Renal Protective Effects Research Articles

In vitro and in vivo evidence of the effectiveness of gallic acid on glycerol-induced acute kidney injuries.

Because acute kidney injuries (AKI) are one of the critical health problems worldwide, studies on the risk factors, mechanisms, and treatment strategies seem necessary. Glycerol (GLY), known to induce cell necrosis via myoglobin accumulation in renal tubules, is widely used as an AKI model. This study aimed to evaluate the protective effects of gallic acid (GA) against GLY-induced AKI. The study utilized both in vivo and in vitro models. In vivo, healthy rats were divided into six groups: control (normal saline), GLY (10mg/kg, intramuscularly), GLY + GA10 (10mg/kg), GLY + GA50 (50mg/kg), GLY + GA100 (100mg/kg), and GA (100mg/kg). GA was administered by gavage for seven consecutive days, followed by a single intramuscular injection of GLY. Kidney biomarkers, lactate dehydrogenase (LDH), oxidative stress markers, inflammatory indices, and histological parameters were assessed 72h post-injection. In vitro, human embryonic kidney 2 (HK-2) cells were incubated with GLY and GA at different concentrations (30, 60, and 125μg/ml) to evaluate cell viability, reactive oxygen species (ROS) production, oxidative stress, and inflammatory cytokines. GLY administration significantly elevated renal dysfunction markers, including blood urea nitrogen and creatinine, alongside oxidative stress and reduced cell viability. GA treatment improved kidney biomarkers, enhanced antioxidant enzyme activity, and reduced inflammatory cytokines. Histological analyses also showed improved kidney structural integrity in GA-treated rats compared to the GLY group. This study confirmed that GLY induces AKI through oxidative stress, inflammation, and structural damage. GA exhibited significant renal protective effects by enhancing antioxidant defenses and reducing inflammation. These findings support GA as a potential natural supplement for preventing or treating renal diseases.

Characterization of diabetic kidney disease in 235 patients: clinical and pathological insights with or without concurrent non-diabetic kidney disease

BackgroundThis study aimed to explore the clinical and pathological features of patients with diabetic kidney disease (DKD), with and without non-diabetic kidney disease (NDKD), through a retrospective analysis. The objective was to provide clinical insights for accurate identification.MethodsA retrospective analysis of 235 patients admitted to the Department of Nephrology at Hangzhou Hospital of Traditional Chinese Medicine was conducted between July 2014 and December 2022. These patients underwent renal biopsy and received a pathology-based diagnosis of DKD. They were categorized into the DKD alone group (93 cases) and the DKD + NDKD group (142 cases).ResultsIn the DKD alone group, gender distribution was even, with ages mainly between 50 and 59 years, and a disease duration of less than 5 years, primarily presenting nodular diabetic glomerulosclerosis. In contrast, the DKD + NDKD group had a higher male incidence, a wider age range, longer disease duration, and prevalent diffuse diabetic glomerulosclerosis. Acute and chronic tubulointerstitial lesions and IgA nephropathy were the predominant types of combined NDKD, accounting for 40.14% and 35.21%, respectively. Clinical correlation analysis revealed associations between glomerular grading, tubulointerstitial lesions, renal arteriolar vitelliform lesions, renal vascular atherosclerosis, and clinical parameters such as 24-hour urine protein, hemoglobin, and urinary specific gravity. Multifactorial logistic regression analysis identified independent factors affecting DKD + NDKD, including body mass index, blood creatinine level, microscopic erythrocyte grade, urinary immunoglobulin G/creatinine ratio, and serum immunoglobulin A.ConclusionThe research underscores distinctions in age, gender distribution, disease duration, and renal pathology between DKD alone and DKD + NDKD groups. Additionally, significant discriminative factors including BMI, blood creatinine level, microscopic erythrocyte grade, UIgG/urine creatinine ratio, and serum IgA levels help differentiate DKD from NDKD, thereby enabling personalized treatment approaches. Furthermore, the study highlights the role of RASi as the most commonly used drug in the treatment of both DKD and NDKD, with emerging drugs such as SGLT2 inhibitors showing promising renal protective effects.

Therapeutic Effects of Tea Polyphenols on Renal Damage Induced by High Uric Acid.

