Search Results (247)

Background/Objectives: Acute kidney injury (AKI) worsens outcomes in COPD exacerbation (COPDe), yet limited data compare the demographics and mortality risk factors of COPDe admissions with and without AKI. Understanding this association may enhance risk stratification and management strategies. The aim of this study was to identify demographic differences and mortality risk factors in COPDe admissions with and without AKI. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 1 January 2016 to 1 January 2021. Patients aged ≥ 35 years with a history of smoking and a diagnosis of COPDe were included. Patients with CKD stage 5, end-stage kidney disease (ESKD), heart failure decompensation, urinary tract infections, myocardial infarction, alpha-1 antitrypsin deficiency, or active COVID-19 infection were excluded. Baseline demographics were analyzed using descriptive statistics. Multivariate logistic regression analysis was used to measure the odds ratio (OR) of mortality. Statistical analyses were conducted using IBM SPSS Statistics V.30, with statistical significance at p < 0.05. Results: Among 405,845 hospitalized COPDe patients, 13.6% had AKI. These patients were older, had longer hospital stays, and included fewer females and White patients. AKI was associated with significantly higher mortality (OR: 2.417), more frequent acute respiratory failure (OR: 4.559), intubation (OR: 10.262), and vasopressor use (OR: 2.736). CVA, pneumonia, and pulmonary hypertension were significant mortality predictors. Hypertension, CAD, and diabetes were associated with lower mortality. Conclusions: AKI in COPDe admissions is associated with worse outcomes. Protective effects from certain comorbidities may relate to renoprotective medications. Study limitations include coding errors and retrospective design. Full article

Objective: Uncovering the renoprotective and anti-inflammatory effects of atorvastatin treatment in diabetic-and-obese rats by employing traditional renal function indicators (urea and creatinine) and four prototypical cytokines (IL-1β, il-6, IL-17α, TNFα). Method: Twenty-eight male Wistar rats, aged 6 months, 350–400 g, were randomized into four groups. The first group, G-I, the denominated control, were fed standard chow over the whole course of the experiments. The rodents in G-II were exposed to a High-Fat Diet. The last two groups were exposed to Streptozotocin peritoneal injection (35 mg/kg of body weight). A short biochemical assessment was performed before diabetes model induction to ensure appropriate glucose metabolism before experiments. Following model induction, only rodents in group G-IV were gradually introduced to the same High-Fat Diet as received by G-II. Model confirmation 10 days after injections marked the start of statin treatment in group G-IV, by daily gavage of atorvastatin 20 mg/kg of body weight/day for 21 days. At the end of the experiments, the biochemical profile of interest comprised typical renal retention byproducts (urea and creatinine) and the inflammatory profile described using plasma levels of TNFα, IL-17α, IL-6, and IL-1β. Results: Treatment with Atorvastatin was associated with a statistically significant improvement in renal function in G-IV compared to untreated diabetic rodents in G-III. Changes in inflammatory activity showed partial association with statin therapy, TNFα and IL-17α mirroring the trend in urea and creatinine values. Conclusions: Our results indicate that atorvastatin treatment yields a myriad of pleiotropic activities, among which renal protection was clearly demonstrated in this model of diabetic-and-obese rodents. The statin impact on inflammation regulation may not be as clear-cut, but the potential synergy of renal function preservation and partial tapering of inflammatory activity requires further research in severely metabolically challenged models. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This investigation sought to determine the nephroprotective potential of Lactobacillus rhamnosus GG (LGG) administration in diabetic nephropathy models. Six experimental cohorts were evaluated: control, probiotic-supplemented control, diabetic, diabetic receiving probiotic therapy, diabetic with antibiotics, and diabetic treated with both antibiotics and probiotics. Diabetic conditions were established via intraperitoneal administration of streptozotocin (50 mg/kg) following overnight fasting, according to validated protocols for experimental diabetes induction. Probiotic therapy (3 × 10⁹ CFU/kg, bi-daily) began one month before diabetes induction and continued throughout the study duration. Glycemic indices were monitored at bi-weekly intervals, inflammatory biomarkers, renal function indices, and urinary albumin excretion. The metabolic profile was evaluated through the determination of HOMA-IR and the computation of metabolic syndrome scores. Microbiome characterization employed 16S rRNA gene sequencing alongside metagenomic shotgun sequencing for comprehensive microbial community mapping. L. rhamnosus GG supplementation substantially augmented microbiome richness and evenness metrics. Principal component analysis revealed distinct clustering of microbial populations between treatment groups. The Prevotella/Bacteroides ratio, an emerging marker of metabolic dysfunction, normalized following probiotic intervention in diabetic subjects. Results: L. rhamnosus GG administration markedly attenuated diabetic progression, achieving glycated hemoglobin reduction of 32% compared to untreated controls. Pro-inflammatory cytokine levels (IL-6, TNF-α) decreased significantly, while anti-inflammatory mediators (IL-10, TGF-β) exhibited enhanced expression. The renal morphometric analysis demonstrated preservation of glomerular architecture and reduced interstitial fibrosis. Additionally, transmission electron microscopy confirmed the maintenance of podocyte foot process integrity in probiotic-treated groups. Conclusions: The administration of Lactobacillus rhamnosus GG demonstrated profound renoprotective efficacy through multifaceted mechanisms, including microbiome reconstitution, metabolic amelioration, and inflammation modulation. Therapeutic effects suggest the potential of a combined probiotic and pharmacological approach to attenuate diabetic-induced renal pathology with enhanced efficacy. Full article

