Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats.

BACKGROUND Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR. Western blot assays were performed to detect the expression and phosphorylation of IRS-1 and Akt, which are 2 critical proteins in the insulin signaling pathway. RESULTS Both urea stimulation and 5/6 nephrectomy induced glucose uptake disorder in skeletal muscle cells (P<0.01). Skeletal muscle IR was aggravated in the Ang II group (P<0.05) but alleviated in the valsartan group (P<0.01). Regardless of the experimental method (in vivo or in vitro), tyrosine phosphorylation of IRS-1 and Akt were significantly lower (P<0.01) and serine phosphorylation was significantly higher (P<0.01) in the model group than in the sham/control group. Compared to the model group, additional Ang II aggravated abnormal phosphorylation (P<0.05); conversely, additional valsartan alleviated abnormal phosphorylation to some extent (P<0.05). CONCLUSIONS There is skeletal muscle insulin resistance in the presence of CRF. This phenomenon can be aggravated by Ang II and partially relieved by valsartan. One of the mechanisms of IR in CRF patients may be associated with the critical proteins in the IRS-PI3k-Akt pathway by changing their phosphorylation levels.

Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease.

BACKGROUND Albuminuria has been associated with cardiovascular events, but whether such an association can be explained by endothelial dysfunction is not fully understood. In this study, we examined the relationship between the urine albumin-to-creatinine ratio (UACR) and biomarkers of endothelial function in patients with chronic kidney disease (CKD). MATERIAL AND METHODS The cross-sectional associations of renal dysfunction and UACR with procoagulant and inflammatory factors were evaluated for 151 consecutive CKD (stage 3-5) patients. Subjects were grouped by UACR (≤300 mg/g or >300 mg/g) and estimated glomerular filtration rate (eGFR) (30≤ eGFR <60, 15≤ eGFR <30, or eGFR <15 ml/min per 1.73 m²). RESULTS A higher UACR level was associated with an increase in von Willebrand factor antigen (vWF: Ag) levels, vWF activity, factor VIII, interleukin-2, and log (interleukin-6), even after adjustment for risk factors. Linear regression analysis indicated that for every 88.5 mg/g increase in UACR, the vWF activity and factor VIII were elevated by 8.3% and 6.3%, respectively. The factorial design ANOVA data showed no statistically significant interaction between UACR and CKD stage with procoagulant and inflammatory factors. CONCLUSIONS Our study shows an eGFR-independent association of higher UACR with elevations in markers of endothelial dysfunction and inflammatory factors in CKD patients.

Decreased Serum C3 Levels in Immunoglobulin A (IgA) Nephropathy with Chronic Kidney Disease: A Propensity Score Matching Study.

BACKGROUND The effects of low serum C3 levels and the activation of the complement system on the development and the prognosis of IgAN are unclear. The present study aimed to determine whether decreased levels of complement C3 influence the prognosis of IgAN patients with chronic kidney disease. MATERIAL AND METHODS We enrolled a total of 1564 patients with primary IgAN diagnosed by renal biopsy at the Chinese PLA General Hospital from January 2011 to March 2015. The endpoint was end-stage renal disease (ESRD) or a doubling of the baseline serum creatinine (D-SCr) level. All patients were using 1: 1 propensity score matching (PSM), and the baseline values were not significantly different between these 2 groups (P>0.05). RESULTS During a follow-up period, 14 patients in the group with decreased C3 levels reached the endpoint, with 12 patients with normal C3 levels. There was no significant difference between the 2 groups in achieving D-SCr or ESRD (P=0.676). In multivariate Cox analysis, adjusted for demographic and laboratory examination, the risk of reaching the endpoint was comparable in the 2 groups (HR, 0.70; 95% CI, 0.27-1.78; P=0.449;). Furthermore, the risk of reaching ESRD (HR, 0.83; 95% CI, 0.25-2.75; P=0.757) and D-SCr (HR, 1.45; 95% CI, 0.20-10.60; P=0.718) did not differ between the 2 groups. CONCLUSIONS Decreased serum C3 levels in IgA nephropathy with chronic kidney disease did not play a decisive role in renal progression.

Hypercoagulable state evaluated by thromboelastography in patients with idiopathic membranous nephropathy.

