ascorbic-acid and Acute-Kidney-Injury

Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients.. We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables.. Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66-0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, -1.34 to -0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02).. Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.

Topics: Acute Kidney Injury; Ascorbic Acid; Clinical Trials as Topic; Critical Illness; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Renal Replacement Therapy

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Antiviral Agents; Apolipoprotein L1; Ascorbic Acid; Azotemia; COVID-19; COVID-19 Drug Treatment; Cytokines; Disease Progression; Glomerulonephritis; Glomerulonephritis, Membranous; Hospital Mortality; Humans; Kidney Tubules, Proximal; Length of Stay; Myoglobin; Nephritis, Interstitial; Nephrosis, Lipoid; Renal Insufficiency, Chronic; Rhabdomyolysis; SARS-CoV-2; Severity of Illness Index; Thrombotic Microangiopathies; Vitamins

The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial.. Online databases were searched up to October 1, 2018.. We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy.. Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis.. Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74-1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52-0.78; p < 0.0001), ICU stay (standardized mean difference, -0.28 d; 95% CI, -0.43 to -0.13 d; p = 0.0003), and hospital stay (standardized mean difference, -0.30 d; 95% CI, -0.49 to -0.10 d; p = 0.002). Furthermore, no differences in postoperative mortality, acute kidney injury, stroke, and ventricular arrhythmia were found.. In a mixed population of ICU patients, vitamin C administration is associated with no significant effect on survival, length of ICU or hospital stay. In cardiac surgery, beneficial effects on postoperative atrial fibrillation, ICU or hospital length of stay remain unclear. However, the quality and quantity of evidence is still insufficient to draw firm conclusions, not supporting neither discouraging the systematic administration of vitamin C in these populations. Vitamin C remains an attractive intervention for future investigations aimed to improve clinical outcome.

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Cardiac Surgical Procedures; Critical Illness; Humans; Intensive Care Units; Length of Stay; Postoperative Complications; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome

To date, universally accepted preventive measures for contrast-induced acute kidney injury (CI-AKI) do not exist, and they warrant further research.. The purpose of this study was to evaluate the efficacy of vitamins, including vitamin C and E, for prevention of CI-AKI.. We electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome of interest was the incidence of CI-AKI.. A total of 19 studies were included in this meta-analysis. Pooled analysis showed that vitamin C plus saline [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49-0.82, p = 0.0005] and vitamin E plus saline (RR = 0.39, 95% CI 0.24-0.62, p < 0.0001) significantly reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C plus saline was further confirmed by trial sequential analysis (TSA). However, TSA indicated that more trials are required to confirm the efficacy of vitamin E plus saline. There was no significant difference in preventing CI-AKI between vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47-1.71, p = 0.75), between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30-1.30, p =  0.20), as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49-1.92, p = 0.93).. Vitamin C plus saline administration is effective at reducing the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context is encouraging, but more trials are required. Furthermore, this meta-analysis and TSA indicated insufficient power to draw a definitive conclusion on the effect of vitamin C plus NAC, versus saline or NAC alone, which needs to be explored further.

Topics: Acetylcysteine; Acute Kidney Injury; Ascorbic Acid; Contrast Media; Humans; Incidence; Sodium Chloride; Vitamin E

Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Kidney; Oxidants; Oxidative Stress; Reactive Oxygen Species; Rhabdomyolysis

This systematic review with meta-analysis sought to determine the strength of evidence in terms of the impact of common antioxidant supplementations, such as N-acetylcysteine (NAC), vitamin C, and polyunsaturated fatty acids (PUFA) on perioperative outcomes after cardiac surgery with particular focus on the incidence of atrial fibrillation (AF) and acute kidney injury (AKI) with associated mortality. A total of 29 trials were identified that reported incidence of AF and 17 trials that reported incidence of AKI. Pooled analysis reported that NAC (OR=0.5; P=.001), vitamin C (OR=0.4; P=.001), and PUFA (OR=0.8; P=.01) administration were associated with significantly reduced incidence of AF. In terms of postoperative AKI, only NAC was shown to be a beneficial supplement that was able to significantly reduce the incidence of AKI (OR=0.7; P=.01), and NAC could also significantly decrease overall mortality (OR=0.3; P=.03) following cardiac surgery. The use of NAC in patients undergoing cardiac surgery should be strongly recommended due to its combined cardio-renal protective effects and reduced mortality. Also, PUFA and vitamin C might be able to significantly decrease the incidence of arrhythmia; however, reno-protective effects and impact on overall mortality of these supplements seem to be less impressive.

Topics: Acetylcysteine; Acute Kidney Injury; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Cardiac Surgical Procedures; Dietary Supplements; Fatty Acids, Unsaturated; Humans; Incidence; Odds Ratio; Risk Factors; Treatment Outcome

Contrast-induced acute kidney injury (CI-AKI) is a common complication of intravascular administration of contrast media used in coronary angiography, percutaneous coronary intervention and other diagnostic and interventional procedures. This review article aims at summarizing the published literature regarding the prevention of CI-AKI, by focusing on available high-quality meta-analyses addressing this matter. Apart from adequate hydration, a number of pharmacologic agents have been proposed as potential candidates to be included in the routine preparation, prior to the patient's arrival in the cardiac catheterization laboratory. Among them, statins and N-acetylcysteine appear to be the most extensively studied ones. Throughout this article we present the available data on CI-AKI prevention and provide a critical clinical appraisal, as well as a summary of currently available guidelines.

Topics: Acetylcysteine; Acute Kidney Injury; Aminophylline; Animals; Ascorbic Acid; Contrast Media; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Purinergic P1 Receptor Agonists; Theophylline

A 69-year-old woman presented with acute kidney failure of unknown cause that ultimately required dialysis. Kidney biopsy revealed the diagnosis of oxalate nephropathy. In retrospect, the patient had several risk factors for this entity, including excessive vitamin C intake, a remote history of Roux-en-Y gastric bypass for weight loss, and chronic kidney disease. This presentation of multiple risk factors for oxalate nephropathy is especially relevant to patients and physicians considering the increase in the United States of vitamin C supplementation use and gastric bypass surgery. It is important for physicians to maintain an awareness of this diagnosis and its risk factors.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Biopsy, Needle; Calcium Oxalate; Dose-Response Relationship, Drug; Emergency Service, Hospital; Female; Follow-Up Studies; Gastric Bypass; Humans; Immunohistochemistry; Kidney Function Tests; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Treatment Outcome

This study sought to perform a systematic review with meta-analysis of randomized controlled trials comparing the use of ascorbic acid with placebo or other treatment options for the treatment of contrast induced-acute kidney injury (CI-AKI) in patients undergoing coronary angiography.. CI-AKI remains the most widely discussed and debated topic in cardiovascular medicine, with its incidence increasing due to an increasing number of contrast media-enhanced radiological procedures being performed.. MEDLINE, Embase, and Cochrane central databases were searched from inception to May 2013, without language restrictions. For a study to be selected, it had to report the incidence of CI-AKI as an outcome measure. Studies were excluded if at least 1 study arm did not have ascorbic acid administered alone or with saline solution hydration. Data were extracted by 1 author, and random checks were made by another author.. Nine randomized, controlled trials reported data on the incidence of CI-AKI in 1,536 patients who had completed the trial and were included in the final analysis. Patients receiving ascorbic acid had 33% less risk of CI-AKI compared with patients receiving placebo or an alternate pharmacological treatment (risk ratio by random-effects model: 0.672; 95% confidence interval, 0.466 to 0.969; p = 0.034).. Ascorbic acid provides effective nephroprotection against CI-AKI and may form a part of effective prophylactic pharmacological regimens.

Topics: Acute Kidney Injury; Ascorbic Acid; Confounding Factors, Epidemiologic; Contrast Media; Coronary Angiography; Humans; Incidence; Odds Ratio; Protective Agents; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome; Vitamins

Paraquat poisoning in Germany is rare. Because plasma levels do not necessarily match the ingested amount of paraquat, repeated measurement of plasma levels is imperative. There is a large potential in the prehospital phase to improve prognosis: further resorption must be terminated by rigorous charcoal administration and early tracheal intubation if necessary. Because paraquat can be resorbed by dermal contact, steps to ensure sufficient protection of emergency medical personnel must be taken.As soon as further resorption has been prevented sufficiently, forced diuresis, renal replacement therapy, and hemoperfusion can be of help, but still remain controversial. To reduce pulmonary fibrosis, inspiratory oxygen concentrations must be adjusted to the minimal amount needed to ensure satisfactory tissue oxygenation. Data supporting the advantageous use of cyclophosphamide combined with methylprednisolone for the treatment of pulmonary fibrosis were recently published. Since the toxic mechanism implies a mismatch of oxidants and anti-oxidants, co-administration of ascorbic acid and N-acetylcysteine are simple treatments with few side effects.

Topics: Acetylcysteine; Acute Kidney Injury; Acute Lung Injury; Adult; Antioxidants; Ascorbic Acid; Combined Modality Therapy; Conscious Sedation; Cooperative Behavior; Critical Care; Dose-Response Relationship, Drug; Emergency Medical Services; Esophagoscopy; Esophagus; Gastric Mucosa; Hemofiltration; Herbicides; Humans; Interdisciplinary Communication; Intermittent Positive-Pressure Ventilation; Intestinal Mucosa; Male; Metabolic Clearance Rate; Oxygen Inhalation Therapy; Paraquat; Prognosis; Pulmonary Edema; Suicide, Attempted

Contrast-induced nephropathy (CIN) is an acute and severe complication after contrast media administration. The most important step in preventing CIN is identifying high-risk patients. In this review, we evaluate and summarize the evidence regarding the CIN prophylaxis, including the withdrawal of the potentially nephrotoxic drugs, hydration by isotonic solution or NaHCO(3), pharmaceutical treatment with N-acetylcysteine (N-AC), adenosine antagonists, ascorbic acid, renal procedures including hemofiltration or dialysis, and to the optimal use of the contrast. We suggest it is possible to reduce the burden of CIN by carefully incorporating these recommendations. After review of published literature in this field, we conclude that the cornerstone of the CIN prevention should be combination of hydration (normal saline or NaHCO(3)) and the use of N-AC.

