Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice.

BACKGROUND: Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage. METHODS: Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney. RESULTS: Cdk5 was found to be activated by HG stimulation both in vitro and in vivo. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of in vivo experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia. CONCLUSION: Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5.

Effect of regulated vitamin D increase on vascular markers in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

AIM: The effect of increased vitamin D levels on vascular function in patients with chronic kidney disease (CKD) is controversial. This meta-analysis aimed to assess the effect of regulated vitamin D increase on vascular markers in patients with CKD. DATA SYNTHESIS: We searched PubMed, Web of Science, Embase and ClinicalTrials.gov from database inception up until July 21, 2023. We included randomized controlled trials assessing the effects of using vitamin D and its analogues on vascular function in patients with CKD. Fixed-effects and random-effects model analyses were performed using weighted mean difference effects for each trial by heterogeneity (I2) assessment. Primary outcomes encompassed blood flow-mediated dilation (FMD)、pulse wave velocity (PWV) and augmentation index (AIx). FINDINGS: From 1964 records we selected 12 trials, 5 (n = 331) on FMD, 8 (n = 626) on PWV and 4 (n = 393) on AIx. Vitamin D and VDRA supplementation failed to significantly improve FMD (WMD 1.68%; 95% CI -0.18 to 3.53; P = 0.08; I2 = 88%)、PWV (WMD -0.41 m/s; 95%CI -0.95 to 0.13; P = 0.14; I2 = 57%)and AIx (WMD -0.53%; 95%CI -1.69 to 0.63; P = 0.37; I2 = 0%). Subgroup analysis revealed that 2 µg paricalcitol significantly improved FMD (WMD 2.09%; 95%CI 1.28 to 2.90; P < 0.00001); I2 = 0%), as did cholecalciferol (WMD 5.49%; 95% CI 4.35 to 6.63; P < 0.00001). CONCLUSION: Supplementation vitamin D and VDRA are associated with improved vascular function as measured by FMD, but not arterial stiffness as measured by PWV and AIx, tentatively suggesting that regulating the increase of vitamin D could not potentially reduce the incidence of cardiovascular disease.

The association between albumin and mortality in patients with acute kidney injury: a retrospective observational study.

BACKGROUND: While the association between decreased serum albumin (ALB) levels and increased risk of acute kidney injury (AKI) is well established, the risk of death among patients with AKI with low serum ALB levels is unclear. We aimed to evaluate the association between serum ALB levels in patients with AKI and mortality, and help guide their clinical management. METHODS: The included patients were those diagnosed with AKI and admitted to Zhejiang Provincial People's Hospital between January 2018 and December 2020. The clinical endpoint was all-cause mortality rate at 90-days and 1-year. Patients were divided into four groups according to the quartiles (Qs) of ALB measurements at admission. Cumulative survival curves were calculated using Kaplan-Meier analysis, and Cox proportional risk models were used to assess the association between serum ALB levels and 90-day and 1-year all-cause mortality. RESULTS: This study included 740 patients with AKI. Patients with measured ALB values were classified into quartiles: Q1 ≤ 26.0 g/L (n = 188); Q2 = 26.1-30.5 g/L (n = 186); Q3 = 30.6-34.7 g/L (n = 183); Q4 ≥ 34.8 g/L (n = 183). Univariate analysis using Cox regression showed that for every 10 g/L increase in ALB, the 90-day and 1-year mortality decreased by 29%. Among the four subgroups, patients with lower ALB levels had a higher risk of death. After adjusting for demographics, comorbid conditions, inflammatory index, and medicine, the lowest ALB quartile (ALB < 26 g/L) was associated with increased risk of 90-day mortality (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.30 to 2.38, P < 0.001) and 1-year all-cause mortality (HR, 1.79; 95% CI, 1.33 to 2.41, P < 0.001). CONCLUSIONS: ALB levels in patients with AKI were significantly correlated with prognosis, and the higher the level, the better the prognosis. Compared to patients with ALB ≥ 34.8 g/L, patients with 26.1 g/L < ALB ≤ 30.5 g/L had an increased risk of 90-day and 1-year all-cause mortality of approximately 40%, and patients with ALB ≤ 26.0 g/L had an increased risk of 90-day and 1-year all-cause mortality of approximately 76% and 79%, respectively.

Progress in the application of the neutrophil-to-lymphocyte ratio in dialysis-related complications.

