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"Latar belakang Sisplatin merupakan pengobatan utama untuk karsinoma nasofaring KNF , tetapi berpotensi menimbulkan nefrotoksisitas. Selain kadar BUN dan kreatinin serum, KIM-1 dan NGAL diduga cukup sensitif untuk mendeteksi nefrotoksisitas. Penelitian ini bertujuan untuk mengevaluasi kadar KIM-1 dan NGAL dalam urin untuk mendeteksi gangguan fungsi ginjal pada pasien KNF stadium lanjut yang mendapatkan kemoterapi berbasis sisplatin.Metode: Penelitian ini merupakan penelitian kohort prospektif. Subyek penelitian dibagi dalam 3 kelompok: pasien yang belum pernah terpapar dan yang sudah pernah mendapatkan kemoterapi berbasis sisplatin 75-100 mg/m serta pasien yang belum pernah mendapatkan kemoterapi sisplatin dan kemudian diberi sisplatin 40 mg/m 2 . Kadar KIM-1, NGAL dalam urin serta kadar BUN dan kreatinin dalam serum diukur pada saat sebelum dan sesudah mendapatkan sisplatin pada ketiga kelompok. Analisis statistik yang digunakan adalah uji ANOVA, uji Pearson, Spearman, Kolmogorov-Smirnov dan SPSS versi 22,0.Hasil: Terdapat perbedaan selisih kadar BUN yang bermakna antara sebelum dan sesudah diterapi pada ketiga kelompok p=0.0001 . Perbedaan selisih kadar NGAL dalam urin pada penelitian ini juga berbeda bermakna antara sebelum dan sesudah diterapi terhadap ketiga kelompok p=0,025 , tetapi ada perbedaan rerata pada sepasang kelompok yang bermakna hanya didapatkan pada kelompok yang belum pernah dikemoterapi 40 mg/m 2 dan kelompok yang sudah pernah diberi kemoterapi 75-100 mg/m 2 p=0,02. Perbedaan selisih kadar KIM-1 tidak bermakna pada ketiga kelompok p=0,275.Kesimpulan: Sisplatin menunjukkan akumulasi nefrotoksisitas yang tergantung pada dosis dose-dependent manner . Pengukuran kadar NGAL dalam urin dapat mendeteksi nefrotoksisitas tahap dini, tetapi belum bisa menggantikan peran BUN. Pengukuran kadar KIM-1 dalam urin tidak dapat mendeteksi gangguan fungsi ginjal.

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Background: Cisplatin is the main treatment for nasopharyngeal carcinoma NPC with a potency of causing nephrotoxicity. In addition to serum BUN and creatinine levels, KIM 1 and NGAL levels is assumed to be quite sensitive in detecting nephrotoxicity. The study was aimed to evaluate urinary KIM 1 and NGAL level to detect kidney dysfunction in patients with advanced stage NPC who received cisplatin based chemotherapy.

Method: The study was a cohort prospective study. Subjects were categorized into 3 groups, i.e. patients who had never received and who had received 75 100 mg m2 cisplatin based chemotherapy as well as those who had never received any cisplatin based chemotherapy and were subsequently received 40 mg m cisplatin. The levels of urinary KIM 1, NGAL and serum level of BUN and creatinine were measured before and after receiving cisplatin in the three groups. Statistical analysis used in our study were ANOVA, Pearson, Spearman, KolmogorovSmirnov test and SPSS version 22.0.

Results: There was a significant difference of delta BUN level before and after treatment in all three groups p 0.0001 . Delta urinary NGAL level was also significantly different between before and after treatment in all groups p 0.025 however, a significant mean difference of a pair group was only found between those who never had 40 mg m 2 chemotherapy and those who had received 75 100 mg m 2 chemotherapy p 0.02 while delta KIM 1 level showed no significant difference in all three groups p 0.275.

Conclusion: Cisplatin may cause accumulated nephrotoxicity, which has dosedependent manner. Measuring urinary NGAL level can detect an early stage of kidney dysfunction however, it still cannot replace the role of BUN. Measurement of urinary KIM 1 level cannot detect kidney dysfunction."