Topics: Acetylcysteine; Acute Disease; Acute Kidney Injury; Adenosine; Ascorbic Acid; Contrast Media; Elective Surgical Procedures; Emergency Treatment; Free Radical Scavengers; General Surgery; Glomerular Filtration Rate; Humans; Hydrotherapy; Preoperative Care; Renal Dialysis; Risk Assessment; Sodium Bicarbonate

N-Acetylcysteine, theophylline, and other agents have shown inconsistent results in reducing contrast-induced nephropathy.. To determine the effect of these agents on preventing nephropathy.. Relevant randomized, controlled trials were identified by computerized searches in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases (up to November 2006). Databases were searched for studies in English, Spanish, French, Italian, and German.. Randomized, controlled trials that administered N-acetylcysteine, theophylline, fenoldopam, dopamine, iloprost, statin, furosemide, or mannitol to a treatment group; used intravenous iodinated contrast; defined contrast-induced nephropathy explicitly; and reported sufficient data to construct a 2 x 2 table of the primary effect measure.. Abstracted information included patient characteristics, type of contrast media and dose, periprocedural hydration, definition of contrast-induced nephropathy, and prophylactic agent dose and route.. In the 41 studies included, N-acetylcysteine (relative risk, 0.62 [95% CI, 0.44 to 0.88]) and theophylline (relative risk, 0.49 [CI, 0.23 to 1.06]) reduced the risk for contrast-induced nephropathy more than saline alone, whereas furosemide increased it (relative risk, 3.27 [CI, 1.48 to 7.26]). The remaining agents did not significantly affect risk. Significant subgroup heterogeneity was present only for N-acetylcysteine. No publication bias was discerned.. All trials evaluated the surrogate end point of contrast-induced nephropathy as the primary outcome. The lack of a statistically significant renoprotective effect of theophylline may result from insufficient data or study heterogeneity. True study quality remains uncertain.. N-acetylcysteine is more renoprotective than hydration alone. Theophylline may also reduce risk for contrast-induced nephropathy, although the detected association was not significant. Our data support the administration of N-acetylcysteine prophylaxis, particularly in high-risk patients, given its low cost, availability, and few side effects.

Topics: Acetylcysteine; Acute Kidney Injury; Ascorbic Acid; Bicarbonates; Clinical Trials as Topic; Contrast Media; Furosemide; Protective Agents; Research Design; Theophylline

Acute renal failure still occurs as a complication after radiographic examination using iodinated radiocontrast medium. The incidence rate of radiocontrast medium-induced nephropathy (radiocontrast nephropathy) is low (2 - 3%) in general. However, the rate is remarkably elevated in patients with pre-existing renal insufficiency. Radiocontrast nephropathy is associated with increased morbidity and mortality, particularly in patients with percutaneous coronary interventions. Although the reduction in renal blood flow and direct toxic action on renal tubular cells are considered to be involved, little is known about the etiology of radiocontrast nephropathy. A number of agents that improve renal circulation have been clinically tested for prevention of radiocontrast nephropathy, but none of them has succeeded. Protection of renal tubular cells against oxidative stress is another approach to avoid radiocontrast nephropathy. Prophylactic effects of antioxidants such as N-acetylcysteine and ascorbic acid have been reported by several investigators, although the effectiveness of these compounds is still a matter of debate. At present, hydration is regarded as the only effective, though incomplete, prophylactic regimen for radiocontrast nephropathy. Recently, we have shown that caspase-dependent apoptosis is an important factor in the pathogenesis of radiocontrast nephropathy and clarified cellular mechanisms underlying the radiocontrast media-induced apoptosis. This review summarizes clinical and experimental evidence for the etiology and prevention of radiocontrast nephropathy.

Topics: Acetylcysteine; Acute Kidney Injury; Adenosine; Alprostadil; Animals; Apoptosis; Ascorbic Acid; Atrial Natriuretic Factor; Contrast Media; Diuretics; Endothelins; Epoprostenol; Fenoldopam; Fluid Therapy; Hemodiafiltration; Hemofiltration; Humans; Iodine Radioisotopes; Kidney Tubules; Models, Biological; Renal Dialysis; Risk Factors

Contrast nephropathy (CN) is a common cause of iatrogenic acute renal failure. Its incidence rises with the growing use of intra-arterial contrast in older patients for diagnostic and interventional procedures. Aim of the present review is to discuss the mechanisms and risk factors of CN, to summarize the controlled studies evaluating measures for prevention, and to conclude with evidence-based strategies for prevention. Pathophysiological mechanisms of CN are intrarenal vasoconstriction, leading to medullary ischemia, direct cytotoxicity, oxidative tissue damage and apoptosis. Nephro-toxicity is related to osmolality, dose and route of the contrast agent and only occurs in synergy with patient factors, such as previous renal impairment, cardiovascular disease, oxidant stress and the use of certain drugs. CN has impact on morbidity and mortality. In patients at risk, the following measures are recommended: discontinuation of potentially nephrotoxic drugs, treatment of intravascular volume depletion, hydration with sodium-bicarbonate (which seems superior to sodium-chloride), limitation of contrast volume and the use of low-osmolal contrast. Furthermore, if starting the day before is feasible, administer oral N-acetylcysteine, or, with urgent interventions, theophylline 200 mg i.v. (once before the intervention) or high dose ascorbic acid. In patients with combined severe cardiac and renal insufficiency, periprocedural hemofiltration may be considered; this is the only intervention with proven clinical improvement. Large randomised controlled trials are necessary to show whether pharmacological interventions can improve clinical outcomes.

Topics: Acetylcysteine; Acute Kidney Injury; Ascorbic Acid; Contrast Media; Humans; Phosphodiesterase Inhibitors; Prostaglandins; Theophylline

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

With the increased use of nonprescription vitamin supplementation, physicians involved in critical care must be aware of the potential complications of these medications. We report the case of a 31-year-old African-American man presenting to the emergency department with acute renal failure. He had previously been well and initially denied the use of any drugs except for vitamin C tablets obtained at a local health food store. This case report and review of the literature is utilized to illustrate the importance of historical data in patients presenting with acute renal failure to a critical care service.

Topics: Acute Kidney Injury; Adult; Antioxidants; Ascorbic Acid; Biopsy; Blood Urea Nitrogen; Dietary Supplements; Humans; Hyperoxaluria; Male; Nonprescription Drugs; Renal Dialysis

Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity. Oxidative stress has been proposed as a cause of postoperative AKI. Ascorbic acid (AA) supplementation was suggested as a novel and promising antioxidant. The aim of this study was to evaluate the capability of AA to reduce the incidence of postoperative AKI in cardiac surgery patients.. A prospective randomized trial was conducted in patients scheduled for on-pump cardiac surgery. Subjects in the AA group received 2 g of AA intravenously during the induction of anesthesia, 2 g before aortic cross-clamp removal and 1 g every 8 hours for five postoperative days (the JERICA protocol). Postoperatively, the patients were monitored for AKI and other complications. Malondialdehyde levels were monitored in a subpopulation of 100 patients to evaluate the effect of AA on oxidative stress level.. Our results do not support the effectiveness of AA supplementation in reducing the incidence of postoperative AKI in on-pump cardiac surgery patients.. This study was registered with the ISRCTN Registry under the trial registration number ISRCTN98572043.

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Cardiac Surgical Procedures; Humans; Incidence; Malondialdehyde; Postoperative Complications; Prospective Studies; Treatment Outcome

Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis.. LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned.. This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis.. clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Antioxidants; Ascorbic Acid; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemolysis; Hospital Mortality; Humans; Hypoglycemia; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Quality of Life; Sepsis; Treatment Outcome; Vasoconstrictor Agents

Even minor postoperative reductions in renal function influence the outcome of cardiac surgery. The mechanisms of postoperative renal injury in cardiac surgery are multifactorial and include ischemia-reperfusion injury. The study investigates the effect of the antioxidant ascorbic acid on the postoperative acute kidney injury after elective CABG surgery.. A prospective randomized single-center trial was conducted in on-pump coronary artery bypass patients. The patients in the ascorbic acid group received 2 grams of ascorbic acid 24 hours and 2 hours preoperatively and 1 gram twice daily five days after the surgery.  Postoperatively, the subjects were monitored for renal dysfunction and other complications.. 100 patients were included, with 50 patients in each study group. The groups were well matched for baseline demographics, preoperative medications, comorbidities, and had similar intraoperative characteristics. The incidence of postoperative acute kidney injury in the ascorbic acid group was 16% and 14% in the control group (P = .779). The groups also did not differ in peak postoperative serum creatinine (83 [33] µmol/L versus 83 [39] µmol/L; P = .434), the lowest postoperative creatinine clearance (96.40 ± 35.78 mL/min versus 90.89 ± 36.18 mL/min; P = .766), and time from surgery to the onset of peak postoperative serum creatinine (1.64 ± 1.34 days versus 1.92 ± 1.54 days; P = .393). There was no dialysis required in any patient. Conclusion: The results of this study did not demonstrate a significant protective effect of ascorbic acid on the incidence of postoperative acute renal injury in elective on-pump CABG patients.

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Coronary Artery Bypass; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Humans; Incidence; Kidney Function Tests; Male; Middle Aged; Pilot Projects; Postoperative Complications; Prospective Studies; Risk Factors; Slovenia; Survival Rate

The aim was to investigate whether the use of N-acetylcysteine and ascorbic acid reduce contrast-induced nephropathy incidence in critical care patients.. This was a one-center, two-arm, prospective, randomized, open-label, controlled trial in the Intensive Care Unit of the University Hospital of Larissa, Greece. Patients with stable renal function, who underwent non urgent contrast-enhanced computed tomography for diagnostic purposes, were included in the study. Patients in the treatment group (NacA, n = 60) received intravenously N-acetylcysteine (1200 mg) and ascorbic acid (2 g) dissolved separately in 100 ml of normal saline 2 hours before, and at 10 hours and 18 hours following the infusion of contrast agent, while control group patients (CG, n = 64) received only normal saline. All patients received additional hydration. Contrast-induced nephropathy was defined as relative increase by 25% of the baseline values of serum creatinine.. Contrast-induced nephropathy in NacA and CG were 18.33% and 15.6%, respectively (p = 0.81). The percentage change median (interquartile range (IR)) of serum cystatin-C (mg/L) from baseline in patients who underwent contrast-induced tomography, were 37.23% (28.53) and 93.20% (46.90) in NacA and in CG, respectively (p = 0.03). The 8-isoprostane serum levels in NacA were significantly lower compared to CG at 2 hours (p = 0.012) and 24 hours (p = 0.006) following radiocontrast infusion. Multivariate analysis revealed that contrast-induced nephropathy was independently associated with a higher baseline ratio of serum urea/creatinine (odds ratio, 1.02; 95 CI%, 1.00-1.05) and with the use of nephrotoxic medications (odds ratio, 0.24; 95 CI%, 0.06-0.94).. Intravenous administration of N-acetylcysteine and ascorbic acid failed to reduce contrast-induced nephropathy in critically ill patients who underwent contrast-enhanced computed tomography, despite a significant reduction of 8-isoprostane levels in treated patients.. ClinicalTrials.gov, NCT01017796 . Registered on 20 November 2009.

