Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/ß-catenin pathway. Here, we collected demographic information and laboratory results from the National Health and Nutrition Examination Survey (NHANES) database in order to investigate the relationship between VD and DN. Then, we established a DN model and treated DN rats with Tan and paricalcitol (Par) for 6 weeks. We subsequently compared the changes in general condition, renal function, pathological changes, and TIF-related protein expression levels of control rats, DN rats induced by STZ, DN rats with Tan at 5.4 mg/kg, DN rats with Tan at 10.8 mg/kg, and DN rats with Par at 0.054 µg/kg, to explore the effect and mechanism of Tan and Par on DN rats. The results showed that VD had a protective effect against DN in diabetic patients. And we found that Tan had a protective effect on renal fibrosis in DN rats, which was superior to Par in improving the symptoms of "three more and one less," reducing fasting blood glucose level, improving renal index, BUN/SCr, and UACR, reducing histopathological damage of kidney, and improving the expression of fibrosis-related proteins in kidney tissue by regulating VDR/Wnt/ß-catenin pathway. Tan was superior to Par in ameliorating tubulointerstitial fibrosis by regulating VDR/Wnt/ß-catenin pathway in rats with diabetic nephropathy.

Chronic Kidney Disease Induces Cognitive Impairment in the Early Stage.

OBJECTIVE: Previous research indicates a link between cognitive impairment and chronic kidney disease (CKD), but the underlying factors are not fully understood. This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early- and late-stage CKD models in Sprague-Dawley rats. METHODS: The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery. Histopathologic examinations were conducted to examine renal and hippocampal damage. Real-time PCR, Western blotting analysis, and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor (BDNF), choline acetyltransferase (ChAT), and synaptophysin (SYP). RESULTS: Compared with the control rats, the rats with early-stage CKD exhibited mild renal damage, while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage. The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats, with further deterioration observed in the rats with late-stage CKD. Additionally, we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD, which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD. CONCLUSION: These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly. In addition, the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.

The Effects of Rhubarb for the Treatment of Diabetic Nephropathy in Animals: A Systematic Review and Meta-analysis.

Background: Rhubarb, also known as Da Huang, is a traditional Chinese medicine, and it was often used as a laxative in the past. Recently, multiple studies have applied rhubarb to treat diabetic nephropathy (DN). Anthraquinones, including emodin and rhein, have been extracted from rhubarb and used to explore the effective components and possible mechanisms of rhubarb for DN. Evaluating the efficacy of rhubarb may provide a scientific reference for the clinical application of rhubarb for the treatment of DN. Objective: 1) To evaluate the efficacy of rhubarb in the treatment of DN; 2) To identify the most effective ingredient of rhubarb for DN; 3) To explore the specific mechanism of rhubarb in treating DN. Methods: Data sources: related studies were identified by searching Cochrane Library, Ovid-EMBASE, PubMed, SinoMed, WanFang, VIP, CNKI, and other Chinese magazines. Assessment and analysis: SYRCLE's risk of bias tool for animal studies was used to assess the quality of articles. The meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Data analysis adopted RevMan 5.3 and STATA 12.0 software. This study was published in the register with PROSPERO, number CRD42020204701. Results: Aggregated data were collected from 27 eligible studies. The results illustrated an intense improvement in the following outcomes in rhubarb-treated animals with DN (p < 0.05): blood glucose, serum creatinine (Scr), blood urea nitrogen (BUN), albumin creatinine ratio (ACR), urine protein (UP), urinary albumin excretion (UAE), renal index (two kidneys weight/body weight, KW/BW), tubulointerstitial injury index (TII), transforming growth factor-beta1 (TGF-ß1) mRNA and protein, alpha-smooth muscle actin (α-SMA) protein, and E-cadherin (E-cad) protein. Of these, DN animals with rhubarb exhibited a significantly higher level of E-cad protein. In addition, the level of the other outcomes mentioned above decreased significantly, while there was no significant association between the intervention and nephrin protein (p > 0.05). Conclusion: This systematic review and meta-analysis demonstrated that rhubarb has a positive therapeutic effect on animals with DN, which may provide confidence and some theoretical reference for clinical application to a certain extent.

Effects of insulin resistance on left ventricular hypertrophy in patients with CKD stage 1-3.

