OBJECTIVE: We undertook this study to investigate the discriminant metabolites in urine from patients with established rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and from healthy individuals. METHODS: Urine samples were collected from 148 RA patients, 41 SLE patients and 104 healthy participants. The urinary metabolomic profiles were assessed using 1H nuclear magnetic resonance spectroscopy. The relationships between discriminant metabolites and clinical variables were assessed. Collagen-induced arthritis was induced in mice to determine if a choline-rich diet reduces arthritis progression. RESULTS: The urinary metabolic fingerprint of patients with established RA differs from that of healthy controls and SLE patients. Markers of altered gut microbiota (trimethylamine-N-oxide, TMAO), and oxidative stress (dimethylamine) were upregulated in patients with RA. In contrast, markers of mitochondrial dysfunction (citrate and succinate) and metabolic waste products (p-cresol sulfate, p-CS) were downregulated in patients with RA. TMAO and dimethylamine were negatively associated with serum inflammatory markers in RA patients. In particular, patients with lower p-CS levels exhibited a more rapid radiographic progression over two years than did those with higher p-CS levels. The in vivo functional study demonstrated that mice fed with 1% choline, a source of TMAO experienced a less severe form of collagen-induced arthritis than did those fed a control diet. CONCLUSION: Patients with RA showed a distinct urinary metabolomics pattern. Urinary metabolites can reflect a pattern indicative of inflammation and accelerated radiographic progression of RA. A choline-rich diet reduces experimentally-induced arthritis. This finding suggests that the interaction between diet and the intestinal microbiota contributes to the RA phenotype.
Animals ; Arthritis* ; Arthritis, Experimental ; Arthritis, Rheumatoid* ; Choline ; Dermatoglyphics ; Diet* ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Inflammation ; Lupus Erythematosus, Systemic ; Magnetic Resonance Spectroscopy ; Metabolome* ; Metabolomics ; Mice ; Oxidative Stress ; Phenotype* ; Spectrum Analysis ; Waste Products

Trimethylamine N-oxide (TMAO) is produced when trimethylamine, a waste product of gut microbes, is converted via hepatic flavin monooxygenases. As TMAO is a potential causative factor in various cardiovascular diseases (CVDs) considerable research interest has arisen on its use as a biomarker. Higher TMAO levels are associated with future risk of both incident CVD in the general population and established CVD, including stroke. The addition of TMAO into models with traditional risk factors significantly improved the prediction of future CVD risk. TMAO promotes atherosclerosis and is associated with platelet hyperreactivity and inflammation, which are in turn associated with the development of stroke and its secondary consequences. Additionally, TMAO may play a key mediator role in the relationship between the diet, gut microbiota, and CVD development. Compelling evidence suggesting that TMAO is both a risk factor and prognostic marker of stroke and CVD. Potential therapeutic strategy of diet and drugs in reducing TMAO levels have emerged. Thus, TMAO is a novel biomarker and target in stroke and CVD prevention.
Atherosclerosis ; Blood Platelets ; Cardiovascular Diseases ; Diet ; Gastrointestinal Microbiome ; Inflammation ; Mixed Function Oxygenases ; Prognosis ; Risk Factors ; Stroke ; Waste Products

With the widespread availability of dialysis, the lives of end-stage renal disease patients have been prolonged over the past fifty years. Hemodialysis relies on the diffusion of molecules across a semipermeable membrane along the concentration gradient. In addition to diffusion, movement of waste products from the circulation into the dialysate can occur as a result of convective clearance. Use of high-flux dialyzer has increased the removal of the middle molecules such as beta2-microglobulin. Recently on-line hemodiafiltration which combined the hemodialysis and hemofiltration to increase the convective clearance of the large molecules has been available. About the hemodialysis adequacy, the result of hemodialysis (HEMO) study suggests that increasing the dose to greater than a single-pool Kt/Vurea 1.4 does not improve the survival of the patients. While the technical and scientific improvement in hemodialysis has led to a noticeable improvement in the survival of the dialysis patients, cardiovascular mortality and event rates are extraordinarily high in dialysis population. In addition to hemodialysis treatment, nephrologists taking care of dialysis patients must recognize and treat the diverse complications that can result from the loss of kidney function.
Dialysis ; Diffusion ; Hemodiafiltration ; Hemofiltration ; Humans ; Kidney ; Kidney Failure, Chronic ; Membranes ; Mortality ; Renal Dialysis* ; Waste Products

