Search Results (813)

Ginkgo biloba extract (GBe) attenuates the transition of cisplatin (CDDP)-induced acute kidney injury to chronic kidney disease (AKI-to-CKD). Purpose: This study aimed to reveal the mechanism by which GBe inhibits CDDP-induced AKI-to-CKD. The potential targets of GBe in alleviating CDDP-induced renal interstitial fibrosis (Cis-RIF) were predicted through network pharmacology. Transcriptomics and metabolomics were used to detect differentially expressed genes (DEGs) and metabolites (DEMs) in renal tissues from Cis-RIF rats. Integrated multi-omics analysis was performed to determine the potential mechanism underlying GBe inhibiting AKI-to-CKD, and experimental verification was conducted in vivo, in vitro, and using siRNA. We identified 100 targets of GBe that could inhibit Cis-RIF using network pharmacology, and these targets were enriched in 194 signaling pathways. Transcriptomics and metabolomics revealed 8907 DEGs (enriched in 51 pathways) and 424 DEMs (enriched in 16 pathways), respectively. Collectively, the phosphatidylinositol signaling pathway was a co-enriched pathway, which may be the key pathway through which GBe inhibits AKI-to-CKD. This was verified experimentally. The related apoptosis and fibrosis indicators, and the key targets of the phosphatidylinositol signaling pathway (PLC, PKC, PIP2, IP3, DAG, Ca²⁺), in rat renal tissues and renal tubular epithelial cells (RTECs) with CDDP-induced AKI-to-CKD were significantly increased. Inhibition of HIF-1α and knockdown of HIF-1α in RTECs reversed the changes the phosphatidylinositol pathway targets. Moreover, both GBe and the HIF-1α inhibitor could inhibit HIF-1α and the phosphatidylinositol pathway targets, as well as the apoptosis and EMT of RTECs. Conclusion: This study reveals for the first time that GBe may inhibit AKI-to-CKD by downregulating apoptosis and EMT in RTECs through the HIF-1α/phosphatidylinositol signaling axis. Full article

Background: Contrast media are essential tools in diagnostic and interventional imaging, but their relationship with acute kidney injury remains clinically relevant and conceptually debated. This narrative review aimed to synthesize current evidence on contrast media-associated nephrotoxicity, including terminology, epidemiology, pathophysiology, risk stratification, prevention, pharmacotherapeutic management, and clinical decision-making. Methods: A structured literature search was conducted in major biomedical databases and complemented by international guidelines and consensus statements addressing contrast-associated and contrast-induced acute kidney injury in adults exposed to intravascular contrast media. Discussion: Contemporary evidence emphasizes the distinction between contrast-associated acute kidney injury, which reflects a temporal association after exposure, and contrast-induced acute kidney injury, which implies causality. The renal risk directly attributable to modern intravenous iodinated contrast media appears to have been historically overestimated, although clinically relevant risk persists in vulnerable patients. Proposed mechanisms include renal vasoconstriction, medullary hypoxia, oxidative stress, mitochondrial dysfunction, tubular epithelial injury, endothelial dysfunction, and inflammatory or apoptotic pathways. Preventive strategies should be individualized, with isotonic saline remaining the main intervention when indicated, whereas routine pharmacologic prophylaxis is not supported by consistent clinically meaningful benefit. Conclusions: Renal safety in contrast-enhanced imaging requires a balanced approach that minimizes avoidable kidney injury in high-risk patients without unnecessarily delaying clinically indicated diagnostic or therapeutic procedures. Full article