Topics: Acetylcysteine; Acute Kidney Injury; Administration, Intravenous; Ascorbic Acid; Blood Urea Nitrogen; Contrast Media; Creatinine; Critical Care; Female; Greece; Humans; Intensive Care Units; Kidney; Male; Middle Aged; Multivariate Analysis; Prospective Studies; ROC Curve; Statistics, Nonparametric; Tomography, X-Ray Computed

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of procedures requiring contrast media associated with rising costs, prolonged hospitalization, and increased mortality. The aim of this study was to assess whether prophylactic administration of standard dosages of intravenous N-acetylcysteine or ascorbic acid reduce the incidence of CI-AKI in patients with chronic renal insufficiency undergoing elective cardiac catheterization.. In a single-center, prospective, randomized, double-blind, placebo-controlled trial, the preventive effects of N-acetylcysteine and ascorbic acid were evaluated in 520 patients with chronically impaired renal function (serum creatinine ≥1.3 mg/dL) undergoing elective cardiac catheterization. The study drugs (600 mg N-acetylcysteine, 500 mg ascorbic acid, placebo) were administered intravenously twice (at 24 hours and 1 hour before the procedure). Serum creatinine, estimated glomerular filtration rate (eGFR) and serum urea were assessed at baseline and at 24 hours and 72 hours after contrast media exposure. CI-AKI was defined as a postangiographical increase in serum creatinine ≥0.5 mg/dL. Results. The incidence of CI-AKI was 27.6% in the N-acetylcysteine group (P=.20 vs placebo group) and in 24.5% in the ascorbic acid group (P=.11 vs placebo group). CI-AKI occurred in 32.1% of the placebo group.. Standard doses of N-acetylcysteine and ascorbic acid did not prevent CI-AKI in patients at high risk undergoing cardiac catheterization with non-ionic, low-osmolality contrast agent.

Topics: Acetylcysteine; Acute Kidney Injury; Administration, Intravenous; Aged; Ascorbic Acid; Cardiac Catheterization; Contrast Media; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Incidence; Kidney; Male; Prospective Studies; Treatment Outcome; Urea

Antioxidant drugs such as N-acetylcysteine (NAC) and ascorbic acid have been evaluated in interventional studies to prevent contrast-induced nephropathy (CIN), however, there are limited data on comparing either or both, with background of standard intravenous saline hydration versus the standard intravenous saline hydration alone in preventing CIN.. We conducted a single-center randomized trial among patients undergoing coronary angiography or percutaneous coronary intervention who had serum creatinine ≥ 1.3 mg/dL or were on diabetes mellitus medication. Eligible patients were randomly assigned to one of the following 4 groups: (1) NAC, (2) ascorbic acid, (3) combination of both drugs, and (4) control group. Additionally, all the groups received the standard intravenous saline hydration. Creatinine was measured 4-5 days after procedure.. A total of 243 patients were randomized; 62 to NAC, 57 to ascorbic acid, 58 to both drugs, and 66 to placebo. The development of 0.5 mg/dL absolute increase of serum creatinine, 25% relative decrease of creatinine clearance, or either (CIN) were measured in the ascorbic acid group (3.6% for all), NAC group (6.8%, 3.4%, 8.5%, respectively), combined group (5.5%, 5.5%, 9.1%, respectively), and control group (6.2%, 6.2%, 7.7%, respectively). None of these differences were significant (P = 0.896 for serum creatinine, P = 0.863 for creatinine clearance, and P = 0.684 for CIN).. In a cohort of patients at risk of developing CIN, we could not detect any significant benefit of the use of ascorbic acid, NAC, or a combination of both drugs over the standard hydration regimen in preventing CIN.

Topics: Acetylcysteine; Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Contrast Media; Creatinine; Drug Therapy, Combination; Female; Fluid Therapy; Free Radical Scavengers; Humans; Male; Middle Aged; Prospective Studies

Some studies have shown that antioxidant ascorbic acid has renal protective effects, but the beneficial effects of contrast-induced nephropathy prevention remain to be clearly shown. Therefore, we aimed to determine whether ascorbic acid pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography.. We conducted a prospective, randomized, controlled trial, involving 156 consecutive patients with chronic renal insufficiency (calculated estimated glomerular filtration rate<60 mL/min/1.73 m(2) and/or serum creatinine≥1.1 mg/dL) undergoing coronary angiography. Patients were randomized to ascorbic acid (n=74, 3 g intravenous injection before the procedure and oral 1 g per day for 2 days after the procedure, ascorbic acid group) or sodium chloride alone (n=82, control group). All patients received pre-and postprocedure hydration.. There was no difference between the ascorbic acid group and control group in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.012±0.146 vs 0.022±0.212 mg/dL respectively, p=0.216). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either≥25% or ≥0.5 mg/dL in serum creatinine, was 5.4% in ascorbic acid-treated patients (4/74) and 6.3% in control group patients (6/82), a nonsignificant difference (p=0.690). There were also no differences between the 2 groups in the inhospital clinical outcomes or length of hospital stay.. Ascorbic acid pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.

Topics: Acute Kidney Injury; Administration, Oral; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Contrast Media; Coronary Angiography; Female; Fluid Therapy; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Premedication; Prospective Studies; Risk Factors; Treatment Failure

Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated.. We conducted a randomized, double-blind, placebo-controlled trial of ascorbic acid in 231 patients with a serum creatinine concentration > or =1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid, 3 g at least 2 hours before the procedure and 2 g in the night and the morning after the procedure, or placebo was administered orally. Contrast-mediated nephropathy was defined by an absolute increase of serum creatinine > or =0.5 mg/dL or a relative increase of > or =25% measured 2 to 5 days after the procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%) in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85; P=0.02). The mean serum creatinine concentration increased significantly in the placebo group (from 1.36+/-0.50 to 1.50+/-0.54 mg/dL, P<0.001) and nonsignificantly in the ascorbic acid group (from 1.46+/-0.52 to 1.52+/-0.64 mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL; 95% CI, 0.00 to 0.17; P=0.049).. Prophylactic oral administration of ascorbic acid may protect against contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure.

Topics: Acute Kidney Injury; Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Contrast Media; Coronary Angiography; Creatinine; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Middle Aged; Osmolar Concentration; Oxidative Stress; Premedication; Risk; Treatment Outcome; Urea

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (μmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) μmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 μmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear.

Topics: Acute Kidney Injury; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiopulmonary Bypass; Child; Child, Preschool; Humans; Infant; Prospective Studies; Risk Factors

Sepsis-associated acute kidney injury is associated with high morbidity and mortality in critically ill patients. Cell-free hemoglobin (CFH) is released into the circulation of patients with severe sepsis and the levels of CFH are independently associated with mortality. CFH treatment increased cytotoxicity in the human tubular epithelial cell line HK-2. To better model the intact kidney, we cultured human kidney organoids derived from induced pluripotent stem cells. We treated human kidney organoids grown using both three-dimensional and transwell protocols with CFH for 48 h. We found evidence for increased tubular toxicity, oxidative stress, mitochondrial fragmentation, endothelial cell injury and injury-associated transcripts compared to those of the untreated control group. To evaluate the protective effect of clinically available small molecules, we co-treated CFH-injured organoids with ascorbate (vitamin C) or acetaminophen for 48 h. We found significantly decreased toxicity, preservation of endothelial cells and reduced mitochondrial fragmentation in the group receiving ascorbate following CFH treatment. This study provides direct evidence that ascorbate or ascorbic acid protects human kidney cells from CFH-induced damage such as that in sepsis-associated acute kidney injury.

Topics: Acute Kidney Injury; Ascorbic Acid; Endothelial Cells; Hemoglobins; Humans; Kidney; Sepsis

Topics: Acute Kidney Injury; Anemia; Ascorbic Acid; Child; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Humans

Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) may deplete micronutrient levels. Patients are also at risk for micronutrient depletion due to underlying illness(s), poor nutrient intake prior to intensive care unit (ICU) admission and/or increased requirements. We determined vitamin and trace element status before, during and after CRRT in critically ill patients.. This prospective observational study performed in mixed medical and surgical ICU patients. Serial serum vitamin B6 and vitamin C concentrations were measured by HPLC and folic acid by ECLIA. Serum chromium, copper, selenium, and zinc were measured using ICP-MS. Serum ceruloplasmin was measured by the Erel method.. Fifty adult ICU patients with AKI were recruited. The median APACHE II score on ICU admission was high at 24.0 (6.0-33.0). The median days on CRRT was 2.0 (2.0-4.0) days. At baseline (within 10-15 minutes of CRRT initiation), serum vitamin C, selenium and zinc were below normal. Serum vitamin B6 levels at 72 hours on CRRT were significantly lower than at 24 hours (p = 0.011). Serum vitamin C values fell significantly at 24 and 72 hours during CRRT (p = 0.030 and p = 0.001), respectively, and remained low 24 and 48 hours after CRRT was stopped (p = 0.021). At baseline and during CRRT, 96% of participants had at least two or more micronutrient levels below the normal range.. Serum vitamin C, selenium and zinc concentrations were below the normal range at baseline. CRRT was associated with a significant further decrease in levels of vitamin C, selenium and zinc.

Topics: Acute Kidney Injury; Adult; Ascorbic Acid; Continuous Renal Replacement Therapy; Critical Illness; Humans; Intensive Care Units; Micronutrients; Prospective Studies; Renal Replacement Therapy; Retrospective Studies; Selenium; Trace Elements; Vitamin B 6; Vitamins; Zinc

Topics: Acute Kidney Injury; Administration, Intravenous; Ascorbic Acid; Humans; Renal Replacement Therapy

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Complement C1 Inhibitor Protein; Kidney; Kidney Tubules; Macrophages; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Transcriptional Activation

Background: Acute kidney injury (AKI) occurs frequently in septic patients and correlates with increased mortality. Because clinical studies investigating hydrocortisone, ascorbic acid, and thiamine (HAT) have demonstrated discordant results, studies were performed using mortality stratification for therapy to identify candidates for therapy and determine mechanisms of organ injury. Methods: Sepsis was induced using the cecal ligation and puncture (CLP) model of sepsis with fluid and antibiotic support. Heart rate (HR) measurements obtained 6 hours after CLP stratified mice into live predicted (P-Live) or die predicted (P-Die). Stratified mice were then randomized for treatment with HAT or vehicle given 7 hours after CLP. Physiologic measurements were taken again at 24 hours, and mice were killed to collect blood and organs. Results: The following five groups were created: (1) P-Live vehicle, (2) P-Live HAT, (3) P-Die vehicle, (4) P-Die HAT, and (5) naive mice. Comparisons were made to test the hypotheses that (1) P-Die vehicle mice will have significant deterioration compared with P-Live mice targeting the kidney and (2) HAT will correct these deleterious changes in P-Die mice. Compared with P-Live, P-Die mice had a significant decline in all measured physiologic parameters (HR, cardiac output, breath rate, and temperature), which were corrected with HAT therapy (P < 0.05 for all parameters). The P-Die mice had declines in the ascorbic acid within the blood, peritoneal lavage, and kidney homogenate compared with P-Live mice indicating consumption, and the decline was corrected with HAT. Elevated IL-6, KC, Macrophage Inflammatory Protein-2, and IL-1RA were found in P-Die mice and decreased with HAT. Markers of endothelial cell injury (glypican 1 and glypican 4) were elevated in the P-Die mice, and these values were decreased with HAT therapy. Low oxygen levels with subsequent oxidative stress (OS) in the kidney were visualized in histologic sections using hypoxyprobe and also with carbonyl proteins and 8-iso-prostaglandin F2α in kidney homogenates. The P-Die mice had significant elevations of renal OSs, which was ameliorated with HAT. Kidney injury was evident in the P-Die mice compared with P-Live mice with elevations in blood urea nitrogen and cystatin C, which were significantly reduced with HAT. There was no evidence of global hypoxia or organ injury because hepatic parameters remained normal. Conclusions: Our data show that in CLP-induced sepsis, P-D

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Hydrocortisone; Kidney; Mice; Oxidative Stress; Sepsis; Thiamine

The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients.. Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU.. Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46-2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003-2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09-2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48-1.31]).. Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.