With the widespread availability of dialysis, the lives of end-stage renal disease patients have been prolonged over the past fifty years. Hemodialysis relies on the diffusion of molecules across a semipermeable membrane along the concentration gradient. In addition to diffusion, movement of waste products from the circulation into the dialysate can occur as a result of convective clearance. Use of high-flux dialyzer has increased the removal of the middle molecules such as beta2-microglobulin. Recently on-line hemodiafiltration which combined the hemodialysis and hemofiltration to increase the convective clearance of the large molecules has been available. About the hemodialysis adequacy, the result of hemodialysis (HEMO) study suggests that increasing the dose to greater than a single-pool Kt/Vurea 1.4 does not improve the survival of the patients. While the technical and scientific improvement in hemodialysis has led to a noticeable improvement in the survival of the dialysis patients, cardiovascular mortality and event rates are extraordinarily high in dialysis population. In addition to hemodialysis treatment, nephrologists taking care of dialysis patients must recognize and treat the diverse complications that can result from the loss of kidney function.
Dialysis ; Diffusion ; Hemodiafiltration ; Hemofiltration ; Humans ; Kidney ; Kidney Failure, Chronic ; Membranes ; Mortality ; Renal Dialysis* ; Waste Products

Urine production is vital for the removal of certain waste products produced by metabolism in the body and for the maintenance of homeostasis in the body. The kidneys produce urine by the following three precisely regulated processes: filtration, reabsorption, and secretion. Urine is composed of water, certain electrolytes, and various waste products that are filtered out of the blood through the glomeruli. The physical features of urine are evaluated carefully to detect any abnormal findings that may indicate underlying diseases in the genitourinary system. A change in urine color may indicate an underlying pathological condition, although many of the causes of abnormal urine color are benign effects of medications and foods. A characteristic and specific odor may be the result of a metabolic disease rather than a concentrated specimen or a simple urinary tract infection. Although transient changes in urine output and nocturia are usually benign conditions, persistent abnormal findings require further work-up, with a thorough medical history taking. This article presents many of the conditions that physicians may encounter and will help them in the diagnosis and in establishing a treatment plan.
Diagnosis ; Electrolytes ; Filtration ; Homeostasis ; Kidney ; Medical History Taking ; Metabolic Diseases ; Metabolism ; Nocturia ; Odors ; Urinary Tract Infections ; Urogenital System ; Waste Products

Genetically engineered mice have provided much information about gene function in the field of developmental biology. Recently, conditional gene targeting using the Cre/loxP system has been developed to control the cell type and timing of the target gene expression. The increase in number of kidney-specific Cre mice allows for the analysis of phenotypes that cannot be addressed by conventional gene targeting. The mammalian kidney is a vital organ that plays a critical homeostatic role in the regulation of body fluid composition and excretion of waste products. The interactions between epithelial and mesenchymal cells are very critical events in the field of developmental biology, especially renal development. Kidney development is a complex process, requiring inductive interactions between epithelial and mesenchymal cells that eventually lead to the growth and differentiation of multiple highly specialized stromal, vascular, and epithelial cell types. Through the use of genetically engineered mouse models, the molecular bases for many of the events in the developing kidney have been identified. Defective morphogenesis may result in clinical phenotypes that range from complete renal agenesis to diseases such as hypertension that exist in the setting of grossly normal kidneys. In this review, we focus on the growth and transcription factors that define kidney progenitor cell populations, initiate ureteric bud branching, induce nephron formation within the metanephric mesenchyme, and differentiate stromal and vascular progenitors in the metanephric mesenchyme.
Animals ; Body Fluids ; Congenital Abnormalities ; Developmental Biology ; Epithelial Cells ; Gene Expression ; Gene Targeting ; Hypertension ; Kidney ; Kidney Diseases ; Mesoderm ; Mice ; Morphogenesis ; Nephrons ; Phenotype ; Stem Cells ; Transcription Factors ; Ureter ; Waste Products