Hyperuricemia (HUA) is a condition characterized by excessive uric acid production and/or inadequate uric acid excretion due to abnormal purine metabolism in the human body. Uric acid deposits resulting from HUA can lead to complications such as renal damage. Currently, drugs used to treat HUA lack specificity and often come with specific toxic side effects. This study aimed to investigate the renal protective effects of an optimized tea polyphenol formula and allopurinol in a rat model of hyperuricemia following renal resection. The goal was to explore the mechanisms underlying these effects. Initially, a blend was formulated based on the distinctive functions of catechins, thearubigins, tea polysaccharides, and theanine. Orthogonal experiments were then employed to select a rational combination. A 5/6 renal resection rat model was successfully established, and the animals were fed a 2% oxonic acid diet to induce hyperuricemia. Urinary protein content was measured using the biuret method, and serum levels of uric acid, creatinine, and urea nitrogen were determined biochemically. Kidney pathology was examined through HE staining and renal tubulointerstitial pathological scoring. The expression of α-SMA, CD34, PCNA, and TGF-β in renal tissue was detected using immunohistochemistry. Apoptosis of renal tubular epithelial cells was assessed using the TUNEL method. Hyperuricemia markedly worsens renal damage in rats following nephrectomy, while tea polyphenols demonstrate the ability to reduce levels of blood uric acid, urea nitrogen, creatinine, and urinary protein. Additionally, tea polyphenols enhance smooth muscle proliferation in renal glomerular arterioles, prevent the loss of interstitial capillaries, alleviate apoptosis of renal tubular epithelial cells, promote their proliferation, and reduce interstitial fibrosis. A significant improvement in the severity of renal damage is observed in rats subjected to nephrectomy combined with hyperuricemia, and this effect surpasses that of allopurinol. Tea polyphenols could effectively alleviate renal damage in rats with nephrectomy combined with hyperuricemia. They demonstrate high cost-effectiveness and minimal side effects, positioning them as a promising new therapeutic option for hyperuricemia- induced renal damage.

The Role of SGLT-2 Inhibitors in Cardiovascular and Renal Protection

SGLT-2 inhibitors have revolutionized the management of chronic diseases, demonstrating profound cardiovascular and renal protective effects that extend beyond their original purpose of glucose-lowering in T2DM. These agents target fundamental pathophysiological mechanisms, including hemodynamic regulation, metabolic efficiency, inflammation, and oxidative stress, making them effective across diverse populations. Landmark clinical trials such as EMPA-REG OUTCOME, CANVAS, DAPA-HF, and DAPA-CKD have shown significant reductions in cardiovascular death, heart failure hospitalizations, and the progression of CKD, even in non-diabetic patients. While generally well-tolerated, SGLT-2 inhibitors require careful patient selection to mitigate risks such as euglycemic diabetic ketoacidosis and volume depletion. Their broad applicability underscores their role as a cornerstone therapy, redefining integrated care for heart failure, CKD, and related conditions. As research expands, SGLT-2 inhibitors promise to further transform chronic disease management, offering improved outcomes, quality of life, and survival for millions worldwide.

Perioperative euglycemic DKA: The YIN and YANG of sodium-glucose cotransporter 2 inhibitors

Abstract Sodium-glucose cotransporter 2 inhibitors are gaining widespread acceptance in managing diabetic patients due to their favorable cardiac and renal protective effects. However, these drugs can cause a lethal complication described as sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis (SAPKA) if they are continued until surgery. The FDA recommends stopping these medications at least 4–6 days before surgery to avoid the risk of euglycemic ketoacidosis, which can present a diagnostic challenge for perioperative physicians. We present three patients undergoing colorectal cancer surgeries who on SGLT2 inhibitors developed perioperative SGLT2i-associated perioperative ketoacidosis.

Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type Polarization and Pyroptosis of Macrophages to Improve Hyperuricemic Nephropathy.