"Latar Belakang: Tujuan penelitian untuk melihat neutrophil gelatinase associated lipocalin (NGAL) pada pasien sepsis. Dimana NGAL merupakan biomarker yang dini untuk acute kidney injury (AKI). Metode Penelitian Penelitian kualitatif dengan desain uji diagnostik Pengambilan sampel secara cross sectional dan consecutive sampling pada 50 orang anak yang sepsis yang terdiri dari 28 sepsis, 22 sepsis berat di ruang rawat intensif anak di RS. Ciptomangunkusomo Jakarta dan RS.Wahidin Sudirohusodo Makassar. Hasil: Kadar NGAL urin pada pasien sepsis berat lebih tinggi dibandingkan sepsis. Nilai sensitifitas NGAL urin 100% dan spesifisitas 63,63%. NGAL urin meningkat lebih dulu bila dibandingkan dengan kreatinin serum. Kesimpulan NGAL dapat dipakai sebagai petanda dini terjadinya AKI.

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Introduction: The aim of this study to observe the neutrophil gelatinase associated lipocalin (NGAL) in pediatric sepsis. From previous study NGAL was early biomarker for AKI. Methods. This study is a qualitative study for diagnostic test. Sample was collected by cross sectional and consecutive sampling on 50 sepsis children, consist of 28 sepsis, 22 severe sepsis in pediatric intensive care unit Ciptomangunkusomo Hospital Jakarta and Wahidin Sudirohusodo Hospital Makassar.

Result: The value of urinary NGAL in severe sepsis is higher than sepsis. The Sensitivity and specificity is 100% and 63,63% this study suggest that urinary NGAL increase earlier than serum creatinine. Conclusion. Therefore urinary NGAL can be used as early biomarker for AKI."

"ABSTRAKLatar Belakang : Para pekerja yang melakukan aktivitas fisik di lingkungan panas tinggi dapat mengalami gangguan pada ginjal. Selain glomerulus, bagian tubulointerstium yang memiliki fungsi penting reabsorsi dan sekresi, diduga juga mengalami gangguan. Ingin diketahui lebih lanjut ada tidaknya gangguan pada sel tubulus ginjal para pekerja setelah 4 jam pajanan panas tinggi melalui pemeriksaan NGAL urin yang lebih spesifik.Metode : Desain penelitian ini adalah baseline study dan pre-post study.Dilakukan di bagian hotpress outsole pabrik sepatu di Tangerang bulan April 2015. Data primer didapat melalui wawancara, pemeriksaan langsung tinggi dan berat badan serta pengambilan sampel NGAL urin dilakukan 2 kali, sebelum dan sesudah 4 jam kerja terpajan tekanan panas tinggi (29,0 oC - 31,05 oC ISBB). Untuk pemeriksaan kadar NGAL menggunakan kit komersial (Quantikine kit Human Lipocalin-2/NGAL Immunoassay).Hasil : 68 pekerja memenuhi kriteria inklusi penelitian dan 100 % adalah laki-laki berusia 20-40 tahun yang sehat. Didapatkan nilai NGAL urin awal sebelum terpajan panas antara 0.03 ng/ mL ? 12,82 ng/mL dengan median 1.52 ng/mL. Dari pemeriksaan setelah 4 jam kerja terpajan panas terdapat 25 responden (36,8% ) mengalami kenaikan nilai NGAL dalam urin dengan median kenaikan sebesar 0,35 mg/dL sedangkan 43 responden (63,2%) tidak mengalami kenaikan nilai NGAL dalam urin .Simpulan: Tidak terdapat peningkatan yang dianggap bermakna pada rerata nilai NGAL dalam urin para pekerja pabrik yang tepajan tekanan panas tinggi selama 4 jam kerja.

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ABSTRACT

Background : Workers performing physical activities in heat-stress environment could have kidney disorder. Beside glomerulus, tubulointerstitium which has important function of reabsorption and secretion, is suspected to also have injury. Further exploration on the impact on kidney tubules cells on the workers after 4 hours exposed to heat-stress through more specific examination of urine NGAL (uNGAL).

Method : Design of this research are baseline study and pre-post study, conducted at the hotpress outsole department at a shoe factory in Tangerang in April 2015. Primary data obtained through interview, direct examination on height and weight and taking sample of uNGAL twice time, before and after 4 hours of moderate working activities in the area of high heat-stress (29,0 oC - 31,05 oC WGBT) . Examining NGAL level by using commercial kit (Quantikine kit Human Lipocalin-2/NGAL Immunoassay).

