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Hubungan antara kadar aminoglikosida dalam plasma dengan kadar kidney injury molecule-1 dalam urin pada neonatus dengan infeksi = Correlation between Aminoglycoside Plasma Concentration and Urinary Kidney Injury Molecule-1 in Neonates with Infection.

Latar belakang: Penelitian ini bertujuan untuk mengetahui apakah kadar aminoglikosida yang diberikan pada neonatus yang dirawat di Rumah Sakit Cipto Mangunkusumo (RSCM) berada pada rentang yang efektif dan aman serta mengetahui hubungannya dengan kadar Kidney Injury Molecule-1 (KIM-1) di urin, suatu penanda nefrotoksisitas baru yang sensitif dan spesifik. Metode: Penelitian observasional ini dilakukan pada neonatus dengan infeksi yang mendapat aminoglikosida (gentamisin dan amikasin) pada November 2010 sampai November 2011 di RSCM. Sampel darah diambil dengan tusukan pada tumit sebelum obat diberikan (kadar lembah) dan 30 menit sesudahnya (kadar puncak). Pengambilan sampel dilakukan pada 1-3 dosis. Kadar aminoglikosida diukur dengan Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) dan Kadar KIM-1 dalam urin diukur dengan ELISA. Hasil: Pada penelitian ini diperoleh 28 neonatus. Dari 27 subyek penelitian yang mendapat gentamisin, dilakukan 34 pengukuran kadar lembah dan kadar puncak gentamisin. Ditemukan 18 kadar lembah gentamisin berada di atas batas aman (2 mcg/mL) dan 3 kadar puncak berada di bawah batas efektif (5 mcg/mL). Dari 5 subyek penelitian yang mendapat amikasin, dilakukan 9 pengukuran kadar lembah dan kadar puncak amikasin. Ditemukan 4 kadar lembah amikasin berada di atas batas aman (10 mcg/mL) dan 3 kadar puncak amikasin berada di bawah batas efektif (20 mcg/mL). Kadar KIM-1 normalisasi pada subyek yang kadar lembah gentamisinnya berada dalam batas aman berbeda bermakna dengan subyek yang kadar lembah gentamisinnya tidak aman (p = 0,037, 95% CI = -7385,95 s.d. 312,06). Terdapat korelasi antara kadar lembah gentamisin dengan log kadar KIM-1 normalisasi (p = 0,007; r = 0,625). Kesimpulan: Pemberian aminoglikosida pada neonatus di RSCM belum menghasilkan kadar yang optimal. Oleh karena itu, direkomendasikan untuk melakukan pemantauan kadar aminoglikosida secara rutin. Peningkatan kadar lembah gentamisin akan menyebabkan peningkatan kadar KIM-1 normalisasi.
Kata kunci: aminoglikosida, gentamisin, amikasin, KIM-1, nefrotoksisitas


Introduction: This study is aimed to determine whether the aminoglycosides plasma concentrations in neonates hospitalized at Cipto Mangunkusumo Hospital (CMH) are within the effective and safe therapeutic range and correlate them with kidney injury molecule-1 (KIM-1), a new sensitive and specific marker for nephrotoxicity. Methods: This is an observational study conducted in neonates with infection treated with aminoglycosides (gentamicin and amikacin) from November 2010 - November 2011 at CMH. Blood sample is taken by a heel prick for 1-3 doses before (trough level) and 30 minutes after (peak level) the drug infusion. Aminoglycoside plasma concentrations are measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS), while urinary KIM-1 levels are measured using ELISA. Result: The present study included 28 neonates. Patients treated with gentamicin (N = 27) was measured for 34 trough and peak level. There was 18 gentamicin trough level above the safe concentration (2 mcg/mL) and 3 peak level below the effective concentration (5 mcg/mL). Patients treated with amikacin (N = 5) was measured for 9 trough and peak level. There was 4 amikacin trough level above the safe concentration (10 mcg/mL) and 3 peak level below the effective concentration (20 mcg/mL). Normalized KIM-1 level in patients within safe gentamicin concentration were significantly different with those who did not (p = 0.037, 95% CI = -7385.95 to -312.06). There was a correlation between gentamicin trough level with log normalized KIM-1 level (p = 0.007; r = 0.625). Conclusion: Aminoglycosides treatment for neonates hospitalized at CMH is not optimal yet. It is highly recommended to conduct aminoglycoside concentration monitoring routinely. Higher gentamicin trough level can increase the normalized KIM-1 level.
Keywords: aminoglycoside, gentamicin, amikacin, KIM-1, nephrotoxicity