Clinical efficacy and safety of warm acupuncture in the treatment of type 2 diabetic kidney disease: A protocol of a randomized controlled trial.

BACKGROUND: Type 2 diabetic kidney disease (DKD) is one of the most common and harmful chronic complications in clinical practice, and there is no reliable and targeted treatment plan at present. As a classic complementary and alternative therapy, evidence have shown that warm acupuncture has advantages in the treatment of type 2 DKD. However, there is still a lack of high-quality and long-term follow-up randomized controlled trials of warm acupuncture in the treatment of type 2 DKD. METHODS: This is a prospective randomized controlled trial to investigate the efficacy and safety of warm acupuncture in the treatment of type 2 DKD. Participants will be randomly assigned in a 1:1 ratio to either the treatment group (treated with conventional Western medicine) or the control group (treated with warm acupuncture added on the basis of the control group). Both groups will receive 12 weeks of treatment followed by 24 weeks of follow-up. Observation indicators include: 24-hour urinary protein quantification, kidney function, TCM syndrome score and adverse reactions. Finally, SPSS21.0 software will be used to analyze the data. DISCUSSION: This study will evaluate the efficacy and safety of warm acupuncture in the treatment of DKD, and the results of this trial will provide clinical evidence for the treatment of type 2 DKD. TRIAL REGISTRATION: The TCTR identification number is TCTR20221104004.

Interval training and Crataegus persica ameliorate diabetic nephropathy via miR-126/Nrf-2 mediated inhibition of stress oxidative in rats with diabetes after myocardial ischemia-reperfusion injury.

Myocardial disorders are the most common cause of renal failure and mortality in diabetic patients, but the molecular mechanism of this process is not yet clear. The reduction of nuclear Erythroid2-related factor-2 (Nrf-2) and positive regulators of Nrf-2 proteins, such as DJ-1 and microRNA-126 (miR-126), after hypoxia and the promotion of reactive oxygen species, might be an intervention indicator in renal failure after myocardial ischemia-reperfusion. Therefore, this study evaluates the renoprotective effect of exercise training and Crataegus persica extract (CE) on myocardial ischemia-reperfusion-induced kidney injury in diabetic rats. Fifty rats were divided into five groups: healthy sedentary control (Con), sedentary diabetic (D), interval trained diabetic (TD), diabetic plus Crataegus persica extract treatment (CD), and interval trained diabetic plus Crataegus persica extract treatment (TCD) groups. The rats in the exercise groups were subjected to moderate-intensity interval training five days per week for ten weeks. The rats in CD and TCD groups received 300 mg/kg of Crataegus persica through gavage for ten weeks. Then, the subjects underwent 30 min of myocardial ischemia and subsequently reperfusion for 24 h. At the end of the experiment, insulin sensitivity, oxidative stress, renal function, histopathology of the kidney, Nrf-2, miR-126, and DJ-1 gene expression levels were evaluated. The results show that the treatments decreased elevated levels of renal oxidative stress, glomerular filtration rate, insulin sensitivity, and pathological score in diabetic rats. Also, the expression of Nrf-2 and miR-126, unlike DJ-1, decreased in diabetic rats due to interval training. Due to the results, diabetes aggravates acute myocardial ischemia-reperfusion-induced kidney injury, while moderate-intensity interval training and Crataegus persica treatment simultaneously ameliorate myocardial ischemia-reperfusion-induced renal injury via miR-126/Nrf-2 pathway and improve insulin sensitivity and renal function in type 1 diabetic rats.

[Protective effect and mechanism of electroacupuncture of "Biao-Ben" acupoints combination for mitochondrial dysfunction in diabetic nephropathy rats].