Topics: Acute Kidney Injury; Administration, Intravenous; Age Factors; Ascorbic Acid; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Propensity Score; Regression Analysis; Retrospective Studies; Sepsis

Colistin is a potent antibiotic which is mainly preferred in the treatment of multidrug-resistant (MDR) gram-negative bacilli. However, due to the increased risk of acute kidney injury following its use, the clinical application is limited. This nephrotoxicity is known to be induced by oxidative stress and related inflammation. In this study on rats, potent antioxidants Dexpanthenol (DEX) and Ascorbic acid (Vit C) have been administered in combination with Colistin to find out whether they would weaken Colistin's nephrotoxic effects.. Inflammation biomarkers were studied with enzyme-linked immunosorbent assay (ELISA) kits, and oxidative stress biomarkers were studied with different photometric methods in blood and tissue samples taken after treatment with DEX and Vit C in rats with colistin nephrotoxicity. In addition, inflammation and necrosis in the kidney tissues were examined pathologically.. It has been observed in the serum and tissue samples that DEX and Vit C decrease oxidative stress and inflammation biomarkers, therefore acting as nephroprotective agents.. These compounds have been found to ameliorate the nephrotoxic effects of Colistin, which were demonstrated in the rats treated with Colistin, as well as the combinations.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Colistin; Disease Models, Animal; Inflammation; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxidative Stress; Pantothenic Acid; Rats; Rats, Sprague-Dawley

COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure.. A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India.. This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

Topics: Acute Kidney Injury; Ascorbic Acid; COVID-19; Fatal Outcome; Graft Rejection; Humans; Hyperoxaluria; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Primary Graft Dysfunction

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCF

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Cell Line; Disease Models, Animal; Humans; Kidney Tubules; Lipopolysaccharides; Male; Mice; Mitochondria; Mitophagy; Protein Kinases; Sepsis; Signal Transduction; Ubiquitin-Protein Ligases; Vitamins

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Biopsy; Creatinine; Crystallization; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Kidney; Male; Oxalates; Powders; Rejuvenation; Renal Dialysis; Severity of Illness Index

Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals.. Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days.. Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1β levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels.. Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Cell Adhesion Molecules; Curcumin; Cystatin C; Down-Regulation; Drug Synergism; Gene Expression; Kidney; Kidney Function Tests; Lead; Male; Organometallic Compounds; Rats, Wistar; Vascular Cell Adhesion Molecule-1

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.

Topics: Acute Kidney Injury; Aged; Antibodies, Monoclonal, Humanized; Antioxidants; Ascorbic Acid; Betacoronavirus; Coronavirus Infections; Corynebacterium; Corynebacterium Infections; COVID-19; Cytokine Release Syndrome; Enzyme Inhibitors; Erythrocyte Transfusion; Hematinics; Humans; Hydroxocobalamin; Hydroxychloroquine; Hypoxia; Male; Methemoglobinemia; Methylene Blue; Pandemics; Pneumonia, Bacterial; Pneumonia, Viral; Renal Replacement Therapy; Respiratory Insufficiency; SARS-CoV-2; Shock, Septic

Oxalate kidney injury can manifest as oxalate nephropathy or nephrolithiasis and present as acute kidney injury or even as end-stage renal disease. There are several known causes for acute oxalate nephropathy; however, the combination of exocrine pancreatic insufficiency with overconsumption of vitamin C has not been described before. In this case, a man in his early 80s presented with anorexia and extreme fatigue for 1 week. He had a history of myalgic encephalomyelitis, also known as chronic fatigue syndrome, for which he took several supplements, including high doses of vitamin C. Furthermore, several years ago, he was diagnosed elsewhere with exocrine pancreatic insufficiency. On admission, acute kidney injury was diagnosed. The kidney biopsy showed oxalate nephropathy as the cause. We diagnosed acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency. Within 14 days, his kidney function got worse and he required renal replacement therapy.

Topics: Acute Disease; Acute Kidney Injury; Aged, 80 and over; Ascorbic Acid; Exocrine Pancreatic Insufficiency; Humans; Hyperoxaluria; Kidney; Kidney Failure, Chronic; Male; Oxalates; Renal Replacement Therapy

Topics: Acute Kidney Injury; Ascorbic Acid; Humans; Male; Middle Aged

Oxalate nephropathy is associated with hereditary hyperoxaluria, Crohn disease, and previous gastric or intestinal surgery, especially in the setting of increased oxalate intake or ethylene glycol ingestion. We present a patient whose intake of vitamin C supplements (2 g/day), exacerbated by predisposing factors of prior small bowel obstruction and resection, and benign prostate hyperplasia (BPH), resulted in acute kidney injury due to oxalate nephropathy. We review past reports of vitamin C-induced oxalate nephropathy and discuss the underlying precipitating factors.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Dietary Supplements; Humans; Intestine, Small; Male; Oxalates; Risk Factors

Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity.. Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated.. CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (P. l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Body Weight; Carnitine; Cisplatin; Creatinine; Electrolytes; Kidney; Male; Oxidative Stress; Rats; Rats, Wistar; Urea

Ingestion of vitamin C is generally regarded as harmless. Oxalate nephropathy is an infrequent condition and is characterized by oxalate deposition in the renal tubules, in some cases resulting in acute kidney injury. It can be caused by overproduction of oxalate in genetic disorders and, more frequently, as a secondary phenomenon provoked by ingestion of oxalate or substances that can be transformed into oxalate in the patient.. We present a case of acute oxalate nephropathy in a 59-year-old black male with type 2 diabetes mellitus, who received a kidney transplant 11 years prior. He ingested a large amount of cashew pseudofruit ("cashew apple") during 1 month and developed acute kidney injury. His previous blood creatinine was 2.0 mg/dL, which increased to 7.2 mg/d; he required hemodialysis. He was subsequently discharged without need for dialysis; 3 months later his blood creatinine stabilized at 3.6 mg/dL.. This pseudofruit is rich in ascorbic acid (vitamin C) and poor in oxalate. Urinary oxalate excretion begins to increase when amounts of ascorbic acid above bodily requirements are ingested, and may provoke acute oxalate nephropathy. The patient's oxalate acute nephropathy, in this case, was attributed to excessive vitamin C ingestion from the cashew pseudofruit associated with decreased renal function.

Topics: Acute Kidney Injury; Anacardium; Ascorbic Acid; Humans; Kidney Transplantation; Male; Middle Aged; Oxalates

Topics: Acute Kidney Injury; Administration, Intravenous; Ascorbic Acid; Humans; Renal Replacement Therapy; Vitamins

Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury.. Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates.. Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3μg/mmol versus 533.6μg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups.. Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Topics: Acute Kidney Injury; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Caspase 3; Contrast Media; Creatinine; Disease Models, Animal; Endovascular Procedures; Immunohistochemistry; In Situ Nick-End Labeling; Iohexol; Kidney; Lipocalin-2; Mice; Mice, Inbred BALB C; Retinol-Binding Proteins, Plasma

Hyperoxaluria can result in oxalate nephropathy with intratubular calcium oxalate crystallization and acute tubular injury. Primary inherited enzymatic deficiency or secondary causes such as excessive dietary intake, enteric increased absorption, or high doses of vitamin C, which is metabolized to oxalate, may underlie hyperoxaluria and oxalate nephropathy. We report a case of acute kidney injury due to oxalate nephropathy in a patient using chelating therapy with oral ethylenediamine tetra acetic acid (EDTA), intravenous supplementation with vitamin C, and chronic diarrhea and discuss the potential kidney damage these factors can cause in particular settings. To our knowledge, this is the first report suggesting an association between oral EDTA and oxalate nephropathy.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Calcium Chelating Agents; Calcium Oxalate; Diarrhea; Edetic Acid; Humans; Hyperoxaluria; Kidney Tubular Necrosis, Acute; Male; Renal Dialysis; Vitamins

There is paucity of literature regarding the nephrotoxicity of antiretroviral drugs and its interaction with plant-based adjuvants. This study investigates the attenuating effect of kolaviron in nevirapine-therapy on the histological structure of the kidneys of adult male Sprague-Dawley rats.. To determine the attenuating influence of anti-oxidant status of kolaviron on the kidneys of experimental animals following nevirapine administration.. Forty eight pathogen-free adult male Sprague-Dawley rats were used for this study. The animals were divided into 8 groups (A-H) with 6 animals in each group. Group A was given normal saline as the control; group B was given nevirapine; group C was given kolaviron; group D was given vitamin C; group E was given nevirapine and kolaviron; group F was given nevirapine and vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after day 28) and group H was given corn oil. The experiment lasted 56 days after which the animals were sacrificed, blood samples were collected through cardiac puncture for serum analysis and the kidneys were harvested and prepared for H& E histological examination.. Nevirapine caused histoarchitectural damage in the glomerular apparatus with resultant increase in kidney/body weight ratio (p<0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine group these parameters were significantly elevated (P<0.05). However, co-administration of nevirapine and vitamin C did not improve the histoarchitecture of the kidney.. Adjuvant treatment with kolaviron (an anti-oxidant) for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model.

Topics: Acute Kidney Injury; Animals; Anti-HIV Agents; Ascorbic Acid; Cytoprotection; Flavonoids; Kidney; Models, Animal; Nevirapine; Rats, Wistar; Reverse Transcriptase Inhibitors; Vitamins

To report a case of acute oxalate nephropathy related to vitamin C intake within the intensive care unit (ICU).. Case report.. ICU and nephrology department of a French university hospital.. A 57-year-old woman with septic shock related to Legionella pneumophila pneumonia complicated by acute respiratory distress syndrome and acute kidney injury who required renal replacement therapy for 75 days.. A renal biopsy was performed on day 72 because of persistent anuria and because the patient showed characteristic features of severe acute oxalate nephropathy. The only cause identified was vitamin C intake received during hospitalization within the ICU (~ 30 g over 2.5 months). At month 6 after ICU admission, estimated glomerular filtration rate was 24 mL/min/1.73m. Compelling evidence obtained from in-vitro and animal studies suggest that vitamin C, a circulating antioxidant, may be a valuable adjunctive therapy in critically-ill patients. Data from humans are more conflicting. Oxalate, a well-known metabolite of vitamin C, is excreted by the kidneys and can exert a toxic effect on epithelial cells and causes direct tubular damage, and/or it can crystallize within the tubular lumen. This case highlights an under-recognized secondary adverse event from vitamin C given to critically-ill patients. The use of high-dose vitamin C should be prescribed with caution in this population.
.

