• Acute kidney injury
• COVID-19
• Histopathology
• Incidence
• Outcomes
• Pathophysiology
• Risk factors
• SARS-CoV-2

• Acute Kidney Injury/epidemiology
• Acute Kidney Injury/pathology
• Acute Kidney Injury/etiology
• Acute Kidney Injury/physiopathology
• Acute Kidney Injury/virology
• Acute Kidney Injury/therapy
• Humans
• COVID-19/complications
• COVID-19/epidemiology
• COVID-19/pathology
• Risk Factors
• Incidence
• SARS-CoV-2
• Kidney/pathology
• Kidney/virology

• Crystalline retinopathy
• Occlusive retinopathy
• Oxalate
• Phosphorus
• Vision loss

• Ascorbic Acid/chemistry
• Ascorbic Acid/pharmacology
• Hydrogen Peroxide/chemistry
• Mice
• Macrophages/metabolism
• Macrophages/drug effects
• Animals
• Cell Line, Tumor
• RAW 264.7 Cells
• Humans
• Ferric Compounds/chemistry
• Ferric Compounds/pharmacology
• Female
• Hydroxyl Radical/chemistry
• Hydroxyl Radical/metabolism
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/metabolism

• P30 CA177558 NCI NIH HHS
• R01 EB026893 NIBIB NIH HHS
• R21 AR078447 NIAMS NIH HHS
• National Institute of Biomedical Imaging and Bioengineering
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
• National Science Foundation
• National Cancer Institute

• Acute kidney injury
• Ascorbic acid
• Ischemia-reperfusion injury
• Vitamin C

• Humans
• Rats
• Animals
• Rats, Sprague-Dawley
• Kidney
• Oxidative Stress
• Acute Kidney Injury/metabolism
• Ascorbic Acid/pharmacology
• Ascorbic Acid/therapeutic use
• Ascorbic Acid/metabolism
• Reperfusion Injury/pathology
• Antineoplastic Agents/pharmacology
• Inflammation/metabolism
• Ischemia/metabolism
• Creatinine

• urology
• microbiome
• renal calculi

• Humans
• Vitamins/therapeutic use
• Calcium
• Gastrointestinal Microbiome
• Kidney Calculi
• Urolithiasis
• Vitamin A
• Vitamin K

• COVID-19
• Vitamin C
• antioxidant
• neurodegenerative
• scurvy

• Humans
• Ascorbic Acid/therapeutic use
• COVID-19/epidemiology
• Pandemics
• Vitamins/therapeutic use
• Antioxidants/therapeutic use

• Anti-cancer mechanism
• Cancer therapy
• Clinical application
• Pre-clinical application
• Vitamin C

• acute kidney injury
• alternative medicine
• secondary hyperoxaluria
• vitamin C nephrotoxicity

• Female
• Humans
• Aged
• Ascorbic Acid/adverse effects
• Hyperoxaluria
• Vitamins/adverse effects
• Kidney Failure, Chronic/therapy
• Complementary Therapies

• COVID-19
• Dietary supplement
• HIF-1α, Hypoxia-inducible factor-1α
• IFN-α, Intererferon alfa
• INF-β, Interferon beta
• Immune system
• NK, Natural killer
• PUFAs, Polyunsaturated fatty acids
• RCTs, Randomized controlled trials
• RDA, Recommended Dietary Allowance
• SARS-CoV-2, Severe Acute Respiratory Syndrome-Coronavirus-2
• TNF-α, Tumor necrosis factor alpha
• Vitamin C
• Zn
• Zn, Zinc

• ACE2
• Acute kidney injury
• COVID-19
• SARS-CoV-2
• TMPRSS2

• Acute Kidney Injury/etiology
• COVID-19/complications
• Humans
• Kidney
• Peptidyl-Dipeptidase A
• SARS-CoV-2

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances and signaling aberrations, can promote carcinogenesis and malignant progression by inducing gene mutations and activating pro-oncogenic signaling, providing a possible rationale for targeting oxidative stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy in cancer remains unproven. Here, we review the rationale for, and recent advances in, pre-clinical and clinical research on antioxidant therapy in cancer, including targeting ROS with nonenzymatic antioxidants, such as NRF2 activators, vitamins, N-acetylcysteine and GSH esters, or targeting ROS with enzymatic antioxidants, such as NOX inhibitors and SOD mimics. In addition, we will offer insights into prospective therapeutic options for improving the effectiveness of antioxidant therapy, which may expand its applications in clinical cancer treatment.

