OBJECTIVETo explore the method for establishing animal models of gouty nephropathy complicated with chronic renal failure.

METHODSSix-eight weeks old male Wistar rats were fed with 10% fodder yeast. The adenine at the daily dose of 100, 150, 200, 250, and 300 mg/kg was administrated to them by gastrogavage. The serum levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) were dynamically monitored. Meanwhile, the pathological changes of rat kidney were observed.

RESULTSCompared with the normal control group, serum BUN, Cr, and UA obviously increased in rats administered with 100 mg/kg for 7 days (P<0.05). Meanwhile, pathological changes as gouty nephropathy occurred. Along with the prolongation of the modeling time, the aforesaid biochemical indices and pathohistological changes of the kidney were more obvious. The blood Cr level just reached the chronic renal failure level on the 26th day of the administration (about the 4th week), and obviously exceeded the renal failure level on the 41st day (about the 6th week). The blood UA level increased to a higher level on the 7th day of modeling, and maintained at a higher level for a long time. It decreased rapidly from the 41st day to the 48th day. The renal pathological examination showed aggravated infiltration of lymphocytes and stromal fibrous proliferation. On the 48th day of modeling, the proliferation of the fibrous tissue and the interstitial fibrosis were obvious on the bases of the aforesaid changes. The serum BUN, Cr, and blood UA obviously increased in the rats administered with 150, 200, 250, and 300 mg/kg when compared with the normal control group, reaching the level of chronic renal failure (P<0.05). These levels obviously decreased 17 days after restoring to normal fodder feeding, and approached the normal levels till the 35th day.

CONCLUSIONIdeal experimental animal models of gouty nephropathy complicated with chronic renal failure could be established in male Wistar rats by feeding with 10% fodder yeast and 100 mg/kg adenine by gastrogavage for 5 weeks.

Animals ; Disease Models, Animal ; Gout ; complications ; Hyperuricemia ; Kidney Failure, Chronic ; etiology ; Male ; Rats ; Rats, Wistar ; Uric Acid ; blood

Acute Kidney Injury ; blood ; diagnosis ; etiology ; Child, Preschool ; Humans ; Hyperuricemia ; blood ; complications ; Kidney ; pathology ; Magnetic Resonance Imaging ; Male ; Uric Acid ; blood

Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Blood Glucose/analysis ; Blood Pressure ; Cholesterol/blood ; Female ; Glomerular Filtration Rate ; Humans ; Hyperuricemia/blood/etiology ; Kidney Diseases/*blood/etiology ; Male ; Middle Aged ; Regression Analysis ; Republic of Korea ; Risk Factors ; Uric Acid/*blood

Following contents were reviewed in this article: More and more experimental studies related with chronic uratic nephropathy were carried out in recent years. In most of these studies, the animal models were established mainly from viewpoints of gene recombination, urinary uric acid inhibition and blood uric acid production promoting. TCM showed good effects in lowering blood uric acid, regulating levels of cytokines and postponing interstitial fibrosis. However, further studies on Chinese herbs and their extracts is necessary.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hyperuricemia ; blood ; Kidney Diseases ; etiology ; Mice ; Phytotherapy ; Purines ; metabolism ; Rats ; Uric Acid ; blood

OBJECTIVETo explore the changes in the clinicopathological features of patients with IgA nephropathy with elevated uric acid level.

METHODSA total of 171 patients with IgA nephropathy diagnosed at biopsy were classified into 3 groups, namely normotensive group with normal level uric acid (group 1), normotensive group with elevated uric acid level (group 2), and hypertensive group with elevated uric acid level (group 3). The clinicopathological features were compared between the 3 groups.

RESULTSFrom group 1 to group 3, the disease duration became elongated, body weight increased, systolic and diastolic pressures elevated, blood urea nitrogen and serum creatinine increased, glomerular filtration rate decreased, and 24-h urine protein increased; the apolipoprotein A, high-density lipoprotein and albumin levels decreased, while apolipoprotein B100, triglyceride, cholesterol and low-density lipoprotein increased. The glomerular damage, tubulointerstitial lesions and arteriole hypertrophy worsened, and Lee's grade III changes were predominant in group 1, grade III or IV in group 2 and grades III-V in group 3. Mesangial proliferative glomerulonephritis was the major pathological type in groups 1 and 2, as compared with focal segmental glomerulonephritis or sclerosing glomerulonephritis in group 3.

