Urinary SIRT2 Reflects Kidney Injury in Type 2 Diabetes.

INTRODUCTION: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. METHODS: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. RESULTS: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), ß2-microglobulin/creatinine ratio (UßCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. CONCLUSION: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.

Probiotics improve renal function, glucose, lipids, inflammation and oxidative stress in diabetic kidney disease: a systematic review and meta-analysis.

AIMS: The role of probiotics in the management of diabetic kidney disease (DKD) has been shown. Several current trials are investigating the effect of probiotics, which are widely used to modulate biomarkers of renal function, glucose, lipids, inflammation and oxidative stress in patients with DKD. However, their findings are controversial. This study aimed to systematically evaluate the impact of probiotics on patients with DKD via meta-analysis. METHODS: PubMed, The Cochrane Library, Web of Science, Scopus, Embase, China National Knowledge Infrastructure, Chinese Wanfang Database and Chinese VIP Database were searched for relevant studies from the establishment of these databases to September 2021. The pooled results evaluated the impact of probiotics on renal function, glucose, lipids, inflammation and oxidative stress indicators in patients with DKD. Additionally, subgroup analysis was performed based on intervention duration, probiotic dose and probiotic consumption patterns, respectively. RESULTS: Ten trials that included 552 participants were identified for analysis. Compared with the controls, probiotics significantly decreased serum creatinine (Scr) [WMD = -0.17 mg/dL; 95%CI = -0.29, -0.05; p = 0.004], blood urea nitrogen (BUN) [WMD = -1.36 mg/dL; 95%CI = -2.20, -0.52; p = 0.001], cystatin C (Cys C) [WMD = -29.50 ng/mL; 95%CI = -32.82, -26.18; p < 0.00001], urinary albumin/creatinine ratio (UACR) [WMD = -16.05 mg/g; 95%CI = -27.12, -4.99; p = 0.004] and natrium (Na) [WMD = -0.94 mmol/L; 95%CI = -1.82, -0.05; p = 0.04] in patients with DKD. Enhanced glycemic control was observed in patients with DKD receiving probiotics compared with controls, as demonstrated by reduced levels of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model of assessment-estimated insulin resistance (HOMA-IR), and increased quantitative insulin sensitivity check index (QUICKI). Probiotics affected lipid metabolism parameters with decreasing triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels in patients with DKD. Probiotics could also could improve inflammation and oxidative stress by decreasing high-sensitivity C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH) and nitric oxide (NO). Additionally, subgroup analysis showed that those who received multiple species probiotics had a statistically significant difference in BUN, FPG, HOMA-IR, high-density lipoprotein cholesterol (HDL-c), MDA, TAC, and NO. Meanwhile, Scr, LDL-c, HDL-c, MDA, and TAC were ameliorated when the intervention duration was more than eight weeks and BUN, FPG, HOMA-IR, and MDA were improved when the probiotic dose was greater than four billion CFU/day. CONCLUSIONS: Our analysis revealed that probiotics could delay the progression of renal function injury, improve glucose and lipid metabolism, and reduce inflammation and oxidative stress in patients with DKD. Subgroup analysis showed that intervention duration, probiotic dose and probiotic consumption patterns had an effect of probiotics on outcomes.

Exercise therapy improves eGFR, and reduces blood pressure and BMI in non-dialysis CKD patients: evidence from a meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high prevalence of cardiovascular diseases, which often lead to physical inactivity that correlates with CKD exacerbation. The benefits of regular exercise to cardiovascular health have been well established in healthy population and highly suggestive in patients with CKD. To further strengthen the evidence base for the management of CKD, this meta-analysis was performed to systematically evaluate the effects of exercise therapy on renal function, blood pressure, blood lipid and body mass index (BMI) in non-dialysis CKD patients. METHODS: This meta-analysis was conducted following a previous protocol. Randomized controlled trials (RCTs) examining the effects of exercise therapy in non-dialysis CKD patients were searched in Pubmed, Embase, Cochrane Library, and three major Chinese biomedical databases (CNKI, WANGFANG and VIP) from their start date to October 30th, 2018. The Cochrane systematic review methods were applied for quality assessment and data extraction, and Revman version 5.3 was used for systematic review and meta-analysis. RESULTS: 13 RCTs, representing 421 patients with non-dialysis CKD, were included in this meta-analysis. Compared to the controls, exercise therapy brought an increase in eGFR (MD = 2.62, 95% CI:0.42 to 4.82, P = 0.02, I2 = 22%), and decreases in systolic blood pressure (SBP) (MD = -5.61, 95% CI:-8.99 to - 2.23, P = 0.001, I2 = 44%), diastolic blood pressure (DBP) (MD = -2.87, 95% CI:-3.65 to - 2.08, P < 0.00001, I2 = 16%) and BMI (MD = -1.32, 95% CI:-2.39 to - 0.25, P = 0.02, I2 = 0%) in non-dialysis CKD patients. Exercise therapy of short-term (< 3 months) decreased triglyceride (TG) level (P = 0.0006). However, exercise therapy did not significantly affect serum creatinine (SCr), total cholesterol (TC), high density lipoprotein (HDL) or low density lipoprotein (LDL) in non-dialysis CKD patients. CONCLUSION: Exercise therapy could benefit non-dialysis CKD patients by increasing eGFR while reducing SBP, DBP and BMI. Additionally, short-term intervention of exercise could decrease TG.

Comparison of microsurgical clipping with intravascular interventional embolization in the treatment of ruptured aneurysms and risk factors for intraoperative rupture and bleeding.

OBJECTIVE: To investigate the effectiveness of microsurgical clipping compared with intravascular interventional embolization in the treatment of ruptured aneurysms and the risk factors for intraoperative rupture and bleeding. METHODS: The data of 116 patients with ruptured aneurysms admitted to the People's Hospital of China Three Gorges University from January 2020 to March 2021 were collected for retrospective analysis. Among them, 61 cases with microsurgical clipping were classified as the control group (CG), and the rest 55 with intravascular interventional embolization were the observation group (OG), and the treatment effects in the two groups were compared. The general conditions of operation (operation time, postoperative hospital stay and intraoperative blood loss) were compared between the two groups. The intraoperative rupture of cerebral aneurysm during operation was counted, and the incidence of complications between the groups was compared. Risk factors affecting intraoperative rupture of cerebral aneurysms were analyzed by logistic regression. RESULTS: The total clinical treatment efficiency was dramatically higher in the OG than that in the CG (P<0.05). The operative time, postoperative hospital stays, and intraoperative bleeding were all higher in the CG than those in the OG (all P<0.001). There was no statistical difference in the incidence of wound infection, hydrocephalus, and cerebral infarction between the two groups (all P>0.05). However, the incidence of intraoperative rupture was markedly higher in the CG than that in the OG (P<0.05). Multifactorial logistic regression analysis revealed that history of subarachnoid hemorrhage, history of hypertension, large diameter of aneurysm, irregular morphology, and anterior communicating artery aneurysm were independent risk factors for intraoperative rupture in patients. CONCLUSION: Intravascular interventional embolization for middle cerebral artery aneurysm rupture is a less invasive procedure with faster recovery time, and history of subarachnoid hemorrhage, history of hypertension, large diameter of aneurysm, irregular morphology, and anterior communicating artery aneurysm are independent risk factors affecting patients with intraoperative rupture.