Treatment Of Diabetic Kidney Disease Research Articles

METTL3/YTHDF2 m6A axis mediates the progression of diabetic nephropathy through epigenetically suppressing PINK1 and mitophagy.

This research aimed to investigate the specific mechanism of methyltransferase like 3 (METTL3) in the progression of diabetic kidney disease (DKD). The model of diabetic kidney disease was established with HK-2 cells and mice in vitro and in vivo. The N6 methyladenosine (m6A) contents in the cells and tissues were detected with a commercial kit and the m6A levels of PTEN induced putative kinase 1 (PINK2) were detected with a MeRIP kit. The mRNA and protein levels were determined with RT-qPCR and western blot. The ROS, TNF-α, and IL-6 levels were assessed with ELISA. The cell proliferative ability was measured by a CCK-8 assay and cell apoptosis was determined with TUNEL staining. The HE and Masson staining was performed to observe the renal morphology. The RIP assay was conducted to detect the interaction between METTL3/YTHDF2 and PINK1. The m6A content and METTL3 levels were prominently elevated in diabetic kidney disease. METTL3 silencing promoted the cell growth and the expression of LC3 II, PINK1, and Parkin, while inhibiting the cell apoptosis and the expression of LC3 I and p62 in the high glucose (HG) stimulated HK-2 cells. METTL3 silencing also decreased the ROS, TNF-α, and IL-6 levels in diabetic kidney disease. PINK1 silencing neutralized the function of sh-METTL3 in the HG stimulated HK-2 cells. The HE and Masson staining showed that METTL3 silencing alleviated the kidney injury induced by DKD. METTL3 silencing decreased the m6A levels of PINK1, while increased the mRNA levels of PINK1 which depended on YTHDF2. METTL3 silencing could inhibit the progression of diabetic nephropathy in vivo and in vitro by regulating the m6A modification of PINK1, which depends on YTHDF2. Our research lays the theoretical foundation for the precise treatment of diabetic kidney disease and the development of targeted drugs in the future.

Pathomechanisms of Diabetic Kidney Disease

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population of individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. The pathogenesis of DKD is intricate, originating with hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, and fibrotic which ultimately lead to renal damage. Within each pathway, several mediators contribute to the development of renal structural and functional changes. Some of these mediators, such as inflammatory cytokines, reactive oxygen species, and transforming growth factor β are shared among the different pathways, leading to significant overlap and interaction between them. While current treatment options for DKD have shown advancement over previous strategies, their effectiveness remains somewhat constrained as patients still experience residual risk of disease progression. Therefore, a comprehensive grasp of the molecular mechanisms underlying the onset and progression of DKD is imperative for the continued creation of novel and groundbreaking therapies for this condition. In this review, we discuss the current achievements in fundamental research, with a particular emphasis on individual factors and recent developments in DKD treatment.

Effectiveness of Chinese herbal medicine compared with angiotensin II receptor blockers in patients with diabetic kidney disease: A hospital-based matched cohort study

Angiotensin II receptor blockers (ARBs) are one of the standard treatments for diabetic kidney disease (DKD). Some patients may opt for Chinese herbal medicine (CHM) of their own free will. However, there is no real-world evidence regarding the effectiveness and safety of CHM. We aimed to explore the effectiveness of CHM for DKD in comparison to ARBs. We enrolled 732 DKD patients (72 used only CHM and 661 used ARBs) from 2007 to 2016, and all patients were followed until December 2016 at China Medical University Hospital in Taiwan. A total of 355 ARB users and 71 CHM users were analyzed after propensity score matching. The estimated glomerular filtration rate (eGFR) after treatment was 84.9 ± 28.1 ml/min/1.73 m2 in CHM users, which was higher than that (67.8 ± 35.4 ml/min/1.73 m2) in ARB users (p < 0.001). The change in the eGFR was −6.0 ± 21.4 ml/min/1.73 m2 in CHM users and −12.9 ± 24.8 ml/min/1.73 m2 in ARB users (p = 0.029). The blood urea nitrogen (BUN) and creatinine levels of patients taking CHM were 22 ± 16 mg/dl and 0.9 ± 0.4 mg/dl, respectively, and were lower than those (30 ± 28 mg/dl and 1.7 ± 2.0 mg/dl) of patients taking ARBs (p = 0.025 and p = 0.003). Using linear regression with adjustments for age, sex, BMI, baseline eGFR, and HbA1c levels, we found that the declines in the eGFR/baseline eGFR and changes in the urine albumin–creatinine ratio (ACR) were comparable between the two groups (p = 0.86 and 0.73). This study suggests that CHM may have comparable effectiveness to ARBs, which provides insights for further investigations.