OBJECTIVE: To study the protective effect of electroacupuncture (EA) at "Biao"-acupoints, "Fenglong"(ST40) and "Zhongwan"(CV12), used for treating symptoms of the disease, and "Ben"-acupoints, "Zusanli"(ST36) and "Guanyuan"(CV4), for treating the root cause of the disease on oxidative stress injury of renal mitochondria through SIRT1/PGC-1α signal pathway in rats with diabetic nephropathy (DN). METHODS: A total of 33 male Wistar rats were randomized into normal (n=10), model (n=12) and EA (n=11) groups.The DN model was established by feeding the rats with high-sugar and high-fat diet for 6 weeks combined with streptozotocin (STZ, 35 mg/kg, i.p.). EA (4 Hz/60 Hz, 1 mA)was applied to ST36-ST40 and CV4-CV12 for 15 min, once every other day for 8 weeks. The rats' body weight was recorded, urine in 24 hours (24-h UP) was collected to measure the urine protein level, and the fasting blood glucose (FBG) level detected by using a glucometer. The levels of serum glycosylated hemoglobin (HbA1c), creatinine (Scr) and urea nitrogen (BUN) were assayed using immunoturbidi-metry, picric acid method and urease method, respectively, and those of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) detected using an automatic biochemical analyzer. The kidney tissue was collected for assaying the activity of superoxide dismutase (SOD) with xanthine oxidase method, glutathione (GSH) activity with dithio-dinitrobenzoic acid method, catalase （CAT） activity with ammonium molybdate spectrometric method, and malondialdehyde (MDA) content with thiobarbituric acid method. Histopathological changes of the kidney tissue were observed by microscope after hematoxylin-eosin staining (HE), periodate Schiff staining (PAS) and Masson staining, separately, and its subcellular structure was observed under transmission electron microscopy. The expression levels of renal SIRT1 and PGC-1α mRNAs and proteins were detected by quantitative real-time PCR and Western blot, and the immunoactivity of renal α-smooth muscle actin (α-SMA), and immunofluorescence density of renal collagen Ⅰ (Col Ⅰ), collagen Ⅳ(Col Ⅳ) and fibronec-tin (FN) detected by immunohistochemistry and immunofluorescence assay, respectively. RESULTS: Compared with the normal group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C, MDA, α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were significantly increased (P<0.01), and the levels of body weight, HDL-C, SOD, GSH, CAT, SIRT1 and PGC-1α mRNAs and proteins were decreased in the model group (P<0.01, P<0.05). In comparison with the model group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C and MDA, and the expressions of α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were markedly down-regulated (P<0.05, P<0.01), and those of body weight, HDL-C, SOD, GSH, CAT, and the expressions of SIRT1 and PGC-1α mRNAs and proteins significantly up-regulated (P<0.01, P<0.05) in the EA group. HE staining showed mesangial dilatation, glomerular hypertrophy and mesangial matrix accumulation; PAS staining showed an increase of the glomerular extracellular matrix deposition; and Masson staining displayed an enhancement of glomerular fibrosis and interstitial space expansion; and electron microscope revealed foot process fusion, basement membrane thickening and organelle injury in the rat's kidney of the model group, which were relatively milder in the EA group. CONCLUSION: EA of ST36-ST40 and CV4-CV12, "Biao-Ben" acupoints combination, can alleviate oxidative stress and mitochondrial dysfunction in DN rats, which may be associated with its functions in up-regulating SIRT1/PGC-1α signaling, and decreasing renal fibrosis.

[Electroacupuncture of "Biaoben acupoints" relieves kidney injury by suppressing oxidative stress in diabetic nephropathy rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of combined "Biao"- and "Ben"-acupoint (for treating symptoms and root causes of the disease, respectively) on the expression of kidney forkhead box O1 (FoxO1) and peroxi-some proliferator-activated receptor-γ coactivator-1α (PGC-1α) in diabetic nephropathy (DN) rats, so as to explore its potential mechanisms underlying improvement of DN. METHODS: Wistar rats were randomly divided into normal control (n=10), DN model (n=12), EA (n=11), EA+inhibitor (AS1842856 targeting FoxO1, n=11) and inhibitor (n=11) groups. The DN model was established by high fat and high glucose diet for 6 weeks and intraperitoneal injection of streptozotocin (55 mg/kg). EA (2 Hz, 1 mA) was applied to bilateral "Zusanli"(ST36), "Guanyuan"(CV4), "Fenglong" (ST40) and "Zhongwan"(CV12) for 15 min, once every other day for 8 weeks. The body mass was recorded, and blood glucose detected. The serum was sampled for detecting creatinine (Scr) content with Jaffe's assay, urea nitrogen (BUN) content with urease method. Urine albumin (ALB) and renal reactive oxygen species (ROS) contents were detected with ELISA, renal superoxide dismutase (SOD) activity with xanthine oxidase method, and renal malondialdehyde (MDA) content with thiobarbituric acid method. The renal subcellular structure was observed under transmission electron microscopy, and the expression levels of PGC-1α and FoxO1 proteins in the kidney tissue were detected using Western blot. RESULTS: Compared with the normal control group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α protein expression were significantly reduced (P<0.01), while the contents of blood glucose, and serum Scr and BUN, urine ALB, renal MDA and ROS levels significantly increased in the model group (P<0.01). In comparison with the model group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α expression were significantly increased in the three treatment groups except SOD, expression of FoxO1 and PGC-1α in the inhibitor group (P<0.01, P<0.05), and the contents of blood glucose, Scr, BUN, ALB, MDA and ROS were obviously decreased in the three treatment groups except ALB and ROS in the inhibitor group (P<0.01, P<0.05). The therapeutic effect of EA was notably superior to that of EA+inhibitor and inhibitor in increasing body mass, SOD activity, and FoxO1 and PGC-1α expression levels (P<0.05, P<0.01), and in down-regulating blood glucose, BUN, ALB and ROS levels (P<0.05, P<0.01), suggesting a reduction of the therapeutic effect of EA after administration of the inhibitor AS1842856 of FoxO1. Results of electron microscopy showed diffusely thickened and vague basement membrane, increased mesangial matrix, fused foot process, and reduced volume of endothelial cells with pykno-tic nucleus of the kidney tissue in the model group, which was obviously milder in both EA and EA+inhibitor groups particularly in the EA group. CONCLUSION: EA increases the expression of FoxO1 and PGC-1α in the kidneys of DN rats, thereby reducing the oxidative stress response and protecting the kidneys.