CONCLUSIONPatients with IgA nephropathy and elevated uric acid level have greater clinicopathological damage than those with normal uric acid level, and hypertension further aggravates such damages.

Adolescent ; Adult ; Creatinine ; blood ; Female ; Glomerulonephritis, IGA ; complications ; pathology ; Humans ; Hypertension ; complications ; pathology ; Hyperuricemia ; etiology ; pathology ; Kidney ; pathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo explore the association of elevated serum uric acid with metabolic disorders and the risk factors of hyperuricemia in type 2 diabetes mellitus (T2DM).

METHODSThe clinical and laboratory data of 159 T2DM patients aged 40-80 years with a Scr level of 51-159 µmol/L (0.6-1.8 mg/dl) were analyzed to explore the association of hyperuricemia (HUA) with metabolic disorders and identify the risk factors of HUA.

RESULTSForty out of 159 T2DM patients (25.2%) were found to have HUA. Univariate analysis showed that male gender, a body mass index ≤25 kg/m(2), hypertension, serum creatinine ≤110 µmol/L, blood urea nitrogen ≤7.0 mmol/L, microalbuminuria :11.2 mg/L, triglyceride :1.70 mmol/L, high-density lipoprotein <1.04 mmol/L, low density lipoprotein ≤3.37 mmol/L were all risk factors of HUA (P<0.05) in T2DM. Binary logistic regression analysis identified serum creatinine, body mass index and triglyceride as independent risk factors of HUA in T2DM. The main risk factors related to HUA had high incidences in T2DM. Patients with HUA had a significantly higher incidences of coronary artery disease, carotid atherosclerosis, cerebral infarction, diabetic nephropathy and diabetic retinopathy than those with normal uric acid level (P<0.05).

CONCLUSIONSeveral risk factors contribute to the occurrence of elevated serum uric acid in T2DM, and metabolic disorders and complications are also closely associated with HUA.

Adult ; Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Female ; Humans ; Hyperuricemia ; etiology ; metabolism ; Male ; Middle Aged ; Risk Factors ; Uric Acid ; blood

An elevated serum concentration of uric acid may be associated with an increased risk of acute kidney injury (AKI). The aim of this study was to investigate the impact of preoperative uric acid concentration on the risk of AKI after coronary artery bypass surgery (CABG). Perioperative data were evaluated from patients who underwent CABG. AKI was defined by the AKI Network criteria based on serum creatinine changes within the first 48 hr after CABG. Multivariate logistic regression was utilized to evaluate the association between preoperative uric acid and postoperative AKI. We evaluated changes in C statistic, the net reclassification improvement, and the integrated discrimination improvement to determine whether the addition of preoperative uric acid improved prediction of AKI. Of the 2,185 patients, 787 (36.0%) developed AKI. Preoperative uric acid was significantly associated with postoperative AKI (odds ratio, 1.18; 95% confidence interval, 1.10-1.26; P<0.001). Adding uric acid levels improved the C statistic and had significant impact on risk reclassification and integrated discrimination for AKI. Preoperative uric acid is related to postoperative AKI and improves the predictive ability of AKI. This finding suggests that preoperative measurement of uric acid may help stratify risks for AKI in in patients undergoing CABG.
Acute Kidney Injury/*etiology ; Coronary Artery Bypass/*adverse effects ; Creatinine/*blood ; Female ; Humans ; Hyperuricemia/*blood ; Kidney Function Tests ; Male ; Middle Aged ; Postoperative Complications/*etiology ; Postoperative Period ; Preoperative Period ; Retrospective Studies ; Uric Acid/*blood

OBJECTIVETo establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model.

METHODSThirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed.