Neferine (Nef) has a renal protective effect. This research intended to explore the impact of Nef on hyperuricemic nephropathy (HN). Adenine and potassium oxonate were administered to SD rats to induce the HN model. Bone marrow macrophages (BMDM) and NRK-52E were used to construct a transwell co-culture system. The polarization of BMDM and apoptosis levels were detected using immunofluorescence and flow cytometry. Renal pathological changes were detected using hematoxylin-eosin (HE) and Masson staining. Biochemical methods were adopted to detect serum in rats. CCK-8 and EDU staining were used to assess cell activity and proliferation. RT-qPCR and western blot were adopted to detect NLRC5, NLRP3, pyroptosis, proliferation, and apoptosis-related factor levels. After Nef treatment, renal injury and fibrosis in HN rats were inhibited, and UA concentration, urinary protein, BUN, and CRE levels were decreased. After Nef intervention, M1 markers, pyroptosis-related factors, and NLRC5 levels in BMDM stimulated with uric acid (UA) treatment were decreased. Meanwhile, the proliferation level of NRK-52E cells co-cultured with UA-treated BMDM was increased, but the apoptosis level was decreased. After NLRC5 overexpression, Nef-induced regulation was reversed, accompanied by increased NLRP3 levels. After NLRP3 was knocked down, the levels of M1-type markers and pyroptosis-related factors were reduced in BMDM. Nef improved HN by inhibiting macrophages polarized to M1-type and pyroptosis by targeting the NLRC5/NLRP3 pathway. This research provides a scientific theoretical basis for the treatment of HN.

The effect of dexmedetomidine on acute kidney injury after elective major abdominal surgery : a retrospective single-center propensity score matched study

BackgroundMajor abdominal surgery is a kind of high-risk surgery type for postoperative acute kidney injury (AKI) among non-cardiac surgeries. Despite dexmedetomidine exerts significant renal protective effects in cardiac surgeries and animal studies, whether it is associated with a lower incidence of AKI in major abdominal surgeries remains unclear.MethodsFrom January 2019 to July 2021, patients undergoing elective major abdominal surgery in West China Hospital were enrolled. Participants were divided into two groups based on exposure to continuous intravenous dexmedetomidine: the Dex group (exposed) and the Control group (not exposed). The primary outcome was the incidence of AKI in the postoperative 7 days. Secondary outcomes included intraopertive average urine output, renal function on the first day after surgery, incidence of postoperative dialysis, postoperative intensive care unit (ICU) admission, in-hospital mortality, length of hospital stay, incidence of intraoperative hypotension and bradycardia, and intraoperative use of inotropes and vasopressors. Propensity score matching (PSM), based on participants’ baseline and intraoperative characteristics, was performed to minimize potential bias. Furthermore, a subgroup analysis was conducted based on the infusion rate and the use of a loading dose to explore the effects of different methods of dexmedetomidine administration on AKI. The subgroups included: loading dose, non-loading dose, low-infusion rate (infusion rate ≤ 0.4 µg/kg/h), and high-infusion rate (infusion rate > 0.4 µg/kg/h).ResultsAfter PSM with a ratio of 1:1, a total of 8836 patients were successfully matched. Dexmedetomidine administration had no association with the incidence of postoperative AKI, serum creatinine (Scr) level on the first postoperative day, incidence of postoperative dialysis, postoperative ICU admission, in-hospital mortality, length of hospital stay, intraoperative hypotension, or the use of inotropes and vasopressors, but had association with increased intraoperative average urine output (122.95 (76.80, 189.27) vs. 104.65 (67.04, 161.07) ml/h, P < 0.001), higher value of estimated glomerular filtration rate (eGFR) (97.33 ± 15.95 vs. 96.13 ± 16.35 ml/min/1.73m2, P < 0.001) on the first day after surgery and a higher incidence of intraoperative bradycardia (37.0% vs. 30.6%; P < 0.001). In the loading dose subgroup, dexmedetomidine use was significantly associated with a reduced incidence of postoperative AKI (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.23–0.76, P = 0.006).The association between dexmedetomidine and postoperative AKI was absent in subgroups of high or low infusion rate and no loading dose use.ConclusionIn this single-center retrospective propensity-matched study, we did not detect a significant overall difference in post-operative AKI rates between patients treated with or without dexmedetomidine during major abdominal surgery. However, though additional prospective data are needed, our study found that administering dexmedetomidine with a loading dose may be associated with lower rates of AKI, potentially indicating a renoprotective effect of loading-dose dexmedetomidine in this setting.