[Effect of electroacupuncture of "Biao-Ben" acupoints on renal function and hemorheology and eNOS level in patients with early diabetic nephropathy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Biao-Ben acupoints" (Biao indicates pathogenic factors of disease; Ben refers to body constitution) on renal function, hemorheology and endothelial nitric oxide synthase (eNOS) level in patients with early diabetic kidney disease (DKD), so as to explore its mechanism underlying relieving early DKD. METHODS: A total of 120 patients with early DKD were selected and randomized into 3 groups: medication, conventional acupoints, and "Biao-Ben"acupoints groups by stratified randomization method, with 40 cases in each group. Patients of the me-dication group were treated by routine symptomatic supportive treatment (gleziquantel tablets or subcutaneous injection of insulin \[for hyperglycemia\], candesartan tablet \[hypertension\], simvastatin tablets \[hyperlipidemia\], etc.).Based on the medication group, patients of the conventional acupoint group were treated by EA of bilateral Feishu (BL13), Weiwanxiashu (EX-B3), Weishu (BL21), Shenshu (BL23), Sanyinjiao (SP6), Taixi (KI3) (main acupoints), etc., and those of the Biao-Ben acupoint group treated by EA of main acupoints Zhongwan (CV12), Fenglong (ST40), Xuehai (SP10) and Taichong (LR3) (Biao acupoints), and Guanyuan (CV4) and Zusanli (ST36) (Ben acupoints). The EA treatment was conducted one daily, 5 days a week for 8 weeks. The urine microprotein level in 24 h was detected using an automatic specific protein analyzer, followed by calcula-ting the urine albumin excretion rate (UAER). The serum creatinine (Scr), urea nitrogen (BUN) and cystatin (CysC) contents were detected by using an automatic biochemical analyzer, and the whole blood low-cut viscosity (ηbL), whole blood mid-cut viscosity (ηbM), whole blood high-cut viscosity (ηbH), plasma viscosity (ηp) and fibrinogen (FIB) levels were detected using an automatic hemorheology tester, and the serum eNOS and nitric oxide (NO) levels assayed using enzyme linked immunosorbent assay. The total clinical effective rates were compared and the adverse reactions of the treatment were recorded. RESULTS: Compared with the values before the treatment in each group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were all significantly decreased (P<0.01), while serum eNOS and NO levels significantly increased in the three groups after the treatment (P<0.01). Compared with the medication group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were notably lower (P<0.01, P<0.05), and serum eNOS and NO contents obviously higher in both the conventional acupoint and "Biao-Ben" acupoint groups (P<0.01). Comparison between the two EA groups showed that the levels of UAER, BUN, ηbL, ηbM, ηbH and ηp were lower (P<0.05), whereas the serum eNOS and NO contents were considerably higher (P<0.05) in the "Biao-Ben" acupoint group than in the conventional acupoint group. After the treatment, the total clinical effective rate of the "Biao-Ben" acupoint group was 89.74%(35/39), being significantly higher than those of both the conventional acupoint group (71.05%, 27/38,P<0.05) and medication group (64.10%, 25/39, P<0.05). CONCLUSION: EA of "Biao-Ben" acupoints can improve renal function and reduce microcirculation disorders in patients with early DKD, which may be related to its function in up-regulating the levels of serum eNOS and NO.

