Comparison of changes in acute kidney injury markers between 15mg.kg vs. 25mg.kg doses of amikacin in critically ill patients

Motahare Mahi birjand,1 Laleh mahmoudi,2,*

1. Student research committee, Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences,
2. Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract


Introduction

Acute kidney injury (aki) is a relatively common complication of therapy with the aminoglycoside antibiotics, including amikacin. serum creatinine and blood urea nitrogen (bun) have typically been used to diagnose aki. serum creatinine is dependent on non renal factors independent of kidney function (eg, age, sex, race, muscle mass, nutritional status, infection, and volume of distribution. several medications alter the tubular secretion of creatinine, leading to changes in serum creatinine independent of gfr. bun is dependent on non renal factors independent of kidney function (eg, production and renal tubular handling, protein intake, catabolic state, upper gastrointestinal bleeding, volume status, and therapy with highdose steroids). there is an urgent need for better biomarkers to permit more timely diagnosis of aki, prediction of injury severity, and safety assessment during drug development. a biomarker that is released into the blood or urine by the injured kidney may be a more sensitive and specific marker of aki than bun and serum creatinine. an ideal biomarker of aki would allow the early detection of kidney injury before an increase in serum creatinine and/or bun. the aim of this study was to compare changes in acute kidney injury markers between 15mg.kg vs. 25mg.kg doses of amikacin in critically ill patients.

Methods

Fourty patients were included in the study between april 2010 to may 2011. all patients received amikacin in combination with a broad-spectrum β-lactam after the diagnosis of hospital-acquired infection. patients were randomized to two treatment groups according to amk dose in two phases. renal function tests were calculated by following plasma creatinine and aki biomarkerlevels from days 1 to 7 looking for the appearance of renal failure, and biomarkers of (aki), including neutrophil gelatinase-associated lipocalin (ngal), interleukin-18 (il-18), and fetuin a, were measured.

Results

There were no significant differences in gender, apache ii score (18.45 + 5.54 and 15±5 in groups 1 and 2 respectively) or sequential organ failure assessment (sofa) score (day 1, 10 ± 3 and 11 ± 3 respectively) between groups. baseline plasma creatinine levels in the different groups were 1.87 ± 1.14, and 1.89 ± 1.19 mg/dl, respectively, and differences did not reach statistical significance. il-18 and fetuin-a levels also didn’t have significant deference between two groups. however, in a sample, a significant deference was found between ngal level in two groups on day 7.(p=0.033).

Conclusion

Renal dysfunction in critically ill patients is variable and multifactorial. no difference in the mortality and renal biomarkers and functions, such as creatinine, were found in two different groups. these biomarkers as useful tools for the earlier diagnosis, identification of mechanism of injury, and assessment of site and severity of injury therefore, our findings suggest that in critical care patients with septic shock there is no indication for loading dose adjustment guided by renal function and we can use doses higher than 15 mg/kg/day in these patients.

Keywords

Amikacin, acute kidney injury biomarkers, critically ill patients