Critical review and analysis of information on the nephro-protective activity of medical plant extractions

Medicinal plants have been used since ancient times to prepare medicines in the form of extracts. Alcoholic and aqueous extracts of various parts of medicinal plants may contain potentially useful chemical compounds with biological activity. Therefore, extracts of some plants are still used to obtain effective and even potent medicines. It is believed that some medicinal plants contain chemical compounds that can have a protective effect on the kidneys in their diseases. However, the existing information on renal-tropic drugs obtained from medicinal plant raw materials and on the biological activity of extracts of medicinal plants does not allow us to draw unambiguous conclusions. A critical analysis of the information is required to sift out the “wheat from the chaff”. In this regard, the article provides a critical review of the available information on the pharmacological activity of extracts of medicinal plants claiming to have a renal protective effect. A list of information and features of the therapy of kidney diseases using extracts of various medicinal plants is provided. It has been shown that the development of effective herbal therapy for the treatment of severe renal diseases requires a systematic study of such properties of finished drugs (extracts) as the volume of solvent (alcohol or water). Attention is drawn to the fact that the analysis of information is not possible without taking into account the single, daily and course dose of water (or alcohol), as well as the physico-chemical properties of the extract taken. Only after taking into account these factors of therapy, it will be possible to critically re-evaluate the therapeutic effect of the applied extracts of medicinal plants, taking into account the dose of water and the physico-chemical properties of the corresponding extracts for specific kidney diseases. Most likely, it is advisable to analyze the effectiveness of specific extracts in such kidney diseases as acute renal failure, nephrotic syndrome and chronic interstitial nephritis. It should be noted that in chronic renal failure, the patient may have a different glomerular filtration rate, namely, be below 30 ml/min. In this regard, different glomerular filtration in patients may have different effects on the pharmacokinetics of drugs, including water and table salt. In addition, it is reported that researchers ignoring the osmotic activity of extracts does not allow taking into account the osmotic component of their effect on diuresis. Also, the traditional approach to the treatment of critical conditions in renal failure includes dialysis and renal replacement therapy, which are difficult to access for some rural residents due to their geographical and economic location. Therefore, it is necessary to take into account the effect of medicinal plant extracts not only on patients, but also on the clinical effectiveness of dialysis and renal replacement therapy. The article analyzes the available information from other sides as well. Certain herbs in herbal collections have proven nephroprotective properties nephroprotective properties. In particular, it is reported that today extracts of plants such as Kanchnar (bauhinia raznolistnaya), Kushmanda (Benincasa Hispid) and Yeshtimadu (licorice naked) can have a more reliable renal protective effect. Nevertheless, the renal-protective activity of these plant extracts has not been scientifically substantiated.

Shensu IV maintains the integrity of the glomerular filtration barrier and exerts renal protective effects by regulating endogenous hydrogen sulfide levels

BackgroundNephrotic syndrome has a significant impact on global health, often leading to cardiovascular disease and high mortality due to limited effective treatments. This study investigates the efficacy of Shensu IV in a puromycin aminonucleoside (PAN)-induced rat model of nephropathy.MethodsRat models and in vitro podocyte PAN nephropathy models were established with PAN and treated with Shensu IV. Renal function was evaluated by measuring urine output and protein content, while hydrogen sulfide (H2S) and oxidative stress markers were quantified in serum and podocyte lysates. We conducted histological examination on kidney tissues and analyzed molecular markers (CD2AP, nephrin, and PI3K/AKT pathway) using RT-qPCR and Western blot.ResultsShensu IV significantly improved urine output and proteinuria, and attenuated glomerular damage, fibrosis, and mitochondrial swelling in PAN-treated rats. Mechanistically, Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.ConclusionShensu IV and NaHS confer renal protection primarily by modulating oxidative stress and restoring the integrity of the glomerular filtration barrier through mechanisms involving the enhancement of the PI3K/AKT pathway and modulation of H2S levels. These findings suggest a promising therapeutic potential for these metabolites in the treatment of nephrotic syndrome.

A Comprehensive Study on the Renal Protective Effects of Polyherbal Extract Formulation and Their Impact on Kidney Function in Rats