[Effect of electroacupuncture on renal function and expression of autophagy-related proteins in kidney of rats with diabetic nephropathy].

OBJECTIVE: To observe the effect of electroacupuncture(EA)on renal function and autophagy-related protein expression in diabetic nephropathy (DN) rats，so as to explore its mechanisms underlying improvement of DN. METHODS: Male Wistar rats were randomly divided into normal control，DN model and EA groups (n=8 rats in each group). The DN model was established by high-fat diet (for 4 weeks) + streptozotocin (STZ，35 mg/kg，i.p.). EA (2 Hz/15 Hz，1 mA) was applied to bilateral "Shenshu"(BL23)and "Zusanli"(ST36)for 20 min，5 times a week for 6 consecutive weeks. The urine volume in 24 h (24 h-UV) was recorded，the levels of urine protein in 24 h (24 h-UP)，blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by using an automatic biochemical analyzer，and the fasting blood glucose (FBG) was detected using rapid blood glucose paper test. The histopathological changes of glomerulus of the left kidney were observed after periodic acid-Schiff stain (PAS) and the ultra-microstructural changes，the numbers of autophagosomes and autophagic vacuoles of the right kidney were observed by transmission electronic microscope (TEM). The expression and localization of podocyte marker protein Nephrin was detected by using immunofluorescence assay，and the expression levels of autophagy-related proteins microtubule associated protein 1 (LC3)，Beclin-1，p62 and Nephrin in the kidney tissue measured by Western blot. RESULTS: Before treatment,compared with the normal control group，the levels of 24 h-UV，24 h-UP and FBG were significantly increased (P<0.01) in the model and EA groups. After treatment, compared with the normal group，the levels of 24 h-UV，24 h-UP，FBG，BUN，Scr and p62 protein expression were signi-ficantly increased (P<0.01)，and the expression levels of LC3Ⅱ，Beclin-1 and Nephrin proteins and ratio of LC3Ⅱ/Ⅰ were significantly decreased (P<0.01) in the model group. Compared with the model group，the levels of 24 h-UV，24 h-UP，FBG，BUN and p62 were apparently decreased (P<0.01，P<0.05)，while the expression levels of LC3Ⅱ，Beclin-1 and Nephrin proteins and ratio of LC3Ⅱ/Ⅰ were obviously up-regulated (P<0.01，P<0.05) in the EA group. No significant changes were found in the level of Scr after EA (P>0.05) and in the expression levels of LC3 Ⅰ after modeling and EA (P>0.05). Outcomes of PAS showed blurred structure of the glomerulus with obvious proliferation of glomerular mesangial cells，increase of cell matrix，and thickening of basement membrane of the glomerulus and renal tubule，atrophy of epithelia cells of renal tubules and infiltration of inflammatory cells in the renal interstitum; and TEM revealed fusion and exfoliation of some foot processes，bareness or thickening of some basement membrane，and reduction of number of autophagosomes or autophagobubbles in podocytes in the model group，which was relatively milder in the EA group. CONCLUSION: EA can effectively alleviate kidney damage in DN rats，which may be related to its function in facilitating autophagy in the kidney.

Mitochondrial Dysfunction and Diabetic Nephropathy: Nontraditional Therapeutic Opportunities.

Diabetic nephropathy (DN) is a progressive microvascular diabetic complication. Growing evidence shows that persistent mitochondrial dysfunction contributes to the progression of renal diseases, including DN, as it alters mitochondrial homeostasis and, in turn, affects normal kidney function. Pharmacological regulation of mitochondrial networking is a promising therapeutic strategy for preventing and restoring renal function in DN. In this review, we have surveyed recent advances in elucidating the mitochondrial networking and signaling pathways in physiological and pathological contexts. Additionally, we have considered the contributions of nontraditional therapy that ameliorate mitochondrial dysfunction and discussed their molecular mechanism, highlighting the potential value of nontraditional therapies, such as herbal medicine and lifestyle interventions, in therapeutic interventions for DN. The generation of new insights using mitochondrial networking will facilitate further investigations on nontraditional therapies for DN.

Effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy and effects on serum miR-126 and miR-342 levels.

