OBJECTIVETo observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism.

METHODSThirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot.

RESULTSHE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01).

CONCLUSIONBHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.

Animals ; Blood Urea Nitrogen ; Bone Morphogenetic Protein 2 ; metabolism ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; pathology ; Kidney Failure, Chronic ; drug therapy ; metabolism ; Kidney Function Tests ; Kidney Tubules ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factors ; metabolism ; Vascular Calcification ; drug therapy

OBJECTIVETo evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis.

METHODSSixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined.

RESULTSThe patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05).

CONCLUSIONSequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.

Adolescent ; Adult ; Aged ; Alprostadil ; therapeutic use ; Blood Urea Nitrogen ; Chronic Disease ; Creatinine ; blood ; Drug Therapy, Combination ; Epoprostenol ; analogs & derivatives ; therapeutic use ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Glomerular Filtration Rate ; Glomerulonephritis ; complications ; Humans ; Kidney Failure, Chronic ; blood ; drug therapy ; etiology ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Count ; Prothrombin Time ; Urological Agents ; therapeutic use ; Young Adult

OBJECTIVETo investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats.

METHODSForty SPF SD rats were divided into sham group (n=10),model group (n=10), Jianpi Qinghua group (n=10) and losartan group (n=10). Rat chronic renal failure was induced by 5/6 nephrectomy (Platt method) in model, Jianpi Qinghua and losartan groups, and rats in sham group received sham operation. Jianpi Qinghua decoction (3.9 g 200 g(-1)) or losartan (3.3 g 200 g(-1)) daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days, respectively, Rats in sham and model groups were orally administered with saline of the same volume. The serum levels of creatinine and urea nitrogen were measured by biochemical method, the expression of MAPK p38 was detected by Western Blot,and renal pathological changes were observed with hematoxylin-eosin staining.

RESULTSCompared to model group,serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly (42.67 ± 5.98 or 40.90 ± 5.07 compared with 60.90 ± 9.54, both P<0.01), the expression of MAPK p38 was significantly down-regulated (0.555 ± 0.004 or 0.587 ± 0.045 compared with 0.930 ± 0.265,both P<0.01) and serum urea nitrogen was also decreased (8.56 ± 0.75 or 7.97 ± 0.86 compared with 8.62 ± 0.62,both P<0.05). The renal pathology in the model group presented glomerular mesangial proliferation,hyperplasia of glomenrulus mesangial cells and interstitial inflammation. Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups.

CONCLUSIONJianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure, which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.

Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; enzymology ; MAP Kinase Signaling System ; Male ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; metabolism

PURPOSE: In patients with diabetic end stage renal disease (ESRD), glycated albumin (GA) reflects recent glycemic control more accurately than glycated hemoglobin (HbA1c). We evaluated the relationship between GA and average blood glucose (AG) level and developed an estimating equation for translating GA values into easier-to-understand AG levels. MATERIALS AND METHODS: A total of 185 ESRD patients, including 154 diabetic and 31 non-diabetic participants, were enrolled (108 hemodialysis, 77 peritoneal dialysis). Patients were asked to perform four-point daily self-monitoring of capillary blood glucose (SMBG) at least three consecutive days each week for four weeks. Serum levels of GA, HbA1c and other biochemical parameters were checked at baseline, as well as at 4 and 8 weeks. RESULTS: Approximately 74.3+/-7.0 SMBG readings were obtained from each participant and mean AG was 169.1+/-48.2 mg/dL. The correlation coefficient between serum GA and AG levels (r=0.70, p<0.001) was higher than that of HbA1c and AG (r=0.54, p<0.001). Linear regression analysis yielded the following equation: estimated AG (eAG) (mg/dL)=4.71xGA%+73.35, and with this formula, serum GA levels could be easily translated to eAG levels. Multivariate analysis revealed significant contributions of postprandial hyperglycemia (beta=0.25, p=0.03) and serum albumin (beta=0.17, p=0.04) in determining serum GA level, independent to other clinical parameters. CONCLUSION: Compared to HbA1c, serum GA levels were better correlated with AG levels. Using the estimating equation, an average blood glucose level of 155-160 mg/dL could be matched to a GA value of 18-19% in patients with ESRD.
Adolescent ; Adult ; Aged ; Blood Glucose/*metabolism ; Female ; Humans ; Kidney Failure, Chronic/*blood/metabolism ; Male ; Middle Aged ; Prospective Studies ; Serum Albumin/*metabolism ; Young Adult

