Renal Effects Research Articles

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway

BackgroundChronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the “gut-kidney axis.” Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation.ObjectivesThis study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway.MethodsThe researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues.ResultsIt was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group.ConclusionMZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.

Preclinical Evidence of Mulberry Leaf Polysaccharides on Diabetic Kidney Disease: a Systematic Review and Meta-Analysis.

Mulberry leaf polysaccharides (MLPs) have a variety of biological activities. Preliminary scattered evidence of preclinical studies have reported their potenzial effects on diabetic kidney disease (DKD). Here, we intended to assess the preclinical evidence of MLPs and explore their potenzial mechanisms on DKD, offering a scientific reference for the therapeutic use of MLPs. The study has been registered under the CRD42022309117 registration number at PROSPERO. Comprehensive search was conducted across eight databases from their establishment till January 2024, and eight studies with 270 animals were included in the meta-analysis. The primary outcome measurements in the MLP group, including serum creatinine (Scr) (P = 0.0005), blood urea nitrogen (BUN) (P = 0.02), 24-hour urinary protein (UP) (P = 0.001), and urinary microalbumin (UAlb) (P < 0.0001), were significantly reduced compared to the control group. Additionally, MLP treatment was significantly correlated with fasting blood glucose (FBG), total cholesterol (TC), protein expression of TGF-β1, CTGF mRNA, and the kidney index (all P values < 0.05) and delayed the progression of local pathological changes in the kidney. Subgroup analysis revealed significant species differences in the efficacy of MLPs. Also, it showed that the dosage of streptozotocin potenzially affected the Scr and UAlb results, while the duration of MLP treatment influenced UAlb results. MLPs may exert potenzial renal protection by delaying renal fibrosis, inhibiting inflammatory reactions, suppressing the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein axis, and regulating the insulin receptor pathway. In summary, MLPs have multifaceted renal protective effects, suggesting their potenzial for treating DKD.

Exploring and comparing renal adverse effects between PARP inhibitors based on a real-world analysis of post-marketing surveillance data

Exploring and comparing renal adverse effects between PARP inhibitors based on a real-world analysis of post-marketing surveillance data

Evaluation of the Renal Protective Effects of Cyperus at Varying Concentrations in a Rat Model of Kidney Disorders

Cyperus plants are frequently utilized around the globe to cure a range of human ailments, including as stomach and intestinal issues, as well as for their diuretic, digestant, and lactodepurant properties. Cyperus is a very promising genus in the Cyperaceae family that is used for health supplementation. So current study aims to improving kidney health using different concentrations of (Cyperus) plant in kidney disorders rats. The experiment was conducted at an animal house. all rats were provided with a standard diet for a duration of one week. Subsequently, the rats were segregated into five groups, each consisting of 6 rats. The first group, serving as the control negative (n=6) and labeled as C-ve, were exclusively fed the basal diet for a duration of 28 days. Thirty rats were administered gentamicin to induce renal problems. The experimental groups were administered different concentrations of Cyperus (5%, 7%, and 15%). The findings indicated that group 5, consisting of rats with renal disorders that were fed with 15% Cyperus powder, had the highest blood glucose levels. Conversely, there were no significant variations seen in HDL levels among group 3 &amp; group 4. While results found that Cyperus significantly reduced in urea and uric acid in kidney disorders rats. The results suggested to use Cyperus powder for kidney disorders rats.

Elucidating the complex interplay between chronic kidney disease and hypertension.

Chronic kidney disease (CKD) and hypertension share a complex relationship, each exacerbating the progression of the other. CKD contributes to hypertension by decreasing renal function, leading to fluid retention and increased plasma volume, whereas hypertension exacerbates CKD by increasing glomerular pressure and causing renal damage. This review examines the intertwined nature of CKD and hypertension, exploring the factors driving hypertension in CKD and how hypertension accelerates CKD progression. It discusses the role of the renin-angiotensin system and inflammatory cytokines in this relationship, as well as the potential of blood pressure management to slow renal decline. While studies suggest that meticulous blood pressure control can help attenuate CKD progression, optimal management strategies remain unclear and require further investigation. This review also evaluates the evidence surrounding strict antihypertensive therapy in patients with CKD, considering both diabetic and non-diabetic cases. It recommends blood pressure targets based on CKD stage and presence of diabetes, emphasizing the importance of individualized treatment approaches. Renin-angiotensin system inhibitors are highlighted as a key pharmacological intervention due to their renal protective effects, particularly in patients with CKD with proteinuria. However, evidence regarding their efficacy in patients with CKD but without proteinuria is inconclusive. This review underscores the need for comprehensive approaches to effectively address the intertwined nature of CKD and hypertension and calls for further research to optimize clinical management strategies in this complex interplay.

Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study

Chronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr1]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr1]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov: NCT03956576. Funded by Kidney Research UK.

Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

The Effect of Nerolidol on Renal Dysfunction following Bilateral Ureteral Obstruction.

Background/Objectives: Obstructive uropathy is a common cause of renal impairment. Recently, there has been a burgeoning interest in exploring natural products as potential alternative remedies for many conditions due to their low toxicity, affordability and wide availability. Methods: We investigated the effect of nerolidol in a rat model of bilateral ureteral obstruction (BUO) injury. Nerolidol, dissolved in a vehicle, was administered orally as a single daily dose of 200 mg/kg to Wistar rats. Sham group (n = 12) underwent sham surgery, whereas the BUO (n = 12) and BUO/NR groups (n = 12) underwent reversible 24-h BUO and received the vehicle or nerolidol, respectively. The treatment started 9 days prior to the BUO/sham surgery and continued for 3 days after reversal. Renal functions were assessed before starting the treatment, just prior to the intervention and 3 days after BUO reversal. Results: Neither nerolidol nor the vehicle affected the basal renal functions. Nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also attenuated the changes in several markers associated with renal injury, inflammation, apoptosis and oxidative stress and mitigated the histological alterations. Conclusions: The findings of this study demonstrated the potent reno-protective effects of nerolidol in mitigating the adverse renal effects of bilateral ureteral obstruction. This is attributed to its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-oxidant properties. These effects were reflected in the partial recovery of renal functions and histological features. These findings may have potential therapeutic implications.

Sirt6 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway

Background Podocyte injury plays an important role in the occurrence and progression of diabetic kidney disease (DKD), which leads to albuminuria. Cytoskeletal remodeling is an early manifestation of podocyte injury in DKD. However, the underlying mechanism of cytoskeletal remodeling has not been clarified. Histone deacetylase sirtuin6 (Sirt6) has been found to play a key role in DKD progression, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway directly regulates the cytoskeletal structure of podocytes. Whereas, the relationship between Sirt6, the PI3K/AKT pathway and DKD progression remains unclear. Methods Renal injury of db/db mice was observed by PAS staining and transmission electron microscope. Expression of Sirt6 in the glomeruli of db/db mice was detected by immunofluorescence. UBCS039, a Sirt6 activator, was used to explore the renal effects of Sirt6 activation on diabetic mouse kidneys. We also downregulating Sirt6 expression in podocytes using the Sirt6 inhibitor, OSS_128167, and induced upregulation of Sirt6 using a recombinant plasmid, after which the effects of Sirt6 on high glucose (HG)-induced podocyte damage were assessed in vitro. Podocyte cytoskeletal structures were observed by phalloidin staining. The podocyte apoptotic rate was assessed by flow cytometry, and PI3K/AKT signaling activation was measured by Western blotting. Results Db/db mice exhibited renal damage including elevated urine albumin-to-creatinine ratio (ACR), increased mesangial matrix, fused podocyte foot processes, and thickened glomerular basement membrane. The expression of Sirt6 and PI3K/AKT pathway components was decreased in db/db mice. UBCS039 increased the expressions of Sirt6 and PI3K/AKT pathway components and ameliorated renal damage in db/db mice. We also observed consistent Sirt6 expression was in HG-induced podocytes in vitro. Activation of the PI3K/AKT pathway via a Sirt6 recombinant plasmid ameliorated podocyte cytoskeletal remodeling and apoptosis in HG-treated immortalized human podocytes in vitro, whereas Sirt6 inhibition by OSS_128167 accelerated HG-induced podocyte damage in vitro. Conclusions Sirt6 protects podocytes against HG-induced cytoskeletal remodeling and apoptosis through activation of the PI3K/AKT signaling pathway. These findings provide evidence supporting the potential efficacy of Sirt6 activation as a promising therapeutic strategy for addressing podocyte injury in DKD.

Analysis of brominated flame retardants exposure-associated chronic kidney disease risk in the US population from the NHANES

BackgroundExposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD. MethodsTotally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD. ResultsAfter adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most. ConclusionSpecific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US.

