Renal Tubular Enzyme Effects of Clarithromycin in Comparison with Gentamicin and Placebo in Volunteers

Abstract

This study assessed the potential nephrotoxicity of clarithromycin in comparison with gentamicin and placebo. Increased urinary excretion of alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) served as markers of renal tubular injury. The study utilised a multiple-dose, double-blind, randomised, parallel group design. 14 healthy male subjects received 1 of 3 treatment regimens: (a) clarithromycin 500 mg orally every 12h for 13 doses and intravenous placebo every 8h (n = 5); (b) oral placebo every 12h and intravenous placebo every 8h (n = 4); and (c) intravenous gentamicin 1.7 mg/kg every 8h for 19 doses and oral placebo every 12h (n = 5). 24h urine collections were obtained daily for determinations of AAP and NAG activities. Gentamicin produced statistically significant increases (p less than 0.0001) in AAP and NAG excretion, with increases as early as the first and second day of dosing. Clarithromycin, when compared with placebo, did not produce significant elevations in AAP or NAG activity. On the basis of these data, it is unlikely that usual doses of clarithromycin have significant potential for causing nephrotoxicity.

Protective Effects of Tribulus terrestris Against Gentamicin Mediated Nephrotoxicity, Oxidative Damage and Apoptosis in Male Rats

“…β2M is filtered by the glomerulus and almost reabsorbed and catabolized by the proximal tubular cells (Miyata et al, 1998), this process impaired in AKI. Elevation in the level of excretion of β2M I the urine has been recorded to be an early marker of tubular injury (Chapelsky et al, 1992) before the elevation in serum creatinine level by 4−5 days (Tolkoff-Rubin et al, 1988). KIM-1 is presented on the tubular epithelial surface in the kidney.…”

Biomarkers of Acute Kidney Injury

“…β 2 M is typically filtered by the glomerulus and almost entirely reabsorbed and catabolized by the proximal tubular cells (37), a process that may be impeded in AKI. Increased urinary β 2 M excretion has been observed to be an early marker of tubular injury in a number of settings, including nephrotoxicant exposure (38), cardiac surgery (39), and renal transplantation (40), preceding rises in serum creatinine by as many as 4−5 days (36). Unfortunately, the utility of β 2 M as a biomarker has been limited by its instability in urine, with rapid degradation observed at room temperature and in urine with a pH less than 6.0 (40a).…”

Urinary biomarkers in assessing the nephrotoxic potential of gentamicin in solitary kidney patients after 7 days of therapy

“…Monitoring of NAG releases would allow identification of patients who present nephrotoxicity and whose treatment is to be interrupted. 36 Unlike gentamicin, clarithromycin does not cause significant increases of urinary NAG. 36 Carver et al appreciate that there is correlation between the doses of gentamicin administered to rats and enzymuria, such as urinary NAG.…”

“…36 Unlike gentamicin, clarithromycin does not cause significant increases of urinary NAG. 36 Carver et al appreciate that there is correlation between the doses of gentamicin administered to rats and enzymuria, such as urinary NAG. 37 The nephrotoxicity of other aminoglycosides, assessed by determination of urinary NAG, is to be mentioned as well.…”