Doxorubicin (DOX)-induced nephrotoxicity remains a major limitation to its clinical use, yet the underlying epigenetic mechanisms are incompletely understood. This study investigated the role of epigenetic dysregulation and MyD88/STAT3 signaling in DOX-induced renal injury and evaluated the renoprotective efficacy of rutin-loaded nanostructured lipid carriers (RUT-NLCs) compared with free rutin (RUT). Thirty-six rats were allocated to six experimental groups, and renal function, oxidative stress, inflammation, DNA damage, epigenetic modifications, MyD88/STAT3 signaling, histopathology, and ultrastructural changes were assessed. DOX administration induced severe renal dysfunction, oxidative stress, DNA damage, tubular injury, global DNA hypermethylation, aberrant histone methylation, Klotho promoter hypermethylation, and activation of the MyD88/STAT3 inflammatory pathway. Treatment with RUT-NLCs significantly attenuated these alterations by restoring antioxidant defenses, normalizing epigenetic markers, reducing DNA damage, suppressing MyD88/STAT3 signaling, and improving renal histopathological and ultrastructural architecture. Overall, RUT-NLCs provided greater nephroprotection than free rutin, suggesting that modulation of epigenetic alterations and MyD88/STAT3 signaling represents a key mechanism underlying their therapeutic efficacy against DOX-induced nephrotoxicity. Full article

Acute kidney injury (AKI) is a critical clinical syndrome with limited effective therapies, in which renal tubular epithelial cell (RTEC) pyroptosis mediated by the NLRP3 inflammasome represents an important pathological contributor. Stress granules (SGs), dynamic membrane-less condensates, enable cells to adapt to various stress conditions, yet their role and regulatory mechanism in AKI remain unclear. Here, we identify SG persistence as a protective mechanism against AKI and show that poly(ADP-ribosyl)ation (PARylation)-mediated regulation of SG dynamics alleviates pyroptosis during renal injury. We found that SGs were prominently formed in RTECs from AKI patients, cisplatin-induced AKI mice, and cisplatin-stimulated HK-2 cells. Poly(ADP-ribose) glycohydrolase (PARG), the key enzyme for reversing PARylation, was significantly upregulated in injured renal tissues and cells. Genetic or pharmacological inhibition of PARG delayed SG disassembly, enhanced SG persistence, and mitigated renal injury. Mechanistically, persistent SGs regulated DDX3X availability and reduced DDX3X-NLRP3 inflammasome activation, thereby attenuating RTEC pyroptosis. These findings uncover a novel mechanism of SG-mediated renoprotection and highlight SG dynamics as a potential therapeutic target in AKI. Full article

Background: Hyperuricemia is a well-established risk factor for both chronic kidney disease and gout. Currently available urate-lowering drugs, however, are frequently compromised by hepatorenal toxicity and gastrointestinal adverse effects. Cinnamaldehyde, the principal bioactive constituent of the traditional Chinese medicine cinnamon, has documented renoprotective properties, yet its integrated effects on hyperuricemia-associated renal injury remain incompletely defined. Objectives: This study investigated the therapeutic effects of cinnamaldehyde on hyperuricemia and explored the molecular mechanisms involved. Materials and Methods: An in vivo hyperuricemia model was established in KM mice by co-administration of potassium oxonate and hypoxanthine for 14 consecutive days, and an in vitro injury model was generated by exposing HK-2 human renal tubular epithelial cells to uric acid. For the in vivo study, mice were divided into five groups (control, model, febuxostat, low-dose CA, and high-dose CA; n = 9 per group) and were treated by oral gavage. Serum biochemical indices, renal and intestinal histopathology, inflammatory cytokines, renal urate transporter proteins (OAT1, OCT2, ABCG2, and SLC2A9), and components related to AIF1 and CMPK2/NLRP3 inflammasome signaling (ASC, caspase-1, IL-18, and IL-1β) were examined. Western blotting, qPCR, immunofluorescence, apoptosis analysis, mitochondrial membrane potential assessment, transmission electron microscopy, siRNA-mediated knockdown, and 16S rRNA gene sequencing were used to characterize the relevant mechanisms. Results: CA reduced serum uric acid (p ≤ 0.001 vs. model), creatinine (p ≤ 0.01 vs. model), and blood urea nitrogen (p ≤ 0.01 vs. model), alleviated renal and intestinal histopathological injury, and decreased circulating and renal inflammatory cytokines. Cinnamaldehyde increased ABCG2, OAT1, and OCT2 protein expression and reduced SLC2A9 expression (all p ≤ 0.05 vs. model). In vivo and in vitro, cinnamaldehyde suppressed AIF1- and CMPK2/NLRP3-related inflammatory proteins, reduced uric acid-induced apoptosis, and preserved mitochondrial membrane potential and ultrastructure. Fecal 16S rRNA sequencing suggested changes in selected microbial taxa, although alpha-diversity and BrayCurtis-based PERMANOVA/ANOSIM analyses did not demonstrate significant global community separation. Conclusions: These findings suggest that CA alleviates hyperuricemia-associated renal injury by regulating renal urate transporters, attenuating AIF1- and CMPK2/NLRP3-related inflammatory signaling, accompanied by compositional shifts in selected gut microbial taxa that warrant further mechanistic investigation. The study provides experimental support for further evaluation of cinnamaldehyde as a multi-target candidate for hyperuricemia-related renal injury. Full article

Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney disease, and to examine how specific adipose depots injure the glomerulus and the tubulointerstitium, and then map these mechanisms onto established and emerging therapies. Throughout, obesity-related kidney disease (ORKD) denotes the full spectrum of diposity-driven renal injury, whereas obesity-related glomerulopathy (ORG) is reserved for the biopsy-defined glomerular lesion. Central, visceral, perirenal and renal-sinus adiposity act first through structural and haemodynamic mechanisms, promoting glomerular hyperfiltration, mechanical renal compression and activation of the adipose-derived renin–angiotensin–aldosterone system (RAAS). In parallel, these depots drive cellular and metabolic injury through lipotoxicity, adipokine imbalance, sterile inflammation, oxidative stress, gut dysbiosis, mitochondrial dysfunction, epigenetic remodelling and cellular senescence. Ectopic lipid accumulation within the renal parenchyma—fatty kidney—offers a unifying description of these changes and is most marked in type 2 diabetes mellitus. These interacting processes converge on podocyte stress, tubular metabolic failure, endothelial dysfunction and interstitial fibrosis, producing a phenotypic continuum that ranges from early albuminuria to obesity-related glomerulopathy and progressive CKD. Within the RAAS limb we highlight two comparatively underappreciated, adiposity-linked routes to injury: adipocyte-derived leptin directly upregulates adrenal aldosterone synthase (CYP11B2), and mast-cell chymase generates angiotensin II independently of angiotensin-converting enzyme, together reinforcing aldosterone- and angiotensin II–mediated damage that conventional RAAS blockade only partially interrupts. We further consider the counter-regulatory ghrelin–leptin axis, in which the suppression of ghrelin that accompanies obesity may withdraw an antioxidant, anti-inflammatory and podocyte-protective signal precisely as leptin-driven glomerular injury intensifies, positioning ghrelin as a plausible modulator and candidate biomarker of obesity-related kidney injury. We also examine how obesity complicates renal risk assessment, drug dosing, dialysis delivery and transplant access. Emerging, mechanism-matched therapies—SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, structured lifestyle intervention, metabolic-bariatric surgery and, most recently, aldosterone synthase inhibitors that suppress the chymase- and leptin-driven aldosterone escaping receptor blockade—now enable a precision cardiovascular-kidney-metabolic framework that aligns adipose-depot biology, biomarkers, histology and treatment response to guide mechanism-based care in ORKD. Full article

