Renal function in Cystic Fibrosis: Proteinuria and enzymuria before and after tobramycin therapy

Abstract

Proteinuria and enzymuria were measured in 27 patients with Cystic Fibrosis before and after tobramycin therapy. Prior to treatment, kidney function was normal in 23 patients. Four patients showed a pathological proteinuria and two haematuria. Renal biopsy in one patient showed segmental basement membrane alterations on electron microscopy; there were no immunoglobulin deposits. During intravenous therapy with tobramycin (10 mg/kg per day) and azlocillin (100 mg/kg per day) mean urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion rose six-fold and mean urinary alaninaminopeptidase excretion increased ten-fold. After cessation of therapy, enzymuria rapidly returned to pretreatment values in all 14 patients. Aerosol tobramycin therapy in four patients did not affect urinary excretion of NAG. It can be concluded that tobramycin did not cause persistent renal damage in our patients, whether given intravenously or as an aerosol.

The effects of intravenous tobramycin on renal tubular function in children with cystic fibrosis

“…Therefore, in our study group the tubular injury appeared to be completely reversible if UrRBP is used as a marker of tubular damage but only partially so if UrNAG is employed. Similar changes in UrNAG during an intravenous tobramycin course have been reported previously by Steinkamp et al [11] although their study documented a rapid and complete return to pretreatment levels in a smaller number of patients who also received concurrent intravenous azlocillin. The changes in UrRBP have not been published before.…”

“…Steinkamp et al reported that inhaled tobramycin produced no alteration in UrNAG activity [11], but Ring et al demonstrated in those patients receiving gentamicin inhalation a positive correlation between UrNAG and the cumulative dose of nebulised gentamicin [14].…”

Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients

“…After limited exposure to aminoglycosides, both antibacterial potency and suppression of bacterial growth continue for The safety of once-daily dosing has been reported to be similar to that of multiple administrations. Serum creatinine usually remains within the normal range [15,29,32,35]. We used more sophisticated markers of acute nephrotoxicity and found transient increases in urinary concentrations of b-NAG and a-1-microglobulin after treatment, which reverted to normal after cessation of therapy.…”

Differentiation of proteinurias with electrophoresis

“…Total protein [35,36], marker proteins such as albumin, alphal-microglobulin [37], and urinary enzymes [38][39][40] have been measured. We have analysed more than 9,000 urine specimens from children and adults with PAGE.…”