Background: The nephroprotective effects of herbal extracts have increasingly gained attention due to the rise in kidney diseases and the limitations of conventional treatments. This study explores the renal protective properties of a polyherbal extract formulation composed of Ziziphus spina-christi, Trigonella foenum-graecum and Nigella sativa (ZTN) in Wistar albino rats. Methods: Three groups of adult male and female Wistar albino rats consisting of the control group that received only water, another group was administered with 100 mg/kg of the polyherbal (ZTN herbal) formulation, while the last group was administered with 250 mg/kg of the ZTN polyherbal extract formulation. The treatments administered for 14 days and thereafter Kidney weight, uric acid, Blood Urea Nitrogen (BUN) and creatinine levels were assessed to assess renal function. Histological analysis was conducted for tissue integrity evaluation. Result: The polyherbal extract formulation of ZTN induced a dose-dependent increase in kidney weight in both male and female rats. Uric acid levels decreased significantly in a dose-dependent manner, with the most substantial reduction at 250 mg/kg. BUN levels also showed a notable decrease, particularly at the higher dose, indicating enhanced renal function. Creatinine levels exhibited a significant dose-dependent reduction, with female rats showing higher baseline levels but greater overall reductions. Histological analysis revealed mild histological changes at 100 mg/mL and severe changes at 250 mg/mL. Histological changes include glomerular hypertrophy and tubular necrosis, more pronounced at higher doses. The polyherbal extract formulation of ZTN demonstrated significant nephroprotective effects, reducing uric acid, BUN and creatinine levels in a dose-dependent manner. Interestingly, an observation of gender-based differences occur in female rats showing higher baseline levels but greater reductions with treatment. These findings support the potential therapeutic use of polyherbal extracts in managing renal health, emphasizing the importance of dose regulation to avoid adverse effects.

GLP-1 Receptor Agonists Alleviate Diabetic Kidney Injury via β-Klotho-Mediated Ferroptosis Inhibition.

Semaglutide (Smg), a GLP-1 receptor agonist (GLP-1RA), shows renal protective effects in patients with diabetic kidney disease (DKD). However, the exact underlying mechanism remains elusive. This study employs transcriptome sequencing and identifies β-Klotho (KLB) as the critical target responsible for the role of Smg in kidney protection. Smg treatment alleviates diabetic kidney injury by inhibiting ferroptosis in patients, animal models, and HK-2 cells. Notably, Smg treatment significantly increases the mRNA expression of KLB through the activation of the cyclic adenosine monophosphate (cAMP) signaling pathway, specifically through the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Subsequently, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway is activated, reprograming the key metabolic processes of ferroptosis such as iron metabolism, fatty acid synthesis, and the antioxidant response against lipid peroxidation. Suppression of ferroptosis by Smg further attenuates renal inflammation and fibrosis. This work highlights the potential of GLP-1RAs and KLB targeting as promising therapeutic approaches for DKD management.

GLP-1RA improves diabetic renal injury by alleviating glomerular endothelial cells pyrotosis via RXRα/circ8411/miR-23a-5p/ABCA1 pathway.

Lipotoxicity has been implicated in diabetic kidney disease (DKD). However, the role of high glucose levels in DKD and the underlying renal protective mechanisms of GLP-1 receptor agonists (GLP-1RAs) remain unclear. To investigate cholesterol accumulation, pyroptosis in glomerular endothelial cells (GEnCs), and the renal protective mechanisms of GLP-1RAs, we used various techniques, including RT-qPCR, Oil Red O staining, Western blotting, lactate dehydrogenase (LDH) activity assays, circRNA microarrays, bioinformatics analysis, gain and loss-of-function experiments, rescue experiments, and luciferase assays. Additionally, in vivo experiments were conducted using C57BL/6J and ApoE-deficient (ApoE-/-) mice. GEnCs exposed to high glucose exhibited reduced cholesterol efflux, which was accompanied by downregulation of ATP-binding cassette transporter A1 (ABCA1) expression, cholesterol accumulation, and pyroptosis. Circ8411 was identified as a regulator of ABCA1, inhibiting miR-23a-5p through its binding to the 3'UTR. Additionally, higher glucose levels decreased circ8411 expression by inhibiting RXRα. GLP-1RAs effectively reduced cholesterol accumulation and cell pyroptosis by targeting the RXRα/circ8411/miR-23a-5p/ABCA1 pathway. In diabetic ApoE-/- mice, renal structure and function were impaired, with resulted in increased cholesterol accumulation and pyroptosis; however, GLP-1RAs treatment reversed these detrimental changes. These findings suggest that the RXRα/circ8411/miR-23a-5p/ABCA1 pathway mediates the contribution of high glucose to lipotoxic renal injury. Targeting this pathway may represent a potential therapeutic strategy for patients with DKD and hypercholesterolemia. Moreover, GLP-1RAs may provide renal protective effects by activating this pathway.