BACKGROUND: Left ventricular hypertrophy (LVH) existed in patients with early stage chronic kidney disease (CKD). But whether insulin resistance (IR) exists in these patients and has some definite relationship with LVH, is unknown. METHODS: Homeostatic model method was used for detecting homeostasis model assessment of insulin resistance (HOMA-IR) in 336 subjects including 286 patients with early stage CKD and 50 control subjects, and HOMA-IR and other clinical data in all subjects were obtained based on standard methods. Then, the relationship between LVH, IR and other relevant clinical data were analyzed. RESULTS: IR and LVH existed in early stage CKD patients. The prevalence of LVH in patients with IR was significantly higher than those without, and patients with LVH had a higher prevalence of IR than those without. The patients with IR or LVH had lower levels of e-GFR, hemoglobin (Hb) and total cholesterol, while higher levels of blood urea nitrogen (BUN), serum creatinine (Scr), intact parathyroid hormone (iPTH), CRP and systolic blood pressure (SBP). HOMA-IR had positive correlations with left ventricular mass index (LVMI). HOMA-IR and LVMI had positive correlations with BUN, Scr, iPTH and CRP, but negative with e-GFR and Hb. Multiple linear stepwise regression analysis showed that e-GFR, FINS, Hb and SBP enter the regression equation. Binary unconditional logistic regression analysis indicated that the main risk factors for LVH were CKD and IR (P < 0.05, respectively). CONCLUSION: Both IR and LVH existed in early stage CKD patients and were more severe with the development of CKD. IR had a significant correlation with LVH. Furthermore, decline of e-GFR, hypertension and anemia were also associated with both IR and LVH and may have some effects in the mechanism of IR on the development of LVH.

[A multi-center survey of hypertension and its treatment in patients with maintenance hemodialysis in Shanghai].

OBJECTIVE: To study the prevalence, treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control. METHODS: We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female. Hypertension was defined as systolic blood pressure (SBP)≥140 and/or diastolic blood pressure (DBP)≥90 mm Hg (1 mm Hg=0.133 kPa). Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey. Hypertension control was defined as blood pressure<140/90 mm Hg before each dialysis session. RESULTS: The prevalence of hypertension in the hemodialysis patients was 86.3%. The treatment rate and control rate in those patients were 96.8% and 25.5% respectively. More than half (50.4%) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more. Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin II receptor blockers (56.4%), centrally acting anti-hypertensive agent (26.4%), beta blockers and alpha, beta-blockers (14.0%). The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease. The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension. The hypertension control rate elevated significantly with the adequate hemodialysis. CONCLUSIONS: There is a very high prevalence of hypertension in maintenance hemodialysis patients. Although the treatment rate is high, the control rate is unsatisfactory. So the control of hypertension in hemodialysis patient is still a clinical challenge. Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.

[The relationship between insulin resistance and left ventricular hypertrophy in patients with early chronic kidney disease.].

OBJECTIVE: To analyze the relationship between insulin resistance (IR) and left ventricular hypertrophy (LVH) in patients with early chronic kidney disease (CKD). METHODS: Homeostatic model method was used for detecting insulin resistance index (Homa-IR) in 108 patients with early CKD and 25 normal healthy cases, and the other clinical data such as Hb, creatinine clearance rate (Ccr), parathyroid hormone (PTH), ambulatory blood pressure monitoring (ABPM) data, including day average systolic blood pressure (dSBP), day average diastolic blood pressure (dDBP), night average systolic blood pressure (nSBP), night average diastolic blood pressure (nDBP), 24-hour mean systolic blood pressure (mSBP), 24-hour mean diastolic blood pressure (mDBP), decline in the percentage of diastolic blood pressure at night (nDPD) and decline in the percentage of systolic blood pressure at night (nDPS) were also measured. Echocardiography was used for measuring LVH relevant data, and left ventricular mass index (LVMI) was calculated. Then, the relationship between LVH and IR and other clinical data were analyzed retrospectively. RESULTS: IR existed in early CKD patients. With the decline of Ccr, both the value of Homa-IR and the incidence of IR increased significantly (both P < 0.05). LVH existed in early CKD patients and with the decline of Ccr, both LVMI value and the incidence of LVH increased significantly (both P < 0.01). Compared with the non-IR group, the IR group had higher LVMI value (P < 0.05) and higher incidence of LVH (P < 0.01). Compared with the non-LVH group, the LVH group had higher levels of FIns, 2hPG, Homa-IR (all P < 0.05), and higher incidence of IR (P < 0.01). The LVH group had significant lower levels of Ccr, Hb and nDPD (all P < 0.05), higher levels of dSBP, dDBP, nSBP, nDBP, mSBP, mDBP and PTH (all P < 0.05) than the non-LVH group. LVMI had significant positive correlations with 2hPG, FIns, Homa-IR, dSBP, nSBP, mSBP and PTH (r = 0.255, 0.373, 0.376, 0.222, 0.199, 0.225, 0.221, 0.246, respectively; all P < 0.05), but significant negative correlations with Hb and Ccr (r = -0.588, -0.313, respectively; both P < 0.01). Multi-factor regression analysis showed that Hb, Homa-IR, and Ccr entered the regression equation (y = 167.106 - 0.755x(1)+0.250x(2)+0.322x(3), y = LVMI; 167.106 = constant, t = 12.138, P = 0.000; x(1) = Hb, t = -6.800, P = 0.000; x(2) = Homa-IR, t = 3.229, P = 0.002; x(3) = Ccr, t = 2.898, P = 0.005). CONCLUSION: IR existed in early CKD patients and become more severe with the decline of renal function. IR had a significant correlation with LVH, and it may be an important risk factor for the development of LVH. Besides, both anemia and decline of renal function are also associated with LVH.