Copper is essential for mitochondrial respiration, antioxidant defense, extracellular matrix maturation, and cellular signaling, yet disturbances in its abundance or intracellular distribution can damage the kidney through mechanistically distinct pathways. Cuproptosis is a specific copper-dependent form of regulated cell death in which copper binds lipoylated mitochondrial proteins, promotes aggregation of tricarboxylic acid cycle components, destabilizes iron–sulfur cluster proteins, and elicits FDX1- and protein lipoylation-dependent proteotoxic stress. This mechanism should be distinguished from broader copper-associated injury, including redox imbalance, glutathione depletion, respiratory-chain inhibition, senescence, apoptosis, and lysyl oxidase-mediated matrix remodeling. This narrative review examines how renal copper uptake, trafficking, and compartmentalization interact with cell-specific metabolism to shape copper-related cell fates across acute kidney injury, nephrotoxicity, renal ischemia–reperfusion injury, crystal- and lipid-related tubular injury, diabetic kidney disease, podocyte injury, chronic kidney disease and renal fibrosis, end-stage renal disease, renal cell carcinoma, and hereditary copper disorders. Mechanistic evidence is strongest in selected acute tubular, crystal-injury, and renal cancer models, in which transporter manipulation, DLAT oligomerization, iron–sulfur perturbation, or functional rescue has been demonstrated. In chronic kidney disease and fibrosis, copper-DLAT interactions, complex IV inhibition, COMMD1-SOD1 dysfunction, and ATP7A-FBLN4-LOX signaling establish pathogenic copper dependence but do not yet demonstrate a complete canonical cuproptosis pathway. By integrating disease-specific evidence with the molecular determinants of copper handling and protein lipoylation, this review identifies current therapeutic opportunities, candidate biomarkers, and key research priorities while preserving the distinction between cuproptosis and other forms of copper-associated kidney injury. Full article

The present study was designed to evaluate the structural and biochemical efficacy of Omega-3 fatty acids in preventing renal injury in streptozotocin (STZ)-induced diabetic kidney injury and to correlate systemic oxidative stress parameters with histological and ultrastructural parameters. Twenty-eight male Wistar Albino rats were randomly divided into four groups (n = 7) as follows: Control, Omega-3 (500 mg/kg, orally), Diabetes Mellitus (DM; 50 mg/kg STZ, i.p.), and DM+Omega-3 (STZ, followed by 500 mg/kg Omega-3 for 42 days). Biochemical analysis of renal function (blood urea nitrogen (BUN) and creatinine) and oxidative status (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) was measured by ELISA. Histopathological scoring and Caspase-3 staining were performed by Hematoxylin and Eosin (H&E) and immunohistochemically, respectively. Transmission Electron Microscopy (TEM) was used to examine the renal tissues. Our results showed that the DM group presented with severe hyperglycemia, uremia, and a significant oxidative shift, as evidenced by increased MDA/TOS levels and depleted antioxidant defenses. Light microscopy showed extensive glomerular damage, tubular degeneration and inflammatory infiltration in the kidneys of diabetic rats. Immunohistochemical analysis revealed strong Caspase-3 expression in the tubular and glomerular compartments. TEM showed severe podocyte effacement and damage to the glomerular basement membrane (GBM). Notably, Omega-3 supplementation significantly reversed renal dysfunction, restored the pro-oxidant/antioxidant balance and reduced histopathological injury scores. Moreover, Omega-3 treatment efficiently blocked Caspase-3-mediated apoptotic signaling and preserved the ultrastructural integrity of the glomerular filtration barrier (GFB) and tubular mitochondria. Our results demonstrate the potent nephroprotective effects of Omega-3 fatty acids in reducing oxidative stress, preventing programmed cell death and maintaining the stability of the renal parenchyma’s microarchitecture. These findings suggest that Omega-3 fatty acids could be an effective adjuvant therapeutic agent for the management of diabetic nephropathy. Full article