The aims of this study were to evaluate the characteristics of hypercoagulable states in patients with membranous nephropathy (MN) via thromboelastography (TEG) and to identify risk factors. 235 MN patients who had undergone TEG examinations from 2011 to 2014 were included. An abnormality in at least two TEG parameters is considered a hypercoagulable state. Patient data was compared between the hypercoagulable and non-hypercoagulable groups. Potential risk factors for hypercoagulability were analyzed by logistic regression models. Subgroup analysis was performed in hypercoagulable patients. Compared to the non-hypercoagulable MN patients, the hypercoagulable patients showed a significantly higher proportion of female patients, urinary protein, platelet count, triglyceride and fibrinogen level, along with more severe hypoproteinemia and a reduction of serum antithrombin III. Correlation analysis showed that hypoproteinemia was the primary risk factor for hypercoagulability in MN patients. Among the hypercoagulable MN patients, a subgroup TEG parameter analysis showed that glucocorticoids-used subgroup and smoker subgroup had shortened time to initial fibrin formation (R value) and increased coagulation index respectively (P < 0.05), indicating a more serious hypercoagulable state. Meanwhile, the time to initial fibrin formation (R value) and time to clot formation (K value) of the statin-used patients were remarkably higher than those of the non-statin patients. TEG examinations facilitated the detection of hypercoagulable states in MN patients, and hypoproteinemia was the most important risk factor for hypercoagulability in these patients. The use of glucocorticoids and smoking may help to aggravate hypercoagulable states, while statin drugs may alleviate hypercoagulability.

Renal Protective Effect of Probucol in Rats with Contrast-Induced Nephropathy and its Underlying Mechanism.

BACKGROUND: Contrast-induced nephropathy (CIN) refers to acute renal damage that occurs after the use of contrast agents. This study investigated the renal protective effect of probucol in a rat model of contrast-induced nephropathy and the mechanism of its effect. MATERIAL AND METHODS: Twenty-eight Wistar rats were randomly divided into the control group, model group, N-acetylcysteine(NAC) group, and probucol group. We used a rat model of iopromide-induced CIN. One day prior to modeling, the rats received gavage. At 24 h after the modeling, blood biochemistry and urine protein were assessed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in renal tissue. Kidney sections were created for histopathological examination. RESULTS: The model group of rats showed significantly elevated levels of blood creatinine, urea nitrogen, 24-h urine protein, histopathological scores, and parameters of oxidative stress (P<0.05). Both the NAC and probucol groups demonstrated significantly lower Scr, BUN, and urine protein levels compared to the model group (P<0.05), with no significant difference between these 2 groups. The NAC group and the probucol group had significantly lower MDA and higher SOD than the model group at 24 h after modeling (P<0.05). The 8-OHdG-positive tubule of the probucol group and NAC group were significantly lower than those of the model group (p=0.046, P=0.0008), with significant difference between these 2 groups (P=0.024). CONCLUSIONS: Probucol can effectively reduce kidney damage caused by contrast agent. The underlying mechanism may be that probucol accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress.

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure.

AIM: Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats. METHODS: Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot. RESULTS: Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group. CONCLUSION: Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

Clinical and pathological analysis of hepatitis B virus-related membranous nephropathy and idiopathic membranous nephropathy.

OBJECTIVE: The Hepatitis B virus infection rate is high in the Chinese population. The implications of HBV infection are widely recognized, and membranous glomerulonephritis is the most common renal lesion associated with HBV infection. We compared the clinicopathologic features of 119 HBV-related membranous nephropathy (HBV-MN) and 143 idiopathic membranous nephropathy (IMN) patients to identify those factors that facilitate their discrimination. METHODS: Cohort analysis of demographic information, clinical manifestations, laboratory parameters, renal pathology and prognostic features of the two groups. RESULTS: Most HBV-MN patients were young or middle-aged; the onset age in the HBVMN group was younger than the IMN group (p < 0.05). A male predominance was found in both groups. And the two groups both presented with heavy proteinuria or nephrotic syndrome. In contrast to IMN patients, the HBV-MN group was presented with a high occurrence of microscopic hematuria (73.95 vs. 35.66%) and renal insufficiency (47.06 vs. 24.48%). Plasma complement C3 and C4 in HBV-MN patients were significantly lower than in IMN patients (p < 0.05). The hyperlipidemia was more severe in IMN patients (p < 0.05). The occurrences of segmental glomerular damage, mesangial cell proliferation and tubulointerstitial damage were more common in the HBV-MN group (p < 0.05). Immunofluorescence staining of polyclonal immunoglobulin and polytypic complement immunoglobulin were more frequent in the HBV-MN group. The followup data showed there were no statistic differences in the prognosis between HBV-MN and IMN. CONCLUSION: HBV-MN patients commonly showed nephrotic syndrome accompanied with renal and hepatic dysfunction which was different from IMN patients. The primary pathological feature of HBVMN was atypical membranous nephropathy, which is usually associated with the inflammatory changes in HBV infection. The renal survival rates did not differ between HBVMN patients and IMN patients.