Background/Objectives: The present study aimed to evaluate the nephroprotective role of Khellin (Khe) against cisplatin (CDDP)-mediated nephrotoxicity in rats. Methods: We assessed oxidative stress markers (MDA, CAT, SOD, GPx, and iNOs), inflammatory markers (TNFα, IL6, IL10, and MCP1), apoptotic markers (Bax and Bcl2), and the renal damage marker (Kim1). Network pharmacology and molecular docking studies were performed. In vitro, Khe effects were tested on normal kidney cells (Vero) and liver cancer cells (HepG2) treated with CDDP. Results: Network pharmacology and docking suggested Khe’s activity primarily affects oxidative stress and inflammatory pathways, notably through MAPK14 and PI3K downregulation. In vitro, Khe reduced CDDP’s cytotoxicity in Vero cells while maintaining anti-proliferative effects on HepG2 cells. In vivo, CDDP significantly increased serum creatinine, urea, Kim1, oxidative stress markers (MDA and iNOS), and inflammatory markers (TNFα, IL6, and MCP1) while decreasing antioxidant markers (SOD, GPx, CAT, and SOD3) and anti-inflammatory cytokine (IL10) levels. Khe treatment dose-dependently attenuated these changes, with the 100 mg/kg dose showing the most significant renoprotection. Histopathological analysis confirmed improved renal tissue integrity in Khe-treated groups. Conclusions: This study demonstrates that Khe exerts significant nephroprotective effects against CDDP-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis while improving renal function and structure. These findings suggest Khe as a promising therapeutic candidate for preventing CDDP-related kidney injury. Full article

High-sodium/low-potassium in the modern diet, potassium excretion, and sodium retention have all been implicated in hypertension. Objectives: This study investigated the differential effects of potassium (K⁺) supplementation on blood pressure, renal function, and oxidative stress in two experimental hypertensive rat models: L-NAME-induced (nitric oxide synthase inhibitor-induced hypertension presenting with reduced NO bioavailability, endothelial dysfunction, vasoconstriction) and DOCA-salt-induced hypertension (deoxycorticosterone acetate + salt mimics volume-dependent hypertension of hypermineralocorticoidism, low renin, high sodium retention and severe cardiac fibrosis and oxidative stress). Methods: Male Sprague Dawley rats were treated with L-NAME or DOCA-salt, with or without 0.75% KCl dietary supplementation for eight weeks. Blood pressure, vascular reactivity, serum electrolytes, renal function markers, and malondialdehyde (MDA) levels were evaluated. Results: Potassium supplementation significantly reduced (20%) mean arterial pressure and (80%) oxidative stress markers in the L-NAME model but not in the DOCA-salt model. In both hypertensive models, K⁺ reduced (15%) vascular contractile response to phenylephrine, though it did not improve acetylcholine-induced vasodilation. Notably, K⁺ supplementation improved glomerular filtration rate (eGFR), sodium–potassium ratio, and renal biomarkers (urea and creatinine) in the L-NAME model, suggesting nephroprotection. However, in the DOCA-salt group, these markers either remained unchanged or worsened. Conclusions: These findings indicate that the antihypertensive and renoprotective effects of potassium are model-specific and depend on the underlying pathophysiological mechanisms, such as nitric oxide bioavailability and mineralocorticoid sensitivity. Dietary potassium may be more effective in patients with endothelial dysfunction-dominant hypertensive subtypes compared with volume-dependent hypertension and may call for K⁺ supplementation studies to be stratified by hypertension subtype. Full article