Paracetamol overdose is a major cause of drug-induced acute kidney injury (AKI), driven by oxidative stress, inflammation, mitochondrial dysfunction, and tubular apoptosis. This study evaluated the nephroprotective efficacy of pH-responsive carboxymethyl cellulose-encapsulated hesperidin-stabilized selenium nanoparticles (CMC@HES-SeNPs) against paracetamol-induced AKI in rats. HES-SeNPs were synthesized using hesperidin as a reducing/stabilizing agent and further coated with CMC. The nanoparticles were characterized by DLS, zeta potential, TEM, and in vitro release kinetics at pH 7.4 and 5.5. 42 Male rats were allocated into groups of control, paracetamol (PAR), paracetamol treated with sodium selenite (PAR&Se), paracetamol treated with hesperidin (PAR&HES), paracetamol treated with hesperidin-loaded selenium nanoparticles (PAR&HES-SeNPs), and paracetamol treated with carboxy methyl cellulose-coated hesperidin-loaded selenium nanoparticles (PAR&CMC@HES-SeNPs). Paracetamol markedly impaired renal function, increasing creatinine, urea, NGAL, KIM-1, and cystatin-C, and induced oxidative/nitrosative stress, Keap-1 upregulation, Nrf2 suppression, NF-κB-mediated inflammation, cytochrome-C release, Bax/Bcl-2 imbalance, caspase-3 activation, and severe renal histopathological injury. CMC@HES-SeNPs displayed sustained, pH-enhanced hesperidin release and produced the strongest renoprotective response, restoring renal biomarkers, associated with restoration of Keap-1/Nrf2-related antioxidant markers, reduction in TNF-α, IL-6, NF-κB, and caspase-3, increased IL-10, and preservation of renal architecture. Collectively, these results indicate that CMC@HES-SeNPs represent a promising multifunctional nanoplatform for mitigating paracetamol-induced AKI in association with coordinated modulation of redox, inflammatory, and mitochondrial apoptotic markers, and highlight CMC encapsulation as a rational strategy to enhance selenium–flavonoid delivery and efficacy for future drug-induced AKI management and translation. Full article

Objectives: Renal ischemia–reperfusion (I/R) injury is one of the most important pathological triggers of acute kidney injury. This study aimed to investigate the protective effects of meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, against renal I/R injury through specific cell death pathways including inflammation, apoptosis, necroptosis, and the MAPK/ERK pathway, which is potentially linked to regulated cell death mechanisms such as ferroptosis. Methods: Male Wistar Albino rats weighing 280–300 g were used in the study and were divided into four groups: Sham, IR (40 min ischemia + 120 min reperfusion), Meloxicam + IR, and Meloxicam + IR1. Bilateral renal ischemia was induced for 40 min via a retroperitoneal approach under anesthesia. Meloxicam was administered intravenously at a dose of 1 mg/kg at the initiation of reperfusion in the Meloxicam + IR group, whereas in the Meloxicam + IR1 group, the same dose was administered 1 h after the onset of reperfusion. Total reperfusion time was 120 min in both groups. Renal function parameters (BUN and creatinine) and oxidative stress markers (TAS and TOS) were measured. Inflammatory cytokines (IL-6, IL-1β, and IL-10), the glomerular filtration injury marker Cystatin C, the tubular injury marker KIM-1, the apoptotic marker Caspase 3, the necroptosis markers RIPK3 and MLKL, and MAPK signaling pathway alterations (ERK1/2 and pERK1/2 levels) associated with cellular survival and death signaling were evaluated. Results: Most notably, meloxicam markedly modulated apoptosis, the expression of necroptosis markers RIPK3 and MLKL, and the activation of pERK1/2, a key node in MAPK signaling that is regulatory in cell survival and cell death processes. The drug also suppressed pro-inflammatory cytokines (IL-6 and IL-1β) while preserving anti-inflammatory IL-10 levels. Furthermore, improvements were observed in the levels of KIM-1, a marker of tubular injury, and Cystatin C, a marker of glomerular filtration impairment. Consequently, meloxicam administration significantly reduced the elevated serum creatinine and TOS levels observed in the IR group, although serum BUN levels remained without notable alteration. Conclusions: The findings of this study suggest that meloxicam may extend beyond its role as a classical anti-inflammatory agent, potentially offering biochemical and functional protection against renal I/R injury in association with the modulation of specific cell death mechanisms, including necroptosis and apoptosis, as well as the MAPK signaling pathway. Full article

