Implications of sedation during the use of noninvasive ventilation in children with acute respiratory failure (SEDANIV Study).

BACKGROUND: The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). METHODS: Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients' level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. RESULTS: A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3-16.1). Two hundred and thirteen children (46.6%) received sedation (sedation group); these patients had a higher heart rate, higher COMFORT-B score, and lower SpO2/FiO2 ratio than did those who did not receive sedation (non-sedation group). A significantly greater improvement in the COMFORT-B score at 3, 6, 12, and 24 h, heart rate at 6 and 12 h, and SpO2/FiO2 ratio at 6 h was observed in the sedation group. Overall, the NIV success rate was 95.6%-intubation was required in 6.1% of the sedation group and in 2.9% of the other group (p = 0.092). Multivariate analysis revealed that the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230-1.611) and respiratory rate at 3 h (OR 1.043; 95% CI 1.009-1.079) were found to be independent predictors of NIV failure. The PICU LOS was correlated with weight, PRISM III score, respiratory rate at 12 h, SpO2 at 3 h, FiO2 at 12 h, NIV failure and NIV duration. Sedation use was not found to be independently related to NIV failure or to the PICU LOS. CONCLUSIONS: Sedation use may be useful in children with ARF treated with NIV, as it seems to improve clinical parameters and comfort status but may not increase the NIV failure rate or PICU LOS, even though sedated children were more severe at technique initiation in the present sample.

Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae).

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL-1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 µg mL-1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.

The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study.

OBJECTIVE: Chronic kidney disease (CKD) is a worldwide public health problem, and proteinuria may accelerate the progression of CKD, being oxidative stress a common mechanism in nondiabetic or diabetic proteinuric kidney disease. This study was designed to evaluate the effect of the dietary supplementation with curcumin (CUR) on the redox status and the nuclear factor erythroid 2-related factor 2 (Nrf2) activation in patients with nondiabetic or diabetic proteinuric CKD. DESIGN: Randomized double-blind placebo-controlled clinical trial. SUBJECTS: A total of 101 Mexican patients from the National Institute of Cardiology "Ignacio Chavez", with nondiabetic or diabetic proteinuric CKD (proteinuria ≥ 1 g protein/24 hours), aged 20 to 70 years; 60% were male, and 51% were diabetic. INTERVENTION: Patients with nondiabetic proteinuric CKD received placebo (n = 26) or CUR 320 mg/day (n = 24) for 8 weeks, and patients with diabetic proteinuric CKD were intervened with placebo (n = 23) or CUR 320 mg/day (n = 28) for the same period. MAIN OUTCOME MEASURE: Anthropometrical, clinical, and biochemical characteristics, as well as oxidative stress markers, antioxidant enzyme activities and Nrf2 activation were evaluated at baseline and after intervention. RESULTS: The intervention with CUR did not improve proteinuria, estimated glomerular filtration rate, or lipid profile. However, in plasma, CUR attenuated lipid peroxidation in individuals with nondiabetic proteinuric CKD (P<.05) and enhanced the antioxidant capacity in subjects with diabetic proteinuric CKD (P<.05). No effect of CUR was observed on the antioxidant enzymes activities or Nrf2 activation. CONCLUSIONS: Dietary supplementation with CUR has the potential to reduce oxidative stress in Mexican patients with nondiabetic or diabetic proteinuric CKD. Studies with higher doses of CUR and longer follow-up are granted to confirm our findings.

Relevance of the novel IASLC/ATS/ERS classification of lung adenocarcinoma in advanced disease.