Result : 68 workers fit with criteria inclusion study and 100% are healthy men aged between 20-40 years. The result of uNGAL initial scores are between 0.03 ng/ mL ? 12,82 ng/mL with median of 1.52 ng/mL. After 4 hours of moderate working activities in the area of high heat-stress there are 25 workers ( 36,8% ) have increase uNGAL level with median of 0,35 mg/dL, while the other 43 workers (63,2%) have not.

Summary : There is no significant changes of urine NGAL score after 4 hours of working within worker population in the area of high heat-stress."

"Latar Belakang: Tuberkulosis paru (TB) masih menjadi salah satu penyebab morbiditas dan mortalitas di seluruh dunia. Dalam dua dekade terakhir penyakit TB resisten obat (TBRO) telah muncul sebagai ancaman bagi kesehatan masyarakat seluruh dunia. NGAL merupakan partikel granulosit neutrofil yang mengalami pematangan dan menjadi gelatinase. NGAL terlibat dalam kekebalan bawaan untuk menghalangi bakteri mengambil zat besi untuk pertumbuhan. Pada pasien dengan komorbid anemia akan terjadi penurunan kekebalan bawaan sehingga pada TBRO dengan anemia bakteri Mtb akan mendapat zat besi dari tubuh manusia untuk bereplikasi. Namun masih belum terdapat data kadar protein serum NGAL pada pasien TBRO dengan anemia.Metode : Penelitian ini merupakan penelitian analitik observasional menggunakan desain potong lintang yang dilakukan di poliklinik dan ruang rawat inap MDR RSUP Persahabatan pada bulan Juli-September 2023. Jumlah subyek penelitian adalah 73 pasien TBRO yang belum memulai pengobatan dengan anemia dan tanpa anemia yang memenuhi kriteria inklusi dan eksklusi. Sampel darah subyek diambil sebanyak 3cc.Serum darah diambil lalu disimpan dalam lemari es suhu -200C. selanjutnya dilakukan pemeriksaan ELISA teknik sandwich dan diambil kadar protein NGAL. Variabel lainnya diambil dari rekam medis RSUP Persahabatan.Hasil : Pada penelitian ini didapatkan pasien TBRO dengan anemia memiliki IMT yang menunjukkan tingkat malnutrisi yang bermakna (p:0,026, OR 2,9(1,1-7,5). Penelitian ini juga mengidentifikasi peningkatan jumlah neutrofil (p:0,002, OR 0,2(0,06-0,5) dan penurunan jumlah limfosit (p:0,006, OR (4,2 (1,4-9,8) pada kelompok pasien anemia, yang tercermin dalam NLR yang meningkat (p:0,028, OR 0,3(0,09-0,9). Hasil yang ditemukan juga menunjukkan bahwa pasien TBRO dengan anemia memiliki lesi paru yang lebih luas secara statistik (p:0,048, OR 2,7(0,9-7,3). Kadar NGAL menunjukkan hasil median 82,76 (67,59) yang lebih tinggi dibandingkan dengan kelompok pasien TBRO anemia dan kelompok TBRO tanpa anemia 59,24(91,98) namun tidak bermakna (p: 0,26). Terdapat korelasi yang bermakna kadar NGAL dengan leukosit (r:0,295, p:0,011), neutrofil (r:0,297, p:0,011), limfosit (r:-0,343,p:0,003) dan NLR (r:0,336,p:0,004).Kesimpulan: Terdapat peningkatan kadar NGAL pada pasien TBRO dengan anemia dibandingkan tanpa anemia namun tidak bermakna secara statistik.

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Background: Pulmonary tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. In the last two decades, drug-resistant tuberculosis (DR-TB) has emerged as a global health threat. NGAL is a neutrophil granulocyte- derived protein that undergoes maturation and becomes gelatinase. NGAL is involved in innate immunity by blocking bacteria from acquiring iron for growth. In patients with anemia, there is a reduction in innate immunity, in patient DR-TB with anemia allowing Mtb bacteria to obtain iron from the human body for replication. However, there is currently no data on serum NGAL protein levels in DR-TB patients with anemia.