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

The CD4+CD25+ T regulatory cells (Tregs) play an important role in immune tolerance in experimental transplantation but the clinical significance of circulating Tregs in the peripheral blood is undetermined. In 50 kidney transplant (KT) recipients, 29 healthy controls and 32 liver transplant (LT) recipients, the frequency of Tregs was measured with flow cytometry before and after transplantation. In the KT recipients, IL-10 secretion was measured with an enzyme-linked immunospot (ELISPOT) assay. The median frequency of circulating Tregs before KT was similar to that in healthy controls but significantly lower than that in LT patients before transplantation. The frequency of Tregs was significantly decreased in patients with subclinical acute rejection compared with those without subclinical acute rejection. Calcineurin inhibitors (CNIs) and anti-CD25 antibody decreased the frequency of Tregs but mTOR inhibitor did not. The frequency of donor-specific IL-10 secreting cells did not correlate with the number of Tregs. The frequency of circulating Tregs in KT recipients is strongly affected by CNIs and anti-CD25 antibody, and a low frequency of Tregs is associated with subclinical acute rejection during the early posttransplant period.
Adult ; CD4-Positive T-Lymphocytes/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Graft Rejection ; Humans ; Interleukin-10/metabolism ; Interleukin-2 Receptor alpha Subunit/*biosynthesis ; Kidney Failure, Chronic/blood/immunology/*therapy ; Kidney Transplantation/*methods ; Male ; Middle Aged ; Nephrology/*methods ; T-Lymphocytes, Regulatory/*immunology

Cardiovascular mortality is associated with vascular calcification (VC) in hemodialysis (HD) patients. The present study was designed to find factors related with medial artery calcification on the plain radiography of feet by comparing C-reactive protein (CRP), plasminogen activator inhibitor type 1 (PAI-1) and lipid profile including oxidized low density lipoprotein (ox-LDL) and to elucidate associations among these factors in HD patients. Forty-eight HD patients were recruited for this study. VC in the feet was detected in 18 patients (37.5%) among total patients and 12 patients (85.7%) among diabetic patients. Diabetes, cardiovascular disease (CVD), pulse pressure, ox-LDL/LDL were higher and high density lipoprotein (HDL) was lower in patients with VC than in patients without VC. Negative associations were found between HDL and CRP, PAI-1. PAI-1 had positive association with ox-LDL/LDL. History of CVD was the only determinant of vascular calcification on the plain radiography of feet. Ox-LDL/LDL, HDL, CRP, and PAI-1 were closely related with one another in HD patients. History of CVD is the most important factor associated with the presence of VC and low HDL and relatively high oxidized LDL/LDL ratio may affect VC formation on the plain radiography in the feet of HD patients.
Aged ; C-Reactive Protein/metabolism ; Cardiovascular Diseases/blood/complications/diagnosis ; Female ; Foot ; Humans ; Kidney Failure, Chronic/blood/complications/diagnosis ; Lipoproteins, HDL/*metabolism ; Lipoproteins, LDL/*metabolism ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1/metabolism ; *Renal Dialysis ; Risk Factors

OBJECTIVETo investigate the effects of alpha-keto acid on the expression of neuropeptide Y in malnutrition rats with chronic renal failure.

METHODSSD rats received 5/6 nephrectomy and were fed with 4% casein to establish models of malnutrition with chronic renal failure. Serum albumin, urea nitrogen, serum creatinine, type-1 insulin like growth factor and body weight of the rats were measured. The rat models were randomized into chronic renal failure group, alpha-keto acid group and normal control group, and after a 4-week treatment as indicated, neuropeptide Y mRNA levels in the hypothalamus were measured by RT-PCR in rats with surgically induced renal failure (two-stage subtotal nephrectomy). The blood neuropeptide Y of the rats were analyzed by radioimmunoassay.

RESULTSMalnutrition occurred in chronic renal failure rats at the end of 10 weeks. Compared with those in the chronic renal failure group, the plasma neuropeptide Y concentrations in alpha-keto acid group were significantly lowered with substantially elevated neuropeptide Y mRNA expression in the hypothalamus.

