Noninvasive identificational diagnosis of diabetic nephropathy and non-diabetic renal disease based on clinical characteristics of Traditional Chinese Medicine symptom pattern and conventional medicine.

OBJECTIVE: To study the clinical characteristics relating to differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). METHODS: The subjects were patients with type 2 diabetes mellitus (T2DM) complicated with chronic kidney disease (CKD). Western medical history data and Traditional Chinese Medicine (TCM) symptom pattern were collected, and logistic regression was used to analyze. RESULTS: Blood deficiency pattern [odds ratio () = 2.269, 0.017] and stagnation pattern ( = 1.999, 0.041) are independently related to DN. CONCLUSIONS: TCM factors blood deficiency pattern and stagnation pattern are relating to differential diagnosis of DN and NDRD.

Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation.

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-ß-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.

Preference between serum homocysteine and urinary periostin as early predictive biomarkers of renal dysfunction among uncontrolled diabetics.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) represents a serious public health problem. Environmental toxins, other than infectious agents or exposures can stimulate immune responses which are associated with the occurrence of T2DM. Diabetic nephropathy (DN) is a serious complication of diabetes that leads to changes in the structure and function of the kidneys. The study aimed to detect diagnostic biomarkers for (DN), at an early stage, to prevent disease progression in these patients and improve their outcomes. METHODS: This study was performed on 102 T2DM patients and 80 normal controls. Blood glucose, HbA1c, serum homocysteine (Hcy) and urinary periostin were assessed. Patients were divided into: controlled (n=46) (HbA1c <6.5%) and uncontrolled diabetics (n=56) (HbA1c >6.5%). RESULTS: The study results revealed a significant rise in blood glucose and HbA1c as well as serum Hcy levels in diabetic groups compared to controls. Also, urinary periostin exhibited significant elevation in diabetic groups. Serum glucose, HbA1c and serum Hcy revealed a highly significant difference between diabetic subgroups and control groups, while urinary periostin demonstrated a non-significant difference. Only, urinary periostin showed a significant increase in uncontrolled diabetics. CONCLUSIONS: The highest levels of serum Hcy and urinary periostin were recorded only in the uncontrolled diabetics. Urinary periostin was demonstrated as a more preferable biomarker being a non-invasive sample for predicting renal insult in diabetic subjects. This biomarker could be performed regularly for early detection of DN. Also, it could be added to the periodic medical examinations of workers occupationally exposed to workplace pollutants inducing diabetes.

Effectiveness of the Shenzhuo formula in the treatment of patients with macroalbuminuria secondary to diabetic kidney disease: protocol update and statistical analysis plan.

BACKGROUND: Diabetic kidney disease (DKD) is a significant complication of diabetes and has garnered considerable attention. Our previous retrospective study indicated that Shenzhuo formula (SZF) potentially reduces macroalbuminuria secondary to DKD. METHODS: This trial is a 24-week, randomized, multicentric, double-blinded, double-dummy clinical trial. A total of 120 patients with DKD will be equally and randomly divided into two groups: SZF+ irbesartan simulator or irbesartan + SZF simulator. The 24-h urinary protein change from baseline to week 24 is the primary outcome measure. The secondary outcome measures include serum creatinine, estimated glomerular filtration rate, urinary albumin excretion rate, improvement in traditional Chinese medicine symptoms, fasting blood glucose, 2-h postprandial plasma glucose, hemoglobin A1c, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, blood pressure, albumin to creatinine ratio, and the Audit of Diabetes-Dependent Quality of Life 19. Our recruitment began in May 2015; currently, we have recruited 100 participants, with a designed maximum sample size of 120. The interim results were reviewed at N = 60, and continuing recruitment was recommended. This statistical analysis plan includes our approach to missing data imputation, primary and secondary outcomes analyses, and safety endpoints. DISCUSSION: This statistical analysis plan will standardize the clinical trial's statistical analysis and avoid outcome selective reporting bias and data-driven analysis. This trial will provide further clinical evidence regarding the effectiveness of SZF in managing macroalbuminuria secondary to DKD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ICR-15006311. Registered on 26 May 2013. http://www.chictr.org.cn/showproj.aspx?proj=10862.

Metabolic and Anti-inflammatory Response to Melatonin Administration in Patients with Diabetic Nephropathy.