Since the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS) reported a new lung adenocarcinoma (ADC) classification, several groups have validated its association with prognosis in early stage disease. To our knowledge, there are no studies in advanced disease. We reviewed 313 patients with invasive lung ADC who were re-classified using the new IASLC/ATS/ERS criteria. Patients received platinum-based chemotherapy. Clinical characteristics, EGFR mutations, response and progression-free survival (PFS) after chemotherapy and overall survival were analysed. ADCs were classified as lepidic 7.4%, acinar 44.7%, papillary 10.1%, micropapillary 3.5% and solid 34.2%. When patterns were lumped into groups, response rates and PFS to platinum-based chemotherapy were better in high-grade ADC (micropapillary, papillary and solid-predominant) versus intermediate-grade ADC (lepidic and acinar-predominant) (36.9% versus 25.4% p=0.034 and 6.4 versus 5.5 months p=0.009, respectively). Overall survival was better in high-grade ADC (25 versus 16.8; p=0.023). Factors associated with better overall survival were Eastern Cooperative Oncology Group (0-1), EGFR mutations and high-grade ADC. Prognostic differences found with the new classification in early disease may not apply to patients with advanced disease. Unlike in early stages, patients with high-grade ADC have longer overall survival compared with intermediate-grade ADC, probably due to a better response to chemotherapy.

Nrf2 and redox status in prediabetic and diabetic patients.

The redox status associated with nuclear factor erythroid 2-related factor-2 (Nrf2) was evaluated in prediabetic and diabetic subjects. Total antioxidant status (TAS) in plasma and erythrocytes, glutathione (GSH) and malondialdehyde (MDA) content and activity of antioxidant enzymes were measured as redox status markers in 259 controls, 111 prediabetics and 186 diabetic type 2 subjects. Nrf2 was measured in nuclear extract fractions from peripheral blood mononuclear cells (PBMC). Nrf2 levels were lower in prediabetic and diabetic patients. TAS, GSH and activity of glutamate cysteine ligase were lower in diabetic subjects. An increase of MDA and superoxide dismutase activity was found in diabetic subjects. These results suggest that low levels of Nrf2 are involved in the development of oxidative stress and redox status disbalance in diabetic patients.

Usefulness of serum carcinoembryonic antigen (CEA) in evaluating response to chemotherapy in patients with advanced non small-cell lung cancer: a prospective cohort study.

BACKGROUND: High serum carcinoembryonic antigen (CEA) levels are an independent prognostic factor for recurrence and survival in patients with non-small cell lung cancer (NSCLC). Its role as a predictive marker of treatment response has not been widely characterized. METHODS: 180 patients with advanced NSCLC (stage IIIB or Stage IV), who had an elevated CEA serum level (>10 ng/ml) at baseline and who had no more than one previous chemotherapy regimen, were included. CEA levels were measured after two treatment cycles of platinum based chemotherapy (93%) or a tyrosine kinase inhibitor (7%). We evaluate the change in serum CEA levels and the association with response measured by RECIST criteria. RESULTS: After two chemotherapy cycles, the patients who achieved an objective response (OR, 28.3%) had a reduction of CEA levels of 55.6% (95%CI [box drawings light horizontal]64.3 to [box drawings light horizontal]46.8) compared to its basal level, with an area under the ROC curve (AURC) of 0.945 (95%CI 0.91-0.99), and a sensitivity and specificity of 90.2 and 89.9%, respectively, for a CEA reduction of ≥14%. Patients that achieved a decrease in CEA levels ≥14% presented an overall response in 78% of cases, stable disease in 20.3% and progression in 1.7%, while patients that did not attain a reduction ≥14% had an overall response of 4.1%, stable disease of 63.6% and progression of 32.2% (p < 0.001). Patients with stable (49.4%) and progressive disease (22.2%) had an increase of CEA levels of 9.4% (95%CI 1.5-17.3) and 87.5% (95%CI 60.9-114) from baseline, respectively (p < 0.001). The AURC for progressive disease was 0.911 (95%CI 0.86-0.961), with sensitivity and specificity of 85 and 15%, respectively, for a CEA increase of ≥18%. PFS was longer in patients with a ≥14% reduction in CEA (8.7 vs. 5.1 months, p < 0.001). Neither reduction of CEA nor OR were predictive of OS. CONCLUSIONS: A CEA level reduction is a sensitive and specific marker of OR, as well as a sensitive indicator for progression to chemotherapy in patients with advanced NSCLC who had an elevated CEA at baseline and had received no more than one chemotherapy regimen. A 14% decrease in CEA levels is associated with a better PFS.