Topics: Acute Kidney Injury; Ascorbic Acid; Critical Illness; Female; Humans; Intensive Care Units; Kidney Diseases; Middle Aged; Oxalates; Renal Replacement Therapy

To evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model.. Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation.. NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III.. The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.

Topics: Acute Kidney Injury; Anesthesia, General; Anesthetics, Inhalation; Animals; Ascorbic Acid; Biomarkers; Disease Models, Animal; Male; Methyl Ethers; Random Allocation; Rats; Rats, Wistar; Sevoflurane; Vitamins

The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries.. In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7-month period (treatment group) with a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.. There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 h in the control group (P < .001).. Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Aged; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Controlled Before-After Studies; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Hydrocortisone; Intensive Care Units; Male; Middle Aged; Retrospective Studies; Sepsis; Shock, Septic; Thiamine; Treatment Outcome; Vasoconstrictor Agents; Vitamin B Complex

We report on a 75-year old woman who presented with acute oliguric renal failure. The kidney biopsy revealed calcium oxalate depositions in the tubular lumen, caused by an overload of intravenous ascorbic acid (cumulative dose of 240 g). Due to a lack of specific therapeutic interventions, the patient remained dialysis-dependent. Iatrogenic causes of kidney failure play an important role in the pathogenesis of kidney diseases and should always be considered in patients with acute renal failure. Detailed evaluation of the patient history is often suggestive, while renal biopsy can establish the diagnosis.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Calcium Oxalate; Female; Humans; Kidney; Oliguria; Vitamins

Topics: Acute Kidney Injury; Ascorbic Acid; Contrast Media; Humans; Vitamin E; Vitamins

Topics: Acute Kidney Injury; Ascorbic Acid; Contrast Media; Humans; Vitamin E; Vitamins

A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported.. A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. Laboratory test results revealed sustained hyperuricemia, which was believed to be due in part to tumor lysis, and a single dose of rasburicase 6 mg i.v. was administered. Subsequently, the patient experienced a decrease in oxygen saturation. Methemoglobinemia was suspected, and the patient's methemoglobin fraction was found to be 14.5%. The patient developed worsening shortness of breath and a drop in hemoglobin concentration, consistent with methemoglobinemia and hemolysis. Ascorbic acid 5 g i.v. every 6 hours was initiated for a total of six doses. Because the patient was assumed to have G6PD deficiency, which was later confirmed, methylene blue was avoided. Within 24 hours, the patient's oxygen saturation values and symptoms improved.. A patient with apparent rasburicase-induced methemoglobinemia and acute kidney injury was treated with i.v. ascorbic acid (5 g every six hours for six doses) because of the possibility, later proved, that he had G6PD deficiency. The methemoglobinemia resolved without worsening of renal function.

Topics: Acute Kidney Injury; Administration, Intravenous; Aged; Ascorbic Acid; Glucosephosphate Dehydrogenase Deficiency; Gout Suppressants; Humans; Male; Methemoglobinemia; Treatment Outcome; Urate Oxidase

A 15-year-old boy presented to emergency services with accidental naphthalene ball ingestion. Following consumption he developed methaemoglobinaemia, massive intravascular haemolysis and acute kidney injury. He had no history suggestive of congenital haemoglobin M disease. Development of severe methaemoglobinaemia and intravascular haemolysis is quite unusual after consumption of a single ball of naphthalene. The patient was managed with ascorbic acid and intravenous N-acetyl cysteine. He also required haemodialysis for acute kidney injury that developed secondary to pigment nephropathy.

Topics: Acute Kidney Injury; Adolescent; Antioxidants; Ascorbic Acid; Cysteine; Hemolysis; Humans; Male; Methemoglobinemia; Naphthalenes; Renal Dialysis

The use of polyethylene glycol (PEG)-based solutions is the gold standard for bowel preparation. However, PEG use might be associated with the risk of acute kidney injury.. We aimed to compare the safety of 2 L PEG plus ascorbic acid (AA) versus 4 L PEG.. Health examinees that underwent colonoscopy and blood tests on the same day at our center were included in this retrospective study. All subjects were prescribed either 2 L PEG plus AA or 4 L PEG for the bowel preparation prior to the colonoscopy. The incidences of electrolyte imbalance and renal impairment after colonic preparation were investigated. Renal impairment was determined if the subject's estimated glomerular filtration rate was measured less than 60 mL/min/1.73 m. Of the 29,789 cases, 14,790 received 2 L PEG plus AA (group A) and 14,999 received 4 L PEG (group B) for colonic preparation. Renal impairment occurred more commonly in group A (n = 467, 3.2 %) than in group B (n = 189, 1.3 %). Electrolyte changes such as hypernatremia and hyperkalemia were more common in group A than group B, whereas hyponatremia, hypokalemia, and hypophosphatemia were more common in group B than group A. Old age, male sex, and the use of 2 L PEG plus AA were independent risk factors for renal impairment.. The evidence strongly suggests that acute kidney injury is more likely to occur when 2 L PEG plus AA is used for the bowel preparation than when 4 L PEG is used.. KCT0001703.

Topics: Acute Kidney Injury; Adult; Age Factors; Ascorbic Acid; Cathartics; Colonoscopy; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypernatremia; Hypophosphatemia; Incidence; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies; Risk Factors; Sex Factors; Water-Electrolyte Imbalance

The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50mg/kg, I.M).. Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50mg/kg, I.M) and vitamin C (100mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50mg/kg, I.M) and vitamin E (250mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1β, interleukin-18, demsin and nepherin expressions in by reverse transcriptase-polymerase chain reaction (RT-PCR).. The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities.. The present data suggest that, vitamin C and vitamin E might play an important role in reducing oxidative stress and kidney damage induced by diclofenac sodium.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cytoprotection; Diclofenac; Disease Models, Animal; Kidney; Male; Oxidative Stress; Rats, Wistar; Uremia; Vitamin E

Nickel is an abundant carcinogenic and nephrotoxic metal whose activity leads to renal impairment. Previous studies have shown a protective effect of simultaneous vitamin C administration on acute and chronic nickel toxicity. However, very little research relating to the effect of vitamin C pretreatment in preventing nickel-induced acute nephrotoxicity is available. Therefore, the present study aimed to determine the efficiency of vitamin C (VC) pretreatment in preventing acute renal toxicity of nickel. Mice were pretreated orally with vitamin C (16.6 mg kg-1 body weight, b.w.) for seven consecutive days, prior to intraperitoneal (i.p.) administration of nickel chloride at different doses (3, 5, and 10 mg Ni kg-1 b.w.) for an exposure period of 24 hours. Thereafter, animals were killed and kidney tissue and blood samples were taken for histological examination and biochemical marker analyses. Vitamin C pretreatment alone did not alter the levels of serum kidney markers (creatinine, urea, and uric acid). However, treatment with Ni alone showed a significant increase in the levels of serum creatinine, urea, and uric acid with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney sections as compared to the control group. Pretreatment with vitamin C and treatment with Ni at all doses tested for 24 hours showed a significant decrease in the levels of serum creatinine, urea, and uric acid, as well as an improvement in histological changes compared to those previously seen in the group treated with Ni alone. It is concluded that vitamin C pretreatment effectively improved renal function and tissue damage caused by nickel.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Chemically-Induced Disorders; Kidney Function Tests; Male; Mice; Nickel; Protective Agents

The present study investigated the possible involvement of nitric oxide/soluble guanylyl cyclase (NO/sGC) pathway in ascorbic acid (AA)-mediated protection against acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia by occluding renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed in terms of measuring creatinine clearance (CrCl), blood urea nitrogen (BUN), plasma uric acid, potassium level, fractional excretion of sodium (FeNa), and microproteinuria. The NO level and oxidative stress in renal tissues were assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione level. AA (50 and 100 mg/kg, p.o.) was administered for 3 days before subjecting rats to AKI. In separate groups, the nitric oxide synthase inhibitor, L-NAME (20 mg/kg, i.p.) and sGC inhibitor, methylene blue (50 mg/kg, i.p.) was administered prior to AA treatment in rats. The significant decrease in CrCl and increase in BUN, plasma uric acid, potassium, FeNa, microproteinuria, and oxidative stress in renal tissues demonstrated ischemia-reperfusion-induced AKI in rats. The AA treatment ameliorated ischemia-reperfusion-induced AKI along with the increase in renal NO level. The pretreatment with L-NAME and methylene blue abolished protective effect of AA. It is concluded that AA protects against ischemia-reperfusion-induced AKI. Moreover, the NO/sGC pathway finds its definite involvement in AA-mediated reno-protective effect.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Creatinine; Drug Evaluation, Preclinical; Guanylate Cyclase; Kidney; Male; Nitric Oxide; Oxidative Stress; Proteinuria; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Soluble Guanylyl Cyclase; Uric Acid

Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.. A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.. Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).. In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidotes; Ascorbic Acid; Blighia; Colistin; Critical Illness; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sepsis; Young Adult

Oxidative stress has been implicated in the pathophysiology of many forms of acute renal failure. The aim was examine the effect of vitamin C on oxidative stress and its relationship with nitric oxide on gentamicin-induced nephrotoxicity in rats.. We utilized 32 Wistar rats allocated in four groups of eight animals each: control (CTL), vitamin C (VIT C), gentamicin (GENTA), and GENTA + VIT C; all groups were treated during seven days.. Serum urea and creatinine, serum and renal tissue malondialdehyde, blood superoxide anion and hydrogen peroxide in GENTA were increased vs CTL and vs VIT C, and decreased in GENTA + VIT C vs GENTA (all P < 0.05). Serum nitric oxide increased in GENTA vs CTL and vs VIT C, and reduced in GENTA + VIT C vs GENTA (P < 0.001). Urinary nitric oxide was reduced in GENTA vs CTL and vs VIT C and increased in GENTA + VIT C vs GENTA (P < 0.001). Severe degeneration of proximal tubules was present in GENTA, but only mild lesions were observed in GENTA + VIT C.. This study suggests that VIT C is a valuable tool to protect against GENTA-induced nephrotoxicity, by reducing reactive oxygen species and increasing the nitric oxide.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Creatinine; Gentamicins; Hydrogen Peroxide; Kidney; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

Ascorbic acid (AA) is an established antioxidant and has been used for treatment of various disorders. Recent reports suggest that administration of AA increases the level of steroids such as progesterone in the body. The present study investigated the protective role of progesterone against ischemia-reperfusion-induced acute kidney injury (AKI) and possible involvement of progesterone receptors in AA-mediated renoprotection in rats.. The male rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The rats were treated with progesterone (5 and 10 mg/kg, intraperitoneally) and AA (500 mg/kg, intraperitoneally for 1, 2, and 5 d) before AKI. In separate groups, mifepristone, the progesterone receptor antagonist was administered to rats before progesterone (10 mg/kg) and AA treatment (5 d). Various parameters including creatinine clearance, serum urea, uric acid, potassium level, fractional excretion of sodium, lactate dehydrogenase, and microproteinuria were used to assess kidney injury. Moreover, renal tissues were subjected to quantification of oxidative stress and evaluation of histopathologic changes.. The exogenous administration of progesterone afforded protection against AKI in a dose-dependent manner that was abolished by mifepristone. The administration of AA for 1, 2, and 5 d induced significant increase in serum progesterone levels and afforded protection against AKI. The antioxidant and renoprotective effect of AA was abolished by prior treatment with mifepristone.. It is concluded that exogenous administration of progesterone exerts significant antioxidant and renoprotective effect. Moreover, the progesterone receptors find their explicit involvement in AA-mediated renoprotection against ischemia-reperfusion-induced AKI in rats.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Iron; Male; Oxidative Stress; Potassium; Progesterone; Rats; Receptors, Progesterone; Reperfusion Injury; Urea; Uric Acid