INTRODUCTION: Data on the effects of melatonin administration on metabolic parameters in patients with diabetic nephropathy (DN) is limited and controversial. This study was performed to analyze the effects of melatonin administration on metabolic status in patients with DN. METHODS: This randomized, double blind, placebo-controlled clinical trial was performed on 60 patients with DN. Patients were randomly assigned into two groups to take either 10 mg/d of melatonin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and 12 weeks after intervention to quantify metabolic parameters. RESULTS: Melatonin administration significantly reduced plasma fasting glucose (ß = -10.64 mg/dL; 95% CI: -20.37 to -0.90; P < .05), insulin (ß = -2.37 µIU/mL, 95% CI: -3.33 to -1.41; P < .001), insulin resistance (ß = -0.67, 95% CI: -0.98 to -0.35; P < .001), significantly increased insulin sensitivity (ß = 0.01, 95% CI: 0.006 to 0.01; P < .05), and plasma HDL-cholesterol levels (ß = 2.75 mg/dL, 95% CI: 0.75 to 4.75; P < .05) when compared with the placebo. Melatonin also caused a significant increase in total antioxidant capacity (TAC) (ß = 140.45 mmol/L; 95% CI: 80.48 to 200.41; P < .001), and glutathione (GSH) levels (ß = 50.36 µmol/L, 95% CI: 94.08 to 0.02; P < .05) when compared with placebo. Ultimately, melatonin could upregulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .05) in comparison with placebo. CONCLUSION: Results of this study indicated that melatonin administration for 12 weeks in DN patients had beneficial effects on glycemic control, HDL-cholesterol, TAC and GSH levels, and gene expression of PPAR-γ, but did not affect other metabolic parameters.

Development and validation of the diagnostic scale of traditional Chinese medicine syndrome elements for diabetic kidney disease.

BACKGROUND: To construct a traditional Chinese medicine (TCM) syndrome elements diagnostic scale for diabetic kidney disease (DKD). METHODS: A total of 492 DKD patients were included in the study. TCM symptoms, signs and tongue manifestation information of the patients were collected, which constituted the items of the TCM syndrome elements diagnostic scale. Frequency dominance method was used to screen the core items. Cluster analysis and factor analysis method were used to identify the syndrome elements. Correlation coefficient and regression analysis were used to determine the syndrome elements. Regression coefficient was used to determine the scale items, and the diagnostic threshold was established by receiver operating characteristic curve. By using the above statistical methods , TCM syndrome elements diagnostic scale was constructed, and confirmed via diagnostic tests of 150 patients. RESULTS: There were 61 items of TCM diagnostic descriptions, and we kept the most useful 32 after filtering. After extracting the syndrome elements, a TCM syndrome elements diagnostic rating scale for DKD containing 9 syndrome elements was constructed, which were qi deficiency syndrome, blood deficiency syndrome, yin deficiency syndrome, yang deficiency syndrome, excessive heat syndrome, qi stagnation syndrome, damp heat syndrome, blood stasis syndrome and phlegm turbidity syndrome. A small-sample clinical validation test of the scale showed sensitivity of 78.8-100%, specificity of 84.3-100%, and accuracy of 82.7-100%. CONCLUSIONS: We constructed a TCM syndrome elements diagnostic rating scale for DKD, providing a basis for the standardized study of TCM syndromes.

Effects of Keluoxin capsule combined with losartan potassium on diabetic kidney disease: study protocol for a randomized double-blind placebo-controlled multicenter clinical trial.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most important microvascular complications of diabetes, and its prevalence has increased dramatically in the past few decades. DKD is responsible for considerable morbidity and mortality of patients with diabetes. Keluoxin capsule (KLX) is a Chinese patent medicine that has been used in the clinic to control DKD for years. Previous studies have shown that KLX appears to reduce proteinuria, but the study protocols as well as the primary outcome need to be improved. Thus, we aim to evaluate whether losartan potassium combined with KLX is more effective than losartan potassium in DKD treatment and to provide validated evidence for the application of KLX in the treatment of DKD. METHODS: We will conduct a randomized double-blind placebo-controlled multicenter clinical trial. A total of 252 participants diagnosed with DKD recruited from 18 institutions will be randomly allocated to either a losartan potassium plus KLX (n = 126) or a losartan potassium plus placebo group (n = 126). The participants will be administered KLX or placebo in addition to losartan potassium for 24 weeks. The primary outcome measure will be the decline in estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2/year) from baseline within 24 weeks, and the secondary outcomes will be the incidence of serum creatinine doubling, the incidence of end-stage renal disease (ESRD), the proportion of subjects with a progressive decline in eGFR > 30%, the percent change in 24 h urinary total protein (UTP), the change in the urinary albumin/creatinine ratio (UACR), and the total effective rate of the traditional Chinese medicine (TCM) syndrome scale scores. Comparison of the differences in the variables between groups will be performed according to the data revealed by independent t tests, chi-squared tests, Fisher's exact tests, or Wilcoxon's tests. All statistical tests will be two-sided, and significance will be considered for p values < 0.05. DISCUSSION: This study will be the first randomized clinical trial to evaluate the efficacy and safety of KLX versus the placebo for the treatment of patients with DKD. The outcome of this trial will provide a basis for prescribing KLX to patients with DKD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR1900021113. Registered on January 29, 2019.