Diabetes mellitus (DM) induces significant endocrine disruption and oxidative stress (OS) within the testes, resulting in impaired spermatogenesis, increased sperm abnormalities, and compromised reproductive function. This study aimed to evaluate the combined protective effects of Semaglutide (SEM) combined with Carica papaya (papaya) juice against type 2 diabetes-induced testicular damage in rats. Forty adult male albino rats were divided into four experimental groups: a control group, a Streptozotocin (STZ)-induced diabetic group, a diabetic group treated with SEM (0.3 mg/kg), and a diabetic group treated with SEM (0.3 mg/kg) in combination with 10% papaya juice, administered for eight weeks. Statistically significant superiority over SEM alone was observed for selected endpoints; the findings primarily support the potential of papaya as a dose-sparing adjunct rather than demonstrating uniformly enhanced efficacy. They significantly improved systemic metabolic parameters, as evidenced by reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA_1c) levels and restoration of the lipid profile. Importantly, it also attenuated diabetes-induced testicular injury, as demonstrated by improved reproductive hormone levels, enhanced sperm parameters, restoration of antioxidant defenses, modulation of inflammatory and apoptotic signaling, and marked histopathological recovery of seminiferous tubular architecture. Antioxidant markers revealed a notable reduction in malondialdehyde (MDA) and cytochrome P450 2E1 (CYP2E1), along with significant increases in reduced glutathione, catalase (CAT), and superoxide dismutase (SOD). Furthermore, a marked modulation of key pro-inflammatory and pro-apoptotic mediators was observed, including forkhead box protein O1 (FOXO1), microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B cell subunit 1 (NF-κB1), interleukin-6 (IL-6), caspase-3 (CASP3), and BCL2-Associated X Apoptosis Regulator (Bax), while a significant upregulation of sirtuin-1 (SIRT1), microRNA-34c (miR-34c), and B-cell lymphoma-2 (Bcl-2) was also detected. Histopathological assessments confirmed the restoration of normal testicular architecture in the treated groups. These findings indicate that the combination strategy may have the potential to achieve dose savings while maintaining efficacy comparable to the standard-dose SEM, through the enhancement of the antioxidant defenses, modulation of inflammation, and apoptosis, specifically via the modulation of the miR-34c/miR-155 and SIRT1/FOXO1 signaling. Full article

Glyphosate is one of the most widely used herbicides in modern agriculture. Toxicological studies have demonstrated that chronic glyphosate exposure is associated with the development of systemic disorders, particularly renal injury. Therefore, the search for effective therapeutic approaches to mitigate glyphosate-induced kidney dysfunction remains an important challenge in contemporary biomedicine. The aim of the present study was to evaluate the effects of C₆₀ fullerenes, as potent antioxidants, on the recovery of renal function following chronic glyphosate intoxication. The experiment was conducted on male Wistar rats that received glyphosate orally at a dose of 10 mg/kg body weight daily for 16 weeks. Following the cessation of glyphosate exposure, animals in the experimental group were treated with a C₆₀ fullerene aqueous solution (C₆₀FAS) at a dose of 1 mg/kg body weight daily for two weeks. The animals exhibited elevated blood creatinine and urea concentrations, a reduced glomerular filtration rate, increased fractional excretion of sodium, an electrolyte imbalance, and enhanced activities of superoxide dismutase and catalase after chronic glyphosate exposure. Therapeutic administration of C₆₀FAS contributed to an average improvement of 20 ± 2% in the investigated biochemical parameters at the end of the experiment, which is consistent with the findings of the histological analysis of kidney tissue. These results demonstrate the pronounced therapeutic effect of C₆₀ fullerenes, attributable to their ability to attenuate oxidative stress and promote the recovery of the filtration, tubular, and metabolic functions of the kidneys following chronic glyphosate intoxication. Full article