There is an interaction between many cell types involved in the pathophysiology of ischemic acute renal failure. Nitric oxide (NO) precursors, especially l-arginine, may have protective effects on tissue ischemia/reperfusion injury (IRI); however, their molecular mechanisms are unclear. In the present study, the interaction between l-arginine, cyclo-oxygenase (COX)-2 and reactive oxygen species (ROS) in the pathogenesis of ischemic acute renal failure was investigated.. Ischemia/reperfusion injury model in rats was used and various biochemical parameters examined. The rat isolated aortic rings served as model for hypoxia/reoxygenation where endothelium dependent and independent relaxations were exerted.. Pre-treatment of rats subjected to IRI with l-arginine (125mg/kg) significantly reduced kidney MDA levels, elevated kidney SOD activity, GSH level and total NO levels at 24 and 48h after reperfusion. Kidney COX-2 level was only different in the l-arginine-treated group 48h after reperfusion compared to the IRI group. Pre-treatment with l-arginine (10(-2)M) alone or in combination with celecoxib significantly potentiated the acetylcholine (Ach)-induced relaxations in control and hypoxic rings. The effect of the combination was synergistic only in hypoxic rings. Addition of ascorbic acid to the celecoxib-arginine combination did not produce further potentiation. Sodium nitroprusside-induced relaxations in control and hypoxic rings were potentiated by l-arginine or celecoxib-arginine combination but not by ascorbic acid.. The protective effect of l-arginine may result from the interaction between NO and ROS and increased NO bioavailability. The protective effects of combined celecoxib and l-arginine against IRI could be attributed to their antioxidant activity which exceeded that of ascorbic acid.

Topics: Acetylcholine; Acute Kidney Injury; Animals; Antioxidants; Aorta; Arginine; Ascorbic Acid; Celecoxib; Cyclooxygenase 2; Drug Synergism; Kidney Function Tests; Nitric Oxide; Nitroprusside; Rats; Reactive Oxygen Species; Reperfusion Injury

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Catalase; Cisplatin; Creatinine; Glutathione; Glutathione Peroxidase; Injections, Intraperitoneal; Kidney; Male; Mice; Oxidative Stress; Pioglitazone; PPAR gamma; Protective Agents; Superoxide Dismutase; Thiazolidinediones

The present study investigated the protective role of antioxidant (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), an organoselenium compound, against the renal injury induced by cisplatin in rats. Canola oil or BPD (50 mg kg(-1)) was administered orally by gavage once a day for 6 days to rats. The first dose of BPD was given 24 h before a single intraperitoneal injection of saline or cisplatin (7 mg kg(-1)). At day 7, animals were killed and parameters related to renal injury were determined. The histological analysis showed that cisplatin caused renal injury in rats, which was accompanied by an increase in urea and creatinine levels in plasma. The increase of plasma creatinine levels negatively correlated with renal antioxidant defenses including ascorbic acid (AA) and reduced glutathione (GSH) content as well as glutathione S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) activities. As revealed by histological analysis, BPD ameliorated tubular injury in rat kidney and reduced plasma markers altered by cisplatin. The administration of BPD to rats attenuated the reduction of renal AA and GSH content in animals exposed to cisplatin. The decrease of GST activity, but not GPx and CAT activities, in rats exposed to cisplatin was totally reversed by BPD administration. BPD was also effective in attenuating the inhibition of a sulfhydryl enzyme sensitive to oxidative stress, δ-aminolevulinic dehydratase, in kidneys of rats exposed to cisplatin. The present study demonstrated that BPD reduced renal injury induced by cisplatin in rats and this effect seems to be related to antioxidant mechanisms.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Catalase; Cisplatin; Creatinine; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Injections, Intraperitoneal; Kidney; Male; Organoselenium Compounds; Oxidative Stress; Rats; Rats, Wistar

Oxalate nephropathy is a rare condition characterized by extensive calcium oxalate deposition in the renal tubules, resulting in kidney injury. There are primary forms of the disease that arise from genetic mutation causing overproduction of oxalate. More commonly, this condition is seen as a secondary phenomenon. The clinical presentation is nonspecific, with acute kidney injury and normal serologic study results. The characteristic finding on kidney biopsy is the presence of acute tubular injury associated with polarizable crystals in the tubular lumen and epithelial cytoplasm. We present a case of acute oxalate nephropathy in a patient with underlying systemic lupus erythematosus who recently received intravenous vitamin C.

Topics: Acute Kidney Injury; Administration, Intravenous; Ascorbic Acid; Complementary Therapies; Female; Humans; Hyperoxaluria; Lupus Erythematosus, Systemic; Middle Aged; Vitamins

Topics: Acute Kidney Injury; Ascorbic Acid; Contrast Media; Coronary Angiography; Humans; Protective Agents; Vitamins

Although cisplatin has been a mainstay for cancer therapy, its use is limited mainly because of nephrotoxicity. Accumulating literature suggest the antioxidant and cytoprotective effect of metformin, a first line antidiabetic drug. With this background, we investigated the effect of metformin on the cisplatin induced nephrotoxicity in rats. A single injection of cisplatin (7.5 mg/kg, i.p.) caused marked renal damage, characterized by a significant increase in blood urea nitrogen (BUN), serum creatinine (Cr) and abnormal histo-architecture of kidney. These were accompanied by significant elevation of malondialdehyde (MDA), total reactive oxygen species (tROS) and caspase-3 levels and decreased antioxidant levels. Metformin treatment significantly attenuated the increase in malondialdehyde and tROS generation and restores the decrease in both enzymatic and non-enzymatic antioxidants. However metformin treatment did not prevent the cisplatin induced renal injury as there was no significant difference of renal function parameters (BUN and Cr), kidney histopathology as well as caspase-3 activity between cisplatin per se and metformin plus cisplatin treated rats. Histopathology studies revealed that similar glomerular and tubular pathological architecture in both cisplatin per se and cisplatin plus metformin group. In conclusion, the present study demonstrated that metformin is not an adjuvant drug to treat nephrotoxicity associated with cisplatin therapy.

Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cisplatin; Glutathione; Kidney; Kidney Function Tests; Lipid Peroxidation; Male; Metformin; Rats; Rats, Wistar; Reactive Oxygen Species

Since gentamicin-induced nephrotoxicity has very important clinical consequences, different potentially therapeutic approaches to prevent or attenuate it have been proposed. Accordingly, this study aimed at determining the possible protective effects of vitamin C against gentamicin-associated acute kidney injury. Experiments were done on 40 adult Wistar rats divided into four groups of 10 animals each. G-group received gentamicin (100 mg/kg) while GVC-group received the same dose of gentamicin and vitamin C (200 mg/kg) by intraperitoneal injections on a daily basis. Animals in VC-group, serving as a positive control, received only vitamin C (200 mg/kg), and those in C-group, serving as a negative control, received saline (1 ml/day), both given intraperitoneally. All groups were treated during 8 consecutive days. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations of kidney were performed by histopathological, morphometrical and biochemical analyses in order to determine potential beneficial effects of vitamin C co-administration with gentamicin. In G-group the proximal convoluted tubules showed cytoplasm vacuolation with dark inclusions in the epithelial cells and coagulation-type necrosis, while in GVC-group necrosis was not observed. The glomerular basement membrane was significantly thickened (p<0.05) in G-group animals than in other groups. Nuclear optical density of the tubular epithelial cells in GVC-group was significantly higher (p<0.05) compared to G-group. Blood urea and serum creatinine concentration were significantly elevated, while potassium concentration was lowered in G-group compared to other groups (p<0.01 for each). Concomitant administration of gentamicin and vitamin C resulted in a significant reduction of morphological and functional kidney alterations.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Cell Nucleus; Cytoprotection; Epithelial Cells; Female; Gentamicins; Kidney Tubules, Distal; Kidney Tubules, Proximal; Male; Necrosis; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species

The aim of this study was to investigate the preventive effects of melatonin and vitamin C as antioxidants on renal injury in chronic alcohol consumption.. A total of 24 adult male Wistar rats weighing 200-250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C; and Group IV: rats were fed on alcohol and 4 mg/kg melatonin.. Light microscopic examination revealed atrophic renal corpuscles, dilatation and congestion of the peritubular vessels, and renal corpuscles with obscure Bowman's space and a few foamy-appearing tubules due to alcohol consumption were observed. Expression of endothelial nitric oxide synthase (eNOS) was localized to glomerulus, distal, and collector tubules. eNOS staining decreased in alcohol treatment group and melatonin and vitamin C encore increased expression pattern of eNOS. Alcohol consumption increased malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities significantly in the alcohol consumption groups compared with that in the control group, while in melatonin give group just MDA level was decreased statistically significant and SOD and CAT activities were also decreased numerically compared with the alcohol consumption groups.. These results indicated that chronic alcohol consumption caused renal damage by increased lipid peroxidation and melatonin and vitamin C administration produced in some degree protection against alcohol-induced damage.