Mechanism of dihydroartemisinin in the treatment of ischaemia/reperfusion-induced acute kidney injury via network pharmacology, molecular dynamics simulation and experiments

ObjectiveTo investigate whether dihydroartemisinin (DHA) attenuates ischaemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) in mice by inhibiting oxidative stress and inflammation and to explore its potential molecular mechanisms. Materials and methodsNetwork pharmacology analysis was used to screen relevant targets, and molecular docking of DHA with core targets was performed. Molecular dynamics simulation of the target with the lowest binding free energy, NQO1-DHA.The renal protective effect of DHA on the IRI-induced AKI mouse model was evaluated. The expression levels of NQO1, Nrf2 and other proteins were detected by Western blotting. The expression levels of Nrf2 and others were detected by immunohistochemistry (IHC) and immunofluorescence (IF). ResultsThrough network pharmacological analysis, we obtained that PI3K/AKT and MAPK signaling pathway may be related to DHA in the treatment of AKI.Molecular dynamics simulation indicated that NQO1 is an important target protein for DHA to exert nephroprotective effects.Moreover, the potential molecular mechanisms were verified by experiments.DHA reduced the serum creatinine (Scr) and urea nitrogen (BUN) levels in AKI mice, significantly improved AKI pathology, alleviated oxidative stress and inflammatory injury, which may be related to its activation of the Nrf2 pathway and regulation of macrophage polarization. ConclusionsThrough network pharmacology, molecular dynamics simulation and experimental validation, we initially investigated that DHA alleviate AKI by ameliorating oxidative stress and inflammatory damage, which may be related to its activation of the Nrf2 pathway and the regulation of macrophage polarisation, which lays the foundation for subsequent in-depth study of the specific mechanism of action.

SGLT2 inhibitors - A novel treatment for congestive heart failure and chronic kidney disease

SGLT2 inhibitors increase renal excretion of sodium and glucose by blocking the SGLT2 transporters in the proximal tubule. Not only do they lower blood sugars levels but also have positive effects on blood pressure and weight. They lead to more efficient energy metabolism in the heart and kidneys, increase the production of red blood cells and decrease fibrosis and inflammation in the heart and the kidneys. Large double blind randomized trials have shown both cardiac and renal protective effects. Patient with heart failure, both with reduced and preserved ejection fraction have shown to benefit from treatment with SGLT2 inhibitors. They have lower risk of death due to cardiovascular causes and decreased risk of hospitalization because of heart failure compared to patient treated with placebo both with and without diabetes type 2. SGLT2 inhibitors are shown to decrease risk of chronic kidney disease stage 5 and dialysis, death due of cardiovascular events and doubling of serum creatinine in patients with chronic kidney disease both with and without diabetes type 2. They are now recommended for treatment of heart failure and chronic kidney disease with the highest evidence grade. SGLT2 inhibitors do not increase risk of hypoglycemia or acute kidney injury but do have a serious uncommon adverse effect that are normoglycemic ketoacidosis and Fournier's gangrene that physicians need to be alert to.

Isoquercitrin improves diabetes nephropathy by inhibiting the sodium-glucose co-transporter-2 pathway.

Diabetic nephropathy (DN) is one of the most severe kidney complications and the primary contributor to end-stage renal disease on a global scale. It exacerbates the morbidity, mortality, and financial burden for individuals with diabetes. Isoquercitrin, a natural compound found in various plants, has demonstrated potential as an antidiabetic agent. However, it remains uncertain whether isoquercitrin exerts a protective effect on DN. Therefore, the objective of this study was to explore whether isoquercitrin confers a protective effect on DN and its potential mechanism. In vivo, a mouse model of DN induced by streptozotocin was established in the study. The hypoglycemic effect of isoquercitrin was assessed by measuring fasting blood glucose levels, insulin tolerance tests, and glucose tolerance test in animals. Urinary albumin creatinine ratio, serum lipid levels, and pathological changes in renal tissues were measured to evaluate the protective effect of isoquercitrin against DN. The expression of Sodium glucose co-transporter-2(SGLT2) was analyzed using real-time quantitative PCR and immunohistochemistry. The studies suggest that isoquercitrin significantly reduces fasting blood glucose levels, enhances the body's capacity to regulate blood glucose and insulin resistance, and facilitates renal pathology and renal function. Simultaneously, it can lower blood lipids (total cholesterol and triglyceride) and improve the risk factors of DN. Meanwhile, isoquercitrin suppressed the expression of SGLT2 in renal tissues of DN mouse models. In vitro, real-time quantitative PCR and Western blot were used to detect the expression of SGLT2 in the human renal tubular epithelial (HK-2) cells. The effects of isoquercitrin on the survival rate and glucose uptake capacity of HK-2cells were determined by Cell-Counting-Kit-8 and glucose uptake methods. The results demonstrate that isoquercitrin suppressed the up-regulation of SGLT2 mRNA and protein in high-glucose-induced HK-2cells. Additionally, isoquercitrin inhibited glucose uptake in HK-2cells and mitigated high-sugar-induced damage. Thus, this study has concluded that isoquercitrin exhibits hypoglycemic and renal protective effects by inhibiting the SGLT2 pathway, indicating its potential as a promising anti-DN drug deserving further clinical investigation.