This study aims to investigate the effect of hyperbaric oxygen combined with alprostadil in the treatment of elderly diabetic nephropathy (DN) and its effect on serum miR-126 and miR-342 levels. The total effective rate of the study group was 91.53% after treatment, which was higher than that (74.58%) of the control group (p<0.05); the levels of UAER, Scr, BUN and HbA1c, FPG, 2h PG were lowered in the two groups after treatment, and the levels of these indexes were lower in the study group than those in the control group (p<0.05); the levels of vWF, ET-1, CD8+, miR-342 were lowered after treatment for the two groups, and the levels of these indexes were lower in the study group than those in the control group; the levels of NO, CD3+, CD4+ and miR-126 were increased after treatment and the levels were higher in the study group than those in the control group (p<0.05). The application of hyperbaric oxygen combined with alprostadil in the treatment of elderly DN patients can improve renal function, lower blood glucose, improve vascular endothelial function and immune function, adjust serum miR-126 and miR-342 levels, thereby increasing curative effect.

Effect of Oral carnosine supplementation on urinary TGF-ß in diabetic nephropathy: a randomized controlled trial.

BACKGROUND: Activation of the transforming growth factor beta (TGF-ß) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a dipeptide that can inhibit TGF-ß synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-ß levels among patients with diabetic nephropathy. METHODS: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-ß level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-ß. RESULTS: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-ß and renal function measurements. Urinary TGF-ß significantly decreased with carnosine supplement (- 17.8% of the baseline values), whereas it tended to increase with placebo (+ 16.9% of the baseline values) (between-group difference P < 0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects. CONCLUSIONS: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-ß level that serves as a marker of renal injury in diabetic nephropathy. TRIAL REGISTRATION: Thai Clinical Trials, TCTR20200724002 . Retrospectively Registered 24 July 2020.

Meta-analysis-based systematic review of effect of traditional Chinese medicine intervention in treatment of diabetic nephropathy on thyroid function.

BACKGROUND: This research sought to systematically evaluate the clinical effects of traditional Chinese medicine (TCM) intervention in the treatment of diabetic nephropathy (DN) and analyze changes in thyroid function in patients with DN. METHODS: The PubMed, Embase, Medline, Ovid, Springer, and self-built databases were searched to screen literature on TCM intervention and the treatment of DN published from the establishment of the databases to January 1, 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was then employed to assess the risk of bias in literature, and Review Manager 5.3 was utilized for the meta-analysis. RESULTS: A total of 20 randomized controlled trials (RCTs) were included in the study, involving 3,566 subjects, and meta-analysis results showed that the clinical treatment efficiency of the experimental group was dramatically higher than the control group [MD =6.22, 95% confidence interval (CI): 3.77-10.25, Z=7.17, P<0.00001]. Moreover, the serum creatinine (Scr), blood urea nitrogen (BUN), urine protein excretion rate (UAER), 24 h postoperative urine protein quantification, and tumor necrosis factor-alpha (TNF-α) of patients after TCM intervention were all remarkably inferior to those of the control group as seen in the following results: Scr, MD =-8.69, 95% CI: -9.92 to -7.47, Z=13.94, P<0.00001; BUN, MD =-1.74, 95% CI: - 2.48 to -1.00, Z=4.6, P<0.00001; UAER, MD =-26.16, 95% CI: -46.89 to -5.44, Z=2.47, P=0.01; 24 h postoperative urine protein quantification, MD =-0.54, 95% CI: -0.68 to -0.4, Z=7.4, P<0.00001; TNF-α, MD =-5.3, 95% CI: -9.15 to -1.46, Z=2.7, P=0.007; and high sensitivity C-reactive protein (hs-CRP), MD =-1.34, 95% CI: -1.9 to -0.78, Z=4.66, P<0.00001. DISCUSSION: TCM intervention in DN is effective in treating the clinical symptoms of patients with this disease and has ideal therapeutic effects.

Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. AIM: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. MATERIAL AND METHODS: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. RESULTS: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. CONCLUSION: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Ketoanalogue supplements reduce mortality in patients with pre-dialysis advanced diabetic kidney disease: A nationwide population-based study.