Background: SGLT2 inhibitors (SGLT2is) lower glucose and have renoprotective effects, including reducing proteinuria. In kidney transplant recipients (KTRs), proteinuria impacts graft and patient survival. While SGLT2is benefits have been reported in diabetic KTRs, the data on non-diabetic KTRs are poor, and no data are available for albuminuria and non-albumin proteinuria. This study assessed the effects of dapagliflozin on urinary protein excretion in KTRs with and without diabetes. Methods: This analysis, from the Salerno CKD Cohort Study, included 66 KTRs (≥1 year post-transplant) with proteinuria despite renin–angiotensin system inhibitor therapy. The patients received dapagliflozin (10 mg/day) for six months, with assessments at the baseline (T0), three months (T1), and six months (T2); adverse events were monitored. The primary outcomes were changes in the urinary total, albumin, and non-albumin proteins. The secondary outcomes included weight, blood pressure, and eGFR. Results: At T1, the urinary total, albumin, and non-albumin proteins were significantly decreased, with a greater reduction in the non-albumin proteins vs. albumin (−27% vs. −9.4%, p = 0.001). No further changes occurred at T2. The patients’ weight and blood pressure also declined, while their eGFR and glucose remained stable. The non-albumin protein reduction was correlated with weight loss and diastolic blood pressure changes. Two patients discontinued use due to adverse events (one with a urinary tract infection, one with hypotension). Conclusions: Dapagliflozin reduces proteinuria, particularly non-albumin proteins, in KTRs with and without diabetes, with a low incidence of adverse effects. Further studies are needed to confirm the long-term benefits, especially in non-diabetic recipients. Full article

Diabetic nephropathy (DN) represents a severe microvascular complication of diabetes mellitus with limited therapeutic options, many of which are accompanied by considerable adverse effects. Opuntia ficus-indica (OFI) fruit, rich in vitamins, dietary fiber, and fatty acids, contains numerous bioactive compounds, including phytosterols, polysaccharides, and flavonoids that demonstrate significant potential in diabetes management. The flavonoid fraction derived from OFI fruit (OFI-F) has exhibited pronounced anti-inflammatory, antioxidant, and gut microbiota modulatory properties. However, the efficacy of OFI-F in ameliorating DN and its underlying mechanisms remain inadequately elucidated. This investigation examined the therapeutic potential of OFI-F in DN and explored its mechanistic pathways. Our findings demonstrate that OFI-F administration significantly attenuated renal injury and intestinal barrier dysfunction in the DN murine model. OFI-F intervention resulted in multiple beneficial outcomes in DN mice, including the mitigation of weight loss, reduction in hyperglycemia, decrease in renal coefficient index, and the attenuation of renal injury. An analysis of gut microbiota composition revealed that OFI-F administration favorably modulated the intestinal microbial community by enhancing the abundance of beneficial bacteria while concomitantly reducing populations of potentially pathogenic bacteria. Additionally, OFI-F treatment promoted the production of short-chain fatty acids (SCFAs), which contributed substantially to renoprotection and inflammatory resolution. Antibiotic intervention studies further confirmed the indispensable role of gut microbiota in mediating the renoprotective effects of OFI-F. In conclusion, this study provides compelling evidence supporting the therapeutic potential of OFI-F in DN management through the concurrent modulation of gut microbiota and renal function, offering a promising nutraceutical approach for alleviating renal injury in DN. Full article