Both SARS-CoV-2 infection and COVID-19 vaccination have been associated with renal complications. In the context of SARS-CoV-2 infection, kidney injury is primarily attributed to a complex interplay of systemic immune dysregulation and vascular damage. Severe infection triggers a cytokine-mediated inflammatory response characterized by elevated levels of pro-inflammatory mediators, resulting in systemic hemodynamic instability, increased capillary permeability, and renal hypoperfusion, ultimately leading to acute tubular injury. In addition, virus-induced endothelial activation promotes a prothrombotic state, microvascular injury, and further impairment of renal perfusion. Collectively, these processes converge to produce acute kidney injury (AKI) and, in severe or prolonged cases, may contribute to chronic tubulointerstitial damage and progressive renal dysfunction. In contrast, renal manifestations following COVID-19 vaccination are relatively uncommon and are thought to arise primarily from immune-mediated dysregulation rather than direct cytopathic effects. Reported cases include minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), acute interstitial nephritis and other glomerulopathies, which present as either new-onset disease or relapses. These lesions are thought to result from transient immune activation following vaccination, including T-cell stimulation and altered humoral responses, which may trigger or unmask an underlying susceptibility to renal injury. Careful post-vaccination monitoring in high-risk populations may be warranted, and further molecular and population-level studies are needed to elucidate the underlying mechanisms and refine risk assessment. Full article

Gout is a systemic metabolic inflammatory disease driven by hyperuricemia and monosodium urate crystal deposition, and is frequently accompanied by chronic kidney disease and uric acid nephrolithiasis. Current evidence indicates that acidic urine, hypocitraturia, and insufficient ammonium excretion are common in gout patients, and may be associated with insulin resistance, impaired renal ammoniagenesis, and abnormalities in tubular acid-base regulation. Persistent urinary acidification may contribute to the development and progression of uric acid stone formation and gout-related renal injury by reducing uric acid solubility, promoting crystal formation and intratubular deposition, and decreasing renal uric acid clearance. Urinary alkalization therapy can increase urine pH, thereby enhancing uric acid solubility and excretion, and has shown potential in some studies to improve serum urate levels, proteinuria, renal function parameters, and gout flare frequency, especially when using citrate-based alkali. However, the currently available evidence is mainly derived from observational studies and small prospective investigations, and recommendations across international guidelines remain inconsistent. High-quality evidence is still lacking regarding the optimal target population, urine pH range, choice of alkalizing agents, monitoring strategies, and long-term efficacy. Well-designed prospective studies are therefore needed to clarify the clinical role of urinary alkalization in renal protection among patients with gout. Full article

Rhabdomyolysis-associated acute kidney injury is driven by myoglobin-mediated oxidative stress, inflammation, mitochondrial impairment, and tubular cell death. This study evaluated the nephroprotective activity of green-synthesized Withania somnifera-functionalized selenium nanoparticles (Ws-SeNPs) in glycerol-induced renal injury and compared their efficacy with native W. somnifera extract and sodium selenite. The chemical profile of the plant extract was characterized by LC–MS/MS, and Ws-SeNPs were evaluated using dynamic light scattering, zeta potential analysis, transmission electron microscopy, and FTIR spectroscopy. Thirty-five male rats were assigned to Control, ARF, ARF & Ws, ARF & selenium, and ARF & Ws-SeNPs. ARF was induced by intramuscular injection of 50% glycerol. Glycerol administration induced marked skeletal muscle injury, renal dysfunction, tubular damage, oxidative stress, inflammation, mitochondrial dysregulation, pyroptosis, apoptosis, and histopathological alterations. Both Ws and sodium selenite provided partial protection, whereas Ws-SeNPs produced the greatest improvement in renal function and tissue architecture. Their protective effect was associated with restoration of Nrf2-dependent antioxidant defenses, suppression of NF-κB/NLRP3/GSDMD-associated inflammatory and pyroptotic signaling, preservation of mitochondrial regulatory pathways, and attenuation of apoptosis. These findings indicate that Ws-SeNPs provide multi-target protection against glycerol-induced rhabdomyolysis-associated renal injury and may represent a promising phytochemical-based selenium nanoformulation for further preclinical investigation. Full article