Treatment of diabetic kidney disease. A network meta-analysis.

Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis. We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others. As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.

β2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting β2-adrenergic receptor (β2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use β2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other β2-AR agonists compared with those with no COPD. These data indicate that β2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting β2-adrenergic receptor (β2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of β2-AR agonist intake, compared with those without COPD. These data indicate that β2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

Candidate composite biomarker to inform drug treatments for diabetic kidney disease.

Current guidelines recommend renin angiotensin system inhibitors (RASi) as key components of treatment of diabetic kidney disease (DKD). Additional options include sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1a), and mineralocorticoid receptor antagonists (MCRa). The identification of the optimum drug combination for an individual is difficult because of the inter-, and longitudinal intra-individual heterogeneity of response to therapy. Using data from a large observational study (PROVALID), we identified a set of parameters that can be combined into a meaningful composite biomarker that appears to be able to identify which of the various treatment options is clinically beneficial for an individual. It uses machine-earning techniques to estimate under what conditions a treatment of RASi plus an additional treatment is different from the treatment with RASi alone. The measure of difference is the annual percent change (ΔeGFR) in the estimated glomerular filtration rate (ΔeGFR). The 1eGFR is estimated for both the RASi-alone treatment and the add-on treatment. Higher estimated increase of eGFR for add-on patients compared with RASi-alone patients indicates that prognosis may be improved with the add-on treatment. The personalized biomarker value thus identifies which patients may benefit from the additional treatment.

Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates mitochondrial dysfunction via PI3K/Akt/eNOS signaling pathway in diabetic tubulopathy

Diabetic tubulopathy (DT) is a recently recognized key pathology of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital pathological factor in different types of metabolic diseases, such as DKD. Finerenone (FIN), a novel non-steroidal mineralocorticoid receptor antagonist, attenuates kidney inflammation and fibrosis in DKD, but the precise pathomechanisms remain unclear. The role of mineralocorticoid receptor (MR) in perturbing mitochondrial function via the PI3K/Akt/eNOS signaling pathway, including mitochondrial dynamics and mitophagy, was investigated under a diabetic state and high glucose (HG) ambiance. To elucidate how the activation of MR provokes mitochondrial dysfunction in DT, human kidney proximal tubular epithelial (HK-2) cells were exposed to HG, and then mitochondrial dynamics, mitophagy, mitochondrial ROS (mitoROS), signaling molecules PI3K, Akt, Akt phosphorylation and eNOS were probed. The above molecules or proteins were also explored in the kidneys of diabetic and FIN-treated mice. FIN treatment reduced oxidative stress, mitochondrial fragmentation, and apoptosis while restoring the mitophagy via PI3K/Akt/eNOS signaling pathway in HK-2 cells exposed to HG ambiance and tubular cells of DM mice. These findings linked MR activation to mitochondrial dysfunction via PI3K/Akt/eNOS signaling pathway in DT and highlight a pivotal but previously undiscovered role of FIN in alleviating renal tubule injury for the treatment of DKD.

Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease.

As diabetes rates surge globally, there is a corresponding rise in the number of patients suffering from diabetic kidney disease (DKD), a common complication of diabetes. DKD is a significant contributor to chronic kidney disease, often leading to end-stage renal failure. However, the effectiveness of current medical treatments for DKD leaves much to be desired. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. Recent studies have demonstrated that H2 not only possesses antioxidant properties but also exhibits anti-inflammatory effects, regulates cell lethality, and modulates signal transduction. Consequently, it is now being utilized in clinical applications. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Hence, we undertook a comprehensive review of the literature focusing on animal models and human clinical trials where H2 demonstrated effectiveness against a variety of renal diseases. The collective evidence from this literature review, along with our previous findings, suggests that H2 may have therapeutic benefits for patients with DKD by enhancing mitochondrial function. To substantiate these findings, future large-scale clinical studies are needed.

Further understanding and paying attention to normoalbuminuric diabetic kidney disease

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). Therefore, early diagnosis and timely prevention and treatment of DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR). However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA (National Kidney Foundation/Food and Drug Administration). Based on the relevant guidelines of DM and chronic kidney disease (CKD) and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, disease diagnosis, clinical characteristics and biomarkers, to arouse the new understanding of NADKD in the medical profession and pay attention to it.

Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms.