Background: Renal fibrosis is a common pathological feature of all progressive chronic kidney disease (CKD). Eucommiae cortex (EC) is a valuable economic tree species endemic to China. The microbial fermentation of Chinese medicines can release their active ingredients as effectively as possible or produce new active ingredients with enhanced efficacy and reduced toxic side effects; Methods: The microbial fermentation of EC can produce pinoresinol (Pin) and dehydrodiconiferyl alcohol (DA). In this study, C57 BL/6 mice were fed a diet containing 0.2% adenine, resulting in a model of chronic kidney disease. The effects of EC and EC ferment (ECF) on CKD were explored by the exogenous supplementation of EC and ECF; Results: The results of the study showed that exogenous supplementation with EC and ECF suc-cessfully reduced creatinine and urea nitrogen levels, down-regulated the expression levels of TGF-β1, α-SMA, Smad3, and phospho-Smad3 in the TGF-β1/Smad signaling pathway, and ameliorated renal fibrosis; Conclusions: Both EC and ECF may have reno-protective effects and provide a reference for relevant clinical drug development. Full article

Hyperuricemia (HUA) is a metabolic disease caused by disrupted purine metabolism, characterized by abnormally elevated uric acid (UA) levels. Stachydrine, an alkaloid in natural foods, exhibits multiple biological activities. This study aimed to evaluate the effects of stachydrine on alleviating HUA. An HUA mouse model was established through high-nucleoside diet induction, and stachydrine’s effects on UA levels and renal injury were investigated. Our findings revealed that stachydrine enhanced uric acid excretion by upregulating ATP-binding cassette subfamily G member 2 (ABCG2). Furthermore, stachydrine mitigated HUA-induced renal inflammation, mitochondrial oxidative stress and apoptosis. Mechanistically, stachydrine facilitated the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by downregulating Kelch-like ECH-associated protein 1 (Keap1), subsequently activating the Keap1/Nrf2 signaling pathway and alleviating local oxidative stress. This study demonstrated the UA-lowering and renoprotective effects of stachydrine, suggesting its potential as a functional food ingredient for mitigating HUA. Full article

Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation. Full article

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as a promising therapeutic option beyond their established role in managing type 2 diabetes mellitus (T2DM) and obesity. Recent research has highlighted their beneficial effects on liver, kidney, and cardiovascular health, mediated by both direct and indirect mechanisms. In the liver, GLP-1 RAs contribute to the improvement of metabolic dysfunction-associated steatotic liver disease (MASLD) by reducing hepatic fat accumulation, inflammation, and oxidative stress. Additionally, they enhance insulin sensitivity and lipid metabolism. Similarly, in diabetic kidney disease (DKD), GLP-1 RAs exhibit renoprotective properties by mitigating inflammation, oxidative stress, and glomerular hypertension. Furthermore, they promote natriuresis and stabilize renal function. Moreover, GLP-1 RAs present significant cardiovascular benefits, including improved myocardial function, reduced atherosclerosis progression, enhanced endothelial health, and decreased major adverse cardiovascular events (MACEs). Additionally, emerging evidence suggests GLP-1 RAs may exert substantial neuropsychiatric benefits, including reductions in depressive symptoms, anxiety, substance use behaviors, and lowering the risk of Alzheimer’s disease, Parkinson’s disease, and other dementias likely mediated by the modulation of neurotransmitter systems and neuroinflammation. Genetic polymorphisms in the GLP1R gene also impact the therapeutic response, highlighting the importance of personalized medicine in optimizing GLP-1 RA efficacy. This review synthesizes preclinical and clinical evidence supporting the multifaceted effects of GLP-1 RAs across multiple organ systems, highlighting their therapeutic potential beyond glycemic control. As research advances, further exploration of their mechanisms of action and long-term clinical outcomes, safety and effectiveness across diverse patient populations will be essential in optimizing their use in treating metabolic and neuropsychiatric conditions. Full article

