Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin

Abstract

The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and 02-microglobulin (02M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and j2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group.Overall, ,2M elimination was variable in all treatment groups. Although the ,2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.

Nephrotoxicity due to Combination Antibiotic Therapy with Vancomycin and Aminoglycosides in Septic Critically Ill Patients

“…Serum creatinine is a late indicator of kidney damage, and its sensitivity as an indicator of renal function is generally considered poor [23] . Therefore, besides serum creatinine, according to Fauconneau et al [12] , Goren et al [10] and Rybak et al [4] , we measured the urinary excretion of enzymes and the low-molecular-weight protein ␤ 2M as early markers of damage due to toxic effects of drugs on renal tubular cells, which precedes the clinical impairment in renal function. The clinical relevance of increased excretion of these markers has not been completely elucidated, but data [24][25][26][27][28] indicate that the measurement of urinary excretion of tubular enzymes and the low-molecular-weight protein ␤ 2M may enable the early identifi cation even of mild and transient renal tubular damage, which is not detectable using more conservative criteria, e.g.…”

“…We considered pathological and hence indicative of nephrotoxicity: (1) a decrease in CL cr equal to or higher than 50% of basal values [7] ; (2) an increase in serum creatinine or urea concentrations, or urinary excretion of proteins, ␤ 2M or enzymes 6 50% of basal values [4,10,12] , or (3) an increase in serum creatinine 1 0.5 mg/dl [5][6][7][8][9] .…”

“…Other parameters proposed to evaluate tubular toxicity, which are more likely to give early detection, are the urinary excretion of proteins, i.e. albumin and different low-molecular-weight proteins [4,10] , and of different tubular enzymes [4,10,12] , e.g. alanine aminopeptidase and ␥ -glutamyltransferase (GGT) specifi c for brush border damage of proximal tubular cells [15] , N-acetyl-␤ -D -glucosaminidase (NAG) specifi c for lysosomal damage [10,12] and lactate dehydrogenase (LDH), which is a cytosolic enzyme [12] .…”

Pharmacodynamic Characterization of Nephrotoxicity Associated with Once‐Daily Aminoglycoside

“…There is little doubt that aminoglycosides may contribute to nephrotoxicity in all patients, especially those with certain risk factors. 3,[13][14][15][16][17] However, questions arise regarding the exact time course for development of the disorder. In one trial, ODA decreased the daily accumulation of aminoglycoside and thus increased the time to reach the threshold required for nephrotoxicity.…”

“…of drug and potentially may decrease nephrotoxicity. 4,12 Risk factors for nephrotoxicity, determined from studies performed in patients treated with TDA, 3,[13][14][15][16][17] include concomitant administration of vancomycin, amphotericin B, or diuretics; patient age and sex; aminoglycoside trough concentrations; vancomycin peak and trough serum concentrations; and duration of therapy.…”