Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD)Noda, Francini, Teles
et alCells (2025) 14 (6)
Abstract: Chronic kidney disease (CKD) is considered an important health issue worldwide. The renin-angiotensin-aldosterone system (RAAS) blockade through the administration of angiotensin II receptor blockers, such as Losartan (LOS), has been considered the best strategy for CKD treatment for decades. However, this approach promotes only partial detention of CKD progression and cannot reverse renal damage. The aim of the present study was to investigate whether the therapeutic administration of extracellular vesicles (EVs) derived from adipose stem cells (ASCs), associated to LOS treatment, would promote additional renoprotection in rats underwent the 5/6 renal ablation CKD model. ASC-derived EV were administered locally, in the renal subcapsular area, 15 days after CKD induction, when LOS therapy also began. Animals were followed for additional 15 days and our results demonstrated that subcapsular injection of ASC-derived EV associated with LOS significantly reduced glomerulosclerosis, renal interstitial infiltration by myofibroblasts, and macrophages in the 5/6 CKD model. Additionally, LOS + EV abrogated systemic hypertension, proteinuria, and albuminuria, and stimulated local gene overexpression of the endogenous anti-inflammatory Il-4. Although more studies are still required to establish the best EV dose and administration route, these findings point to therapy with ASC-derived EV as a potential adjuvant in CKD treatment.
Electrolyte Imbalances and Metabolic Emergencies in Obesity: Mechanisms and Clinical ImplicationsCrintea, Cindrea, Mederle
et alDiseases (2025) 13 (3)
Abstract: Electrolyte imbalances are a frequently overlooked yet critical component of obesity-related metabolic dysfunction, contributing to an increased risk of cardiovascular disease, kidney impairment, and metabolic emergencies such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and acute kidney injury (AKI). These disturbances arise from insulin resistance, chronic inflammation, hormonal dysregulation, and renal dysfunction, leading to sodium retention, potassium depletion, and deficiencies in calcium and magnesium homeostasis. Managing electrolyte imbalances is essential in obesity management, as imbalances exacerbate hypertension, metabolic acidosis, neuromuscular complications, and insulin resistance. This review explores the pathophysiology of electrolyte disturbances in obesity and their impact on fluid balance, acid-base status, and metabolic health. Effective management strategies include individualized electrolyte monitoring, dietary sodium restriction, potassium supplementation, vitamin D and magnesium correction, and pharmacologic interventions targeting renin-angiotensin-aldosterone system (RAAS) activity and insulin resistance. Additionally, lifestyle interventions, including dietary modification, weight loss strategies, and hydration optimization, play a key role in preventing metabolic complications. Future research should investigate the long-term impact of electrolyte imbalances in obesity, the role of emerging therapies, and how lifestyle interventions can optimize electrolyte homeostasis and metabolic outcomes. A personalized, multidisciplinary approach integrating endocrinology, nephrology, and clinical nutrition is essential to improving the prevention and management of electrolyte imbalances in obese individuals.
ACE2 Deficiency Protects Against Heme Protein-Induced Acute Kidney InjuryCroatt, Singh, Grande
et alAm J Physiol Renal Physiol (2025)
Abstract: Angiotensin-converting enzyme 2 (ACE2) exerts countervailing effects on the renin-angiotensin aldosterone system. ACE2 also engages the spike protein of SARS-CoV-2. ACE2 protein has been shown recently to avidly bind heme. We examined the pathobiologic relevance of this heme-binding property of ACE2 by employing the glycerol-induced model of heme protein mediated AKI (HP-AKI) which is characterized by increased kidney heme content. We studied the response of ACE2-wildtype (ACE2+/y) and ACE2-deficient (ACE2-/y) mice to HP-AKI and quantitated kidney and cellular content of heme under relevant conditions. ACE2-deficient mice, compared with ACE2-wildtype mice, were significantly protected against HP-AKI as reflected by filtration markers, less histologic injury, and less expression of apoptosis and ferroptosis markers. ACE2-deficient mice also evinced lesser kidney heme content and a blunted induction of HO-1. HEK293 ACE2-overexpressing cells, compared with HEK293-native, when exposed to heme, retained higher amounts of heme. In HP-AKI, ACE2 expression and activity were reduced, and myoglobin and heme, administered independently, reduced ACE2 expression in the otherwise intact mouse kidney. Finally, with more severe HP-AKI, the protective effect of ACE2 deficiency was attenuated. We conclude that ACE2 deficiency confers protection against HP-AKI. We suggest that this reflects the recently recognized binding of heme to ACE2, such binding serving to facilitate renal entry of heme, a known nephrotoxin. These findings uncover a novel pathway of heme-dependent acute kidney injury. This is the first demonstration of the biologic relevance of chemical binding of heme by ACE2. Finally, we identify heme proteins and heme as novel determinants of ACE2 expression.
[Role of inflammation in heart failure with preserved ejection fraction: from nephro-metabolic interactions to future therapeutic implications]D'Elia, Benvenuto, Battistoni
et alG Ital Cardiol (Rome) (2025) 26 (4), 223-236
Abstract: Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity frequently associated with chronic kidney disease (CKD). Recent studies indicate that 50-60% of HFpEF patients also have CKD, and the prevalence of HFpEF among CKD patients is similarly high. Chronic low-grade systemic inflammation is common to both conditions and is linked to risk factors such as obesity, insulin resistance, and diabetes. The hyperactivation of the mineralocorticoid receptor plays a central role in this process, contributing to interstitial fibrosis and inflammation. Additional factors, including metabolic acidosis, gut dysbiosis, and reduced expression of the α-Klotho protein, amplify the inflammatory response. This systemic inflammation reduces nitric oxide production, impairing cardiac diastolic function and, together with metabolic syndrome and aging, further exacerbates the already complex cardiac pathology. Therapeutic strategies aimed at reducing inflammation, such as renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors, show promising potential. Additionally, the use of anti-inflammatory drugs and novel interventions to restore gut microbiota balance may offer new opportunities to improve prognosis in patients with HFpEF and CKD. Further studies are needed to clarify the clinical efficacy of these approaches and their role in optimizing the management of this complex patient population.
膜杰作
Star Staining