Effect of Artemisia absinthium ethanolic extract on oxidative stress markers and the TLR4, S100A4, Bax and Bcl-2 genes expression in the kidney of STZ-induced diabetic rats.

OBJECTIVES: The present study was conducted to examine antidiabetic effects of Artemisia absinthium ethanolic extract [A. absinthium] and to investigate its effects on oxidative stress markers and the expression of TLR4, S100A4, Bax and Bcl-2 genes in the kidney of STZ-induced diabetic rats. METHODS: Thirty six rats (weight 200-250 g) were randomly divided into diabetes and control groups. Induction of diabetes was performed using STZ (55 mg/kg.bw). Biochemical parameters and oxidative stress markers (SOD and MDA) were measured using spectrophotometry after 60 days of treatment. The expression of TLR4, S100A4, Bax and Bcl-2 were analyzed by real-time PCR. One-way analysis of variance (ANOVA) and Bonferroni post hoc test were used to compare the data. RESULTS: Diabetes significantly impairs the serum fasting blood glucose (FBG), lipid profile, urea, creatinine and albumin. At the end of treatment with A. absinthium extract, these parameters were close to the normal range. The results showed that the A. absinthium extract significantly decreased the kidney expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress markers (SOD and MDA) in the kidney tissues of treated rats. Also, all of these beneficial effects of the A. absinthium were dose-dependent. CONCLUSIONS: The extract of A. absinthium possesses antidiabetic effects. A. absinthium decreased the expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress. Therefore, this herbal extract can be used as an adjuvant treatment for diabetic complications.

Role of Vitamin D and Its Analogues in Diabetic Nephropathy: A Meta-analysis.

BACKGROUND: Diabetic nephropathy remains one of the most common causes of chronic kidney disease in the United States and is associated with significant morbidity and mortality. Recently, there have been emerging data highlighting the role of vitamin D and its analogue in chronic kidney disease especially diabetic nephropathy independent of its effect on bone metabolism. METHODS: This study aimed to evaluate effect of supplementing vitamin D and its analogues on halting or slowing progression of diabetic nephropathy. Electronic databases (PubMed, Scopus, Google scholar) were searched and randomized controlled trials (RCTs) that investigated the use of vitamin D and its analogs for diabetic nephropathy were studied. This meta-analysis of RCTs performed in accordance with Preferred Reporting Items for Systematic review and Meta-analysis statement. RESULTS: This meta-analysis included 9 RCTs and suggested a favorable trend with respect to an effect of vitamin D and its analogues on albuminuria though this did not reach statistical significance (MD, -0.17; 95% CI, -0.34-0.01; P = 0.06]. Serum calcium was unaffected suggesting safe use of these agents. CONCLUSIONS: Use of vitamin D and its analogues may have potential as an adjuvant therapy for reducing albuminuria and slowing progression of diabetic nephropathy but further studies are needed.

The effects of vitamin D3 supplementation on some metabolic and inflammatory markers in diabetic nephropathy patients with marginal status of vitamin D: A randomized double blind placebo controlled clinical trial.