Klotho plays a crucial role in the renal-protective effect of allopurinol on renal ischemia-reperfusion injury.

Allopurinol, a xanthine oxidase inhibitor, recovers histological alterations and renal dysfunction induced during renal ischemic-reperfusion injury. This study investigated the cross-talk between the allopurinol and soluble Klotho. Rats were randomly divided into three equal groups (n = 8 per group): The sham-operated group without renal ischemia, the BIR (bilateral ischemia-reperfusion) group which underwent renal ischemia, and BIR+Allo (allopurinol) group which was pretreated with allopurinol (100 mg/kg- gavage) 30 min before the renal ischemia. After recovery from the anesthesia, all animals were placed in metabolic cages to collect their urine after 24 h, plasma was extracted from blood samples taken from the tail vein-plasma and urine samples were saved at -20 °C. Kidneys were harvested and weighed. The left kidney was dropped in the buffer of 10 % formalin for H&E staining, and the right kidney was located in liquid nitrogen and saved at -80 °C for the oxidative stress analysis. After renal ischemia-reperfusion, serum creatinine, blood urea nitrogen, xanthine oxidase, and total oxidative stress levels significantly increased. However, plasma Klotho level and total antioxidative capacity decreased in the BIR group. There was a reverse correlation between Klotho and xanthine oxidase levels. The pre-treatment with allopurinol increased plasma Klotho, induced a protective effect on renal histopathological changes, and corrected functional biomarkers. Our results showed that allopurinol enhanced the antioxidative effects by increasing Klotho activity. Therefore, Klotho may be involved in the protective effects of allopurinol on the renal injury induced by BIR.

Dexamethasone: a cheap and convenient way to alleviate subsequent stenosis after thermal injury on ureter.

Ureteral thermal injury (UTI) occurs when the ureter is exposed to high temperatures during surgical procedures, leading to tissue damage and ureteral stricture. Dexamethasone (DEX) has been widely used to treat a variety of diseases for its anti-inflammatory and immunosuppressant effects. However, its role in treating UTI remains unclear. The aim of this study was to determine the efficacy of treatment in mice with UTI. Thirty C57BL/6J mice were randomly divided into three groups (n=10 per group): (I) control group, (II) UTI group, (III) UTI + DEX group. UTI mouse models were constructed using a fast-pack pro-obturation pack handpiece instrument, and the therapeutic effect of DEX (2.5 mg/kg) on UTI was investigated via intraperitoneal injection for two weeks. Pathological changes in the ureter, renal function, extracellular matrix protein deposition, and inflammatory markers in the kidneys were evaluated in mouse models. Ureteral histopathological changes were more severe in the UTI group than in the control group; however, DEX treatment alleviated these changes to a certain extent. Mice in the UTI group exhibited elevated renal function. Although DEX alleviated renal function deterioration, the difference was not statistically significant. Moreover, in comparison to the control group, kidney samples from the mice in the UTI group revealed increased messenger RNA (mRNA) levels of inflammation markers, indicating a progressive inflammation response, while DEX significantly reversed interleukin-1β (IL-1β) expression at the protein level. Additionally, fibrosis-related markers were markedly increased in the kidneys of UTI mice. These findings were significantly reversed by DEX treatment, revealing its anti-inflammatory and anti-fibrotic activities. DEX reduces the severity of renal fibrosis and inflammation after UTI and exerts a significant renal protective effect.

Effect of dapagliflozin on renal haemodynamics in hyperfiltering T2D patients.