BACKGROUND & AIMS: Metabolism dysregulation and protein energy wasting occur in patients with chronic kidney disease (CKD) and are associated with poor survival, especially in patients prior to starting dialysis. Accumulating evidence indicates that dietary supplementation with ketoanalogues (KAs, a mixture of branched-chain amino acids) exerts a variety of beneficial effects for patients with CKD. However, the role of KAs in diabetic kidney disease (DKD), one of the major causes of CKD, is still controversial. The aim of this study was to explore the impact of KA supplements on survival in patients with stage 5 DKD who have not yet started dialysis (DKD-5-ND). METHODS: We analyzed a nationwide cohort retrieved from the National Health Insurance Research Database in Taiwan to study the long-term impact of KA supplements in patients with DKD-5-ND. We enrolled 15,782 incident pre-dialysis DKD patients between January 1, 2004 and December 31, 2007. Landmark analysis was used to eliminate immortal bias, and overlap weighting was used to balance differences between the KA users and nonusers in the beginning. The primary study endpoint was all-cause mortality, and the occurrence of permanent dialysis (presenting the end-stage renal disease, ESRD) and major adverse cardiovascular events (MACEs) was also evaluated. All patients were followed for five years or until death. RESULTS: The prevalence of KA usage in the DKD-5-ND patients was 6.3%. The 5-year all-cause mortality rate in the KA users was lower than that in the nonusers (34.7% vs 42.7%). After adjusting for known covariates, the KA users still had a lower risk of mortality (adjusted hazard ratio [aHR]: 0.73, 95% confidence interval [CI]: 0.66-0.82). In addition, the incidence of ESRD was also slightly lower among the KA users (90.9% for users vs 91.2% for nonusers, adjusted cause-specific hazard ratio [aCSHR]: 0.65, 95% CI: 0.61-0.69), and the occurrence of MACEs was lower (adjusted incidence rate ratios [aIRR]: 0.76, 95% CI: 0.67-0.86). Although the all-cause mortality was higher among patientsolder than 70 years (60.5% for KA users vs 46.5% for nonusers) the risk reduction seemed prominent among older patients (aHR: 0.65, 95% CI: 0.56-0.76 for patients aged ≥70 years; aHR: 0.82, 95% CI: 0.71-0.96 for patients aged < 70 years). The reduction in risks of mortality was consistent in subgroup analysis and sensitivity tests. CONCLUSIONS: The use of KA supplements seemed to be beneficial for patients with DKD-5-ND; further in-depth analysis of using KA for these patients is warranted.

Ameliorative effect of white tea from 50-year-old tree of Camellia sinensis L. (Theaceae) on kidney damage in diabetic mice via SIRT1/AMPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney damage (DKD) is one of the most common complications of diabetes, which is known as a chronic inflammatory kidney disease caused by persistent hyperglycemia. White tea was originally used as a folk medicine to treat measles in ancient China. What arouses our interest is that there is a traditional method to treat diabetes with white tea taken from over 30-year-old tree of Camellia sinensis L. However, there are few reports on the renal protection of white tea. AIM OF THE STUDY: This present study was designed to study the potential protective effects of white tea (WT) and old tree white tea (OTWT) on high-fat-diet (HFD) combined with streptozotocin (STZ)-induced type 2 diabetic mice to explore the possible mechanism of WT/OTWT against DKD. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into four groups: NC, T2D, WT (400 mg/kg·b.w, p.o.), OTWT (400 mg/kg·b.w, p.o.). Diabetes was established in all groups except NC group, by six weeks of HFD feeding combined with STZ (50 mg/kg, i.p.) for 3 times, treatments were administered for six weeks and then all the animals were decapitated; kidney tissues and blood samples were collected for the further analysis, including: levels of insulin, lipid metabolism (TG, TC, HDL, LDL, FFA), antioxidative enzymes (catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPx)), blood urea nitrogen (BUN) and creatine, inflammatory cytokines (TNF-α, IL-1ß, COX-2, iNOS, MCP-1), advanced glycation end products (AGE), receptor of AGE (RAGE), Nrf2, AMPK, SIRT1, and PGC-1α. H&E, PAS and Masson staining were performed to examine the histopathological alterations of the kidneys. RESULTS: Our data showed that WT and OTWT reversed the abnormal serum lipids (TG, TC, HDL, LDL, FFA) in T2D mice, upregulated antioxidative enzymes levels (CAT, SOD, GPx) and inhibit the excessive production of proinflammatory mediators (including MCP-1, TNF-α, IL1ß, COX-2 and iNOS) by varying degrees, and OTWT was more effective. In histopathology, OTWT could significantly alleviate the accumulation of renal AGE in T2D mice, thereby improving the structural changes of the kidneys, such as glomerular hypertrophy, glomerular basement membrane thickening and kidney FIbrosis. CONCLUSIONS: Both WT and OTWT could alleviate the diabetic changes in T2D mice via hypoglycemic, hypolipidemic, anti-oxidative and anti-inflammatory effects, while OTWT was more evident. OTWT could prominently alleviate the accumulation of AGE in the kidneys of T2D mice, thereby ameliorating the renal oxidative stress and inflammatory damage, which was associated with the activation of SIRT1/AMPK pathway.