Higher HOMA-IR index and correlated factors of insulin resistance in patients with IgA nephropathy.

OBJECTIVE: To investigate the index of homeostasis model of insulin resistance (HOMA-IR) in IgA nephropathy (IgAN) patients, and to explore the possible correlated factors contributing to insulin resistance (IR) within these patients. MATERIAL: There were 255 IgAN patients and 45 membranous nephropathy (MN) patients in our database. We identified 89 IgAN subjects and 21 MN subjects without diabetes and undergoing glucocorticoid therapy for at least 6 months. METHODS: Data regarding physical examination, blood chemistry and renal pathology were collected from 89 IgAN subjects and 21 MN subjects. Then 62 IgAN patients and 19 MN patients with chronic kidney disease (CKD) Stage 1 - 2 were selected for the comparison of HOMA-IR index, 89 IgAN patients were selected for multiple regression analysis to test for correlated factors of HOMA-IR index with IgAN patients. RESULTS: Comparison between IgAN and MN show that HOMA-IR index was significantly higher in IgAN patients with CKD Stage 1 - 2. After logarithmic transformation with urine protein (UPr), Ln(UPr) (b = 0.186, p = 0.008), eGFR (b = -0.005, p = 0.014), > 50% of glomeruli with mesangial hypercellularity (b = 0.285, p = 0.027) and body mass index (BMI) (b = 0.039, p = 0.008) were correlated factors of HOMA-IR index in the multiple regression analysis. CONCLUSION: IgAN patients had higher HOMA-IR index compared with MN in the stages of CKD 1 - 2. For IgAN patients, more UPr, lower eGFR, > 50% of glomeruli with mesangial hypercellularity and higher BMI were correlated with IR.

[Protective effects of compound shenhua tablet on diabetic nephropathy rats].

OBJECTIVE: To observe the renal protection effects of Compound Shenhua Tablet (CST) on diabetic nephropathy (DN) rats. METHODS: DN rats were given a normal diet for 9 months after they were induced by intraperitoneal injection of STZ at the dose of 65 mg/kg after uninephrectomized. They were randomly divided into 4 groups, i. e., the normal control group, the model control group, the CST group, and the Irbesartan group. The intervention was given by gastrogavage for 6 weeks. The general state, 24 h urine protein, urine micro-albumin (mAlb), serum creatinine (SCr), blood urea nitrogen (BUN), glucose (GLU), triglyceride (TG), total cholesterol (TC), total protein (TP), and albumin (ALB) levels were observed before and after intervention. Renal pathological changes were observed by PAS staining and transmission electron microscope. RESULTS: After 6 weeks of drug intervention, when compared with the model control group, the general state was improved in the CST group and the Irbesartan group. The levels of 24 h urine protein, urine mAlb, SCr, BUN, GLU, TG, and TC were obviously lower in the CST group and the Irbesartan group than in the model group as well as in the same group before treatment (P<0.05, P<0.01). There was no statistical difference between the two treatment groups (P>0.05). The renal pathological changes and the renal ultrastructure were improved to some degree in the two groups when compared with those in the model control group. CONCLUSIONS: CST could attenuate the renal damage of diabetes and delay renal deterioration process. Its effectiveness was equivalent to that of Irbesartan.

Nomogram prediction model for renal anaemia in IgA nephropathy patients.

In this study, we focused on the influencing factors of renal anaemia in patients with IgA nephropathy and constructed a nomogram model. We divided 462 patients with IgA nephropathy diagnosed by renal biopsy into anaemic and non-anaemic groups. Then, the influencing factors of renal anaemia in patients with IgA nephropathy were analysed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model for predicting renal anaemia was established. Eventually, nine variables were obtained, which are easy to apply clinically. The areas under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve reached 0.835 and 0.676, respectively, and the C-index reached 0.848. The calibration plot showed that the model had good discrimination, accuracy, and diagnostic efficacy. In addition, the C-index of the model following internal validation reached 0.823. Decision curve analysis suggested that the model had a certain degree of clinical significance. This new nomogram model of renal anaemia combines the basic information, laboratory findings, and renal biopsy results of patients with IgA nephropathy, providing important guidance for predicting and clinically intervening in renal anaemia.

Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium.

GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H2O2 (hydrogen peroxide)-treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H2O2-treated cells in a dose-dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose-dependent manner in H2O2-treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 microM GSE, 2.0 microM TG (thapsigargin) and 20.0 microM 2-APB (2-aminoethoxydiphenyl borate) instead of 0.25 microM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p-AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up-regulation of eNOS and NO expression via inhibiting InsP3Rs (inositol 1,4,5-trisphosphate receptors)-mediated intracellular excessive calcium release and by activating p-AKT in endothelial cells.

Influences of renal anemia on the pathology of IgA nephropathy: a study based on propensity score matching.

OBJECTIVE: This study aims to investigate the influences of renal anemia on the pathogenesis of IgA nephropathy using propensity score matching (PSM). METHODS: Renal biopsies from 462 patients with IgA nephropathy were enrolled in this study. PSM was used to balance intergroup covariates, and matching results were verified using a dot-plot of standardized mean differences and histograms of the propensity score distribution and distance distribution. The matched data were used to analyze the impact of renal anemia on the pathological indicators of IgA nephropathy by logistic regression. RESULTS: A total of 132 pairs of patients from the renal anemia group and the non-renal anemia group were matched by PSM; after matching, the standard deviations of 13 covariates were within 0.25. Multivariate logistic regression results suggested that the CKD4-5 stage of IgA nephropathy and tubular atrophy/interstitial fibrosis >50% were independent risk factors for renal anemia. CONCLUSIONS: Via PSM, we demonstrated that decreased eGFR and severe tubular atrophy/interstitial fibrosis are correlated with renal anemia in IgA nephropathy. In clinical practice, renal anemia in patients with IgA nephropathy of CKD3 stage or above should be closely monitored and managed.

Clinical and pathological factors of renal anaemia in patients with IgA nephropathy in Chinese adults: a cross-sectional study.

OBJECTIVE: Few studies with large sample populations concerning renal anaemia and IgA nephropathy have been reported worldwide. The purpose of this cross-sectional study was to examine the clinical and pathological characteristics and influencing factors associated with renal anaemia in patients with IgA nephropathy, which is the most common aetiology of chronic kidney disease. METHODS: A total of 462 hospitalised patients with IgA nephropathy confirmed by renal biopsy who met the inclusion criteria were consecutively recruited from January 2014 to January 2016. Their general information, routine blood test results, blood chemistries, estimated glomerular filtration rates (eGFRs) and renal pathologies were collected. The Oxford classification was used to characterise the renal pathologies. Univariable and multivariate logistic regression models were used to analyse the influencing factors of anaemia associated with IgA nephropathy. RESULTS: The incidence of renal anaemia was 28.5% (132/462 patients) in our study (21.3% in males and 38.9% in females). The anaemia type was primarily normocytic and normochromic. The rate of anaemia in patients with eGFR values of 30-59 mL/min/1.73 m2 was higher than that in patients with an eGFR >60 mL/min/1.73 m2 (42.9% vs 17.8%, p<0.001). Notably, in the group with eGFR values <15 mL/min/1.73 m2, the anaemia rate was 100%. Logistic regression analysis showed that factors affecting anaemia in patients with IgA nephropathy included being female (OR 3.02, 95% CI 1.76 to 5.17), low albumin levels (OR 0.87, 95% CI 0.82 to 0.93), reduced eGFR values (OR 0.98, 95% CI 0.97 to 0.99) and renal tubulointerstitial lesions >50% (OR 2.57, 95% CI 1.22 to 5.40). CONCLUSIONS: The female sex, hypoalbuminaemia, reduced eGFR levels and severe renal tubulointerstitial lesions were correlated with renal anaemia in patients with IgA nephropathy. These results provide new insight into our understanding of anaemia in IgA nephropathy and may improve the management and treatment of clinical renal anaemia.

Protective Effects and Mechanisms of Shenhua Tablet () on Toll-Like Receptors in Rat Model of Renal Ischemia-Reperfusion Injury.