The neutrophil-to-lymphocyte ratio (NLR) is a novel predictive biomarker that reflects systemic inflammatory status and is routinely measured in blood tests. Owing to its ease of use and affordability, it is being increasing used as a prognostic indicator of cardiovascular disease, tumors, autoimmune disorders, and kidney disease. In recent years, a number of studies have demonstrated the clinical utility of the NLR in identifying and predicting complications associated with hemodialysis and peritoneal dialysis, including cardiovascular disease and infection. This review aimed to provide a new perspective on the application of the NLR as a valuable tool enabling clinicians to better assess the occurrence and prognosis of complications in patients undergoing dialysis.

Effect of bioelectrical impedance technology on the prognosis of dialysis patients: a meta-analysis of randomized controlled trials.

Managing patient 'dry weight' according to clinical standards has deficiencies. Research has focused on the effectiveness of using bioelectrical impedance technology for fluid management in dialysis patients. Whether bioelectrical impedance monitoring can improve dialysis patients prognoses remain controversial. We performed a meta-analysis of randomized controlled trials to determine whether bioelectrical impedance was effective in improving dialysis patients prognoses. The primary outcome was all-cause mortality (13.6 ± 9.1 months). Secondary outcomes were left ventricular mass index (LVMI), arterial stiffness assessed using Pulse Wave Velocity (PWV), and N-terminal brain natriuretic peptide precursor (NT-proBNP). Of 4,641 citations retrieved, we identified 15 eligible trials involving 2763 patients divided into experimental (n = 1386) and control (n = 1377) groups. In 14 studies with mortality data, the meta-analysis showed that bioelectrical impedance intervention reduced the risk of all-cause mortality (rate ratios [RR]: 0.71; 95% confidence interval [CI]: 0.51, 0.99; p = .05; I2 = 1%). Subgroup analysis of patients on hemodialysis (RR: 0.72; 95% CI: 0.42, 1.22; p = .22) and peritoneal dialysis (RR: 0.62; 95% CI: 0.35, 1.07; p = .08) showed no significant mortality difference between intervention and control groups. It reduced the risk of all-cause mortality in the Asian population (RR: 0.52; p = .02), and reduced NT-proBNP (mean difference [MD]: -1495.73; p = 0.002; I2=0%) and PWV (MD: -1.55; p = .01; I2=89%). Bioelectrical impedance intervention reduced the LVMI in hemodialysis patients (MD: -12.69; p < .0001; I2=0%). Our analysis shows that in dialysis patients, bioelectrical impedance technology intervention could reduce, but not eliminate, the risk of all-cause mortality. Overall, this technology can improve the prognosis of dialysis patients.

Application of nanoparticles in the diagnosis and treatment of chronic kidney disease.

With the development of nanotechnology, nanoparticles have been used in various industries. In medicine, nanoparticles have been used in the diagnosis and treatment of diseases. The kidney is an important organ for waste excretion and maintaining the balance of the internal environment; it filters various metabolic wastes. Kidney dysfunction may result in the accumulation of excess water and various toxins in the body without being discharged, leading to complications and life-threatening conditions. Based on their physical and chemical properties, nanoparticles can enter cells and cross biological barriers to reach the kidneys and therefore, can be used in the diagnosis and treatment of chronic kidney disease (CKD). In the first search, we used the English terms "Renal Insufficiency, Chronic" [Mesh] as the subject word and terms such as "Chronic Renal Insufficiencies," "Chronic Renal Insufficiency," "Chronic Kidney Diseases," "Kidney Disease, Chronic," "Renal Disease, Chronic" as free words. In the second search, we used "Nanoparticles" [Mesh] as the subject word and "Nanocrystalline Materials," "Materials, Nanocrystalline," "Nanocrystals," and others as free words. The relevant literature was searched and read. Moreover, we analyzed and summarized the application and mechanism of nanoparticles in the diagnosis of CKD, application of nanoparticles in the diagnosis and treatment of renal fibrosis and vascular calcification (VC), and their clinical application in patients undergoing dialysis. Specifically, we found that nanoparticles can detect CKD in the early stages in a variety of ways, such as via breath sensors that detect gases and biosensors that detect urine and can be used as a contrast agent to avoid kidney damage. In addition, nanoparticles can be used to treat and reverse renal fibrosis, as well as detect and treat VC in patients with early CKD. Simultaneously, nanoparticles can improve safety and convenience for patients undergoing dialysis. Finally, we summarize the current advantages and limitations of nanoparticles applied to CKD as well as their future prospects.