AIMS: Diabetic nephropathy is known to be an independent risk factor in the progression of renal and cardiovascular disorders. Due to the association between vitamin D deficiency and diabetic nephropathy, vitamin D deficiency in the diabetic nephropathy population, this study conducted to examine the effects of Vitamin D3 on metabolic and inflammatory parameters in patients with diabetic nephropathy. METHODS: This eight-week, randomized, double-blind, placebo-controlled trial was carried out on 50 diabetic nephropathy patients with marginal status of vitamin D. Participants were randomly assigned to two groups: control and intervention. Participants received a vitamin D3 (50000 IU) supplement weekly on a specific day. Fasting blood samples were collected from all patients at their entry to the study, and eight weeks after intervention. RESULTS: Analyses showed significance differences in physical activity between the intervention and placebo groups (P = 0.018). There were no significant differences between the percentage changes of HbA1c, insulin and, inflammatory parameters such as TNF-α and IL-6 (P > 0.05), while the percentage change of FBS was significantly higher in the placebo group compared to the treatment one (P < 0.0001). Lower levels of FBS (P < 0.0001), insulin (P < 0.069), HOMA-IR (P < 0.001), TNF-α (P< 0.002) and IL-6 (P < 0.037) were found after supplementation in treatment group. However, the phosphorous and protein percentage change in urine were lower (P = 0.07) and higher (P = 0.003) between groups. CONCLUSIONS: It was found that vitamin D supplementation can be regarded as an effective way to prevent the progression of diabetic nephropathy by reducing levels of proteinuria, and inflammatory markers such as TNF-α and IL-6.

The effects of vitamin D supplementation on lipid profiles and oxidative indices among diabetic nephropathy patients with marginal vitamin D status.

AIMS: Diabetic nephropathy is one of the major microvascular complications of type 2 diabetes which insufficient vitamin D might -have a role in it's incidence. This study evaluated the effects of vitamin D supplementation on lipid profiles and oxidative/anti-oxidative indices in marginal vitamin D status patients with diabetic nephropathy. METHODS: For the current paralleled, randomized, double-blinded, placebo-controlled clinical trial, 50 diabetic nephropathy patients with marginal serum vitamin D were selected. Intervention group received 1,25-dihydroxycholecalciferol (50000 IU/week, n = 25), and placebo group (n = 25) received an identical placebo, for 8 weeks. Lipid profiles (LDL, HDL, TG and TC) and oxidative/anti-oxidative markers (TAC, SOD, CAT, GPX and MDA) were measured. RESULTS: Vitamin D supplementation significantly increased vitamin D status in the intervention group, compared to the control group (P = 0.001). The reductions in the serum levels of TG, LDL and TC were significant (P = 0.04, P = 0.006 and P = 0.02, respectively) in the intervention group. The changes in oxidative/anti-oxidative markers and HDL levels were not significant after intervention. CONCLUSION: In conclusion, vitamin D supplementation for 8 weeks among diabetic nephropathy patients has beneficial effects on serum vitamin D status and dyslipidemia.

Effects of traditional Chinese herbal medicine in patients with diabetic kidney disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus and the primary cause of end-stage renal disease. Existing therapies for DKD are not sufficiently effective. We report the protocol of a pragmatic randomized controlled trial of the use of traditional Chinese herbal medicine to treat patients with DKD. METHODS/DESIGN: This will be a multicenter randomized controlled trial. A total of 266 patients with DKD (106 with early stage, 80 with middle-stage, and 80 with advanced-stage disease) with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2will be included. Participants with DKD of each stage will be randomly allocated at a 1:1 ratio to either the experimental group, which will receive Xiaozhen formula and basic treatment, or the control group, which will receive basic treatment only. The study duration will be 24 weeks. The primary outcome will be urinary microalbumin excretion rate for early stage DKD, 24-h urinary protein for middle-stage DKD, and eGFR for advanced-stage DKD. Adverse events will also be evaluated. Data for all outcome indicators will be collected at baseline and weeks 4, 12, and 24. DISCUSSION: This study will provide evidence of the effectiveness and safety of traditional Chinese herbal medicine in treating patients with DKD. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR-IOR-16010072 . Registered on 2 December 2016.

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 µmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311 . Registered on 15 April 2015.

Effects of Coenzyme Q10 Supplementation on Gene Expressions Related to Insulin, Lipid, and Inflammation Pathways in Patients With Diabetic Nephropathy.