OBJECTIVES: To investigate the protective effects and potential mechanisms of Shenhua Tablet (, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI). METHODS: Sixty male Wistar rats were randomly divided into 5 groups: sham surgery, model control, astragaloside (150 mg•kg-1•d-1), low- and high-dose SHT (1.5 and 3.0 g•kg-1•d-1, repectively) groups. One week after drug treatment, rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling, serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiffstaining. TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry, Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay. RESULTS: Compared with the sham group, the model group exhibited severe change in renal function (Scr: 189.42±21.50, P<0.05), pathological damage (damage score: 4.50±0.55, P<0.05), and the expression levels of TLR2, TLR4, MyD88, TNF-α, IL-6 were significantly higher than other groups. Meanwhile, the levels of TLRs in model group showed upward tendency from 24 to 72 h, unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent, and, in addition to TLRs, presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (P<0.05); in particular, the most significant mitigation of these changes was observed in the SHT-H group (P<0.05). CONCLUSION: TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.

Blood coagulation system in patients with chronic kidney disease: a prospective observational study.

OBJECTIVES: Thromboembolic events are the major factor affecting the prognosis of patients with chronic kidney disease (CKD). Haemostatic alterations are possible causes of these complications, but their roles remain poorly characterised. In the prospective observational study, we investigated the entire coagulation process in patients with CKD to elucidate the mechanisms of their high thromboembolic risk. METHODS: A total of 95 patients with CKD and 20 healthy controls who met the inclusion criteria were consecutively recruited from September 2015 to March 2016. The platelet count, platelet aggregation, von Willebrand factor antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), fibrinogen, factor V (FV), FVII, FVIII, antithrombin III, protein C, protein S, D-dimer, standard coagulation tests and thromboelastography were measured in patients with CKD and controls. Associations between the estimated glomerular filtration rate (eGFR) and haemostatic biomarkers were tested using multivariable linear regression. RESULTS: The adjusted and unadjusted levels of vWF:Ag, vWF:RCo, fibrinogen, FVII, FVIII and D-dimer were significantly higher in patients with CKD than that in the healthy controls, and were elevated with CKD progression. However, after adjustment for baseline differences, platelet aggregation and thromboelastography parameters showed no significant differences between patients with CKD and healthy controls. In the correlation analysis, vWF:Ag, vWF:RCo and FVIII were inversely associated with eGFR (r=-0.359, p<0.001; r=-0.391, p<0.001; r=-0.327, p<0.001, respectively). During the 1-year of follow-up, one cardiovascular event occurred in patients with CKD 5 stage, whereas no thromboembolic event occurred in the CKD 3 and 4 and control groups. CONCLUSIONS: Patients with CKD are characterised by endothelial dysfunction and increased coagulation, especially FVIII activity. The abnormal haemostatic profiles may contribute to the elevated risk of thrombotic events but further longer-term study with large samples is still required to more precisely determine the relationship between the elevation of procoagulant factors and clinical outcomes.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Protective effects of astragaloside in rats with adriamycin nephropathy and underlying mechanism.

The present study was designed to determine the mechanism underlying the treatment of nephrotic syndrome using astragaloside by observing the effects of astragaloside on the expression of nephrin and podocin proteins and genes in kidneys of rats with adriamycin nephropathy. The rats were injected with adriamycin and, after successful model establishment, randomly divided into a model group, a Methylprednisolone (MP) group, and an astragaloside group. The 24-h complete urine samples were collected. Biochemical indicators were monitored, and kidney tissues were collected for pathological analysis using light microscopy and electron microscopy. The mRNA expression of nephrin and podocin was measured in the kidney tissues using the real-time qPCR, and the protein expression levels of nephrin and podocin were detected using Western blot analysis. At the end of 12 weeks of drug intervention, the urinary protein level was lower in the MP and astragaloside groups than that in the model group (P = 0.008 and P = 0.01, respectively). Serum albumin was higher in the MP and astragaloside groups than in the model group (P < 0.001 and P = 0.012, respectively). Podocytes in the MP group were nearly normal, and fusion of podocytes in the astragaloside group was significantly less than that in the control group. The nephrin and podocin mRNA and protein expression levels in the intervention groups were higher (P < 0.05) than that in the model group. Due to the increased expression of podocyte-related nephrin and podocin proteins, astragaloside maintained slit diaphragm integrity and decreased the level of proteinuria in rats with adriamycin nephropathy.

Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy.