To investigate the effect of sodium-glucose co-transporter 2 inhibitor [SGLT-2i] therapy on renal haemodynamics in T2D patients with glomerular hyperfiltration. Sixty T2D patients with elevated [HYPER] and normal [NORMO] GFR were randomized to dapagliflozin 10 mg/day [DAPA/HYPER, n = 15; DAPA/NORMO, n = 15] or to metformin/glipizide [CONTROL/HYPER, n = 15; CONTROL/NORMO, n = 15] to reach similar glycaemic control after 4 months. GFR was measured with Iohexol and hyperfiltration was empirically defined as >125 mL/min/1.73 m2. GFR, renal plasma flow [RPF], mean arterial pressure [MAP], filtration fraction [FF], and renal vascular resistance [RVR] were determined before/after therapy. HbA1c decreased similarly in all 4 groups. GFR declined by ~18% in DAPA/HYPER and by ~7% in DAPA/NORMO and did not change in CONTROLS (p < 0.05 vs. DAPA). RPF remained unchanged in all four groups. Thus, FF (%) declined from 0.23 ± 0.01 to 0.18 ± 0.01 in DAPA/HYPER and from 0.17 ± 0.01 to 0.15 ± 0.01 in DAPA/NORMO and remained unchanged in CONTROLS (p < 0.05 vs. DAPA). MAP (mmHg) decreased from 95.4 ± 1.4 to 88.1 ± 1.3 in DAPA/HYPER and from 95.6 ± 1.3 to 91.8 ± 0.8 in DAPA/NORMO and remained unchanged in CONTROLS (p < 0.05 vs. DAPA). RVR [mmHg/L/min] declined in DAPA/HYPER (92.7 ± 7.8 to 80.4 ± 6.1) and DAPA/NORMO (90.1 ± 3.0 to 81.4 ± 2.1) but not in CONTROLS (p < 0.05 vs. DAPA). Despite comparable glycaemic control, dapagliflozin treatment, but not metformin and /or glipizide, reduced glomerular hyperfiltration in T2D patients and decreased both filtration fraction and renal vascular resistance. These findings suggest that a post-glomerular vasodilatory action of SGLT2 inhibitors contributes to their renal protective effect in T2D.

Simvastatin reduces chronic kidney disease and renal failure risk in type 2 diabetes patients: post hoc ACCORD trial analysis

ObjectiveType 2 diabetes mellitus (T2DM) poses a substantial global health concern. Statins are widely used among T2DM patients for managing dyslipidemia, preventing cardiovascular disease (CVD), and offering renal protection. However, the extent to which their renal protective effects contribute to reducing the incidence of severe renal complications, including chronic kidney disease (CKD) and renal failure, is not well-defined.MethodsThis investigation scrutinizes the impact of simvastatin versus placebo on renal outcomes among T2DM patients utilizing data from the ACCORD trial. It encompasses incidence rate comparisons, Kaplan-Meier estimates, Cox proportional hazards models, and mediation analyses.ResultsThe study consisted of 3,619 individuals diagnosed with T2DM, among which 2,753 were treated routinely with simvastatin, while 866 did not receive any statin therapy. After adjusting for baseline characteristics and time-dependent covariates, simvastatin treatment was associated with a 71% reduction in the risk of CKD (HR 0.29, 95% CI 0.27–0.31, p < 0.01) and a 47% reduction in the risk of renal failure (HR 0.53, 95% CI 0.44–0.65, p < 0.01) compared to the statin-free group. Further subgroup analysis, accounting for the initial lipid and kidney profiles, indicated variable impacts of simvastatin on CKD and renal failure outcomes. Nevertheless, a consistent reduction in CKD risk was observed across all subgroups within the statin-treated population. Additional mediation analysis revealed that the reduction in low-density lipoprotein cholesterol (LDL-C) may be a potential mediator in the association between simvastatin and CKD, with a mediation effect of 14.9%, (95% CI 0.11–0.19, p < 0.01).ConclusionAdministering statins, specifically simvastatin, to T2DM patients at elevated risk for CVD, is likely to offer augmented renal advantages, notably in lowering the occurrence of CKD and renal failure. This protective effect against CKD manifests regardless of initial lipid profiles, albuminuria, and estimated glomerular filtration rate (eGFR) levels. The association between simvastatin and CKD may be partially mediated by LDL-C reduction.

Renal protective effects of Porphyra dentate aqueous extract in diabetic mice

Renal protective effects of Porphyra dentate aqueous extract in diabetic mice