Besides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious outcomes of the above pathways, apoptosis, senescence, or epithelial-to-mesenchymal transition (EMT) were evaluated. Albumin caused reactive oxygen species (ROS) overproduction and protein modification, and a UPR assessed the level of crucial molecules involved in this pathway. ROS also induced a DDR evaluated by critical molecules involved in this pathway. Apoptosis ensued through the extrinsic pathway. Senescence also occurred, and the RPTECs acquired a senescence-associated secretory phenotype since they overproduced IL-1β and TGF-β1. The latter may contribute to the observed EMT. Agents against endoplasmic reticulum stress (ERS) only partially alleviated the above changes, while the inhibition of ROS upregulation prevented both UPR and DDR and all the subsequent harmful effects. Briefly, albumin overload causes cellular apoptosis, senescence, and EMT in RPTECs by triggering UPR and DDR. Promising anti-ERS factors are beneficial but cannot eliminate the albumin-induced deleterious effects because DDR also occurs. Factors that suppress ROS overproduction may be more effective since they could halt UPR and DDR.

Background and Objectives: Emerging evidence is placing the Mediterranean diet (MD) in the spotlight as a potential dietary model that could benefit inflammatory bowel disease (IBD) patients in terms of prevention and progress of the disease. The main aim of the present study is to shed some light on the relationship between the adherence to the MD and the degree of disease activity, as well as the quality of life in patients with Crohn’s disease (CD). Materials and Methods: An administered questionnaire was used to assess and record a number of parameters, including recent medical and weight history, anthropometric characteristics, disease activity (in remission or active disease), and quality of life of both male and female CD patients. Moreover, the level of compliance of the participants to the Mediterranean diet model was evaluated and its relationship with disease activity and quality of life was investigated. Results: Adherence to the MD was significantly higher in patients with inactive disease than in those with active disease (p = 0.019). According to the correlation analysis conducted, adherence to the MD was negatively correlated with disease activity (p = 0.039) and positively correlated with quality of life (QoL) (p = 0.046) of the participants. Intake of fruits, vegetables, and dairy products was significantly higher in remission patients (p = 0.046, p = 0.001, p = 0.041, respectively). Conclusions: We conclude, according to the findings of the study, that adherence to the MD is associated with disease activity and QoL in patients with CD. Future research should focus on MD intervention studies on IBD patients in order to assess its effect on modulating disease activity/course and related inflammatory biomarkers.

Ischemia‐reperfusion (I‐R) injury is the most common cause of acute kidney injury. In experiments involving primary human renal proximal tubular epithelial cells (RPTECs) exposed to anoxia‐reoxygenation, we explored the hypothesis that mitochondrial malate dehydrogenase‐2 (MDH‐2) inhibition redirects malate metabolism from the mitochondria to the cytoplasm, towards the malate‐pyruvate cycle and reversed malate‐aspartate shuttle. Colorimetry, fluorometry, and western blotting showed that MDH2 inhibition accelerates the malate‐pyruvate cycle enhancing cytoplasmic NADPH, thereby regenerating the potent antioxidant reduced glutathione. It also reversed the malate‐aspartate shuttle and potentially diminished mitochondrial reactive oxygen species (ROS) production by transferring electrons, in the form of NADH, from the mitochondria to the cytoplasm. The excessive ROS production induced by anoxia‐reoxygenation led to DNA damage and protein modification, triggering DNA damage and unfolded protein response, ultimately resulting in apoptosis and senescence. Additionally, ROS induced lipid peroxidation, which may contribute to the process of ferroptosis. Inhibiting MDH‐2 proved effective in mitigating ROS overproduction during anoxia‐reoxygenation, thereby rescuing RPTECs from death or senescence. Thus, targeting MDH‐2 holds promise as a pharmaceutical strategy against I‐R injury.

A 57-year-old male patient, who underwent a preemptive living donor renal transplant from his mother 22 years earlier, was switched from everolimus to tacrolimus after 21 years because of development of proteinuria. Four months after transition of medication, the patient presented with anemia and reduced reticulocyte count, whereas leukocyte and platelet counts remained within normal limits. Investigation into the cause of anemia ruled out deficiencies in iron, folate, or vitamin B12, as well as inflammation, monoclonal gammopathy, hemolysis, and hypothyroidism. Gastroscopy and colonoscopy revealed no abnormalities. The patient showed a gradual increase in serum creatinine levels. Serological testing for human parvovirus B19 revealed a positive immunoglobulin M result. The patient was treated with intravenous immunoglobulin, after which hemoglobin levels began to rise within a few days. Three weeks after treatment, hemoglobin levels returned to baseline, and serum creatinine levels improved. A follow-up polymerase chain reaction test for human parvovirus B19 was negative. This case highlights the importance of maintaining vigilance for pure red cell aplasia caused by human parvovirus B19 infection, even long after kidney transplant, particularly when interventions are implemented that may increase the intensity of immunosuppression.

Ischemia-reperfusion (I-R) injury represents a predominant etiology of acute kidney injury (AKI), for which effective treatments remain unavailable. In contrast, hibernating mammals exhibit notable resistance to cell death induced by I-R injury. However, the impact of I-R injury on cellular senescence—an important factor in AKI—has not been extensively studied in these species. Comparative biology may offer novel therapeutic insights. Renal proximal tubular epithelial cells (RPTECs) from the native hibernator Syrian hamster or mouse RPTECs were subjected to anoxia-reoxygenation. Proteins involved in DNA damage response (DDR) and cellular senescence were assessed using western blotting, reactive oxygen species (ROS) levels and cell death were quantified colorimetrically, and IL-6 with ELISA. Anoxia-reoxygenation induced oxidative stress in both mouse and hamster RPTECs; however, cell death was observed exclusively in mouse cells. While anoxia-reoxygenation elicited a DDR and subsequent senescence in mouse RPTECs, such responses were not detected in hamster RPTECs. Thus, RPTECs from the Syrian hamster exhibited increased ROS production upon reoxygenation but did not show DDR or cellular senescence. Further research is required to elucidate the specific protective molecular mechanisms in hibernators, which could potentially lead to the development of novel therapeutic approaches for I-R injury in non-hibernating species, including humans.

Enteral feeds can be classified as two major types: commercial enteral formulas and blenderized enteral feeds. When deciding the most appropriate type of feed for a patient, several parameters need to be taken into consideration. Benefits associated with the use of blenderized tube feeds include giving a sense of normalcy to patients, having a positive impact on anthropometric indices, allowing for careful control over known food allergens, being associated with improved gastrointestinal tolerance and improved gut microbial composition (mainly in pediatric populations) and being generally less costly compared with commercial formulas. On the other hand, commercial enteral formulas have the advantages of being generally sterile, less likely to cause tube clogging and having a known and consistent nutrition composition. Further studies, specifically well-designed randomized controlled trials including adult populations, that will emphasize the impact of blenderized enteral feeds on various clinical outcomes are warranted. Clinicians need to be conscientious and educated regarding safe food practices for blended food preparation, as well as the characteristics of commercial formula options available to help assist patients in selecting the proper feed for their nutritional needs and clinical condition.