Background/Objectives: The kidney plays a crucial role in regulating normal blood pressure and is one of the major organs affected by hypertension. The present study aimed to investigate the hypotensive and renoprotective effects of four specific green tea peptides extracted from green tea dregs on spontaneously hypertensive rats (SHRs) and to investigate the underlying mechanisms. Methods: Four specific green tea peptides (40 mg/kg) were gavaged to SHRs for 4 weeks, and blood pressure, renal function, renal pathological changes, renal tissue fibrosis indexes, and inflammation indexes were examined in SHRs to analyze the role of the four green tea peptides in alleviating hypertension and its renal injury. Results: The results showed that the four TPs significantly reduced systolic and diastolic blood pressure (20–24% and 18–28%) in SHR compared to the model group. Meanwhile, gene levels and protein expression of renal fibrosis-related targets such as phospho-Smad2/3 (p-Smad2/3) (26–47%), Sma- and Mad-related proteins 2/3 (Smad2/3) (19–38%), transforming growth factor-β1 (TGF-β1) (36–63%), and alpha-smooth muscle actin (alpha-SMA) (58–86%) were also significantly reduced. In addition, the reduced expression levels of medullary differentiation factor 88 (MyD88) (14–36%), inducible nitric oxide synthase (iNOS) (58–73%), and nuclear factor-κB p65 (NF-kB p65) (35–78%) in kidneys also confirmed that TPs attenuated renal inflammation in SHR. Therefore, green tea peptides could attenuate the fibrosis and inflammatory responses occurring in hypertensive kidneys by inhibiting the Ang II/TGF-β1/SMAD signaling pathway and MyD88/NF-κB p65/iNOS signaling pathway. Conclusions: The results showed that green tea peptides may be effective candidates for lowering blood pressure and attenuating kidney injury. Full article

Chronic kidney disease (CKD) involves inflammation, oxidative stress, and fibrosis, leading to renal dysfunction. Dapagliflozin, an SGLT2 inhibitor, shows renoprotective effects beyond glucose control, but its precise molecular mechanisms remain unclear. This study utilizes network pharmacology and molecular docking to elucidate its multi-target effects in CKD. Dapagliflozin’s SMILES structure was analyzed for ADMET properties. Potential targets were identified via SwissTargetPrediction, GeneCards, and SEA, and common CKD-related targets were determined. A protein–protein interaction (PPI) network was constructed, and key pathways were identified using GO and KEGG enrichment analyses. Molecular docking was conducted to validate dapagliflozin’s binding affinities with hub proteins. A total of 208 common targets were identified, including EGFR, GSK3β, and IL-6. GO and KEGG analyses highlighted key pathways, such as PI3K-Akt, MAPK, and AGE-RAGE, involved in inflammation, oxidative stress, and metabolic regulation. Molecular docking confirmed strong binding affinities with EGFR (−8.42 kcal/mol), GSK3β (−7.70 kcal/mol), and IL-6 (−6.83 kcal/mol). Dapagliflozin exhibits multi-target therapeutic potential in CKD by modulating inflammation, oxidative stress, and metabolic pathways. This integrative approach enhances the understanding of its mechanisms, supporting future experimental validation and clinical application in CKD management. Full article

Diabetic nephropathy (DN), one of the most common complications of diabetes mellitus (DM), accounts for a major cause of chronic kidney disease (CKD) worldwide, with a complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is a classical ligand-activated nuclear transcription factor. It is expressed in the renal intrinsic and immune cells, especially macrophages. Over-activation of the MR was observed in patients with DN and was associated with DN prognosis. The renoprotective role of a new generation of non-steroidal selective mineralocorticoid receptor antagonist (MRA), finerenone, has been confirmed in DM and CKD patients. However, the mechanism by which finerenone improves renal inflammation in DN has yet to be completely understood. It was found in this research that the oral administration of finerenone attenuated the kidney injuries in established DN in db/db mice, and particularly improved the pathological changes in the renal tubulointerstitia. Specifically, finerenone inhibited the over-activation of the MR in macrophages, thereby reducing the expression of G protein subunit alpha i2 (GNAI2, Gnαi2), a key downstream component of the C5aR1 pathway. Animal experiments demonstrated that C5aR1 knockout alleviated renal injuries, confirming the critical pathogenic role of C5aR1 in DN. Moreover, finerenone mitigated inflammatory and chemotaxis responses by downregulating Gnαi2 in macrophages. These effects were reflected by reduced expressions of the pro-inflammatory chemokines CXCL15 and CCL2, the regulation of macrophage polarization and improvements in apoptosis. This study intends to understand the protective role of finerenone in DN, which is conducive to revealing the pathophysiological mechanism of DN and further optimizing the treatment of DN patients. Full article