Uremia results in many different compounds being retained by the body. With the failure of the kidneys, these compounds can build up to dangerous levels. There are more than 90 different compounds that have been identified. Some of these compounds can be toxic to the body. + Uremic solutes Solute group Example Source Characteristics Peptides and small proteins β2-microglobulin shed from major histocompatibility complex poorly dialyzed because of large size Guanidines guanidinosuccinic acid arginine increased production in uremia Phenols ρ-cresyl sulfate phenylalanine, tyrosine protein bound, produced by gut bacteria Indoles indican tryptophan protein bound, produced by gut bacteria Aliphatic amines dimethylamine choline large volume of distribution, produced by gut bacteria Polyols unknown tightly protein bound Ucleosides pseudouridine tRNA most prominent of several altered RNA species Dicarboxylic acids oxalate ascorbic acid formation of crystal deposits Carbonyls glyoxal glycolytic intermediates reaction with proteins to form advanced glycation end-products Uremic toxins Uremic toxins are any biologically active compounds that are retained due to kidney impairment. Many uremic salts can also be uremic toxins. Urea was one of the first metabolites identified. Its removal is directly related to patient survival but its effect on the body is not yet clear. Still, it is not certain that the symptoms currently associated with uremia are actually caused by excess urea, as one study showed that uremic symptoms were relieved by initiation of dialysis, even when urea was added to the dialysate to maintain the blood urea nitrogen level at approximately 90 mg per deciliter (that is, approximately 32 mmol per liter). Urea could be the precursor of more toxic molecules but it is more likely that damage done to the body is from a combination of different compounds which may act as enzyme inhibitors or derange membrane transport. Indoxyl sulfate is one of the better characterized uremic toxins. Indoxyl sulfate has been shown to aggravate vascular inflammation in atherosclerosis by modulating macrophage behavior. + Potential uremic toxins Toxin Effect References Urea At high concentrations >300 mg/dL(>50 mmol/L): headaches, vomiting, fatigue, carbamylation of proteins Creatinine Possibly affects glucose tolerance and erythrocyte survival Cyanate Drowsiness and hyperglycemia, carbamylation of proteins and altered protein function due to being a breakdown product of urea Polyols (e.g., myoinositol) Peripheral neuropathy Phenols Can be highly toxic as they are lipid-soluble and therefore can cross cell membranes easily "Middle molecules" Peritoneal dialysis patients clear middle molecules more efficiently than hemodialysis patients. They show fewer signs of neuropathy than hemodialysis patients β2-Microglobulin Renal amyloid Indoxyl sulfate Induces renal dysfunction and cardiovascular dysfunction; associated with chronic kidney disease and cardiovascular disease Table 2: Microbial metabolites: their synthesis, mechanisms of action, and effects on health and disease Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease ρ-cresyl sulfate Accumulates in and predicts chronic kidney disease Biochemical characteristics Many regulatory functions of the body are affected. Regulation of body fluids, salt retention, acid and nitrogenous metabolite excretion are all impaired and can fluctuate widely. Body fluid regulation is impaired due to a failure to excrete fluids, or due to fluid loss from vomiting or diarrhea. Regulation of salt is impaired when salt intake is low or the vascular volume is inadequate. Acid excretion and nitrogenous metabolite excretion are impaired with the loss of kidney function. + Biochemistry Retained nitrogenous metabolites Fluid, acid-base, and electrolyte disturbances Carbohydrate intolerance Anormal lipid metabolism Altered endocrine function Urea Fixed urine osmolality Insulin resistance (hypoglycemia may also occur) Hypertriglyceridemia Secondary hyperparathyroidism Cyanate Metabolic acidosis Plasma insulin normal or increased Decreased high-density lipoprotein cholesterol Altered thyroxine metabolism Creatinine Hyponatremia or hypernatremia or hypercalcemia Delayed response to carbohydrate loading Hyperlipoproteinemia Hyperreninemia and hyperaldosteronism Guanidine compounds Hyperchloremia Hyperglucagonemia Hyporeninemia "Middle molecules" Hypocalcemia Hypoaldosteronism Uric acid Hyperphosphatemia Decreased erythropoietin production Hypermagnesemia Gonadal dysfunction (increased prolactin and luteinizing hormone, decreased testosterone) Decreased sodium-potassium ATPase activity Increased serum gastrin and melanocyte-stimulating hormone
complications of Kidney disease
medical cause of Chronic kidney disease
complications of Acute liver failure
complications of Hypoalbuminemia
complications of Cirrhosis
complications of Hypercalcaemia
complications of Cardiovascular disease
symptom of Kidney cancer