Guihua Jian

Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through α3β1 Integrin Upregulation in Vitro and in Vivo

Background: Decreased expression of α3β1 integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α3β1 integrin expression under diabetic condition in vitro and in vivo. Methods: Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100μg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α3β1 integrin expression were measured in vitro and in vivo. Results: HG decreased podocyte adhesive capacity and α3β1 integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α3β1 integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg-1· d-1) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α3β1 integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats. Conclusion: NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α3β1 integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.

Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy

We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.

Analysis of 24-hour ambulatory blood pressure monitoring in patients with diabetic nephropathy: a hospital-based study.

BACKGROUND AND AIMS The present study was designed to characterize and compare the ambulatory blood pressure changes of patients with Type 2 diabetic nephropathy (DN) and non-diabetic chronic kidney disease (CKD), and to investigate the features of ambulatory blood pressure in patients with Type 2 diabetic nephropathy (DN) in comparison with those of non-diabetic chronic kidney disease (CKD) in our medical center. MATERIALS AND METHODS 62 patients with Type 2 diabetic nephropathy (DN) in compliance with the diagnosis criteria of CKD were enrolled in the study, without renal replacement therapy. Their 24-h ambulatory blood pressure monitoring (ABPM) results were observed and compared with the ambulatory blood pressure results of 152 non-diabetic CKD patients with matching age, sex, renal function and other aspects. RESULTS Analysis of ABPM data from 62 patients with Type 2 DN and 152 patients with nondiabetic CKD indicated: 1. The average 24-h systolic blood pressure (SBP), daytime and nighttime systolic blood pressure (SBP) in the patients with DN were all significantly higher than those of patients with non-DN. 2. Blood pressure variability did not differ considerably between the two groups; nighttime blood pressure decline was small in both groups, but not significantly different. 3. The systolic blood pressure loads in the patients with DN were all significantly higher than those of patients with non-DN. 4. The prevalence of abnormal Circadian BP rhythm was 90.3% in patients with DN, which did not differ considerably from the patients with non-DN represented by 81.6%. 5. The nighttime SBP was correlated with 24-h urinary protein in patients with both non-DN and DN. CONCLUSIONS Systolic blood pressure control of patients with intermediate or advanced diabetic nephropathy was worse than that of patients with non-diabetic CKD, and non-dipping rhythm was quite common. The nighttime SBP correlated with 24-h urinary protein excretion.

Combination of Mean Platelet Volume/Platelet Count Ratio and the APACHE II Score Better Predicts the Short-Term Outcome in Patients with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy

Background/Aims: Both the Acute physiology and Chronic Health Evaluation (APACHE II) score and mean platelet volume/platelet count Ratio (MPR) can independently predict adverse outcomes in critically ill patients. This study was aimed to investigate whether the combination of them could have a better performance in predicting prognosis of patients with acute kidney injury (AKI) who received continuous renal replacement therapy (CRRT). Methods: Two hundred twenty-three patients with AKI who underwent CRRT between January 2009 and December 2014 in a Chinese university hospital were enrolled. They were divided into survivals group and non-survivals group based on the situation at discharge. Receiver Operating Characteristic (ROC) curve was used for MPR and APACHE II score, and to determine the optimal cut-off value of MPR for in-hospital mortality. Factors associated with mortality were identified by univariate and multivariate logistic regression analysis. Results: The mean age of the patients was 61.4 years, and the overall in-hospital mortality was 48.4%. Acute cardiorenal syndrome (ACRS) was the most common cause of AKI. The optimal cut-off value of MPR for mortality was 0.099 with an area under the ROC curve (AUC) of 0.636. The AUC increased to 0.851 with the addition of the APACHE II score. The mortality of patients with of MPR > 0.099 was 56.4%, which was significantly higher than that of the control group with of ≤ 0.099 (39.6%, P= 0.012). Logistic regression analysis showed that average number of organ failure (OR = 2.372), APACHE II score (OR = 1.187), age (OR = 1.028) and vasopressors administration (OR = 38.130) were significantly associated with poor prognosis. Conclusion: Severity of illness was significantly associated with prognosis of patients with AKI. The combination of MPR and APACHE II score may be helpful in predicting the short-term outcome of AKI.

