Inulin, excretion

Most contrast agents elicit nephrotoxicity because they are primarily excreted by the kidneys. However, when administered in small doses, they constitute a rich source of GFR markers. The two major classes of contrast agents that are finding clinical utility as GFR markers are iodinated aromatic compounds and metal complexes. lodinated aromatics such as iohexol and iothalamate (Fig. 13) are commonly used as contrast agents for computed tomography (GT). They also have pharmacokinetics similar to inulin and hence are useful indicators of renal status [215]. The iodinated molecules used for GFR measurements consist of a triiodo-benzene core and hydrophilic groups to enhance solubility in aqueous medium. 

Clearance. Renal clearance is used as a quantitative measure of renal function. It is defined as the plasma volume cleared of a given substance per unit of time. Inulin, a fructose polysaccharide with a mass of ca. 6 kDa (see p. 40) that is neither actively excreted nor resorbed but is freely filtered, has a clearance of 120mb min in healthy individuals. 

Crystals (or amorphous substances) are also formed in living bodies as a result of biological activities to act as a reservoir for necessary components (for example, amorphous silica in grass cells, and calcium oxalate or inuline crystals in dahlias and begonias), or crystals are formed by excretion processes or due to illness (for... 

Moslen. M.T.. Poisson. L.R. Reynolds, E.S. (1985) Cholestasis and increased biliary excretion of inulin in rats given 1,1-dichloroethylene. Toxicology, 34, 201-209... 

Ellegard, L., Andersson, H., and Bosaeus, I. 1997. Inulin and oligofructose do not influence the absorption of cholesterol, or the excretion of cholesterol, Ca, Mg, Zn, Fe, or bile acids but increases energy excretion in ileostomy subjects. Eur. J. Clin. Nutr. 51, 1-5. 

In each sample the concentration of a glomerular marker, such as inulin, and the concentration of the substance under study are measured. Fractional excretion of the substance and the glomerular marker are plotted versus the cumulative urinary volume. 

FIGURE 6.4 Kinetic analysis of urea ( ) and inulin H (A) plasma concentrations (upper panel) and renal excretion rates (middle panel) before, during, and after dialysis of a dog with intact kidneys. Inulin was not dia-lyzable but urea concentrations entering and leaving the dialyzer are both shown. The bottom panel shows CLg estimates for urea (—) and inulin (—), and measured plasma renin activity ( ). (Reproduced with permission from Bowsher DJ, Krejcie TC, Avram Mf, Chow MJ, del Greco F, Atkinson AJ Jr. J Lab Clin Med 1985 105 489-97.)... 

In patients with normal renal function, 70 to 90% of an intravenous dose of vancomycin is excreted in the urine unchanged by glomerular filtration. The serum elimination half-life in patients with normal renal function is variable, but averages 6 hours [171]. However, terminal half-lives ranging from 3 to 11 hours have been observed [184]. In anuric patients, the serum half-life increases markedly to 6 to 10 days [171]. The liver may also be involved in the disposition of vancomycin as dose adjustments have been required in patients with severe liver dysfunction [172]. An interesting study by Golper et al that compared systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin and para-aminohippurate demonstrated a substantial non-renal clearance of vancomycin of 30%. In addition, the researchers found that the non-renal clearance of vancomycin was concentration dependent with a 10% greater clearance at serum concentrations of 14 mg/ ml as compared to 7 mg/ ml [185]. 

Figure 24-8 The relationship between serum creatinine concentration and GFR, measured as the clearance of inulin, in 171 patients with glomerular disease.The hypothetical relationship between GFR and serum creatinine is shown as a continuous line, assuming that only filtration of creatinine takes place.The dashed horizontat tine represents the upper limit of a normal serum creatinine (1.4mg/dL). Because of creatinine secretion and/or a creatinine deficit through gut excretion, the serum creatinine consistently overestimates the GFR. (From Sfiemesfi O, Golbetz H, Kriss JP, /Myers BD. Limitations of creatinine os a filtration marker in glomerulopathic patients. Kidney Int I98S 28 830.)...

Miller BE, Winkler AW. The renal excretion of endogenous creatinine in man Comparison with exogenous creatinine and inulin. J Clin Invest 1938 17 31-40. 

In healthy adults, the value for inulin is in the range of 120-125 ml/day. Since inulin is neither absorbed nor secreted in the tubules, this value corresponds to the inulin clearance. Per day a total filtered volume of 1801 results, which is 60 times the plasma volume or 4 times the total body water. Because only 1-1.51 urine is excreted per day the reabsorption of water is similar to the filtration rate. 

Results. Excellent correlation between in vitro and in vivo release rates was observed (Figure 1). As in internal control, the inulln polymer squares were removed from the rats at the end of 450 hrs and rat urine analyzed 4.5 hrs later. As shown in Figure 1, the recovery rate of H-inulin dropped 300 fold. This control confirmed that H-inulin is rapidly cleared from the blood stream and excreted into the urine. Thus inulin is an excellent marker for directly assessing release rates from the polymer implant. 

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