Municipal wastewater is usually problematic for the environment. The process of oleaginous microalgal culture requires large amounts of nutrients and water. Therefore, we studied the feasibility of oleaginous microalgal culture of Scenedesmus dimorphus in bubbled column photobioreactor with municipal wastewater added with different nutrients. S. dimorphus could adapt municipal nutrient-rich wastewater by adding some nutrients as nitrogen, phosphorus, ferric ammonium citrate and trace elements, and the amounts of such nutrients have significant effects on cell growth, biomass yield and lipid accumulation. At optimum compositions of wastewater medium, the algal cell concentration could reach 8.0 g/L, higher than that of 5.0 g/L in standard BG11. Furthermore, S. dimorphus had strong capacity to absorb inorganic nitrogen and phosphorus from its culture water. There was almost no total nitrogen and phosphorus residues in culture medium after three or four days culturing when the adding mounts of nitrate and phosphate in wastewater medium were no more than 185.2 mg/L and 16.1 mg/L respectively under the experimental conditions. As a conclusion, it was feasible to cultivate oleaginous microalgae with municipal nutrient-rich wastewater, not only producing feedstock for algal biodiesel, but also removing inorganic nitrogen and phosphorus from wastewater.
Biofuels ; Cities ; Culture Techniques ; methods ; Lipids ; biosynthesis ; Microalgae ; metabolism ; Photobioreactors ; Scenedesmus ; growth & development ; metabolism ; Waste Disposal, Fluid ; methods ; Waste Products

Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by alpha-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.
Actins ; Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Anthocyanins ; Antineoplastic Agents ; Aspartate Aminotransferases ; Bilirubin ; Collagen ; Diet ; Dietary Supplements ; Dimethylnitrosamine ; Fibrosis ; Flavonoids ; Fruit ; Hepatic Stellate Cells ; Hydroxyproline ; Liver ; Liver Cirrhosis ; Malondialdehyde ; Muscles ; Phenol ; Rats ; Seeds ; Serum Albumin ; Skin ; Vitis ; Waste Products

Acute kidney injury (AKI), formerly referred to as acute renal failure (ARF) is defined as the sudden impairment of kidney function (estimated from the glomerular filtration rate [GFR]) that results in the lack of excretion of waste products. More than 30 definitions of AKI exist in the literature, most of which are based on serum creatinine. Lack of a uniform and multidimensional AKI definition has led to failure to recognize significant renal injury, delays in treatment, and inability to generalize single-study results. The RIFLE criteria were developed to standardize the diagnosis of ARF and in the process the term AKI has been proposed to encompass the entire spectrum of the syndrome from minor changes in renal function to requirement for renal replacement therapy. Large prospective studies are needed to test definitions and to better understand risk factors, incidence, independent outcomes, and mechanisms that lead to poor short- and long-term outcomes. Early biomarkers of AKI need to be explored in critically ill neonates.
Acute Kidney Injury ; Biomarkers ; Creatinine ; Critical Illness ; Glomerular Filtration Rate ; Humans ; Incidence ; Infant, Newborn ; Kidney ; Renal Replacement Therapy ; Risk Factors ; Waste Products

Acute renal failure is the generic term for an abrupt and sustained decrease in renal function resulting in retention of nitrogenous and non nitrogenous waste product. This may results in life threatening consequences including volume overload, hyperkalemia, and metabolic acidosis. Acute renal failure is both common and carries high mortality rate, but as it is often preventable, identification of patients at risk and and appropriate management are crucial. This review summarized the most recent information on definition, epidemiology, clinical causes and management of acute renal failure in pediatric patients.
Acidosis ; Acute Kidney Injury* ; Epidemiology ; Humans ; Hyperkalemia ; Mortality ; Nitrogen ; Pediatrics* ; Waste Products