Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin.
OBJECTIVE
Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance].


METHODS
We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy.


RESULTS
Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased.


CONCLUSIONS
We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.
Halacova
M
M
Department of Clinical Biochemistry and Pathobiochemistry, Charles University, 2nd Medical Faculty and University Hospital Motol, Prague, Czech Republic. milada.halacova@lf2.cuni.cz
Kotaska
K
K
Kukacka
J
J
Vavrova
V
V
Kuzelova
M
M
Ticha
J
J
Prusa
R
R
D000118:Acetylglucosaminidase / Q000652:urine; D000293:Adolescent; D000328:Adult; D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood / Q000652:urine; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D003550:Cystic Fibrosis / Q000097:blood / Q000188:drug therapy*; D016903:Drug Monitoring; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D012372:ROC Curve; D013997:Time Factors
D000900:Anti-Bacterial Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D000583:Amikacin; D003404:Creatinine; D000118:Acetylglucosaminidase