Methods: This study is an observational research using a cross-sectional design conducted in the outpatient clinic and inpatient ward of MDR RSUP Persahabatan in July-September 2023. The research subjects were 73 subject DR-TB patients who not yet started treatment with or without anemia and met the inclusion and exclusion criteria. Blood samples of the subjects were collected as much as 3cc. The blood serum was separated and stored in a -20°C freezer. Furthermore, ELISA examination using the sandwich technique was performed, and NGAL protein levels were measured.

Results: In this study, DR-TB patients with anemia had BMI indicating significant malnutrition (p: 0.026, OR 2.9(1.1-7.5). This study also identified an increase in the number of neutrophils (p: 0.002, OR 0.2(0.06-0.5) and a decrease in the number of lymphocytes (p: 0.006, OR 4.2(1.4-9.8) in the anemia patient group, as reflected in the increased NLR (p: 0.028, OR 0.3(0.09-0.9). The findings also showed that DR-TB patients with anemia had statistically larger lung lesions (p: 0.048, OR 2.7(0.9-7.3). NGAL levels showed a higher median result between the DR-TB patient group with anemia 82,76 (67,59) and the group without anemia 59,24 (91,98), but it was not statistically significant (p: 0.26). NGAL have significant corelation among leukocyte (r:0,295, p:0,011), neutrophil (r:0,297,p:0,011), limphocyte (r:-0,343,p:0,003) and NLR (r:0,336,p:0,004)

Conclusion: There is a increase in NGAL levels in DR-TB patients with anemia compared to those without anemia. However, this findings do not reach statistical significance."

"Latar Belakang. Mortalitas akibat sepsis di ICU masih cukup tinggi meskipun telah semakin cepatnya diagnosis dan perbaikan perawatan suportif dan angkanya semakin meningkat dengan insiden acute kidney injury yang merupakan bagian dari disfungsi organ akibat sepsis. Asam askorbat dikatakan dapat memperbaiki disfungsi organ disebabkan efeknya yang sinergis terhadap patofisiologi sepsis. Peranan asam askorbat dalam menurunkan disfungsi organ masih kontroversial. Penelitian ini ingin menganalisis efek pemberian asam askorbat intravena terhadap perbaikan fungsi ginjal pada pasien sepsis/ syok sepsis yaitu dengan melihat efek terhadap kadar urin neutrophil gelatinase associated lipocalin (uNGAL), produksi urin dan balans kumulatif. Metodologi. Penelitian ini merupakan penelitian uji klinis dengan desain penelitian uji acak terkontrol, dilakukan pada pasien usia > 18 tahun dengan sepsis berdasarkan kriteria sepsis-3 yang masuk ICU dalam 6 sampai 24 jam pascaresusitasi setelah diagnosis sepsis. Kriteria penolakan yaitu pasien dengan gangguan ginjal kronik dengan hemodialisis, kelainan batu ginjal, dengan masalah ginjal dalam 3 bulan terakhir. Pasien akan dikeluarkan apabila diberikan kortikosteroid dan mendapatkan terapi pengganti ginjal dalam < 72 jam observasi. Penelitian dilakukan di ICU Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo pada April 2019-Juli 2019. Sebanyak 33 sampel dirandomisasi secara randomisasi sederhana dan dikelompokan menjadi kelompok perlakuan (18 sampel) dan kontrol (15 sampel). Data demografik dasar dicatat saat masuk ICU. NGAL urin (ng/mL) diperiksa pada jam 0, 24, 48 dan 72 setelah terapi. Produksi urin (ml/kg/jam) dan balan kumulatif (L) dicatat pada jam 24, 48 dan 72 setelah terapi. Analisis statistik dengan uji Mann Whitney untuk data numerik dengan persebaran tidak normal, uji T independen untuk data dengan persebaran normal dan uji Fisher untuk data kategorik perbandingan antara kedua kelompok intervensi. Analisis multivariat untuk pengukuran serial menggunakan generalized estimating equations (GEE) untuk membandingkan antara kedua kelompok dalam waktu pengukuran yang berulang. Nilai signifikansi dengan nilai p < 0,05. Hasil. Tidak terdapat perbedaan pada kadar NGAL urin, produksi urin, balans kumulatif antara dua kelompok di setiap jamnya. Kesimpulan. Pada penelitian ini pemberian asam askorbat intravena tidak mempunyai efek terhadap kadar NGAL urin, produksi urin, balans kumulatif.