12467 Ethical Challenges During Medication Scarcity

Abstract Disclosure: K. Seetharaman: None. R. Alvi: None. V. Roth: None. J. Maheswaran: None. Ethical considerations while rationing GLP-1 RA during medication scarcity crisis: The prevalence of type 2 diabetes and obesity have risen over the past decade. Type 2 diabetes affects nearly 29 million Americans, and one in 3 Americans are obese. Prompt treatment of type 2 diabetes can result in prevention and progression of several diabetes related complications. In the past 3 decades, advancements in scientific research has led to invention of newer therapeutic agents such as the glucagon like peptide-1 receptor agonist (GLP-1 RA) for management of type 2 diabetes and these medications have shown to provide cardiovascular benefit and renal protective effects. More recently, with increasing benefits of GLP-1 RA in treating obesity even in the absence of diabetes, the prescription rates of GLP-1 RA has increased sharply leading to acute medication scarcity and the resultant crisis has created a chaos in health care having multi-faceted repercussions.We present a short movie enacting 2 clinical scenarios with doctor and patients to initiate discussions on how to ration GLP-1 receptor agonists during times of medication scarcity crisis and the bioethical aspects to consider while making such decisions. We further include discussions by enacting pharmacy care coordinator, bioethicist, critique and defense discussion. Bioethics involved in medication scarcity crisis:https://hu-my.sharepoint.com/:v:/g/personal/kseetharaman_hsph_harvard_edu/EZIHpFRCgb5AsoKLk898TgUBsdp8JNjdAGQ6vOIpZIP1Qg?e=TkxRhz We hope our enacting of various scenarios has given you all valuable ethical perspectives to consider while rationing during times of medicine scarcity.

The effect of Traumeel LT ad us. vet. on the perioperative inflammatory response after castration of stallions: a prospective, randomized, double-blinded study.

Stallion castration is a standard procedure with a risk of post-surgical complications. Castration induces an acute phase response (APR). Serum Amyloid-A (SAA) is a well-studied major acute phase protein (APP), that has been shown to be a good marker for the development of post-surgical complications. The current gold standard for reducing the APR after castration is Flunixin-Meglumin, which is a non-steroidal anti-inflammatory drug (NSAID) inhibiting COX1/2. In contrast, Traumeel LT ad us. vet. can modulate the APR by induction of the inflammation resolution. The aim of this study was to compare the effect of Flunixin-Meglumin and Traumeel LT ad us. vet. on the acute phase response. A total of 60 stallions were recruited and 54 stallions entered the study with 27 stallions in each treatment group. The stallions were treated pre- and postoperatively with either Flunixin-Meglumin (FL) or with Traumeel LT ad us. vet. (TR). Blood was taken before and 24 h, 48 h and 72 h after castration. The following main parameters were assessed: SAA, fibrinogen, iron, white blood cells, neutrophils, Interleukin1ß, and cortisol. Wound healing and pain were assessed at 8 time points. The main variable SAA was increased after surgery reaching a mean value of 122 µg/ml in the FL group and a mean SAA of 226 µg/ml in the TR group 48 h after surgery, reaching a significant difference only at the 24 h timepoint (p = 0.03). All stallions had the highest pain summary score 8 hours after surgery, with decreasing values thereafter. The pain scores were not statistically different at any time point. In the FL group five stallions developed a suture dehiscence compared to only one stallion in the TR group (p = 0.001). Within the limitations of this study, Traumeel LT ad us. vet. seems to have proresolving effects on the inflammation induced by surgery making it a valuable treatment to reduce the APR induced by castration. Due to its different mode of action, Traumeel LT ad us. vet. might be an alternative treatment option if gastrointestinal side effects or renal side effects of NSAIDs should be avoided. Further studies are needed combining Traumeel LT ad us. vet. and Flunixin.

The Addition of a Non-Steroidal Anti-Inflammatory Drug (NSAID) in Local Infiltration Analgesia During Total Knee Arthroplasty Increases the Risk of Acute Kidney Injury in Patients Who Have Renal Impairment: A Propensity-Matched Retrospective Cohort Study