Diabetic kidney disease (DKD) is a serious complication of diabetes that can lead to end-stage kidney disease. Despite its significant impact, most research has concentrated on the glomerulus, with little attention paid to the tubulointerstitial region, which accounts for the majority of the kidney volume. DKD's tubulointerstitial lesions are characterized by inflammation, fibrosis, and loss of kidney function, and recent studies indicate that these lesions may occur earlier than glomerular lesions. Evidence has shown that inflammatory mechanisms in the tubulointerstitium play a critical role in the development and progression of these lesions. Apart from the renin-angiotensin-aldosterone blockade, Sodium-Glucose Linked Transporter-2(SGLT-2) inhibitors and new types of mineralocorticoid receptor antagonists have emerged as effective ways to treat DKD. Moreover, researchers have proposed potential targeted therapies, such as inhibiting pro-inflammatory cytokines and modulating T cells and macrophages, among others. These therapies have demonstrated promising results in preclinical studies and clinical trials, suggesting their potential to treat DKD-induced tubulointerstitial lesions effectively. Understanding the immune-inflammatory mechanisms underlying DKD-induced tubulointerstitial lesions and developing targeted therapies could significantly improve the treatment and management of DKD. This review summarizes the latest advances in this field, highlighting the importance of focusing on tubulointerstitial inflammation mechanisms to improve DKD outcomes.

Identification of basement membrane markers in diabetic kidney disease and immune infiltration by using bioinformatics analysis and experimental verification.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide. Basement membranes (BMs) are ubiquitous extracellular matrices which are affected in many diseases including DKD. Here, the authors aimed to identify BM-related markers in DKD and explored the immune cell infiltration in this process. The expression profiles of three datasets were downloaded from the Gene Expression Omnibus database. BM-related differentially expression genes (DEGs) were identified and Kyoto encyclopaedia of genes and genomes pathway enrichment analysis were applied to biological functions. Immune cell infiltration and immune function in the kidneys of patients with DKD and healthy controls were evaluated and compared using the ssGSEA algorithm. The association of hub genes and immune cells and immune function were explored. A total of 30 BM-related DEGs were identified. The functional analysis showed that BM-related DEGs were notably associated with basement membrane alterations. Crucially, BM-related hub genes in DKD were finally identified, which were able to distinguish patients with DKD from controls. Moreover, the authors observed that laminin subunit gamma 1(LAMC1) expression was significantly high in HK2 cells treated with high glucose. Immunohistochemistry results showed that, compared with those in db/m mouse kidneys, the levels of LAMC1 in db/db mouse kidneys were significantly increased. The biomarkers genes may prove crucial for DKD treatment as they could be targeted in future DKD treatment protocols.

Efficacy of "Dihuang pill prescriptions" combined with conventional treatment for diabetic kidney disease: A network meta-analysis and systematic review.

With the increasing incidence of diabetic nephropathy, there is currently no means to completely cure the disease. However, a large number of clinical data proved that traditional Chinese medicine combined with modern medical conventional treatment of diabetic kidney disease has achieved better efficacy than simple Western medicine conventional treatment. Based on the mesh meta-analysis method, the objective evaluation of clinical efficacy of conventional treatment of diabetic kidney disease and comparison provided more evidence-based basis for the treatment of diabetic kidney disease and further select effective intervention measures to delay the process of diabetic kidney disease. 41 randomized controlled trials were included, involving 4 kinds of "Dihuang pill prescriptions," with a total sample size of 3562 cases, including 1793 patients in the experimental group and 1769 patients in the control group. Network meta-analysis suggested that the best SUCRA-ranked 2 interventions were Jingui Shenqi pills/decoction + Western medicine routine" and Jisheng Shenqi pills/decoction + Western medicine routine in terms of reducing 24-hour urinary protein. In terms of reducing urinary albumin excretion rate, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/decoction + Western medicine routine and Liuwei Dihuang Pills/decoction + Western medicine routine. In terms of reducing serum creatinine, the top 2 SUCRA ranked interventions were Jisheng Shenqi pills/decoction + Western medicine routine, Zhibai Dihuang Pills/decoction + Western medicine routine. In terms of lowering fasting blood glucose, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/ decoction + Western medicine routine and Jisheng Shenqi pills/decoction + Western medicine routine. The results showed that the treatment plan of conventional Western medicine combined with Chinese patent medicine could reduce serum creatinine, 24-hour urinary protein, fasting blood glucose urine protein excretion rate and improve the total clinical effective rate. The combination of medicine was obviously better than conventional Western medicine alone.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.

Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/ regulatory T-cell balance through the programmed death 1 / programmed death-ligand 1 pathway.