Electro-Acupuncture Protects Diabetic Nephropathy-Induced Inflammation Through Suppression of NLRP3 Inflammasome in Renal Macrophage Isolation.

BACKGROUND: With the increasing prevalence of diabetes in recent years, diabetic nephropathy (DN) has also become a dangerous disease that greatly endangers human health. The study was designed to determine the mechanism and effect of Electro-acupuncture (EA) in alleviating DN-induced inflammation. METHODS: Mice were intraperitoneally injected with STZ (streptozotocin, 50 mg/kg, S0130, Sigma, St. Louis, MO, USA) for five consecutive days. After 12 weeks of induction, blood glucose levels were measured (>300 mg/dL). RESULTS: The serum levels of IL-1ß and IL-6 were decreased in EA-treated DN mice, and EA protected renal injury. EA could suppress HMGB1/NLRP3/NF-κB pathway. HMGB1 inhibition increased the anti-inflammatory effects of EA on DN by suppressing NLRP3/NF-κB pathway. The activation of HMGB1 attenuated the anti-inflammatory effects of EA on DN by inducing NLRP3/ NF-κB pathway. CONCLUSION: These results suggested that EA protected DN-induced inflammation through the suppression of NLRP3 inflammasome.

Efficacy and safety of Shenkang injection as adjuvant therapy in patients with diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy is a frequent microvascular complication of diabetes mellitus that causes end-stage renal disease most of the time. In China, Shenkang injection is one of widely used traditional Chinese medicine for treating chronic kidney disease, but its efficacy and safety have not yet been clarified. We will systematically review the current randomized controlled trial (RCT) evidence to summarize the efficacy and safety of Shenkang injection in treating diabetic nephropathy. METHODS: We will search 7 literature databases including PubMed, EMBASE, Cochrane Library, Sinomed, Chinese National Knowledge Infrastructure, Wanfang, and VIP. Two trial registry platforms will also be searched. The time frame of the search will be from the inceptions of the databases to December 31, 2020. RCTs assessing Shenkang injection combined with basic treatments versus basic treatments alone for treating diabetic nephropathy will be included. The risk of bias within the individual RCTs will be evaluated using criteria proposed by the Cochrane Handbook 5.1.0. The primary outcomes to be investigated are glomerular filtration rate and serum creatinine; the secondary outcome will include 24-hour urine albumin excretion rate, blood urea nitrogen, fasting blood glucose, postprandial blood glucose, hemoglobin A1c, total cholesterol, triglyceride, response to treatment, and incidence of adverse events. The effect data of individual RCTs by performing random-effects model meta-analysis. Statistical heterogeneity will be measured by the Cochran Q test and I-squared statistics. Three subgroup analyses, set based on clinical experience, will be performed to explore the sources of heterogeneity. Sensitivity analyses excluding RCTs with high risk of bias and using fixed effect model will be done to test the robustness of the meta-analytic results. Publication bias across included RCTs will be evaluated by funnel plots and Egger test. RESULTS: This study will provide systematic review on the efficacy and safety of Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy by rigorous quality assessment and reasonable data synthesis. The results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This systematic review will provide the best evidence currently on Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy. INPLASY REGISTRATION NUMBER: INPLASY2020110014.

Clinical efficacy of adjuvant therapy with hyperbaric oxygen in diabetic nephropathy.