• antioxidants
• cancer therapy
• oxidative stress
• reactive oxygen species

• acute kidney injury
• oxalate nephropathy
• pathology
• primary hyperoxaluria
• secondary hyperoxaluria

• Ascorbic acid
• Cancer
• Clinical trials
• IVC
• Metabolomics
• Proteomics
• Transcriptomics
• Vitamin C

• Antioxidant
• Ascorbic acid
• Kidney transplantation
• Oxidative stress
• Vitamin C

• Ascorbic Acid/administration & dosage
• Ascorbic Acid/adverse effects
• Ascorbic Acid/therapeutic use
• Humans
• Vitamins/administration & dosage
• Vitamins/adverse effects
• Vitamins/therapeutic use

• Calcium oxalate
• Calcium phosphate
• Crystalline nephropathies
• MGRS
• Urate

• Administration, Intravenous
• Aged
• Anti-Inflammatory Agents/administration & dosage
• Anti-Inflammatory Agents/therapeutic use
• Ascorbic Acid/administration & dosage
• Ascorbic Acid/therapeutic use
• Drug Therapy, Combination
• Female
• Hospital Mortality
• Humans
• Hydrocortisone/administration & dosage
• Hydrocortisone/therapeutic use
• Male
• Middle Aged
• Shock, Septic/drug therapy
• Shock, Septic/mortality
• Thiamine/therapeutic use
• Vasoconstrictor Agents/therapeutic use
• Vitamins/administration & dosage
• Vitamins/therapeutic use

• Parkinson’s disease
• calcium oxide dihydrate
• crystals
• iron oxide
• substantia nigra
• titanium dioxide

• Ascorbic acid
• case report
• dialytic clearance
• oxalate removal
• oxalosis
• peritoneal dialysis (PD)
• retinopathy
• supplements
• vision loss
• vitamin C

• critically ill
• glucose
• point of care
• sepsis
• vitamin C

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.

• Acute kidney injury
• Acute renal injury
• Ascorbic acid
• Cashew
• Cashew pseudofruit
• Dialysis
• Oxalate nephropathy
• Renal function
• Renal transplant
• Vitamin C

• Acute renal failure
• Dialysis
• Vitamin C

• Acute Kidney Injury/chemically induced
• Aged
• Ascorbic Acid/adverse effects
• Dietary Supplements/adverse effects
• Humans
• Intestine, Small/surgery
• Male
• Oxalates/analysis
• Risk Factors

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C administration? Is IVC safe? Does IVC interfere with chemotherapy or radiotherapy? Does IVC decrease the toxic side effects of chemotherapy and improve quality of life? What are the relevant mechanisms of action of IVC? What are the optimal doses, frequency, and duration of IVC therapy? Researchers have made massive strides over the last 20 years and have addressed many of these important aspects, such as the best route for administration, safety, interactions with chemotherapy, quality of life, and potential mechanisms of action. However, we still do not know the answers to a number of fundamental questions around best clinical practice, such as how much, how often and for how long to administer IVC to oncology patients. These questions point the way forward for both basic research and future clinical trials.

• ascorbate
• cancer
• chemotherapy
• enzyme cofactor
• intravenous vitamin C
• pharmacokinetics
• quality of life
• vitamin C

Little is known of the clinical outcomes of secondary oxalate nephropathy. To inform clinical practice, we performed a systematic review of case reports and case series to examine the clinical characteristics and outcomes of patients with secondary oxalate nephropathy.

