during follow-up.Survival analysis was performed by Kaplan-Meier method in patients with T2 DN.The effect of SUA on renal prognosis in patients with T2 DN was analyzed by COX regression model.The ROC curve was used to assess the predictive value of SUA level for renal outcome events in patients with T2 DN.Results: Among the 3199 patients with T2 DN included in the baseline study,the overall prevalence of HUA was 29.82%.The prevalence of HUA were 27.00% in males and 35.21% in females,which was significantly higher in females than in males(P<0.001).The prevalence of HUA in CKD1-5 stage were 15.39%,23.90%,51.57%,76.54% and 86.26%,respectively,which was increasing gradually with the progression of CKD stage(P<0.001).Patients in the macroalbuminuria group had a significantly higher prevalence of HUA than those in the non-macroalbuminuria group,which were 61.69% and 19.35%,respectively(P<0.001).Compared with patients in the normal uric acid(NUA)group,patients in the HUA group had a higher incidence of hypertension,carotid artery disease,diabetic retinopathy,insulin resistance,macroalbuminuria and decreased renal function.The level of BMI,SBP,FINS,HOMA-IR,UACR,UTP,BUN,Scr,TC and TG was significantly higher in patients with HUA than those in the NUA group,while the proportion of males,HbA1 c,FBG,Hb,eGFR,ALB and HDL were lower(P<0.05).With the increase of SUA quartiles,the incidence of hypertension,carotid artery disease,diabetic retinopathy,insulin resistance,macroalbuminuria and decreased renal function gradually increased,the level of BMI,SBP,DBP,FINS,HOMA-IR,UACR,UTP,BUN,Scr,TC,TG and LDL also gradually increased,while the level of HbA1 c,FBG,Hb,eGFR,ALB and HDL gradually decreased(P<0.05).Spearman analysis showed that SUA was positively correlated with BMI,SBP,HOMA-IR,UACR,UTP,BUN,SCr,TC and TG,and negatively correlated with HbA1 c,FBG,Hb,eGFR and HDL(P<0.05).Of these,the correlations between SUA and renal impairment parameters were UACR(r=0.408),UTP(r=0.335),BUN(r=0.383),SCr(r=0.533)and eGFR(r=-0.421),respectively.Multivariate logistic regression analysis revealed that SUA was still an independent risk factor for macroalbuminuria(OR=1.007,95%CI:1.006~1.008,P<0.001)and decreased renal function(OR=1.011,95%CI:1.010~1.012,P<0.001)in T2 DN patients after adjusting for the effects of multiple confounding factors.The T2 DN patients with HUA had a 3.231-fold increased risk of macroalbuminuria(OR=4.231,95%CI: 3.428~5.222,P<0.001)and a 3.886-foldincreased risk of decreased renal function(OR=4.886,95%CI: 3.883~6.148,P<0.001)compared with those patients with normal SUA.Among 1004 T2 DN patients who participated in follow-up,the incidence of renal outcome events in patients with HUA was 29.00%,which was significantly higher than 13.61% in patients with normal SUA(P<0.001).Kaplan-Meier survival analysis suggested that the T2 DN patients with HUA had worse renal prognosis(P<0.001),and the cumulative survival rate without renal outcome events gradually decreased with the increase of quartiles of SUA level in T2 DN patients(P<0.001).Multivariate COX regression analysis showed that diabetic retinopathy(HR=1.643,95%CI: 1.179~2.288,P=0.003),UACR(HR=1.004,95%CI: 1.002~1.006,P<0.001),SUA(HR=1.003,95%CI: 1.001~1.005,P=0.001)and TC(HR=1.162,95%CI: 1.047~1.290,P=0.005)were independent risk factors for renal outcome events in T2 DN patients,while Hb(HR=0.989,95%CI:0.982~0.995,P<0.001),ALB(HR=0.919,95%CI: 0.896~0.943,P<0.001)and baseline eGFR(HR=0.978,95%CI: 0.971~0.985,P<0.001)were protective factors.The area under the ROC curve(AUC)suggested that the AUC of SUA for the diagnosis of renal outcome events in T2 DN were 0.686(95%CI: 0.649~0.721,P<0.001)in males and 0.670(95%CI: 0.617~0.719,P<0.001)in females.The cut-off value were 347μmol/L with a sensitivity of 74.19% and a specificity of 54.41% in male patients and 324μmol/L with a sensitivity of 66.67% and a specificity of 63.48%in female patients.Conclusions: The prevalence of HUA was higher in T2 DN patients.SUA was closely related to renal damage and was an independent risk factor for macroalbuminuria and decreased renal function in patients with T2 DN.Those T2 DN patients with HUA had a worse renal prognosis.The baseline SUA had certain predictive value for renal prognosis in T2 DN patients.Therefore,in addition to monitoring traditional risk factors such as BMI,blood pressure and blood lipid,it is necessary to pay more attention to SUA in the clinical prevention and treatment of T2 DN.For those patients with HUA or relatively high SUA level despite being in the normal range,clinical intervention should be actively given to maintain SUA level in appropriate range,which will help to delay the disease progression and improve the renal prognosis to some extent. |
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