Severe spinal cord injury in craniocervical dislocation. Case-based update.

BACKGROUND: Craniocervical distraction injuries, including atlanto-axial dislocation (AAD) and atlanto-ocipital dislocation (AOD), are often associated with severe spinal cord involvement with high morbidity and mortality rates. Many patients with these injuries die at the accident scene, but advances in emergency resuscitation and transport permit that many patients arrive alive to hospitals. DISCUSSION: Children with craniocervical distraction injuries usually present with a severe cranioencephalic traumatism that is the most relevant lesion at admission. After resuscitation and hemodynamic stabilization, the spinal cord damage appears as the main lesion. Apnea and quadriparesis, or quadriplegia, are usually present at the onset. Early diagnosis and management perhaps decrease life-threatening manifestations of the spinal lesion. But even so, the primary spinal cord insult is often irreversible and precludes obtaining a satisfactory functional outcome. PATIENTS AND METHODS: We report the findings of four children with craniocervical distraction injuries (AOD and AAD) who presented with severe spinal cord damage. All patients were admitted with respiratory distress or apnea together with significant brain injuries. The medical records pertaining to these patients are summarized in regard to clinical features, management, and outcome. CONCLUSIONS: In spite of timely and aggressive management, craniocervical injuries with spinal cord involvement continue to have a dismal prognosis. Outcome is closely related to the severity of the initial brain and spinal cord damage and is nearly always fatal in cases of complete spinal cord transection. Priority should be given to life-threatening complications. Ethic issues on indications for surgery deserve a detailed discussion with the children's parents.

Acute disseminated encephalomyelitis (ADEM)-like illness in a pediatric patient following COVID-19 vaccination.

Since the inception of the COVID-19 pandemic, over 60 cases of acute disseminated encephalomyelitis (ADEM) or ADEM-like clinically isolated syndromes have been linked to COVID-19 infection. However, cases linked to COVID-19 vaccination remain exceptionally rare. To the author's knowledge, eight published cases of ADEM or ADEM-like clinically isolated syndrome have been described after patients received COVID-19 vaccinations, all of which occurred in adults. This report details the first documented case of an ADEM-like illness in a pediatric patient, which developed shortly after receiving the Pfizer (Pfizer-BioNTech, Germany) COVID-19 vaccination. The patient made a near complete clinical recovery over 10 days after receiving a 5-day course of intravenous immunoglobulin therapy.

Prevalence, Risk Factors and Impact of Nutrition Interruptions in Critically Ill Children.

Background: Enteral nutrition interruptions (ENI) are prevalent in the pediatric intensive care unit (PICU), but there is little evidence of their characteristics. Methods: This is a cross-sectional multicenter study including critically ill children on enteral nutrition. ENIs were classified as PICU procedures, procedures performed outside the PICU (PPOP), feeding intolerance and other criteria. The number and features of ENIs were collected. Results: A total of 75 children were enrolled. There were 41 interruptions affecting 37.3% of the patients with a median duration of 5 ± 9.4 h. The most common reason for ENI was PPOP (41.5%), followed by other criteria. Interruptions were considered preventable in 24.4% of the cases, but only eight were compensated. ENIs were more prevalent among children with cardiac disease (p = 0.047), higher PRISM (p = 0.047) and longer PICU stay (p = 0.035). There was association between PRISM and total interruption time (p = 0.02) and lower caloric intake (p = 0.035). Patients with respiratory illness (p = 0.022) and on noninvasive ventilation (p = 0,028) had fewer ENIs. ENI total time was associated with lower caloric (p = 0.001) and protein (p = 0.02) intake. Conclusions: ENIs are prevalent in PICU, especially in children with higher PRISM, longer PICU stays and cardiac disease, and result in lower caloric and protein intake.

Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.

OBJECTIVES: The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. DESIGN: A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. SUBJECTS: All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). CONCLUSIONS: This is the largest study to estimate prospectively the pediatric population-based acute respiratory distress syndrome incidence and the first incidence study performed during the routine application of lung protective ventilation in children. Our findings support a lower acute respiratory distress syndrome incidence and mortality than those reported for adults. PaO2/FIO2 ratios at acute respiratory distress syndrome onset and at 24 hrs after onset were helpful in defining groups at greater risk of dying (clinical trials registered with http://www.clinicaltrials.gov; NCT 01142544).

Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death.

UNLABELLED: Curcumin is a phenolic yellow curry pigment with anti-inflammatory and antioxidant activities and α-mangostin is a xanthone isolated from mangosteen fruit with antioxidant properties. Iodoacetate (IAA) is an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase that induces a model of metabolic inhibition in neurons where reactive oxygen species (ROS) production is a significant mechanism. Furthermore, it has been shown that the induction of heme oxygenase-1 (HO-1) protects against IAA-induced neuronal death. OBJECTIVES: To study the effects of α-mangostin and curcumin against the IAA-induced cell death and on HO-1 expression in primary cultures of cerebellar granule neurons (CGNs). METHODS: CGNs were treated with curcumin or α-mangostin before the addition of IAA. Cell viability and ROS production were measured 24 and 4 hours after IAA addition, respectively. HO-1 expression was measured by western blot. RESULTS: Both α-mangostin and curcumin pretreatment ameliorated the neuronal death induced by IAA in a concentration-dependent way, which was associated with an amelioration of IAA-induced ROS formation. In addition, it was found that α-mangostin and curcumin induced HO-1 expression. DISCUSSION: Treatment with α-mangostin and curcumin provided a neuroprotective effect against IAA in primary cultures of CGNs, an effect associated with an amelioration of the IAA-induced ROS production. HO-1 induced by these antioxidants may also be involved in the neuroprotective effect. Future work will be required to determine whether α-mangostin may cross the blood-brain barrier and achieve enough bioavailability to elicit a protective response in the brain being an effective nutraceutical compound for preventive therapy of neurodegenerative diseases.

Pediatric crushing head injury: biomechanics and clinical features of an uncommon type of craniocerebral trauma.

BACKGROUND: Head injuries constitute one of the leading causes of pediatric morbidity and mortality. Most injuries result from accidents involving an acceleration/deceleration mechanism. However, a special type of head injury occurs when the children sustain a traumatism whose main component is a static load in relation to a crushing mechanism with the head relatively immobile. PATIENTS AND METHODS: We report a series of children who sustained a craniocerebral injury of variable severity produced by head crushing. We also analyze epidemiological and clinical data, and biomechanics in these injuries. RESULTS: Mean age of the group (13 boys/6 girls) was 4.1 years. All patients showed external lesions (scalp wounds or hemorrhage from the nose, ears, or throat). Eleven children were initially unconscious. Six children presented cranial nerve deficits in addition to impaired hearing. Skull base fractures were seen in most cases with extension to the vault in 11 instances. Fourteen patients had an associated intracranial lesion, including two with diffuse axonal injury. Surgery was performed in three instances. Only seven patients were left with sequelae. DISCUSSION AND CONCLUSIONS: The observed skull, brain, and cranial nerve lesions corresponded to a mechanism of bilateral compression of the children's heads mainly occasioned by a static load, although an associated component of dynamic forces was also involved. The skull and its covering and the cranial nerves were the most severely affected structures while the brain seemed to be relatively well preserved. Most crush injuries appear to be preventable by the appropriate supervision of the children.

