Uremic serum

Serum Uremic syndrome Control rats (6/5) LC-MS Indoxyl sulfate, phenyl sulfate, hippuric acid, and p-cresyl-sulfate (57)... 

In uremia there are present in the serum a variety of known and unknown metabolites that can produce aberrant laboratory results. Significant differences in glucose concentration have been observed in such specimens analyzed by ferricyanide (F2a) or Fe (II)-5-pyridylbenzo-diazepin-2-one reduction methods compared to glucose oxidase procedures (K7a). In a patient with elevated creatinine (15 mg/100 ml) and uric acid (10 mg/100 ml), the glucose value determined by the automated alkaline ferricyanide procedure was overestimated by 20 mg/100 ml (C4). In uremic patients undergoing chronic hemodialysis there is a decrease in transaminase activity. In 11 of 19 such patients, there was... 

Inhibitors of lactic dehydrogenase have been reported in commercial preparations of NAD+ and NADH (B4, M6, S28). The concentration of inhibitory substances varied from lot to lot. In a serum lactic dehydrogenase study with NAD+ from 8 sources, activities were found to vary from 145 to 75 units (B4). Inhibitors of lactic dehydrogenase activity have also been observed in dialyzates in uremic patients (W8) and in human urine (G8). The purity of available substrate can also effect enzyme activity. Schwartz and Bodansky observed that, in 6 batches of fructose 6-phosphate, all weighed to a 0.5 mM concentration, the actual concentration varied from 0.13 mAf to 0.55 mM (S14). 

Drug/Lab test interactions Thiazides may decrease serum PBI levels without signs of thyroid disturbance. Thiazides also may cause diagnostic interference of serum electrolyte, blood, and urine glucose levels (usually only in patients with a predisposition to glucose intolerance), serum bilirubin levels, and serum uric acid levels. In uremic patients, serum magnesium levels may be increased. Bendroflumethiazide may interfere with the phenolsulfonphthalein test due to decreased excretion. In the phentolamine and tyramine tests, bendroflumethiazide... 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Akpolat T, Gumus T, Bedir A, Adam B. Acute effect of trandolapril on serum erythropoietin in uremic and hypertensive patients. J Nephrol 1998 11 94-7. 

The addition of bilirubin or uremic toxin CMPF, which are strongly bound to HSA, alters the shape of the melting curve of serum albumin producing a bimodal curve, and causes a shift of the temperature maximum of the first peak to the right (Fig. 29.2) [7,8]. 

Serum albumin is a natural transporter of hydrophobic metabolites it binds toxic ligands reversibly, and if the ligand can be removed from the complex then the melting curve of unloaded albumin should return to that of pure protein. However this remains a difficult task, and neither exhaustive dialysis, nor the use of conventional carbonic sorbents, influence the shape of melting curves of albumin isolated from blood plasma of uremic patients and patients with hepatic insufficiency (Fig. 29.3) [9]. 

The serum half-life averages 1 hour, and the intracellular half-life of the phosphorylated compound is 3.3 hours. Zidovudine is eliminated primarily by renal excretion following glucuronidation in the liver. Clearance of zidovudine is reduced by approximately 50% in uremic patients, and toxicity may increase in patients with advanced hepatic insufficiency. 

When there is inadequate elimination of aluminum from the body, as in nondialyzed uremic patients, increased aluminum concentrations are detected in serum, bone tissue, liver, spleen, brain, and skeletal muscle (Alfrey et al. 1980 Arieff et al. 1979). In hemodialysis patients exposed by infusion to large amounts of aluminum over long periods of time (with inadequate removal of aluminum by the kidneys and dialysis machines), increased aluminum concentrations are observed mostly in the spleen, followed by the liver and skeletal system (Alfrey 1980 Alfrey et al. 1980). 

Figure 16.7 Gamblegrams illustrating serum cation and anion distributions in normal, diabetic, and uremic individuals. (Reproduced by permission from Hoffman WS. The Biochemistry of Clinical Medicine, 4th ed. Chicago Yearbook, 1970, p. 249.)...

Because of poor phosphate removal with dialysis, the use of Al or calcium phosphate binders has been required for lowering serum phosphate levels in uremic patients. A prospective, controlled study of pediatric patients... 

