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Cystic fibrosis (CF) is a chronic respiratory, life limiting illness in the Caucasian population. Chronic infection with Pseudomonas aeruginosa occurs in more than 80% of adults and this contributes to deterioration in lung function over time.1 A reported long term complication includes renal impairment from presumed cumulative aminoglycoside antibiotics. Aminoglycosides are highly effective against Pseudomonas aeruginosa and effectively penetrate the sputum of patients with CF, achieving more effective bacterial killing.2 The nephrotoxicity of aminoglycosides is reported to be caused by proximal tubular alteration of cell function and cell necrosis.3
The study by Smyth et al4 demonstrates increased renal toxicity measured by plasma creatinine following a case controlled analysis of patients undergoing gentamicin therapy for the treatment of cystic fibrosis exacerbation. The authors did not specify the timing of plasma creatinine measurements in relation to gentamicin dosing (ie, was it collected before the gentamicin dose was given or at an interval following the dose). This would have been important to clarify whether renal impairment was present prior to dosing or occurred subsequently. Of further interest is the measurement of creatinine levels following cessation of gentamicin to elucidate whether renal impairment was persistent or document evidence of renal function recovery. Plasma creatinine reflects glomerular function rather than tubular function, which was not measured in this study. Plasma creatinine levels are subject to factors such as dehydration, nutrition and body size, and may not be a sensitive test in detecting renal impairment until well established disease has occurred.5
The challenge in quantifying renal impairment in cystic fibrosis is to describe the site of damage (ie, renal tubules versus renal glomeruli) and manifestations of early injury. Early and more accurate measurements of glomerular filtration rate may be attained by measuring the protein, cystatin C,6 or by utilising nuclear medical scans which provide validated measures by renal clearance of exogenous filtration markers, most commonly diethylenetriaminepentaacetate (DTPA).7 With regard to tubular injury, excretion of urinary proteins have been proposed as early markers of aminoglycoside induced tubular toxicity. Steinkamp et al8 demonstrated that acute tubular injury measured by excretion of urinary enzymes achieve almost complete recovery after 4 weeks from cessation of aminoglycosides. Ideally, prospective studies should measure renal function (both glomerular and tubular) in aminoglycoside naïve cystic fibrosis subjects and document early renal changes following aminoglycoside administration in a dose dependent manner.
Competing interests: None.