To investigate the therapeutic effects and immunomodulatory mechanisms of human placenta-derived mesenchymal stem cells (PMSCs) in diabetic kidney disease (DKD). Streptozotocin-induced DKD rats were administered an equivalent volume of saline or PMSCs (1 × 106 in 2 mL phosphate-buffered saline per rat) for 3 weeks. Eight weeks after treatment, we examined the biochemical parameters in the blood and urine, the ratio of T helper 17 cells (Th17) and regulatory T cells (Treg) in the blood, cytokine levels in the kidney and blood, and renal histopathological changes. In addition, we performed PMSC tracing and renal transcriptomic analyses using RNA-sequencing. Finally, we determined whether PMSCs modulated the Th17/Treg balance by upregulating programmed death 1 (PD-1) in vitro. The PMSCs significantly improved renal function, which was assessed by serum creatinine levels, urea nitrogen, cystatin C levels, urinary albumin-creatinine ratio, and the kidney index. Further, PMSCs alleviated pathological changes, including tubular vacuolar degeneration, mesangial matrix expansion, and glomerular filtration barrier injury. In the DKD rats in our study, PMSCs were mainly recruited to immune organs, rather than to the kidney or pancreas. PMSCs markedly promoted the Th17/Treg balance and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-17A and IL-1β) in the kidney and blood of DKD rats. In vitro experiments showed that PMSCs significantly reduced the proportion of Th17 cells and increased the proportion of Treg cells by upregulating PD-1 in a cell-cell contact manner and downregulating programmed death-ligand 1 (PD-L1) expression in PMSCs, which reversed the Th17/Treg balance. We found that PMSCs improved renal function and pathological damage in DKD rats and modulated Th17/Treg balance through the PD-1/PD-L1 pathway. These findings provide a novel mechanism and basis for the clinical use of PMSCs in the treatment of DKD.

Active role of amino acid metabolism in early diagnosis and treatment of diabetic kidney disease.

Diabetic Kidney Disease (DKD) is one of the significant microvascular consequences of type 2 diabetes mellitus with a complex etiology and protracted course. In the early stages of DKD, the majority of patients experience an insidious onset and few overt clinical symptoms and indicators, but they are prone to develop end-stage renal disease in the later stage, which is life-threatening. The abnormal amino acid metabolism is tightly associated with the development of DKD, which involves several pathological processes such as oxidative stress, inflammatory response, and immune response and is also closely related to autophagy, mitochondrial dysfunction, and iron death. With a focus on taurine, branched-chain amino acids (BCAAs) and glutamine, we explored the biological effects of various amino acid mechanisms linked to DKD, the impact of amino acid metabolism in the early diagnosis of DKD, and the role of amino acid metabolism in treating DKD, to offer fresh objectives and guidelines for later early detection and DKD therapy.

Effects of liraglutide on extraglycemic inflammatory markers and renal hemodynamic parameters in diabetic kidney disease (DKD).

Diabetic kidney disease (DKD) was the leading cause of kidney disease, which has been a crucial public health. Liraglutide is a drug, widely used for DKD treatment globally. However, the extraglycemic inflammatory markers and renal hemodynamic parameters of DKD patients treated with liraglutide has been not reported. In this study, 160 patients with early DKD were enrolled, 80 cases in the control group and 80 cases in the treatment group, respectively. The individuals in the control group were treated with metformin, while the individuals in the treatment group were treated with liraglutide and metformin for 3 months. The urinary microalbumin and urinary creatinine was measured to calculate the ratio (UACR), while the Doppler ultrasound were measured before and after treatment. After 3 months of treatment, body mass index (BMI), waist circumference (WC) and low-density lipoprotein cholesterol (LDL) in the treatment group were significantly decreased compared with before and after treatment in the control group; the levels of cystatin and UACR in treatment group were lower than before treatment and control group; The end-diastolic blood flow velocity (EDV) of renal artery and segment artery in treatment group was significantly higher than that before treatment and control group; The levels of CRP, TNF-α and IL-6 in the treatment group after treatment were lower than those before treatment and those in the control group. After 3 months of treatment, blood cystatin in the treatment group decreased significantly compared with before treatment and after treatment in the control group, with statistical significance After 3 months of treatment, the EDV of renal artery and renal segment in treatment group was significantly higher than that before treatment and control group, the peak systolic blood flow velocity (PSV) and EDV of renal interlobar artery in treatment group were significantly higher than those before treatment and control group. The resistance index (RI) was significantly lower than that before treatment and control group. Liraglutide can reduce inflammatory indicators, renal artery blood flow and renal function indicators in early DKD patients.

Effects of Niaoduqing granules on inflammatory response of diabetic kidney disease: A meta‑analysis.

