Evaluation Of Related Factors For Hyperuricemia In CKD Patients And Intervention

Hyperuricemia(HUA)is defined as a fasting serum uric acid concentration greater than 416 μmol/l in men and postmenopausal women while greater than 357 μmol/l in premenopausal women in the normal purine diet state for two times in different days.The current prevalence of HUA is increasing year by year worldwidely.Epidemiological survey found that HUA is an important risk factor for chronic kidney disease(CKD).Several studies have shown that urate lowering therapy(ULT)is of benefit to renal function improvement.In this study,we conducted the epidemiological investigation in HUA outpatient,and discussed the related factors of HUA in hospitalized CKD patients.We established hyperuricemic nephropathy rat model and explored the possible uric acid lowing effects of dietary supplement,in order to provide new ideas for HUA treatment in CKD patients.In the first part of the study,we conducted the epidemiological investigation in HUA outpatients from 2016.3-2016.12 by means of questionnaires,suggesting that physical examination is the best way to find asymptomatic HUA.The patient mission need to be strengthened in clinical work because the outpatients do not fully cognize HUA.In this study,renal urate underexcretion-type,urate overproduction-type and the combined-type were 85.6%,0.5% and 13.8% respectively in primary HUA,suggesting promoting excretion of uric acid is suitable for Chinese with primary HUA.The prevalence of CKD in primary HUA patients was 60.8%.Vitamin D and vitamin B2 dificiency was common in these patients.In addition,dietary supplements play a role in uric acid lowing and the mechanism is worthy of in-depth discussion.In the second part of the study,HUA was analyzed in the most common secondary glomerulonephritis-lupus nephritis and the most common primary glomerulonephritis-Ig A nephropathy in our hospital.Firstly,CKD1-3 LN patients presenting to our department of nephrology from 2011.1-2016.1 were recruited.The demographic,clinical,laboratory,pathological indicators were compared between the HUA and non-HUA patients.Multivariate stepwise logistic regression was performed to establish the statistical model on detecting LN patients at risk of HUA and be optimized.A total of 177 patients were enrolled and the prevalence of HUA was 40.11%.Renal urate underexcretion was the main cause of HUA in this population(67.7%),urate overproduction-type and the combined-type were 22.6% and 9.7% respectively.Compared with non-HUA patients,there were more hypertension,higher levels of blood urea nitrogen(BUN),triglycerides(TG),blood phosphorus,parathyroid hormone(PTH),24 h urinary albumin(24h UAb),24 h urine al-microglobulin(24h Uα1-MG),lower levels of glomerular filtration rate,blood calcium,C3 and 24 hours urinary calcium(24h UCa)in LN patients with HUA.The optimal statistical model was log(?)= – 0.5 + 2.5 BUN + 0.7 PTH – 0.9(24h UCa)+ 0.9 TG – 0.7 C3 + 0.6(24h UAb)– 0.8(24h Uα1-Mic),P refers to the probability of HUA.Secondly,we collected the data of 914 non-dialysis Ig A nephropathy patients aged 18 years and older in our department from 2005.1 to 2009.1.The prevalence of HUA was 37.3%.Logistic regression analysis showed that the risk factors for HUA were CKD stages(OR = 2.612,CI: 2.108-3.236,p <0.001)and TG(OR = 1.297,CI: 1.125-1.497,p = 0.001).The TG level was further divided into five groups from the lowest to the fifth,the multivariate OR of HUA increased with increasing serum TG levels(P for trend <0.001).The study suggested that both CKD1-3 LN patients and Ig A nephropathy patients have a high prevalence of HUA which may be associated with impaired renal function and metabolic disorders.The risk prediction model will be beneficial to the prevention and treatment of HUA in LN patients at early stages of CKD.In the third part of the study,36 male SD rats were randomly divided into 6 groups: normal control group,HUA untreated group,benzbromalone intervention group and dietary supplement 1/2/3(extracts from fruits and vegetables)intervention group.A hyperuricemic nephropathy rat model was established and benzbromalon,dietary supplement were simultaneously given after the rats were fed with modeling drugs for a week.Blood was also taken once a week for the measurement of serum uric acid,serum creatinine,24 h urinary uric acid,24 h urinary albumin,urinary ACR for 4 weeks.Compared with the normal control group,the serum uric acid level in HUA group was significantly increased at 1 week after the rats were fed with the modeling drugs(P <0.05),and then maintained a high level.The serum creatinine increased significantly at the 4th week(P <0.05).Renal pathology showed that tubular epithelium degeneration,swelling,atrophy,and renal interstitial inflammatory cells infiltration and fibrosis,suggesting that the hyperuricemic nephropathy rats model being developed successfully.Benzobarbamate and dietary supplements 1,2,3 effectively reduced the serum level of uric acids,significantly improved renal function and pathological change.In the aspect of ULT,dietary supplement 1 was similar with bromambromon,and dietary supplements 2,3 were better than benzbromarone.However,the level of 24 hours urinary uric acids in the dietary supplement 2/3 group was significantly lower than that in the bromambromone group(P<0.05).Compared with the normal control group,the expression of URAT1 protein and m RNA in HUA non-intervention group and four intervention groups showed a decreasing trend,among which the differences of bromambromone and dietary supplements 1 were statistically significant(P < 0.05).The results suggested that dietary supplements in this study have a good uric acid lowering and kidney protection effect,which may be achieved by inhibiting uric acid production and increasing uric acid excretion.In summary,this study found that there was a high prevalence of CKD in primary HUA outpatients and vitamin D and B2 dificiency was common in HUA patients.Renal urate underexcretion was the main cause of HUA.It was found that the prevalence of HUA was high in both lupus nephritis patients and Ig A nephropathy patients.HUA in these patiens was closely related to renal damage and metabolic disorder.Animal experiments confirmed that dietary supplements extracted from fruits and vegetables have a good uric acid lowering and kidney protection effect,and the mechanism was worthy of in-depth study.This study provides the theoretical basis and new ideas for the early prevention and treatment of HUA in CKD patients.