Patterns of urinary beta 2-microglobulin excretion by patients treated with aminoglycosides

Abstract

Aminoglycoside antibiotics are relatively mild nephrotoxins, but their action is site-specific to the proximal tubule. Therefore, use of these drugs presents a unique opportunity to study the temporal relation between the damage to the cells lining the renal proximal tubule and the subsequent rise in the serum creatinine concentration. Our study of 52 aminoglycoside-treated patients included measurements of daily serum creatinine, daily 24-hour urinary beta 2-microglobulin (beta 2M) excretion, and determination of aminoglycoside tissue accumulation. An elevation in beta 2M excretion above the baseline value occurred in 37 of 52 (71%), whereas the serum creatinine concentration rose in only 17 of 52 (33%) of patients. Even fewer patients (10 of 52) demonstrated all three criteria for aminoglycoside nephrotoxicity. These 10 patients had elevated tissue accumulation, evidence of renal tubular damage, and a rise in serum creatinine concentration. The increased beta 2M excretion greater than 50 mg/day preceded the serum creatinine rise by 2 to 7 days. An abnormal baseline beta 2M was not a risk factor for a subsequent rise in creatinine concentration or vice versa. Although each test is primarily site specific, widespread and severe renal proximal tubular damage, regardless of cause, will eventually lead to an elevation of serum creatinine. Thus, serial monitoring of proximal tubular function with urinary beta 2M excretion has potential value in the assessment of insults to this site, but cannot be expected to explain all changes in serum creatinine.