BackgroundLocal infiltration analgesia (LIA) is a crucial component of pain management during total knee arthroplasty (TKA). Various formulations of the LIA drug cocktail have been described, with non-steroidal anti-inflammatory drugs (NSAIDs) commonly included. Although NSAIDs are highly effective in improving postoperative pain, they are associated with adverse renal, gastrointestinal, and cardiovascular effects. This study aimed to investigate whether the addition of an NSAID in LIA affects the incidence of acute kidney injury (AKI) in TKA patients, especially those who have pre-existing renal impairment. The secondary aim was to determine overall AKI incidence. MethodsA retrospective cohort study was conducted on elective, primary TKA patients in a single tertiary institution between January 2020 and April 2024. Data was obtained from a prospectively collected institutional knee arthroplasty registry. Patients were administered LIA intraoperatively, with or without an NSAID (30 mg of ketorolac). The study population was divided into two subpopulations, patients who did or did not have chronic kidney disease (CKD), and analyzed separately. Propensity matching was performed on the CKD group, correcting for age, sex, BMI, ASA score, and presence of diabetes mellitus/hypertension. The outcome of interest was the incidence of AKI. A t-test or Chi-square test was used, where appropriate, to determine the statistical significance of the results. ResultsIn patients who had CKD (n = 114), the presence of ketorolac in LIA was associated with a higher AKI incidence (12.7 versus 2.0%, P = 0.041). In patients who did not have CKD (n = 870), the presence of ketorolac in LIA was not associated with a higher AKI incidence (2.0 versus 1.9%, P = 1.0). Overall AKI incidence was 2.6%. ConclusionIn patients who have CKD, orthopaedic surgeons should be highly cautious of administering ketorolac in LIA during TKA, as it is associated with a higher risk of AKI. Patients who have normal renal function can be safely given ketorolac in LIA without an elevated risk of AKI. Further studies are needed to examine AKI incidence when other NSAIDs are used in LIA.

Integrative Multi-Omics and Network Pharmacology Reveal the Mechanisms of Fangji Huangqi Decoction in Treating IgA Nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

Renal protective effect of Isaria felina mycelium powder on diet and STZ-induced diabetes mice and the identification of major chemical constituents

Type 2 diabetes is a group of metabolic diseases mainly characterized by chronic hyperglycemia. Diabetic kidney disease is the most common microvascular complication of diabetes.The aim of this study was to investigate the therapeutic effect of Isaria felina mycelium powder (IFMP) on diet and streptozotocin (STZ)-induced diabetic mouse model. And we analyze the main chemical constituents of Isaria felina mycelium powder.The main chemical constituents of the alcohol-soluble IFMP were prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The fasting blood glucose and renal index of the mouse model was determined. Serum levels of triglyceride (TG), total cholesterol (TC), serum creatinine (Scr) and blood urea nitrogen (BUN) were detected. The levels of CD2AP and nephrin proteins in the kidney were detected by ELISA kits.A total of 32 compounds were identified, including nucleosides (16 types), amino acids (13 types), sterols (one type) and glycosides (two types). The experimental results showed that compared with the diabetes model group, IFMP reduced fasting blood glucose, food intake and water intake. Biochemical analysis indicated that IFMP reduced the serum levels of TG, TC, BUN and Scr, and increased the levels of CD2AP and nephrin proteins in the kidneys.Therefore, IFMP has the potential to treat diabetes and prevent kidney damage induced by hyperglycemia.

Obtusifolin inhibits podocyte apoptosis by inactivating NF-κB signaling in acute kidney injury.

Acute kidney injury (AKI) is a common clinical condition and is associated with unacceptable morbidity and mortality. Obtusifolin is an anthraquinone extracted from the seeds of Cassia obtusifolia with anti-inflammatory properties. This study focused on the role and mechanism of obtusifolin in AKI. The mouse podocyte cell line MPC5 was exposed to lipopolysaccharide (LPS) to establish a cell model of AKI. The viability of MPC5 cells treated with obtusifolin and/or LPS was detected by 3-(4, 5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay. Cell apoptosis was analyzed by flow cytometry. The levels of podocyte injury- and apoptosis-related proteins as well as the nuclear factor-kappaB (NF-κB) signaling pathway was examined using western blotting analysis. The renal protective effects of obtusifolin were determined using an LPS-induced mouse model of AKI. Serum creatinine and blood urea nitrogen levels were measured. Hematoxylin-eosin staining of kidney sections was performed to evaluate renal histology. We found that MPC5 cells treated with LPS showed suppressed cell viability (p < 0.01) and increased cell apoptosis (p < 0.001). LPS reduced the protein expression of Bcl-2, nephrin, and synaptopodin as well as increased the protein levels of Bax and Cleaved Caspase-3 in podocytes in a concentration-dependent manner (p < 0.01). In addition, 10μg/ml LPS-repressed cell viability was rescued by obtusifolin in a concentration-dependent manner (p < 0.01). Moreover, LPS-induced increase in MPC5 cell apoptosis was reversed by obtusifolin treatment (p < 0.01). Obtusifolin administration ameliorated LPS-induced kidney injury and reduced blood urea nitrogen and serum creatinine levels in mice (p < 0.001). Additionally, obtusifolin inhibited LPS-induced activation of NF-κB signaling in vitro and in vivo (p < 0.01). Overall, obtusifolin was effective in protecting renal function against LPS-induced AKI via inactivation of NF-κB signaling, which suggested that obtusifolin may act as a valuable agent for AKI therapy.