Diabetic kidney disease (DKD) is one of the most severe chronic microvascular complications of diabetes and the leading cause of end-stage kidney disease worldwide. The mechanism of inflammation underlying DKD has been attracting attention over recent years, but effective therapeutic strategies have remained elusive. Niaoduqing (NDQ) granules are one of the most commonly used drugs for the treatment of DKD in China, and it has therapeutic effects against inflammation in DKD. Therefore, the aim of the present analysis was to evaluate the inflammatory response outcomes and safety of NDQ granules for the treatment of DKD. The following databases were searched from their inception to 31st of May 2023 to obtain published accounts of relevant randomized controlled trials: China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, The Chinese Biomedicine, PubMed, Web of Science and Cochrane Library. The 'risk of bias' evaluation tool produced by the Cochrane Collaboration Handbook was used for evaluating the quality, whereas Revman software (version 5.3) was used for meta-analysis. In total, 16 studies were included into the present study according to criteria, with a total of 1,526 patients. Compared with those in the control group, the results of the meta-analysis revealed that the combination of conventional treatment and NDQ granules may further decrease C-reactive protein [standardized mean difference (SMD), -1.33; 95% confidence interval (CI), -1.76, -0.91; P<0.00001], TNF-α (SMD, -1.90; 95% CI, -2.35,-1.45; P<0.00001) and IL-6 (SMD, -1.72; 95% CI, -2.52,-0.91; P<0.0001) levels, whilst increasing the clinical effective rate (risk ratio, 1.22; 95% CI, 1.14,1.29; P<0.00001), in patients with DKD. In terms of safety, a total of 34 and 39 patients included in the intervention and in the control group, respectively, developed adverse reactions. Results from the present analysis suggest that NDQ granules may be beneficial in suppressing inflammation caused by DKD when used in combination with conventional treatment, potentially guiding future directions in clinical practice. However, further high-quality studies are needed to confirm the anti-inflammation response in the future.

Hedysarum polybotrys polysaccharide attenuates renal inflammatory infiltration and fibrosis in diabetic mice by inhibiting the HMGB1/RAGE/TLR4 pathway.

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive. The present study utilized db/db mice as a DKD animal model administered with low (30 mg/kg) and high doses (60 mg/kg) of HPS, in addition to glyburide (7.2 mg/kg). Blood and urine samples were collected from mice and blood glucose, serum creatinine, urinary albumin excretion and urinary β2-microglobulin were measured. In addition, apoptosis and histological changes in kidney tissue were observed using TUNEL and HE staining, respectively, and the secretion and expression of inflammatory factors in kidney tissue were detected using EILSA and reverse transcription-quantitative PCR. Furthermore, we the expression of fibrosis-related proteins and NF-κB signaling pathway proteins was determined using western blot analysis. HPS was found to reduce the blood glucose concentration, serum creatinine levels, urinary albumin excretion rates and urinary β2-microglobulin in a dose-dependent manner. In addition, HPS treatment mitigated apoptosis and pathological damage in the kidney tissues of DKD mice. The expression levels of fibrosis-related proteins fibronectin, α-smooth muscle actin and TGF-β1 were observed to be decreased in kidney tissues of DKD mice following HPS treatment. The secretion levels of inflammatory factors (IL-6, TNF-α and IL-1β) were also reduced in kidney tissues, with high-dose HPS treatment found to be more effective, similar to the effects mediated by the glyburide. Further mechanistic analysis revealed that the therapeutic effects of HPS on DKD mice may be mediated by inhibiting the high mobility group box 1/receptor for advanced glycation end-products/toll-like receptor 4 pathway. In conclusion, the present findings could provide insight for the treatment of DKD.

Research progress on extracellular vesicles in the renal tubular injury of diabetic kidney disease.

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes and is a chronic progressive condition. It is also a common cause of end-stage renal disease (ESRD), which is characterized by proteinuria or a progressive decline in the glomerular filtration rate. Due to their dependence on high-energy and aerobic metabolism, renal tubules are more susceptible to the metabolic disturbances associated with DKD, leading to inflammation and fibrosis. Consequently, tubular injury has become a recent research focus, and significant advancements have been made in studying the role of extracellular vesicles in DKD-associated tubular injury. This review aimed to elucidate the mechanisms and potential applications of different types of extracellular vesicles in tubular injury in DKD to provide new insights for the prevention and treatment of DKD.

Hyperoside mediates protection from diabetes kidney disease by regulating ROS-ERK signaling pathway and pyroptosis.

Renal tubular injury is a key factor in the progression of diabetic kidney disease to end-stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen-activated protein kinase signaling pathway, thereby alleviating proteinuria-induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment.