Disertasi

Neutrophil gelatinase associated lipocalin dalam serum dan urin sebagai prediktor histopatologi ginjal tikus dengan cedera ginjal iskemik dini. = Serum and urinary neutrophil gelatinase associated lipocalin as predictors of rat kidney histopathology with early ischemic kidney injury.

Latar Belakang. Tingkat keparahan cedera ginjal iskemia-reperfusi berhubungan erat dengan tingginya angka kesakitan dan kematian. Dalam penelitian pada manusia dan hewan, NGAL telah terbukti dapat mendeteksi dan memprediksi terjadinya cedera ginjal iskemik dini. Tujuan penelitian ini adalah untuk membuktikan bahwa peningkatan kadar NGAL serum dan urin berhubungan dengan kerusakan epitel tubulus ginjal dan peningkatan kadar NGAL serum dan urin telah terjadi pada fase cedera ginjal iskemik dini yang ditandai dengan histopatologi ginjal tikus yang mengalami iskemia-reperfusi. Metode Penelitian. Digunakan 28 ekor tikus Sprague-Dawley sebagai model hewan coba, dibagi dalam 4 kelompok: sham 4 jam (Sham 4), sham 8 jam (Sham 8), iskemia 10 menit reperfusi 4 jam (I/R 4), dan iskemia 10 menit reperfusi 8 jam (UR 8). Diambil sampel darah, urin, dan jaringan ginjal. Kadar kreatinin serum diperiksa dengan Metode Jaffe, NGAL serum dan urin dengan ELISA metode direct sandwich. Tingkat kerusakan jaringan dihitung secara semi kuantitatif setelah pemeriksaan jaringan ginjal pewamaan Hematoksilin Eosin. Deskripsi kelainan diperjelas melalui gambaran mikroskop elektron. Ekspresi NGAL pada jaringan ginjal dihitung secara semi kuantitatif setelah pemeriksaan dengan metode Imunohistokimia (IHK). Hasil. Korelasi bermakna ditemukan di antara kadar NGAL serum dan tingkat kerusakan ginjal (PSpeannan = 0,701, P < 0,001), kadar NGAL urin dan tingkat kerusakan ginjal (PSpearman = 0,689, p < 0,001). Kadar NGAL serum dan urin (Mann-Whitney, U = 0, p < 0,001), tingkat kerusakan ginjal (t-test, t = - 5,028, p < 0,001) dan ekspresi NGAL jaringan (t-test, t = -26635,046, p < 0,001), lebih tinggi pada kelompok UR dibanding Sham. Pada ambang batas 136,95 nglmL dan 58,69 ng/mL untuk masing-masing NGAL serum dan urin diperoleh sensitivitas 1, spesifisitas 1. Simpulan. Peningkatan kadar NGAL serum dan urin berhubungan dengan kerusakan epitel tubulus dan telah terjadi pada fase pemulaan yang ditandai dengan kerusakan histopatologi ginjal tikus yang mengalami cedera ginjal iskemik dini.
Kata kunci: Cedera ginjal iskemik dini, histopatologi ginjal, NGAL.



Background. The severity of ischaemia-reperfusion kidney injury is highly correlated with mortality and morbidity rate. Based on result of human and animal research, it has proved that NGAL predict kidney, injury at early phase. The objective of this study is to prove that the increase in serum and urinary NGAL are correlated with kidney tubular epithelial damage, particulary it has occurred in early phase, indicated by rat kidney histopathology undergoing ischaemia- reperfusion. Methods. Twenty eight male Sprague-Dawley rats were divided into 4 groups: 4 hour sham (Sham 4), 8 hour sham (Sham 8), 10 minute ischaemia 4 hour reperfusion (I/R 4), and 10 minute ischaemia 8 hour reperfusion (I1R 8). Blood, urine and kidney samples were collected. Serum creatinine level was measured with Jaffe method, serum and urinary NGAL level was measured with direct sandwich ELISA method. Degree of kidney damage were measured semiquantitatively in tissue stained with Hematoxylin Eosin. Electron microscopy were used to confirm the abnormality. NGAL tissue expression were measured semiquantitatively in tissue after examined with Immunohistochemistry (IHC) method. Results. Significant correlation were found between serum NGAL and degree of kidney tissue damage (PSpearrnan = 0.701, p < 0.001), urinary NGAL and degree of kidney tissue damage (PSpearman = 0.689, p < 0.001). Serum and urinary NGAL levels (Mann-Whitney, U = 0, p < 0,001), degree of kidney damage (Hest, t = - 5,028, P < 0,001), and NGAL tissue expression (Hest, t = -26635,046, P < 0,001), were higher in I1R group than Sham. With cut-off points of 136.95 ng/mL and 58.69 ng/mL for serum and urinary NGAL respectively, it is found that sensitivity = 1, specificity = 1. Conclusions. The increase of serum and urinary NGAL are significantly correlated with epithelial tubular damage and have occured in initiation phase, indicated by rat kidney histopathology undergoing ischaemia-reperfusion,
Keywords: early ischemic kidney injury, kidney histopathology, NGAL.