Topics: Acute Kidney Injury; Alcoholic Intoxication; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Ethanol; Immunohistochemistry; Kidney; Lipid Peroxidation; Male; Melatonin; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Wistar; Vitamins

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Contrast Media; Female; Humans; Male; Premedication

Topics: Acetylcysteine; Acute Kidney Injury; Adult; Ascorbic Acid; Charcoal; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Diuretics; Fatal Outcome; Furosemide; Gastric Lavage; Hemoperfusion; Humans; Immunosuppressive Agents; Male; Paraquat; Poisoning; Pulmonary Fibrosis; Respiration, Artificial; Respiratory Insufficiency; Rhabdomyolysis; Suicide, Attempted; Vitamin E

Following our long-standing interest in the mechanisms involved in selenium toxicity, the aim of this work was to extend our previous studies to gain a better understanding of mercuric chloride (HgCl₂) + diphenyl diselenide (PhSe)₂ toxicity. Mice received one daily dose of HgCl₂ (4.6 mg kg(-1) , subcutaneously) for three consecutive days. Thirty minutes after the last injection of HgCl₂, mice received a single dose of (PhSe)₂ (31.2 mg kg(-1) , subcutaneously). Five hours after (PhSe)₂ administration, mice were euthanized and δ-aminolevulinate dehydratase, catalase (CAT), glutathione S-transferase (GST) and Na(+) , K(+) -ATPase activities as well as thiobarbituric acid-reactive substances (TBARS), ascorbic acid and mercury levels were determined in kidney and liver. Parameters in plasma (urea, creatinine, protein and erythropoietin), whole blood (hematocrit and hemoglobin) and urine (protein) were also investigated. HgCl₂ + (PhSe)₂ exposure caused a decrease in renal GST and Na(+) , K(+) -ATPase activities and an increase in renal ascorbic acid and TBARS concentrations when compared with the HgCl₂ group. (PhSe)₂ potentiated the increase in plasma urea caused by HgCl₂. HgCl₂ + (PhSe)₂ exposure caused a reduction in plasma protein levels and an increase in hemoglobin and hematocrit contents when compared with the HgCl₂ group. There was a significant reduction in hepatic CAT activity and an increase in TBARS levels in mice exposed to HgCl₂ + (PhSe)₂ when compared with the HgCl₂ group. The results demonstrated that (PhSe)₂ did not modify mercury levels in mice. In conclusion, (PhSe)₂ potentiated damage caused by HgCl₂ affecting mainly the renal tissue.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Benzene Derivatives; Catalase; Creatinine; Erythropoietin; Glutathione Transferase; Kidney; Liver; Male; Mercuric Chloride; Mercury; Mice; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Thiobarbituric Acid Reactive Substances; Urea

This study investigated the role of reactive oxygen species (ROS) in the pathogenesis of triptolide-induced renal injury in vivo. Rats were randomly divided into 4 groups (n=5 in each): triptolide group in which the rats were intraperitoneally injected with triptolide solution at a dose of 1 mg/kg of body weight on day 8; control group in which the rats received a single intraperitoneal injection of 0.9% physiological saline on day 8; vitamin C group in which the rats were pretreated with vitamin C by gavage at a dose of 250 mg/kg of body weight per day for 7 days before the same treatment as the control group on day 8; triptolide+vitamin C group in which the rats were first subjected to an oral administration of vitamin C at a dose of 250 mg/kg of body weight per day for 7 days, and then to the same treatment as the triptolide group on day 8. All the rats were sacrificed on day 10. Blood samples were collected for detection of plasma creatinine (Pcr) and plasma urea nitrogen (PUN) concentrations. Both kidneys were removed. The histological changes were measured by haematoxylin-eosin (HE) staining. The production of ROS was determined by detecting the fluorescent intensity of the oxidation-sensitive probe rhodamine 123 in renal tissue. Renal malondialdehyde (MDA) content was measured to evaluate lipid peroxidation level in renal tissue. TUNEL staining was performed to assess apoptosis of renal tubular cells. Renal expression of apoptosis-related proteins Bcl-2, Bax, Bid, Bad, Fas and FasL, as well as corresponding encoding genes were assessed by Western Blotting and real-time PCR. The results showed that triptolide treatment promoted the generation of a great amount of ROS, up-regulated the expression of Bax, Bid, Bad, Fas and FasL at both protein and mRNA levels, as well as the ratio of Bax to Bcl-2, and caused the apoptosis of renal tubular cells and renal injury. However, pretreatment with an antioxidant, vitamin C, significantly reduced the generation of ROS and effectively inhibited the triptolide-induced apoptosis of renal tubular cells and renal injury. It was concluded that ROS plays a critical role in triptolide-induced apoptosis of renal tubular cells and renal injury. The protective administration of vitamin C may help alleviate triptolide-induced renal injury and nephrotoxicity.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Ascorbic Acid; Diterpenes; Epoxy Compounds; Kidney Tubules; Male; Phenanthrenes; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups: group 1 (control; dissection of the right renal pedicle without nephrectomy), group 2 (sham operated; unilateral nephrectomy), group 3 (I/R; unilateral nephrectomy + I/R); and group 4 (AA+I/R; unilateral nephrectomy and I/R treated with ascorbic acid, 250mg kg(-1) i.p., for one hour prior to ischemia). On the 15th day following nephrectomy, groups 3 and 4 were subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. At the end of the treatment period, kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Glutathione; Lipid Peroxidation; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Higher doses of antioxidant vitamins C and E have been proved to be effective against cisplatin-induced nephrotoxicity in animals. However, the possible effective equivalent dose in human was found to be higher than that of the upper tolerable intake level (UL) for these vitamins. Hence, the current study was aimed to evaluate the protective effect of co-supplementation of single and multi doses of vitamins C and E against cisplatin-induced acute renal failure in mice. Single dose of vitamin C (500 mg/kg), vitamin E (500 mg/kg), and vitamin C plus vitamin E (250 mg/kg each) were administered orally 1 h prior to cisplatin (12 mg/kg, i.p) injection, whereas in a multidose study they were administered 1 h prior, and 24 and 48 h after the cisplatin injection. Serum urea and creatinine levels were estimated 72 h after the injection of cisplatin. Renal concentrations of glutathione (GSH) and malondialdehyde (MDA) were also determined. Co-supplementation of vitamins significantly protected the cisplatin-induced increased levels of serum urea, creatinine, renal MDA, and the declined renal GSH level. Administration of single and multi doses of vitamin C plus E (250 mg/kg each) rendered significant nephroprotection. Therefore, accounting for the rare side effect from high intake of vitamins C and E observation of this study indicates that a multidose combination therapy of these vitamins at their lower doses can be effective in protecting the cisplatin-induced renal damage. The protection is partially mediated through the antioxidant effect of the vitamins.

Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cisplatin; Glutathione; Male; Malondialdehyde; Mice; Vitamin E

In this study we postulated that during acute renal failure induced by gentamicin the transient or dynamic response of blood vessels could be affected, and that antioxidants can prevent the changes in dynamic responses of blood vessels. The new approach to ex vivo blood vessel experiments in which not only the end points of vessels response within the time interval is considered, but also dynamics of this response, was used in this paper. Our results confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals. The beneficial effects of vitamin C administration to gentamicin-treated animals are also confirmed through: lower level of blood urea and creatinine and higher level of potassium. The pressure dynamic responses of isolated blood vessels show a faster pressure change in gentamicin-treated animals (8.07 +/- 1.7 s vs. 5.64 +/- 0.18 s). Vitamin C administration induced slowdown of pressure change back to the control values. The pressure dynamic properties, quantitatively defined by comparative pressure dynamic and total pressure dynamic, confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals and beneficial effects of vitamin C administration.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Blood Vessels; Creatinine; Gentamicins; Kidney; Potassium; Rats; Sodium; Urea

The production of free radicals can cause renal injury and play a role in the pathogenesis of acute renal failure (ARF). The indirect markers of reactive oxygen species (ROS) were evaluated in children with ARF and controls. Forty patients with ARF aged 0-10 years were selected. Twenty age- and gender-matched healthy children were included as controls. Plasma malondialdehyde, protein carbonyl, nitrite, copper, ascorbic acid, zinc, and ceruloplasmin levels were estimated in patients with ARF and controls. The plasma malondialdehyde (p < 0.01), copper (p < 0.001), ascorbic acid (p < 0.05), and ceruloplasmin (p < 0.001) levels were significantly raised in ARF patients in comparison with controls. Significantly higher levels of plasma malondialdehyde (p < 0.01), nitrite (p < 0.001), copper (p < 0.001), and ceruloplasmin (p < 0.001) and lower plasma zinc (p < 0.01) were found in ARF nonsurvivors in comparison with survivors. The cutoff levels of plasma nitrite and ceruloplasmin were found to be most accurate in predicting mortality in ARF patients and had maximum sensitivity (100%) and specificity (60.7%) among the parameters studied. In conclusion, the increased levels of oxidants and antioxidants suggest the production of ROS and their possible role in ARF pathogenesis. Plasma nitrite and ceruloplasmin concentrations demonstrated predictive ability in relation to mortality.

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Biomarkers; Ceruloplasmin; Child; Child, Preschool; Copper; Female; Humans; Infant; Infant, Newborn; Male; Malondialdehyde; Nitrites; Predictive Value of Tests; Protein Carbonylation; Reactive Oxygen Species; Zinc

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Biopsy, Needle; Disease Models, Animal; Glycerol; Immunohistochemistry; Kidney Function Tests; Kidney Tubular Necrosis, Acute; Male; Malondialdehyde; Myoglobinuria; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Rhabdomyolysis; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Although daily ingestion of high-dose vitamin C is generally regarded as largely innocuous, fatal nephrotoxicity can occur in some rare circumstances. We report a case where the patient, who chose to forgo any advanced conventional medical intervention (dialysis and mechanical ventilation), had failed to disclose his use of high-dose vitamin C and subsequently died. Intra-renal oxalate crystal deposition was demonstrated at autopsy. Directed enquiry with the family then revealed his high-dose vitamin C usage. Even though fully-informed discussion was limited by incomplete prospective disclosure, it remains the prerogative of any competent patient to decline any treatment, including those that may be considered life-saving.

Topics: Acute Kidney Injury; Aged; Ascorbic Acid; Blood Chemical Analysis; Critical Illness; Drug Overdose; Fatal Outcome; Humans; Male; Treatment Refusal; Vitamins

Topics: Acetylcysteine; Acute Kidney Injury; Antioxidants; Ascorbic Acid; Biomarkers; Cell Death; Cell Hypoxia; Consensus; Contrast Media; Creatinine; Epithelial Cells; Fluid Therapy; Humans; Inflammation; Infusions, Intravenous; Kidney Tubules; Multicenter Studies as Topic; Oxidative Stress; Practice Guidelines as Topic; Protective Agents; Randomized Controlled Trials as Topic; Renal Circulation; Treatment Outcome

Cisplatin is a widely used antineoplastic agent that exhibits dose limiting nephrotoxicity. We have previously shown that the administration of cisplatin results in decrease in the activities of renal brush border membrane (BBM) enzymes and transport of inorganic phosphate (Pi) across BBM vesicles. In the present study we have investigated the effect of pre-treatment with vitamin C (ascorbic acid) on cisplatin-induced nephrotoxicity and changes in BBM enzymes and Pi transport. Administration of a single dose of cisplatin (6 mg/kg body weight) caused nephrotoxicity in rats that manifested biochemically as an elevation of serum urea nitrogen and creatinine levels. Treatment of rats with a single dose of vitamin C, six hours prior to administration of cisplatin, protected the kidney from the damaging effect of cisplatin. Vitamin C pre-treatment significantly decreased the urea nitrogen and creatinine levels. It attenuated the cisplatin-induced reduction in the activities of BBM and anti-oxidant enzymes and also Pi transport. These results suggest that vitamin C is an effective chemoprotectant against cisplatin-induced acute renal failure and dysfunction of the renal BBM in rats.