Tanshinone IIA Attenuates Contrast-Induced Nephropathy via Nrf2 Activation in Rats

Background/Aims: Tanshinone IIA is a chemical compound extracted from Salvia miltiorrhiza Bunge, a perennial plant also known as red sage used in traditional Chinese medicine. Tanshinone IIA has been shown to protect against various organ injuries. In this study, we hypothesized that Tanshinone IIA could play an anti-oxidative role in contrast-induced nephropathy (CIN) through enhancing Nrf2/ARE activation. Methods: To test whether Tanshinone IIA can attenuate CIN, oxidative stress, and apoptosis, we utilized two models: an in vivo Sprague-Dawley rat model of ioversol-induced CIN and an in vitro cell model of oxidative stress in which HK2 cells, a human renal tubular cell line, are treated with hydrogen peroxide (H2O2). Rats were randomly assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (ioversol-induced CIN rats pretreated with vehicle), and Tanshinone IIA group (ioversol-induced CIN rats pretreated with 25mg/kg Tanshinone IIA). Renal functions, renal injuries and apoptosis were evaluated by using serum creatinine, histological scoring, and TUNEL staning respectively. Malondialdehyde, 8-hydroxy-2’ –deoxyguanosine, and intracellular reactive oxygen species were used for oxidative stress assessment. Levels of Nrf2 and heme oxygenase-1 (HO-1) were measured in vivo and in vitro. Results: Tanshinone IIA attenuated renal tubular necrosis, apoptosis and oxidative stress in rats and oxidative stress in HK2 cells. Furthermore, Tanshinone IIA activated Nrf2, and up-regulated HO-1 expression in vivo and in vitro, resulting in a reduction in oxidative stress. Conclusion: Tanshinone IIA may protect against CIN through enhancing Nrf2/ARE activation.

Increased Serum Uric Acid Level Is a Risk Factor for Left Ventricular Hypertrophy but Not Independent of eGFR in Patients with Type 2 Diabetic Kidney Disease

Background Although the relation between serum uric acid (SUA) and left ventricular hypertrophy (LVH) has been studied for decades, however, their association remains debatable. Methods This is a retrospective study in which a total of 435 hospitalized Chinese patients with type 2 DKD were enrolled. The subjects were stratified into quartiles according to SUA level. LVH was assessed by two-dimensional guided M-mode echocardiography. Results There was a significant increase in the prevalence of LVH in patients with type 2 DKD across SUA quartiles (28.9, 26.5, 36.1, and 49.5%; p < 0.001). The Spearman analysis indicated that SUA was positively correlated to LVMI and negatively correlated to eGFR. The logistic regression analysis revealed that the odd ratio for LVH in the highest SUA quartile was 2.439 (95% CI 1.265–4.699; p = 0.008; model 1) or 2.576 (95% CI 1.150–5.768; p = 0.021; model 2) compared with that in the lowest SUA quartile. However, there was no significant increased risk of LVH in the subjects with the highest SUA quartile after adjusting the eGFR (OR = 1.750; 95% CI 0.685–4.470; p = 0.242; model 3). Conclusions In selected population, such as type 2 DKD, the elevated SUA level is positively linked with the increased risk of LVH, but this relationship is not independent of eGFR.

Impact of hemodialysis and uremia on serum levels of tumor markers

Objective: The aim was to study the possible impact of uremia and hemodialysis on tumor markers including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, neuron-specific enolase, CA242, ferritin, β-human chorionic gonadotropin, alpha 1-fetoprotein, human growth hormone, CA153, CA125, prostate-specific antigen (PSA), and free PSA (fPSA). Materials and Methods: Under a controlled study design, we assigned 143 uremia patients receiving maintenance hemodialysis into hemodialysis group, 143 uremia patients (chronic kidney disease phase 5) who did not receive hemodialysis into nonhemodialysis group, and 429 healthy people into the control group. Serum levels of tumor markers were determined using protein chip and were compared among groups. Patients in hemodialysis group were further divided into two subgroups according to the duration of hemodialysis: Group A (maintenance hemodialysis was over 3 mo), Group B (maintenance hemodialysis was <3 mo), and serum levels of tumor markers were compared between these two subgroups. Results: Ferritin levels were 22.1% and 5.8% in hemodialysis and nonhemodialysis groups, respectively, with statistically significance (P < 0.05), but any of the other tumor marker levels in these two groups were without statistical differences (P > 0.05). In hemodialysis group, 12.23% of patients were found with higher serum levels of CA125 than normal, 9.75% with higher levels of PSA than normal, and 11.3% with higher levels of fPSA than normal. In nonhemodialysis group, 14.91% of patients were found with higher levels of CA125 than normal, 8.76% with higher levels of PSA than normal, and 10.8% with higher levels of fPSA than normal. In the control group, patients with higher levels of the above markers accounted for <5%. Conclusion: Ferritin, CA19-9 and CA125 are elevated to various degrees in patients with uremia who are receiving hemodialysis or do not receive hemodialysis. Hemodialysis is not able to eliminate tumor markers.