Background and objective: Diabetic kidney disease (DKD) is the most common microvascular chronic complication of diabetes mellitus. Hyperbaric oxygen (HBO2) therapy will increase the partial pressure of oxygen (PaO2) and may improve cell repair processes, which can lead to better renal function. The objective of this study was to quantify the efficacy of adjuvant HBO2 to increase the glomerular filtration rate and urinary albumin excretion in diabetic patients, as well as determine its effectiveness to modify the clinical course of DKD. Materials and methods: An experimental study was performed on patients with stage 3 and 4 DKD. Twenty sessions of HBO2 or ambient air in a hyperbaric chamber were administered. Estimated glomerular filtration rate, urine albumin:creatinine ratio calculation and clinical stage stratification were made prior to and after HBO2 administration. A descriptive, inferential and clinical efficacy analysis was performed. Results: Urinary albumin/creatinine (UACR) mean values prior to HBO2 were 1452.9 ± 644.3 mg/g and decreased to 876.1 ± 504.0 mg/g at the end of the study (p=0.06). The patients in the control group showed a UACR mean of 2784.5 ± 2128.6 mg/g and 2861.4 ± 2424.2 mg/g at baseline and at the end of the study, respectively (p=0.82). Patients in the experimental/HBO2 group showed an estimated GFR of 27.3 ± 9.5 mL/min /1.73m2 before HBO2, with a 34.4 ± 6.9 mL/min/1.73m2 after treatment (p=0.017); control group eGFR was 30.1 ± 9.2 mL/min/1.73m2, decreasing to 22.2 ± 6.8 mL/min/1.73m2 (p=0.004). Relative risk 0.00, relative risk reduction -100%, absolute risk reduction -71.4%, 95% CI (-104.9% to -38.0%), NNT 1, 95% CI (1 to 3). Conclusions: Management with HBO2 for DKD was associated with decreased excretion urinary albumin, improved GFR and clinical stage of patients in stages 3 and 4 of kidney damage unlike those receiving ambient air..

Effect of acupressure at Sanyinjiao on albuminuria in patients with early diabetic nephropathy: A single-blind, randomized, controlled preliminary study.

BACKGROUND: Elevated urinary albumin excretion is a clinical manifestation of early-stage diabetic nephropathy (DN). PURPOSE: To investigate effect of acupressure at Sanyinjiao on albuminuria in patients with early DN. METHODS: Total included 53 patients with DN and albuminuria; 21 were assigned to the sham group without acupressure, and 32 were assigned to the experimental group with acupressure at Sanyinjiao (SP6) for 8weeks. The experimental group was divided into experiment A (acupressure <45 days) and experiment B (acupressure ≥45 days). The primary outcome measure was the urine albuminuria/creatinine ratio (UACR) or logarithmic transformed urine microalbumin creatinine ratio (log-UACR) changes, and the secondary outcome measures were the estimated glomerular filtration rate and hemoglobin A1c. RESULTS: The difference in UACR and log-UACR before and after the study was higher in the experiment B group than in the experiment A and sham groups. CONCLUSION: Acupressure at Sanyinjiao for 8 weeks may reduce albuminuria in patients with DN. However, this study was a preliminary design.

Clinical research on individualized hemodialysis preventing unconventional hypotension in diabetic nephropathy patient.

OBJECTIVE: This study aims to evaluate the effectiveness of individualized hemodialysis for unconventional hypotension in diabetic nephropathy patients. METHODS: A total of 60 patients were selected and randomly divided into study group and control group. The control group used the standard dialysis model, while the study group used the individualized hemodialysis scheme, in which the dialysis was performed using an individualized dialysis machine temperature control, pattern of natrium, and pattern of step ultrafiltration in combination with dialysate-containing glucose. RESULTS: The total occurrence rate of hypotension, dry weight standard-reaching rate, and blood quality during and after dialysis in the study group were superior to those in the control group (P < 0.05). Furthermore, the symptom scores in the study group (dizziness score, chest distress score, sweating score, muscle spasm score, gastrointestinal symptom score, and temporary mind change score) were lower than those in the control group (P < 0.05). The serum sodium, potassium, and chloride concentration in these two groups after dialysis was not statistically different (P > 0.05). CONCLUSION: The combined application of low temperature, pattern of natrium, pattern of step ultrafiltration, and dialysate-containing glucose individualization is safe and effective for preventing and controlling the occurrence of intradialytic hypotension (IDH), improve symptoms, and improve the dry weight standard-reaching rate.

Effectiveness comparisons of acupuncture for diabetic nephropathy proteinuria: A systematic review and meta-analysis: study protocol.

INTRODUCTION: Diabetic nephropathy (DN) is one of the microvascular complications of diabetes (DM). Proteinuria is the most important clinical feature of DN and an independent risk factor for the progression of DN. Therefore, reducing urinary protein is the primary goal of DN treatment. Acupuncture has long been widely used in the treatment of DN. Therefore, this paper conducted a meta-analysis of the clinical efficacy of acupuncture in the treatment of DN proteinuria, in order to comprehensively analyze the role of acupuncture in the treatment of DN. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to September 2019.We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of DN proteinuria. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture for DN proteinuria. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019139705.