Renal Cell Type-Associated Therapeutic Effects of Semaglutide in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease

Renal Cell Type-Associated Therapeutic Effects of Semaglutide in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease

Diabetic Ketoacidosis Complications in Pediatrics: A Narrative Review

Introduction: Around the world type I diabetes mellitus (T1D) is becoming more prevalent among pediatrics. The most common cause of mortality in children is diabetic ketoacidosis (DKA). It affects up to one-third of people with T1D. The most common complication of pediatric diabetic ketoacidosis is cerebral edema; however, it is not the only adverse effect of DKA that necessitates continuous observation. Methods: This study was conducted as a narrative review obtaining all applicable data on complications of diabetic ketoacidosis (DKA) in the pediatrics age group. Conclusion: This review of literature discusses the effects of DKA on different body systems including neurological, coagulopathy, pulmonary, gastrointestinal, infectious, and renal effects. Aim: To educate families and healthcare professionals about the significance of strict glycemic control and early identification of DKA in order to prevent the onset of those consequences, we examine each of those multisystem impacts in children

Assessing the Sympatholytic Effects of SGLT2 Inhibitors in Anuric Haemodialysis Patients Using Microneurography: Study Protocol for a Mechanistic Proof-of-Concept Trial

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been shown to provide effective cardiorenal protection, reducing mortality in conditions such as heart failure and chronic kidney disease. While several mechanisms have been identified, recent research has shed light on the drug’s ability to attenuate sympathetic nervous system (SNS) activity. Controversy exists on whether this is due to the extra-renal effects of the drug, or simply due to its renoprotective effects. However, recent trials have highlighted the persistent efficacy of SGLT2i despite declining renal function. Therefore, investigating the ability of SGLT2i to attenuate the SNS independently of the kidney could lead to more insight into its mechanism of action. So far, there has been limited research done on investigating the extra-renal effects of SGLT2i in human subjects on dialysis where the glycosuric renal effects of SGLT2i are negligible. This current study therefore aims to investigate the effects of SGLT2i on the SNS in anuric haemodialysis patients. Methods: We developed a protocol for a mechanistic study to investigate the extra-renal effects of SGLT2i on the SNS. The study will be an investigator-led, open-label, prospective study involving 20 adult (aged ≥18 years) haemodialysis patients with a residual urine output of ≤250 mL/day. Participants will be administered empagliflozin 25 mg/day for 6 weeks. Baseline SNS activity will be measured before and after administration by microneurography to assess central SNS outflow. Secondary outcomes such as changes from baseline in SNS stressor response, heart rate variability, and endothelial function will also be examined. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive in anuric haemodialysis patients. Discussion: This will be the first study evaluating the effects of SGLT2i on the SNS in haemodialysis subjects. This study aims to enhance our understanding of the potential role of SGLT2i-induced SNS reduction in the setting of markedly reduced renal function. The study has received ethics approval from the Royal Perth Hospital Human Research Ethics Committee (RGS0000003840) (Australian New Zealand Clinical Trials Registry [ANZCTR] ID: ACTRN12623001237673).

New drugs on the horizon for acute kidney injury

Purpose of review Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients. Currently, no effective therapy to prevent or treat AKI is available. This review highlights recently published developments on pharmacological treatments that aim to prevent AKI or to alleviate the severity of AKI in critical ill patients. Recent findings Studies on pharmacological interventions aimed to improve hemodynamics, renal perfusion, to mediate inflammation-associated renal damage and to reduce oxidative stress are presented, including several observational studies and randomized trials focused on the potential renal protective effects in relevant patient populations. Different existing and novel compounds are being investigated for the effects on renal endpoints and several show potential to prevent or alleviate the occurrence of AKI. It is now ac knowledged that different underlying pathophysiological processes are relevant in the development of AKI. Recognition of these sub-endotypes of AKI and knowledge of the therapeutic target of different compounds is of paramount importance to select the right patient for the right treatment at the right time. Summary The discovery of reno-protective therapies is hampered by the timely detection and recognition of the overriding mechanism of AKI. Nevertheless, several compounds are under investigation, which hold promise for a future treatment.