Assessment of Nutritional Status by Dual-Energy X-Ray Absorptiometry in Chronic Kidney Disease Patients without Dialysis

Objective: The objective was to evaluate the assessment of nutritional status by dual-energy X-ray absorptiometry (DEXA) in chronic kidney disease (CKD) patients not receiving dialysis. Patients and Methods: A total of 143 patients in stage 4-5 without receiving dialysis were enrolled and classified into well-nourished and malnourished groups by subjective global assessment. Biochemical and anthropometric measurements were performed. Simultaneously, body composition including lean body mass (LBM) and fat mass (FM) was evaluated by DEXA. Results: Compared with well-nourished patients, malnourished patients showed lower pre-albumin (ALB) levels, but higher C-reactive protein (CRP) levels. There was no significant difference in serum ALB between both groups. For either men or women, body weight, body mass index, and glomerular filtration rate (GFR) were lower in the malnourished group. For the men, triceps skin-fold thickness (TSFT), mid-arm circumference (AC), mid-arm muscle circumference (AMC), LBM-DEXA and FM-DEXA were significantly lower in the malnourished patients. For the women, TSFT, mid-AC and FM-DEXA, but mid-AMC and LBM-DEX, were not significantly lower in the malnourished patients. There was a significant correlation between LBM-DEXA and mid-AMC. A significant correlation also existed between FM-DEXA and TSFT. Multiple logistic regressions showed that low percentage of FM, high serum CRP level and low GFR were independent risk factors for malnutrition. Conclusions: Low percentage of FM, high serum CRP and low GFR are independent risk factors for malnutrition. Estimation of LBM and FM by dual X-ray absorptiometry is in consistent with traditional anthropometric measurements. Its noteworthy that DEXA, a reliable and easy-to-perform assessment method, can sensitively detect early malnutrition and may be useful in monitoring nutrition changes in CKD patients.

Investigate the initiation time of continuous blood purification in the multiple organ dysfunction syndrome patients complicated with acute kidney injury

Objective: The objective was to discuss the initiation time of continuous blood purification (CBP) in the multiple organ dysfunction syndrome (MODS) patients complicated with acute kidney injury (AKI). Materials and Methods: We retrospectively analyzed 84 MODS patients combined AKI treated with CBP in intensive care unit during January 2006 to December 2009. The Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and other medical records were reviewed. Different indications for CBP (1 - azotemia, 2 - fluid overload, 3 - hyperklemia, 4 - oliguria, and 5 - metabolic acidosis) were recorded. Patients were characterized as early or late starters, based upon whether the blood urea nitrogen was less than or greater than 25 mmol/L, prior to CBP initiation. Compare the medical records and the mortality of the two groups. Results: The overall mortality in hospital rate was 60.7%. The most indications for CBP initiation were azotemia (95.2%) and oliguria (78.6%). The mortality of the early was 32%, the late was 72.9% ( P = 0.000). Conclusion: Earlier initiation of CBP may improve the prognosis of the MODS patients with AKI.

Ambulatory blood pressure as a predictor of diabetic nephropathy

Objective: The aim was to study the ambulatory blood pressure as a predictor of diabetic nephropathy (DN). Materials and Methods: A total of 73 patients with DN at Stage III were selected as DN group and 73 cases with 5-10 years of diabetes were as diabetes group. The results of blood routine, biochemical indexes, dynamic blood pressure and the diversity index, which as the predictors of DN, analyzed by multivariate logistic regression analysis and compared between two groups. Results: Body mass index, the dose of oral glucose (GLU)-lowering drugs, the levels of fasting plasma GLU, HbA1c, total cholesterol, triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein index had no statistically significant difference in two groups in the course of the disease. There were significant differences in peripheral blood leukocyte count, platelet count, erythrocyte sedimentation rate, uric acid, estimated glomerular filtration rate, average daytime systolic blood pressure (SBP), average nighttime SBP, average daytime diastolic blood pressure (DBP), average night DBP, 24 h SBP variability, daytime SBP variability and nighttime SBP variability between the two groups. In univariate analysis, we found that platelet count ( P = 0.03), average night DBP ( P = 0.01), nighttime SBP variability ( P Conclusion: Platelet count, average diastolic pressure and SBP at night are the independent predictors of DN.