Aluminium overload in uremic patients can lead to a microcytic hypochromic anemia (45). The mechanism is unknown, but it appears to involve inhibition of heme synthesis, either by inhibition of enzyme activity or by interference with the incorporation or utilization of iron. Exposure for 3 months is sufficient to reduce hematological values and cause significant increases in serum and urinary aluminium (46). The anemia can be reversed by lowering the aluminium intake or by chelation therapy with deferoxamine. 

In all patients with chronic renal insufficiency, strict supervision of total aluminium intake is vital. The administration of aluminium should be stopped as soon as the serum concentration exceeds 150 pg/ml or at the appearance of the first symptoms of encephalopathy (81). According to current recommendations, dia-lysate solutions should contain less than 10 pg/l of aluminium (82). There is some controversy about the view that aluminium-containing medications used to control serum phosphate concentrations in uremic subjects should be replaced by calcium-containing phosphate binders (83). Another approach used to reduce the toxic risks of aluminium hydroxide may be to tailor doses to the phosphate concentration in serum, that is individualizing aluminium gel therapy (SED-12, 515). 

There are four potential clinical presentations for acute CSA nephrotoxicity asymptomatic increases in serum creatinine (SCr) without overt renal dysfunction, acute kidney injury, delayed graft function after renal transplantation and recurrent or de novo hemolytic uremic syndrome (Table 2). 

Although there are still some discrepancies in the hterature regarding zinc levels in dialysis patients, most studies have found decreased levels of the element in serum [64,65] and muscles whereas the levels in bone [63] and other tissues seem to be normal or even increased suggesting translocation of the element in uremia. The dialysis treatment itself seems to have little or no effect on the serum zinc concentrations. Zinc deficiency in uremic patients has been associated with anorexia, disturbances in taste and sexual performance [66] whereas decreased plasma zinc seem to correlate with erythrocyte superoxide dismutase levels [67]. As evaluated by Tiirk et al. [68], zinc supplementation did not have any effect on the restoration of immune parameters or enhancement of the antibody response to multivalent influenza vaccine in hemodialysis patients. On the ofher hand however, has zinc supplementation been reported an effective means of improving serum levels of zinc and cholesterol in the hemodialysis patient [69]. 

Dobbie JW, Smith MJB Urinary and serum silicon in normal and uremic individuals. Ciba FoundSymp 1986 121 194-213. 

Cresol can be considered as a prototype of protein-bound uremic retention solutes, with a protein binding of >99% in healthy subjects and approximately 90% in uremic patients. Several recent studies suggest that p-cresol interferes with various biochemical and physiological functions at concentrations currently observed in uremia. Concentrations of phenol and / -cresol in uremic serum are significantly higher than those in normal serum. 

Phenol and / -cresol noticeably accumulate in the serum of undialyzed and dialyzed uremic patients they play a role in the development of uremic coma and defective platelet aggregation. They are synthesized in the small intestine from phenylalanine and tyrosine through... 

Only a few methods are available for the determination of / -cresol concentration in serum. In addition, these methods have only been used for the determination of total / -cresol. In particular, the evolution of free (nonprotein-bound) /7-cresol is of concern because, conceivably, this is the biologically active fraction. However, the concentration of free p-cresol is markedly lower than that of total p-cresol, in view of its important protein binding. Methods enabling the measurement of total and free p-cresol concentration in the serum of healthy controls and uremic patients are also reported in literature. 

HPLC methods can use fluorescence as a detector for quantifying serum phenol and p-cresol in uremic patients on hemodialysis. 

Uremic toxins are chemicals and waste products normally excreted by the kidneys and are responsible for many of the signs of kidney disease. Since 1840, more than 2000 toxic substances were reported in uremic blood. Obviously, the determination of such compounds is crucial for diagnosis and monitoring of renal disease and metabolic disorders. The concentrations of several uremic toxins in blood serum and urine are among the most important parameters in biochemistry and clinical chemistry. 

Sjoholm, I., Kober, A., Odar-Cederlof, I. Borga, O. (1976) Protein binding of drugs in uremic and normal serum the role of endogenous inhibitors. Biochemical Pharmacology, 25, 1205-1213. 

Skeletal muscle that is diseased or damaged (such as by extreme exercise) may contain significant proportions of CK-MB owing to the phenomenon of fetal reversion, in which fetal patterns of protein synthesis reappear. Thus serum CK-MB isoenzyme may increase in such circumstances. This explanation may also account for the elevated CK-MB values sometimes observed in chronic renal failure (uremic myopathy). 

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