Electronic databases were searched for case reports and case series of individual cases or cohorts of patients with biopsy-proven oxalate nephropathy in native or transplanted kidneys from 1950 until January 2018.

Fifty-seven case reports and 10 case series met the inclusion criteria, totaling 108 patients. The case series were meta-analyzed. Mean age was 56.4 years old, 59% were men, and 15% were kidney transplant recipients. Fat malabsorption (88%) was the most commonly attributed cause of oxalate nephropathy, followed by excessive dietary oxalate consumption (20%). The mean baseline serum creatinine was 1.3 mg/dl and peaked at 4.6 mg/dl. Proteinuria, hematuria, and urinary crystals was reported in 69%, 32%, and 26% of patients, respectively. Mean 24-hour urinary oxalate excretion was 85.4 mg/d. In addition to universal oxalate crystal deposition in tubules and/or interstitium, kidney biopsy findings included acute tubular injury (71%), tubular damage and atrophy (69%), and interstitial mononuclear cell infiltration (72%); 55% of patients required dialysis. None had complete recovery, 42% had partial recovery, and 58% remained dialysis-dependent. Thirty-three percent of patients died.

Secondary oxalate nephropathy is a rare but potentially devastating condition. Renal replacement therapy is required in >50% of patients, and most patients remain dialysis-dependent. Studies are needed for effective preventive and treatment strategies in high-risk patients with hyperoxaluria-enabling conditions.

• acute kidney injury
• chronic kidney disease
• nephrolithiasis
• oxalate nephropathy
• oxalosis
• secondary oxalosis

A few cases associating high dose intravenous vitamin C (IVC) administration with renal stone formation have been reported in the literature, however, no long-term studies investigating IVC administration and reported renal stones have been carried out. Our aim was to measure the frequency of reported renal stones in patients receiving IVC therapy. We carried out a prospective case series study of 157 adult patients who commenced IVC therapy at Integrated Health Options clinic between 1 September 2011 and 31 August 2012, with follow-up for 12 months. Inquiries into the occurrence of renal stones were conducted at enrolment, 6 and 12 months, and renal function blood tests were conducted at enrolment, 4 weeks and every 12 weeks thereafter in a subgroup of patients. No renal stones were reported by any patients in the study, despite 8% of the patients having a history of renal stones. In addition, the majority of patients investigated had stable renal function during the study period as evidenced by little change in serum creatinine levels and estimated glomerular filtration rate (eGFR) following IVC. In conclusion, IVC therapy was not associated with patient-reported renal stones. Although not the primary focus of this study, it was also observed that there was no significant change in mean serum creatinine or eGFR for those who had follow-up renal function blood tests.

• creatinine
• glomerular filtration rate
• intravenous vitamin C
• kidney stones
• oxalate
• renal function
• renal stones
• vitamin C

• Death
• Dietary supplement
• Herb
• Kidney
• Renal
• Toxicity
• Transplant

Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients.

Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients’ daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model.

Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d).

Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.

• C-reactive protein
• Critical illness
• Enteral nutrition
• Hypovitaminosis C
• Intensive care
• Parenteral nutrition
• Sepsis
• Septic shock
• Vitamin C

• Ascorbate
• Metabolism
• Oxalate
• Vitamin C

• inflammatory bowel disease
• kidney stones
• oxalate
• transplantation
• urolithiasis

Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma, profound tubular damage and interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to end-stage renal disease (ESRD). This sequence of events, well recognized in the past in primary and enteric hyperoxalurias, has also been documented in a few cases of dietary hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide, thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions. Studies addressing this question have the potential of improving population health and should be undertaken, alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate, and into the mechanisms of development of oxalate-induced renal parenchymal disease. Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.

• Dietary hyperoxaluria
• Chronic oxalate nephropathy
• Acute oxalate nephropathy
• Acute tubular necrosis
• Interstitial nephritis
• Nephrocalcinosis
• Calcium oxalate nephrolithiasis
• Oxalate transporters
• Inflammasomes