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Background. Sepsis-related mortality in intensive care unit (ICU) remains despite improved diagnostic technology and supportive treatment. Acute kidney injury, one of frequent organ dysfunctions in sepsis, increases risk of mortality. Ascorbic acid could improve organ dysfunction because its direct effect on sepsis pathophysiology. The role of ascorbic acid on improving organ dysfunction remains controversial. This study wished to analyze the effects of intravenous ascorbic acid on kidney function improvement among septic patients by evaluating urine neutrophil gelatinase associated lipocalin (uNGAL), urine output and cumulative fluid balance.

Method. This study was randomized controlled trial held in Cipto Mangunkusumo Hospital from April to July 2019. The inclusion criteria were adult patients aged > 18 years who met sepsis-3 criteria and were admitted to the ICU within 6-24 h after resuscitation and sepsis recognition. The exclusion criteria were patients with hemodialysis-dependent chronic kidney disease, kidney stones or other kidney problems within last 3 months. The drop out criteria were patients underwent renal replacement therapy in the ICU and given corticosteroid less than 72 h after recruitment. Subjects were randomized using simple randomization and divided into two groups with treatment (18 subjects) and control (15 subjects). Baseline demographic data was recorded on the first day. Daily measurements of urine NGAL (ng/ mL) was started as baseline level and continued at 24, 48 and 72 h after treatment. Urine output (ml/kg/h), cumulative fluid balance (L) was recorded at at 24, 48 and 72 h after treatment. Comparison between both groups was analysed by using Mann Whitney test (not normally distributed data), T independent test (normally distributed data) for numerical data and Fisher test for categorical data. Multivariate analysis using generalized estimating equations was used for serial measurement analysis. Level of significant was determined at p-value <0.05.

Result. There were no significant differences in uNGAL, urine output, cumulative fluid balance between the two groups at each hour respectively.

Conclusion. This study showed that intravenous vitamin CMultin administration had no effect on urine NGAL, urine output, cumulative fluid balance."

"Latar belakang: Tingkat keparahan cedera ginjal iskemia-reperfusi (I/R) berhubungan erat dengan tingginya angka kesakitan dan kematian. Hasil penelitian terdahulu pada manusia dan hewan telah mebuktikan bahwa Neutrophil Gelatinase Associated Lipocalin (NGAL) dapat mendeteksi dan memprediksi terjadinya cedera ginjal I/R dini. Tujuan penelitian ini adalah untuk membuktikan bahwa peningkatan kadar NGAL serum dan urin berhubungan dengan kerusakan epitel tubuli ginjal pada tikus yang mengalami iskemia reperfusi dini.Metode: Peneltian ini menggunakan 28 ekor tikus Sprague-Dawley jantan sebagai hewan model, dikelompokkan 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 (I/R 8). Analisis kadar kreatinin serum diperiksa dengan metode Jaffe, sedangkan NGAL serum dan urin menggunakan metode ELISA Direct Sandwich. Evaluasi tingkat kerusakan jaringan ginjal dilakukan secara semi kuantitatif pada sediaan histologi dengan pulasan HE. Deskripsi kelainan tingkat seluler ginjal diperjelas melalui evaluasi menggunakan mikroskop elektron dan Imunohistokimia (IHK).Hasil: Kadar NGAL serum berkorelasi bermakna dengan tingkat kerusakan ginjal (ρSpearman NGAL serum = 0,701, p < 0,001), juga kadar NGAL urin berkorelasi bermakna dengan tingkat kerusakan ginjal (ρSpearman = 0,689, p < 0,001). Tingkat ekspresi NGAL lebih tinggi pada kelompok I/R dibanding sham (t-test, t = -26635,046, p < 0,001), juga tingkat kerusakan ginjal tikus (t-test, t = -5,028, p < 0,001), dan kadar NGAL serum dan urin pada kelompok I/R berbeda nyata dibanding sham (Mann-Whitney, U = 0, p < 0,001). Pada cutoff point 136,95 ng/mL dan 58,69 ng/mL berturut ? turut untuk NGAL serum dan urin diperoleh sensitivitas = 1, spesifisitas = 1.Kesimpulan: Peningkatan kadar NGAL serum dan urin berkorelasi dengan kerusakan epitel tubuli ginjal pada tikus yang mengalami cedera ginjal iskemia reperfusi dini.

