Excretion of albumin

The separation of proteins and peptides mixtures is the objective of protein biochemisdy. Albumin (Mr 66 000) concentration in a biological fluid (seaim, urine or cerebrbrospinal fluid) is assayed as markers for a series disease, such as nephritic syndrome or chronic glomuleronephritis. In diabetic patients the progression of microalbuminuria is accompanied by an increase in urinary concentrations of human semm albumen. In normal the excretion of albumin is 20 (tg/ml, in pathology - 20-200 p.g/ml. 

Grubb A. Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clin Nephrol 1992 38(Suppl 1) S20-S27. Tencer J,Thysell H, Grubb A. Analysis of proteinuria Reference limits for urine excretion of albumin, protein HC, immunoglobin G, k- and 1-chain immunoreactrivity, orosomucoid and al-antitrypsin. Scand J Clin Lab invest 1996 56 691-700. 

Roels et al. [63] and Buchet et al. [118] observed a slightly higher prevalence of elevated urinary excretion of albumin, transferrin, retinol binding protein and the tubular enzyme [l-galactosidase in chloralkali workers with a urinary excretion of mercury exceeding 50 pg/ g creatinine. 

Askergren A, Allgen LG, Karlsson C, et al. 1981. Studies on kidney function in subjects exposed to organic solvents 1. Excretion of albumin and B-2- microglobulin in the urine. Acta Med Scand 209 479-483. 

Nephropathy is initially manifested as a persistent urinary excretion of albumin, a decreasing glomerular filtration rate and increasing blood pressure. Once proteinuria occurs, patients have a poor prognosis. The median survival is about 10 years, which is determined by diastolic blood pressure, dietary protein intake and the severity of diabetes exposure. A family history of longevity, however, may be helpful and also regular clinical contact. 

Attempts to define threshold levels for effects have produced mixed results. A no-efifect level of 72 g Hg/g creatinine was determined for urinary excretion of albumin, 2-microglobulin, or retinol binding protein (Bernard et al. 1987). However, other studies have shown increases in urinary albumin at urinary mercury levels >50 g Hg/g creatinine (Buchet et al. 1980) and increases in urinary /V-acetyl-... 

Microalbuminuria is defined as an increase in urinary excretion of albumin above the reference mterval for healthy nondiabetic subjects but at a concentration that is not generally detectable by crude clinical tests, such as dipsticks designed to measure total protein. With improved methodology, these low concentrations of albumin can now be measured, and microalbuminuria is now considered a clinically important indicator of deteriorating renal function in diabetic subjects. For example, it is now accepted by both European and U.S. diabetes societies that regular screening... 

Rowe (Rl) was able to prove that purified albumin prepared from nephrotic serum and urine had the same molecular weight as that from normal serum he concludes that the increased excretion of albumin by nephrotic patients is not the result of a reduction of its molecular dimensions, but rather that the abnormality resides in the kidney. Ultrafiltration experiments showed (Fig. 23) that a selective molecular filtration may be reproduced by a suitable membrane in vitro. Rowe concludes that it is not necessary to invoke tubular activity to account for the composition of the uroproteins. 

ALA aminolevulinic acid ALAD 5-(5)aminolevulic acid dehydratase, an enzyme which is involved in the biosynthesis of the hemin-porphyrin skeleton decrease in its activity is monitored, e.g. in the case of increased exposure to lead albumin a group of proteins found in nearly every animal and in many vegetable tissues, e.g. semm albumin albuminuria increased excretion of albumin in the urine can indicate damage to the kidney... 

The absorption of metoprolol after po dosing is rapid and complete. The dmg undergoes extensive first-pass metabolism in the liver and only 50% of the po dose in bioavailable. About 12% of the plasma concentration is bound to albumin. The elimination half-life is 3—7 h and less than 5% of the po dose is excreted unchanged in the urine. The excretion of the dmg does not appear to be altered in patients having renal disease (98,99,108). 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

The viability and function tests described above are used to evaluate the hepatocytes within the slice. Up to now, tests to measure the viability of the non-parenchymal cells have not been reported. The presence of the latter cell types is one of the conceptual advantages of slices as compared to isolated hepatocytes. As some drug targeting devices are designed to target non-parenchymal cells in the liver, the development of tests for the sinusoidal cell types deserves more attention. For example, the uptake of substrates such as succinylated human serum albumin (Suc-HSA,which is specifically endocytosed by endothelial cells [79]), or hyaluronic acid [80], can be used to assess the functionality of endocytotic pathways in the endothelial cells in the liver [81]. Other modified proteins that are specifically taken up by Kupffer cells such as mannosylated HSA, may be used to assess the functionality of the endocytotic pathway in Kupffer cells [79]. Another parameter which can be used to assess the functionality of these non-parenchymal liver cells, is the excretion of cytokines in response to pro-inflammatory stimuli. Non-parench5mal cell function in liver slices will be described in more detail in the Section 12.7. 

Pregnancy Increased blood volume Increased renal blood flow and GFR Reduced plasma albumin Increased hepatic metabolism Altered drug distribution between protein bound and free forms Greater excretion of renally-cleared drugs May need increased dose to maintain effective Cp... 

Warfarin is generally administered as the sodium salt and has 100% bioavailability. Over 99% of racemic warfarin is bound to plasma albumin, which may contribute to its small volume of distribution (the albumin space), its long half-life in plasma (36 hours), and the lack of urinary excretion of unchanged drug. Warfarin used clinically is a racemic mixture composed of equal amounts of two enantiomorphs. The levorotatory S-warfarin is four times more potent than the dextrorotatory R-warfarin. This observation is useful in understanding the stereoselective nature of several drug interactions involving warfarin. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

Albumin is of great importance in animal physiology in mail it constitutes about 50% of the plasma proteins (blood) and is responsible to a great extent for tile maintenance of osmotic equilibrium in the blood. The high molecular weight (68,000) of the albumin molecule prevents its excretion in the urine the appearance of albumin may indicate kidney damage. 

By age 11 years his renal function decreased, as measured by a creatinine clearance of 71 mL/min (normal is 105 mL/min). He also developed protein-losing nephropathy with a 24-hour urinary protein excretion of 600 mg that increased to 14 g after albumin infusions... 

Increased albumin usually indicates glomerular injury, although it is not a specific marker for any one nephron site (Guder and Hofmann 1992 Price et al. 1996 Finn and Porter 1998). High levels of albumin in urine are invariably the result of glomerular malfunction. Low level increases in urine albumin, especially in circumstances where total urine protein excretion is not elevated ( microalbuminuria ) can result either from increased glomerular filtration or decreased tubular reabsorption, and albumin values... 

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