OBJECTIVE: The study aimed to evaluate the effects of oral administration of irbesartan in adriamycin-induced nephropathy considering laboratory changes, kidney histology, and expression of proteins related to slit diaphragm and cytoskeleton of the podocyte. METHODS: The animals were divided into control, model, methylprednisolone (MP), and irbesartan groups. The 24-hour urinary protein and biochemical indicators were determined, and renal pathological changes were observed. The mRNA and protein expression of nephrin, podocin, CD2-associated protein (CD2AP), and desmin in the kidney tissue were analyzed. RESULTS: The urinary protein excretion levels in the MP and irbesartan groups were lower than those in the model group (p<0.01). Electron microscopy showed that fusion of the glomerular foot processes of the rats in the irbesartan group was significantly reduced. The mRNA and protein expression levels of nephrin and podocin in the renal tissue in the MP and irbesartan groups were up-regulated compared with the model group (p<0.05), whereas the mRNA and protein expression levels of CD2AP and desmin were significantly down-regulated (p<0.01). CONCLUSIONS: For rats with adriamycin-induced nephropathy, irbesartan could significantly reduce proteinuria. As a possible mechanism, irbesartan may improve the slit diaphragm protein of the glomerular podocyte and stabilize the cytoskeleton of the podocyte.

Impact of acute kidney injury on coagulation in adult minimal change nephropathy.

A hypercoagulable state exists in patients with nephrotic syndrome (NS), which more easily leads to venous thromboembolism (VTE). However, whether acute kidney injury (AKI), a common complication of NS, affects the hypercoagulable state and VTE has rarely been elucidated. In this study, we aimed to explore coagulation changes and analyze relevant influencing factors in NS-AKI patients.A total of 269 consecutive NS patients with minimal change disease (MCD) between 2011 and 2016 were included in this observational study. Ninety-one cases were in the AKI group and 178 cases in the non-AKI group. The 1:1 propensity score matching (PSM) method was applied to match the baseline information. The coagulation biomarkers were compared, and the thrombosis events were recorded. Linear correlation was performed to detect any relation between D-dimer and clinical data.The PSM method gave matched pairs of 88 MCD patients with AKI and non-AKI patients, resulting in no differences in baseline information. The D-dimer, fibrinogen, and thromboelastography parameters maximum amplitude (MA), G values of the MCD-AKI patients were significantly higher than the levels of the MCD patients without AKI (D-dimer: 1.8 [1.0, 3.3] vs 1.1 [0.6, 1.7] mg/L, P < 0.001; fibrinogen: 7.0±2.0 vs 6.5 ±â€Š1.4 g/L, P = 0.036; MA: 74.6 ±â€Š5.0 vs 70.5 ±â€Š5.3 mm, P = 0.020; G: 15.7 ±â€Š5.3 vs 12.5 ±â€Š3.3, P = 0.034). For the MCD patients, the serum creatinine, white blood cell count, and interleukin-6 levels in the patients with D-dimers >1 mg/L were significantly higher than those of patients with D-dimers ≤1 mg/L. The correlation analysis showed that the D-dimer level was correlated with serum creatinine, white blood cell count, and interleukin-6 (r = 0.410, P =  < 0.001; r = 0.248, P =  < 0.001; r = 0.306, P =  < 0.001, respectively). Five deep vein thrombosis events occurred in the AKI group and 1 pulmonary embolism event occurred in the non-AKI group after adjusting the propensity score value. AKI appeared to have an association with higher incidence of VTE, but the difference was not statistically significant (RR: 4.9, 95% CI: 0.6-42.7, P = 0.154).The MCD-NS patients complicated with AKI had a more severe hypercoagulable state, which might be associated with the active inflammation of AKI that mediated activation of the coagulation system.

[Effect of compound shenhua tablet on macrophage migration inhibition factor in renal tissue of 5/6 nephrectomized rats].

OBJECTIVE: To observe the effect of compound shenhua tablet (CST) on the residual kidney expressed macrophage migration inhibition factor (MIF) in rats. METHODS: CST was used to treat 5/6 nephrectomized rats for 12 weeks and the conditions of blood pressure, urinary protein, blood biochemical indices (creatinine, blood urea nitrogen), kidney pathologic change and MIF expression were observed. RESULTS: CST could significantly lower the serum levels of creatinine (P < 0.05), and 24 hrs urinary protein (P < 0.01), reduce the MIF expression and macrophage infiltration in renal glomerulus and tubular mesenchym, and lower the degree of renal glomerular sclerosis and interstitial fibrosis. CONCLUSION: The inhibition on the highly expressed MIF may be an important mechanism of the drug in restraining chronic inflammation in residual kidney, delaying the sclerosis and fibrosis progression and protecting renal function.