RESULTSCompared with control group, the abdominal fat content (0.74+/-0.63 vs. 1.36+/-0.65 g, P<0.05) and abdominal fat index (0.44%+/-0.30% vs. 0.85%+/-0.30%, P<0.01) as well as live lipid index (3.61%+/-0.65% vs. 11.33%+/-2.14%, P<0.01) in model group significantly increased; the levels of serum uric acid (210.61+/-94.76 vs. 304.25+/-141.94 micromol/L, P<0.05), total cholesterol (4.20+/-0.51 vs. 20.10+/-11.25 mmol/L, P<0.01), LDL-C (1.16+/-0.29 vs. 10.78+/-6.48 mmol/L, P<0.01), and FFA (0.39+/-0.14 vs. 0.55+/-0.15 mmol/L, P<0.01) in model group significantly increased; HDL-C (5.85+/-0.95 vs. 4.14+/-2.03 mmol/L, P<0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P>0.05); the activities of ADA (9.71+/-3.05 vs. 17.19+/-5.10 U/ml, P<0.01) and XOD (10.58+/-6.88 vs. 19.22+/-9.44 U/L, P<0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P>0.05).

CONCLUSIONSHigh fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may be the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.

Abdominal Fat ; pathology ; Animals ; Body Weight ; Coturnix ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Hypercholesterolemia ; etiology ; metabolism ; pathology ; Hyperuricemia ; etiology ; metabolism ; pathology ; Lipid Metabolism ; Lipids ; blood ; Liver ; metabolism ; Male ; Uric Acid ; blood

OBJECTIVETo evaluate the relationship between uric acid (UA) and peripheral arterial disease (PAD) in Chinese patients with coronary heart disease (CHD).

METHODSUA levels and PAD were evaluated in 3251 Chinese hospitalized patients with CHD (age > or = 50 years). PAD was diagnosed when the ankle-brachial index was < 0.9 but patients with an ankle-brachial index of > 1.4 were excluded because of false negative rate. Potential confounding variables with P < 0.10 were adjusted for multivariate analysis.

RESULTSIn univariate analysis, UA levels were higher in patients with PAD than in those without PAD (349.80 micromol/L +/- 128.45 micromol/L vs. 323.00 micromol/L +/- 110.72 micromol/L, P < 0.001). Rate of hyperuricemia in patients with PAD and without PAD were 31.62% and 22.48% (P < 0.001) respectively. Prevalence rates of PAD for quintiles of UA level were 23.2%, 27.4%, 36.1%, 43.2% and 72.7%, respectively (P-trend < 0.05). With UA level as a continuous variable, the multivariate-adjusted odds ratio for PAD was 1.002 (95% confidence interval: 1.001 - 1.002) (P < 0.001). The optimal cut-off point for UA as determined by the receiver operating characteristic curve, was 227.2 micromol/L. The sensitivity and specificity at this cut-off point were 84.6% and 20.3%, respectively. The area under curve was 0.521 (95% confidence interval: 0.504 - 0.547) and the multivariate-adjusted odds ratio for PAD for UA above this level was 1.292 (95% confidence interval: 1.047 - 1.596) (P < 0.01). The results, however, after exclusion those cases who used diuretics, were similar.

CONCLUSIONElevated uric acid level seemed a significant and independent risk factor for PAD in Chinese hospitalized patients with CHD (age > or = 50 years).

Analysis of Variance ; Ankle Brachial Index ; China ; Coronary Disease ; blood ; complications ; Humans ; Hyperuricemia ; complications ; Middle Aged ; Odds Ratio ; Peripheral Vascular Diseases ; etiology ; Prevalence ; ROC Curve ; Risk Factors ; Sensitivity and Specificity ; Uric Acid ; blood

BACKGROUND: To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism. METHODS: A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg), and 7.46, 3.73, or 1.87 g•kg•d PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum. RESULTS: Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05). CONCLUSION PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.
AMP-Activated Protein Kinases ; physiology ; Animals ; Chemokine CCL2 ; blood ; Disease Models, Animal ; Fallopia japonica ; Forkhead Box Protein O3 ; physiology ; Hyperuricemia ; complications ; Kidney Diseases ; drug therapy ; etiology ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Uric Acid