INTRODUCTION: Data on the effects of coenzyme Q10 (CQ10) on gene expression related to insulin, lipid, and inflammation in patients with diabetic nephropathy (DN) are scarce. This study aimed to determine the effects of CQ10 supplementation on gene expression related to insulin, lipid, and inflammation pathways in patients with DN. MATERIALS AND METHODS: Forty patients with DN, aged 40 to 85 years old, were randomly assigned into 2 groups to receive either 100 mg/d of CQ10 supplements (n = 20) or placebo (n = 20), for 12 weeks. Gene expression related to signaling pathway of insulin, lipid, and inflammation were determined in blood samples using a reverse transcriptase polymerase chain reaction method. RESULTS: Quantitative results of reverse transcriptase polymerase chain reaction demonstrated that compared with the placebo, CQ10 administration upregulated gene expression of peroxisome proliferator-activated receptor-γ (P = .02) in peripheral blood mononuclear cells of the patients with DN. In addition, compared with the placebo, CQ10 supplementation downregulated gene expression of interleukin-1 (P = .003) and tumor necrosis factor-α (P = .02). No significant effects were observed on gene expression of oxidized low-density lipoprotein, lipoprotein(a), glucose transporter-1, transforming growth factor-ß in the CQ10 group. CONCLUSIONS: Overall, CQ10 supplementation for 12 weeks in DN patients significantly improved gene expression of peroxisome proliferator-activated receptor-γ, interleukin-1, and tumor necrosis factor-α.

Is Fish Oil a Potential Treatment for Diabetic Peripheral Neuropathy?

BACKGROUND: Peripheral neuropathy affects about 50% of the diabetic population. The manifestations range from pain, numbness, paresthesia and ulceration in the extremities and it is the major cause of non-traumatic amputations. Currently there is no effective treatment for peripheral neuropathy. With the prevalence of obesity and type 2 diabetes and associated complications reaching epidemic levels, there is a critical need for finding a treatment to preserve nerve function. INTRODUCTION: This article will review the potential for fish oil as a treatment for diabetic peripheral neuropathy. METHODS: A through search of the PubMed database was performed and relevant articles on the topic were included in this review. RESULTS: Many studies support a role for fish oil in cardiovascular health. However, less information is available regarding the effect of fish oil on diabetes complications including neuropathy. Pre-clinical studies from my laboratory using diabetic rodent models have demonstrated that fish oil can slow progression and reverse diabetic neuropathy as determined by examining multiple endpoints. Mechanistically fish oil has been shown to have anti-inflammatory properties. Lowering the omega-6/omega-3 fatty acid ratio has been shown to be anti-thrombotic. Moreover, metabolites of eicosapentaenoic and docosahexaenoic acids, the main polyunsaturated fatty acids found in fish oil, commonly referred to as resolvins and neuroprotectin have been shown to be neuroprotective and can stimulate neuron outgrowth in vitro. CONCLUSION: Additional studies are required but existing data suggests that dietary enrichment with omega-3 fatty acids contained in fish oil may be beneficial treatment for diabetic neuropathy.

Metabolic Response to Mulberry Extract Supplementation in Patients With Diabetic Nephropathy: a Randomized Controlled Trial.

INTRODUCTION: This study aimed to evaluate the effects of mulberry extract administration on markers of insulin metabolism, lipid concentrations, and biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy (DN). MATERIALS AND METHODS: Sixty patients were randomly allocated into 2 groups to receive either 300 mg/d of mulberry extract (n = 30) or placebo (n = 30), twice per day for 12 weeks. Fasting blood samples were taken at the onset of the study and 12 weeks after supplementation to examine markers of insulin metabolism, lipid concentrations, and biomarkers of inflammation and oxidative stress. RESULTS: Mulberry extract, compared to placebo, resulted in significant reductions in serum triglycerides (-37.3 ± 64.7 mg/dL versus 3.0 ± 78.8 mg/dL, P = .03) and very low-density lipoprotein cholesterol (-7.4 ± 12.9 mg/dL versus 0.6 ± 15.8 mg/dL, P = .03), and a significant increase in high-density lipoprotein cholesterol concentration (0.5 ± 4.0 mg/dL versus -2.0 ± 5.0 mg/dL, P = .03). Other significant changes were in serum high-sensitivity C-reaction protein (-2.3 ± 4.5 µg/mL versus -0.1 ± 2.2 µg/mL, P = .02), plasma glutathione (87.8 ± 159.7 µmol/L versus -24.2 ± 138.8 µmol/L, P = .005) and malondialdehyde (-0.03 ± 0.5 µmol/L versus 0.7 ± 1.0 µmol/L, P < .001).   Conclusions. These findings showed that mulberry extract administration had favorable effects on serum lipids, HSCRP, glutathione, and malondialdehyde levels in DN patients; however, it did not affect markers of insulin metabolism or biomarkers of inflammation and oxidative stress.

Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease.

BACKGROUND: Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. METHODS AND RESULTS: Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% (P<0.001) in diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase (P<0.001). Change in ACR was directly correlated with change in systolic blood pressure (r=0.394, P=0.01). CONCLUSIONS: EPA and DHA supplementation attenuated progression of albuminuria in subjects with type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727.

Kidney Function Improvement by Soy Milk Containing Lactobacillus plantarum A7 in Type 2 Diabetic Patients With Nephropathy: a Double-Blinded Randomized Controlled Trial.

INTRODUCTION: Even with the ultimate medical management, more than one-third of diabetic patients develop diabetic nephropathy. To our knowledge, there is no study that has examined the effect of probiotic soy milk on kidney function in type 2 diabetic patients with nephropathy. This clinical trial aimed to assess the effects of consumption of probiotic soy milk, compared with conventional soy milk, on kidney-related indexes in patients with diabetic nephropathy. MATERIALS AND METHODS: In a randomized double-blinded placebo-controlled trial, 44 patients were randomly assigned to receive 200 mL/d of either soy milk containing Lactobacillus plantarum A7 or conventional soy milk for 8 weeks. Primary endpoints included urinary albumin excretion, estimated glomerular filtration rate, interlukin-18, serum sialic acid, and serum creatinine. Fasting blood samples and morning fasting spot urine samples were collected at the beginning and after 8 weeks for evaluation of biochemical parameters. RESULTS: Forty patients completed the study. Administration of probiotic soymilk resulted in a significant reduction in albuminuria (P = .03), serum creatinine (P < .001), serum interleukin-18 (P = .002), and serum sialic acid (P = .001) compared with conventional soy milk. Probiotic soymilk supplementation also led to a significant improvement in estimated glomerular filtration rate (15.9 ± 10.8 mL/min versus 3.2 ± 8.4 mL/min, P < .001) compared with the control group. CONCLUSIONS: Probiotic soy milk was safe and well-tolerated by patients with diabetic nephropathy for 8 weeks. Probiotic soy milk also improved indexes of kidney function in type 2 diabetic patients with nephropathy.

Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects.

This study determined the effects of probiotic supplementation on glycemic control, lipid concentrations, biomarkers of inflammation and oxidative stress in 60 diabetic patients on hemodialysis in a parallel randomized double-blind placebo-controlled clinical trial. Participants were initially matched based on sex, duration of dialysis and diabetes, body mass index and age. Subsequently, they were randomly divided into two groups to take either a capsule containing the probiotics Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum or placebo for 12 weeks. Based on three-day dietary records throughout the trial, there was no significant change in dietary macro- and micro-nutrients or total dietary fiber to confound results. After the 12 weeks, analysis of patients who received probiotic supplements compared with the placebo showed they had significantly decreased fasting plasma glucose (-22.0 vs. +6.6 mg/dl), serum insulin (-6.4 vs. +2.3 µIU/ml), homeostasis model of assessment-estimated insulin resistance (-2.9 vs. +2.5), homeostasis model of assessment-estimated beta-cell function (-14.1 vs. +6.1) and HbA1c (-0.4 vs. -0.1%,), and improved quantitative insulin sensitivity check index (+0.03 vs. -0.02). Additionally, compared with the placebo, probiotic supplementation resulted in significant reductions in serum high-sensitivity C-reactive protein (-1933 vs. +252 ng/ml), plasma malondialdehyde (-0.3 vs. +1.0 µmol/l), subjective global assessment scores (-0.7 vs. +0.7) and total iron binding capacity (-230 vs. +33 µg/dl), and a significant increase in plasma total antioxidant capacity (+15 vs. -88 mmol/l). Thus, probiotic supplementation for 12 weeks among diabetic hemodialysis patients had beneficial effects on parameters of glucose homeostasis, and some biomarkers of inflammation and oxidative stress.

Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology.

This position paper of the study group "Conservative treatment of Chronic Kidney Disease-CKD" of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin-angiotensin-aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.