Nutraceuticals for Complementary Treatment of Multisystem Inflammatory Syndrome in Children: A Perspective from Their Use in COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) has been widely reported in some children diagnosed with SARS-CoV-2. Clinical signs of MIS-C are manifested at 2 to 4 weeks after SARS-CoV-2 infection, where elevated biomarkers of inflammation and cardiac dysfunction are the hallmark of this syndrome when infection or exposure to SARS-CoV-2 has been confirmed. However, after two years of acknowledgment, MIS-C treatment is still under research to reach safety and effectiveness in the acute phase in children. Therefore, in this review, we discuss the potential use of natural compounds with antioxidant and anti-inflammatory effects to reduce collateral damage caused by hyperinflammation in MIS-C pathology for new research in treatment and interventions.

A ketogenic diet attenuates acute and chronic ischemic kidney injury and reduces markers of oxidative stress and inflammation.

BACKGROUND: Ischemic kidney injury is a common clinical condition resulting from transient interruption of the kidney's normal blood flow, leading to oxidative stress, inflammation, and kidney dysfunction. The ketogenic diet (KD), a low-carbohydrate, high-fat diet that stimulates endogenous ketone body production, has potent antioxidant and anti-inflammatory effects in distinct tissues and might thus protect the kidney against ischemia and reperfusion (IR) injury. MAIN METHODS: Male Wistar rats were fed a KD or a control diet (CD) for three days before analyzing metabolic parameters or testing nephroprotection. We used two different models of kidney IR injury and conducted biochemical, histological, and Western blot analyses at 24 h and two weeks after surgery. KEY FINDINGS: Acute KD feeding caused protein acetylation, liver AMPK activation, and increased resistance to IR-induced kidney injury. At 24 h after IR, rats on KD presented reduced tubular damage and improved kidney functioning compared to rats fed with a CD. KD attenuated oxidative damage (protein nitration, 4-HNE adducts, and 8-OHdG), increased antioxidant defenses (GPx and SOD activity), and reduced inflammatory intermediates (IL6, TNFα, MCP1), p50 NF-κB expression, and cellular infiltration. Also, KD prevented interstitial fibrosis development at two weeks, up-regulation of HSP70, and chronic Klotho deficiency. SIGNIFICANCE: Our findings demonstrate for the first time that short-term KD increases tolerance to experimental kidney ischemia, opening the opportunity for future therapeutic exploration of a dietary preconditioning strategy to convey kidney protection in the clinic.

Prevalence of SARS-CoV-2 infection in Baja California, Mexico: Findings from a community-based survey in February 2021 in the Mexico-United States border.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics.

Mechanisms of Fasting-Mediated Protection against Renal Injury and Fibrosis Development after Ischemic Acute Kidney Injury.

Ischemia-reperfusion injury of the kidney may lead to renal fibrosis through a combination of several mechanisms. We recently demonstrated that fasting protects the rat kidney against oxidative stress and mitochondrial dysfunction in early acute kidney injury, and also against fibrosis development. Here we show that preoperative fasting preserves redox status and mitochondrial homeostasis at the chronic phase of damage after severe ischemia. Also, the protective effect of fasting coincides with the suppression of inflammation and endoplasmic reticulum stress, as well as the down-regulation of the mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in the fibrotic kidney. Our results demonstrate that fasting targets multiple pathophysiological mechanisms to prevent renal fibrosis and damage that results after renal ischemia-reperfusion injury.

Fasting reduces oxidative stress, mitochondrial dysfunction and fibrosis induced by renal ischemia-reperfusion injury.

Food deprivation protects against ischemia-reperfusion (IR) injury through unknown mechanisms. In an experimental rat model of acute IR injury, we found that preoperative fasting for 3 days protects rats from tubular damage and renal functional decline by increasing antioxidant protection independently of the NF-E2-related factor 2 (Nrf2), and by maintaining mitochondrial morphology and function. In addition, further analysis revealed that fasting protects against tubulointerstitial fibrosis. In summary, our results point out to fasting as a robust nutritional intervention to limit oxidative stress and mitochondrial dysfunction in early acute kidney injury and also to promote long-term protection against fibrosis.