CONCLUSIONalpha-keto acid capsule can improve malnutrition in rats with renal insufficiency possibly by up-regulating neuropeptide Y mRNA expression in the hypothalamus and reducing the level of blood neuropeptide Y.

Animals ; Hypothalamus ; metabolism ; Keto Acids ; pharmacology ; therapeutic use ; Kidney Failure, Chronic ; blood ; Male ; Malnutrition ; blood ; drug therapy ; Neuropeptide Y ; blood ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the field planting of Bacillus bifidus and Bacillus acid lactic on mucosa membrane of gaster, jejunal, ileum, ascending colon, and descending colon in rats with renal failure, and to observe their decomposition of creatinine (Cr), urea nitrogen (UN),and uric acid (UA). METHODS: Forty SD rats were randomly divided into 4 groups. Group A was normal control group,and 10 of them were sham-operated. Thirty of them were operated with 5/6 nephrectomy. Group B was pathological control group. Group C were fed Bacillus bifidus and Group D were fed lactobacillus. After 1 week all rats were sacrificed as samples of blood, digestive juice and gastrointestinal mucosa were taken.Bacteria on the gastrointestinal mucosa were counted. The concentration of UN, Cr,and UA of blood and digestive juice was determined. RESULTS: The number of bacteria on the gastrointestinal mucosa of Group B was less than that of Group A (P<0.05), but that of Group C and D was more than that of Group A and B. The bacteria number on the gastric mucosa was least and that on the descending colon was most. There was significant difference in the bacteria number and concentration of Cr, UN,and UA in various sites of the gastrointestinal tract (P<0.05). The concentrations of Cr, UN, and UA in the digestive juice of various sites and serum in Group C and D were lower than those in Group B (P<0.05). Bacteria planting number in the digestive tract has obvious negative correlation with the concentration of Cr,UN, and UA in the blood and digestive tract. CONCLUSION Field planting of lactobacillns and Bacillus bifidus, and the concentration of low molecule urotoxin are different in various sites of the gastrointestinal tract. It can decrease the concentration of BUN,Cr,and UA in rats with renal failure by feeding lactobacillus and Bacillus bifidus.
Animals ; Bifidobacterium ; growth & development ; metabolism ; Blood Urea Nitrogen ; Creatinine ; metabolism ; Gastrointestinal Tract ; microbiology ; Kidney Failure, Chronic ; etiology ; metabolism ; microbiology ; Lactobacillus ; growth & development ; metabolism ; Male ; Nephrectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uric Acid ; metabolism

This study was designed to examine how such factors as hemodialysis parameters, body mass index, renin and aldosterone concentrations, sympathetic nervous activity, and parathyroid hormone concentrations are associated with the control of hypertension in hemodialysis patients. Hemodialysis patients (n=114) were grouped into four categories. Group 1 had normal BP without antihypertensive medication. Group 2 needed one antihypertensive drug, Group 3 needed combination of two or three categories of antihypertensive drugs without minoxidil. Group 4 needed more than three categories of antihypertensive drugs including minoxidil. Parathyroid hormone, beta2-microglobulin, renin and aldosterone, epinephrine, norepinephrine, and hemodialysis parameters were measured. The fractional clearance of urea as Kt/V urea was significantly lower in Group 3 and Group 4 than in Group 2 (p<0.01). Concentrations of parathyroid hormone were significantly higher in Group 4 than the other groups (p<0.01). Pre-hemodialysis norepinephrine concentrations were significantly higher in Group 4 than the other groups (p<0.05). Traditional factors associated with hypertension did not seem to be relevant to the degree of hypertension in hemodialysis patients in the present study. In conclusion, poor Kt/V urea, elevated parathyroid hormone concentrations, and elevated concentrations of plasma norepinephrine seemed to be the factors that might be associated with control of hypertension in hemodialysis patients.
Adult ; Aged ; Aldosterone/*blood ; Analysis of Variance ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects/*physiology ; Epinephrine/blood ; Female ; Humans ; Hypertension/blood/drug therapy/physiopathology ; Kidney Failure, Chronic/blood/physiopathology/therapy ; Male ; Middle Aged ; Norepinephrine/blood ; Parathyroid Hormone/*blood ; *Renal Dialysis ; Renin/*blood ; Sympathetic Nervous System/*physiology ; Urea/metabolism