Topics: Acute Kidney Injury; Alkaline Phosphatase; alpha-Glucosidases; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Catalase; Cisplatin; Creatinine; Disease Models, Animal; Dose-Response Relationship, Drug; Enzymes; gamma-Glutamyltransferase; Kidney; Kidney Cortex; Leucyl Aminopeptidase; Lipid Peroxidation; Male; Microvilli; Phosphates; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase

Contrast media-associated acute renal failure represents the third most common cause of in-hospital renal function deterioration after decreased renal perfusion and post-operative renal insufficiency. Although generally benign, this complication is associated with a mortality rate ranging from 3.8 to 64%, depending on the increase of creatinine concentration. Multiple drugs have been tested in an attempt to prevent this complication. Central to the pathophysiology of contrast-induced nephrotoxicity (CIN) is an alteration in renal hemodynamics. In an effort to reverse these hemodynamic changes, vasodilators and diuretics have been tested as prophylactic drugs. However, their effectiveness has not been confirmed. Recently, considerable interest has resulted from the initial positive data on the effectiveness of prophylactic administration of antioxidant compounds, such as acetylcysteine and ascorbic acid. In this review, we focus on the effectiveness of pharmacologic therapies for preventing CIN.

Topics: Acetylcysteine; Acute Kidney Injury; Antioxidants; Ascorbic Acid; Calcium Channel Blockers; Contrast Media; Dopamine; Humans; Kidney; Kidney Diseases; Randomized Controlled Trials as Topic; Vasoconstriction

Peroxisome proliferator activated receptor-gamma (PPAR-gamma), a nuclear transcription factor, modulates angiotensin II (AII) or thromboxane A(2) (TxA(2)) response in the vasculature via transcriptional regulation of their gene or receptor expression. Increased AII or TxA(2) vasoconstriction and deteriorating renal function observed in glycerol-induced acute renal failure (ARF) may be attributed to a down-regulated PPAR-gamma expression/activity probably via an increased free radical generation. In this study, we investigated the effect of PPAR-gamma induction in glycerol-induced ARF by examining renal vascular reactivity to AII and TxA(2) and by renal expression/activity of PPAR-gamma. Vascular responses to AII or U46619, a TxA(2) mimetic were determined in rat isolated perfused kidney following induction of ARF with glycerol (50%, v/v, i.m.). Extent of renal damage and function were assessed with or without pre-treatment with ciglitazone (9 nmol kg(-1) x 21 days), a PPAR-gamma inducer. In ARF, vasoconstriction was enhanced to AII (three-fold; p<0.05) and U46619 (82%; p<0.05). Ciglitazone reduced AII and U46619 vasoconstriction by 59+/-1% (p<0.05) and 56+/-1% (p<0.05), respectively. Ciglitazone reduced proteinuria (38+/-3%) which was two-fold higher in ARF. Similarly, ciglitazone enhanced Na(+) excretion by 1.5 times while reducing BUN by 49+/-6%. On the contrary, ciglitazone did not change plasma creatinine which was significantly higher in ARF rats. Ciglitazone reduced free radical generation by 30+/-3% while elevating nitrite excretion approximately 2-fold. PPAR-gamma expression and activity were significantly lower in ARF rats and ciglitazone enhanced PPAR-gamma protein expression and activity by 45+/-3% and 52+/-4%, respectively. Data from this study suggest that reduced PPAR-gamma expression and activity may be involved in the pathology of glycerol-induced ARF and induction of PPAR-gamma by ciglitazone confers protection through reduced AII and TxA(2) vasoconstriction and/or enhanced renal function via reducing free radical generation.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acute Kidney Injury; Angiotensin II; Animals; Ascorbic Acid; Clofibrate; Down-Regulation; Free Radicals; Glycerol; Kidney; Male; Nitric Oxide; Nitriles; PPAR gamma; Rats; Rats, Sprague-Dawley; Renal Circulation; Thiazolidinediones; Thromboxane A2; Vasoconstriction

To elucidate the role of peripheral dopamine D1 receptors in cisplatin-induced acute renal injury, effect of zelandopam (YM435, (-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a selective renal dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats was studied. Rats were divided into six groups: control, cisplatin and cisplatin plus zelandopam (30, 100, 300 mg/kg p.o. twice, 75 and 15 min before cisplatin injection) or the free radical scavenger CV-3611 (2-O-octadecylascorbic acid, 10 mg/kg p.o., 75 min before cisplatin injection) treated groups. Rats received intraperitoneal injection of cisplatin at a dose of 5 mg/kg. Four days after cisplatin injection, plasma creatinine, blood urea nitrogen and body weight were measured and the kidneys were removed for histological examination. Cisplatin induced acute renal failure characterized by the increases in plasma creatinine and blood urea nitrogen with tubular damage, and decreased body weight. Zelandopam dose-dependently prevented all these changes. The free radical scavenger CV-3611 significantly attenuated a decrease in body weight and renal dysfunction without reducing tubular damage. The present study is the first demonstration for that a selective dopamine D1 receptor agonist is effective in preventing acute renal failure induced by cisplatin.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Epithelial Cells; Isoquinolines; Kidney Tubules; Male; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Tetrahydroisoquinolines

Topics: Acute Kidney Injury; Antioxidants; Ascorbic Acid; Humans; Hydrogen-Ion Concentration; Myoglobin; Oxidation-Reduction; Rhabdomyolysis; Urinalysis

This study aims to investigate the role of oxidants in cisplatin-induced nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single dose (5 mg/kg) and guinea pigs were killed either after 24 h or 7 days. The same experiment was performed using animals treated with vitamins C and E combination and a natural antioxidant extract (SARMEX). The kidneys were then removed to be used in the analyses. Blood samples were also obtained from the animals to be used in routine biochemical assays. Twenty-four hours after treatment there was a significant decrease in the renal activities of total superoxide scavenger activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic activities was far greater, while the increase in blood urea (BUN) and creatinine (CRE) was marked. Treatment with antioxidants causes significant increases in renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24 h and 7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH-Px) activity and decreases renal MDA (24 h and 7 day), blood BUN (7 day) and CRE (7 day) levels. Our results suggest that cisplatin treatment impairs both enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the renal tissue, which leads to kidney failure. Antioxidant supplementation strengthens the renal antioxidant system, eliminates oxidation reactions, and prevents cisplatin-induced kidney failure.

Topics: Acute Kidney Injury; Animals; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Catalase; Cisplatin; Creatinine; Female; Glutathione Peroxidase; Guinea Pigs; Kidney; Malondialdehyde; Superoxide Dismutase; Vitamin E

Topics: Acute Disease; Acute Kidney Injury; Adenocarcinoma; Anuria; Ascorbic Acid; Humans; Infusions, Intravenous; Kidney Calculi; Male; Middle Aged; Oxalates; Prostatic Neoplasms

Topics: Acute Kidney Injury; Adult; Ascorbic Acid; Biopsy; Calcium Oxalate; Humans; Kidney; Kidney Diseases; Male; Renal Dialysis

Cortinarius poisoning is generally caused by orellanine, a hydroxy bipyridine N, N-dioxide. This intoxication is characterized by acute nephritis which can lead to death without treatment. We reported a highly sensitive and simple fluorimetric technique to analyse orellanine by thin-layer chromatography on the basis of its characteristic photodecomposition into orelline. Using this procedure, we detected and assayed orellanine for the first time in plasma and renal biopsies of a woman who had deliberately ingested two fruit-bodies of Cortinarius orellanus. An early original treatment was carried out based on hemodialysis, combination plasmapheresis-hemoperfusion, and amino acids and diltiazem administration. These results indicate that it is now possible to make a precise diagnosis of orellanine poisoning.

Topics: 2,2'-Dipyridyl; Acute Disease; Acute Kidney Injury; Adult; Agaricales; Amino Acids; Ascorbic Acid; Biopsy; Chromatography, Thin Layer; Combined Modality Therapy; Diltiazem; Dopamine; Female; Fluorometry; Furosemide; Hemoperfusion; Humans; Kidney; Mushroom Poisoning; Mycotoxins; Photochemistry; Plasmapheresis; Renal Dialysis

Oxygen free radicals have recently been found to mediate cell injury after ischemia in the kidney. We sought to determine whether oxygen free radicals mediate damage in mercuric chloride (HgCl2)-induced acute renal failure, a toxic model of acute renal failure. Neither superoxide dismutase nor allopurinol, which scavenges or inhibits production of superoxide radical, respectively, provided protection against renal dysfunction after HgCl2. Similarly, the hydroxyl radical scavengers tryptophan, N-acetyl-tryptophan, and ascorbic acid were unable to protect against HgCl2. However, dimethylthiourea and dimethyl sulfoxide, both hydroxyl radical scavengers, were beneficial. Dimethylthiourea completely prevented the rise in plasma creatinine concentration after HgCL2. In control rats plasma creatinine concentration rose from 0.4 mg/dl to 3.2 +/- 0.8, 5.1 +/- 1.0, and 6.1 +/- 1.6 mg/dl at 24, 48, and 72 hours after HgCl2. Dimethylthiourea-treated rats had plasma creatinine concentration less than 0.5 mg/dl at all times. Furthermore, a mixture of HgCl2 and equimolar amounts of dimethylthiourea was less toxic than HgCl2 alone. Dimethyl sulfoxide attenuated the HgCl2-induced rise in creatinine concentration: 1.3 +/- 0.2, 3.2 +/- 0.3, and 3.1 +/- 0.2 mg/dl at 24, 48, and 72 hours after HgCl2. Measurement of kidney malondialdehyde content after HgCl2 provided no evidence for oxygen free radical-mediated lipid peroxidation. We conclude that there is no convincing role for oxygen free radicals in the pathogenesis of HgCl2-induced acute renal failure. The ability of dimethylthiourea and dimethyl sulfoxide to protect against HgCl2-induced renal dysfunction may be related to their ability to form complexes with Hg2+.

Topics: Acute Kidney Injury; Allopurinol; Animals; Ascorbic Acid; Creatinine; Dimethyl Sulfoxide; Drug Interactions; Kidney Cortex; Lipid Peroxides; Male; Mercuric Chloride; Rats; Superoxide Dismutase; Thiourea; Tryptophan

A single 45-g dose of intravenous ascorbic acid, a metabolic precursor of oxalate, was administered to a patient as adjuvant therapy for primary amyloidosis and the nephrotic syndrome. Acute oliguric renal failure occurred. Postmortem histopathologic examination of renal tissue revealed extensive intratubular deposition of crystalline material, which was confirmed as calcium oxalate by a microincineration technique. There were no extrarenal deposits of calcium oxalate. Plasma oxalate and ascorbic acid concentrations were increased. We conclude that therapy with high-dose ascorbic acid is a potential cause of oxalate nephropathy.

Topics: Acute Kidney Injury; Ascorbic Acid; Calcium Oxalate; Female; Humans; Injections, Intravenous; Kidney Tubules; Middle Aged

Topics: Acute Kidney Injury; Adult; Ascorbic Acid; Biotransformation; Female; Humans; Oxalates; Parenteral Nutrition; Parenteral Nutrition, Total

Topics: Acute Kidney Injury; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Crush Syndrome; Hypothalamus; Male; Pituitary Gland; Rats; Shock, Traumatic; Time Factors

Topics: Acute Kidney Injury; Ascorbic Acid; Humans; Kidney; Kidneys, Artificial; Renal Dialysis