11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the non-selective renal mineralocorticoid receptor from the endogeneous glucocorticoid cortisol. Thus, drugs inhibiting 11 beta-OHSD might enhance urinary loss of potassium. In an attempt to find drugs inhibiting 11 beta-OHSD, 23 commonly used agents known to interfere with the potassium metabolism have been screened for inhibitory effect on 11 beta-OHSD. Furosemide appeared as the only inhibitor. Its inhibition constant (Ki) was 19.5 microM when kidney and 21.3 microM when liver microsomes were used as a source of 11 beta-OHSD. The type of inhibition was competitive. For confirmation that furosemide specifically inhibits 11 beta-OHSD, the complementary DNA (cDNA) of 11 beta-OHSD was transfected into COS-1 cells devoid of spontaneous expression of 11 beta-OHSD. In these cells, oxidation of corticosterone (Ki = 17.4 microM) and reduction of dehydrocorticosterone (Ki = 12.5 microM) was inhibited by furosemide. To establish whether this inhibition also occurs in vivo, the 11 beta-hydroxysteroid prednisolone was administered with and without furosemide to rats. The concentration ratio of prednisolone to its 11-ketometabolite prednisone increased in kidney and liver tissue after furosemide administration, indicating inhibition of 11 beta-OHSD. These data suggest that furosemide modulates in vivo the access of 11 beta-OH glucocorticoids to their target organs.
Creatinine has been used as a convenient tool to determine and follow various aspects of renal function. The aim of this article is to review creatinine kinetics in peritoneal dialysis and its clinical applications, such as monitoring dialysis adequacy and the nutritional status of a patient, control of adherence to an individual dialysis prescription, and modeling of dialysis prescriptions according to the individual needs of a patient.
Creatinine MetabolismMost of the creatinine in the human body is produced from nonenzymatic hydrolysis of phosphocreatine. Since muscle is the main reservoir of creatine, total muscle mass and its metabolism account for the majority of creatinine production. The dietary intake of preformed creatinine, or its precursor creatine in meat-based diets, is an additional source. Creatinine is a relatively inert solute of low molecular weight (1 13 daltons) that is excreted unchanged in the urine. Extrarenal degradation in the gut occurs in patients with elevated serum creatinine levels (1).Endogenous creatinine production can be calculated by the formulas of Cockcroft and Gault (2) as modified by Mitch, Collier, and Walser (3): daily creatinine production in men (mg/kg) = 28 -(0.2 x age in years) 23.8 -(0.17 x age in years) daily creatinine production in women (mg/kg) = According to the formula of Mitch, Collier, and Walser (3), the amount of extrarenal degradation of creatinine (mg/day) can be calculated as: 0.38 x serum Cr (mg/dL) x body weight (kg) Creatinine is traditionally used as a marker for nonmeasurable low molecular weight toxins that accumulate in renal failure. High creatinine levels are implicated in uremic thrombopathy (4) and in decreased erythrocyte survival (5) but have otherwise not proven to be toxic in the uremic state (6).
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