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Background: The severity of ischemia-reperfusion (I/R) kidney injury is highly correlated with mortality and morbidity rate. Research on human and animal prove that NGAL predicts 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, and this increase has occurred in initiation phase, indicated by rat kidney histopathology in an early I/R model.

Methods: Twenty eight male Sprague-Dawley rats were divided into 4 groups: 4 hour sham (Sham 4), 8 hour sham (Sham 8), 10 minute ischemia 4 hour reperfusion (I/R 4) and 10 minute ischemia 8 hour reperfusion (I/R 8). Blood, urine and kidney samples were collected. Serum creatinine level was analyzed with Jaffe method, while serum and urinary NGAL level were analyzed with direct sandwich ELISA method. Evaluation of kidney damage were measured semi quantitatively in tissue stained with HE. Further evaluation to confirm cellular changes on kidney was performed by electron microscope and immunohistochemistry.

Results: Serum NGAL was found significantly correlated with degree of kidney tissue damage (ρSpearman NGAL serum = 0.701, p < 0.001), also urinary NGAL (ρSpearman = 0.689, p < 0.001). NGAL expression differs significantly between I/R group and sham (t-test, t = -26635.056, p < 0.001), also kidney damage (t-test, t = -5.028, p < 0.001), and serum and urinary NGAL levels (Mann-Whitney, U = 0, p < 0.001). With cutoff points of 136.95 ng/mL and 58.69 ng/mL subsequently for serum and urinary NGAL , it is found that sensitivity = 1, specificity = 1.

Conclusion: Elevation of serum and urinary NGAL are significantly correlated with epithelial tubular kidney damage on rat undergoing early ischaemia reperfusion."

"ABSTRAKLatar belakang: Sepsis merupakan masalah kesehatan penting yang dapat menyebabkan insidens kematian sampai 50% pada pasien dengan sepsis berat. Antibiotik aminoglikosidaterutama amikasin semakin banyak digunakan untuk mengobati infeksi kuman Gram negatif pada pasien sepsis di ICU, meskipun penggunaan obat tersebut pada dosisterapi dapat meningkatkan risiko kerusakan ginjal sekitar 10-25%. Pemantauan kadar lembah amikasin serta biomarker dini diperlukan untuk mencegah kerusakan ginjal pada pasien sepsis yang dirawat di ICU. Penelitian ini dilakukan untuk mengetahui hubungan kadar lembah amikasin pada pasien ICU dewasa yang dirawat di Rumah Sakit Cipto Mangunkusumo yang diberikan amikasin 1000 mg/hari denganpeningkatan kadar KIM-1 normalisasi dalam urin yang merupakan biomarker dini nefrotoksisitas.Metode:Penelitian ini merupakan penelitian pendahuluan yang dilakukan pada 12 pasien sepsis dewasa yang dirawat di ICU RSCM dan diberikan amikasin 1000 mg/hari pada bulan Mei-September 2015. Kadar lembah amikasin dosis ketiga dihubungkan dengan peningkatan kadar KIM-1 normalisasi yang diukur melalui urin 24 jam setelah pemberian amikasin dosis pertama/kedua dan dosis ketiga.Hasil:Dari 12 subyek penelitian, didapatkan 3 subyek penelitian dengan kadar lembah amikasin di atas 10 g/mL, sedangkan 9 subyek penelitian kadar lembahnya ada dalam batas aman (di bawah 10 g/mL). Delapan dari 12 subyek penelitian (66,7%) mengalami peningkatan kadar KIM-1 normalisasi dalam urin hari ketiga dibandingkan hari pertama. Tidak ada hubungan antara kadar lembah amikasin dengan peningkatan kadar KIM-1 normalisasi dalam urin (p=0,16; r=0,43).Kesimpulan:Pasien sepsis yang mendapat amikasin 1000 mg/hari di ICU RSCM selama 3 hari memperlihatkan kadar lembah amikasin plasma dalam batas aman untuk ginjal.

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ABSTRACT

Background: Sepsis is a common caused of mortality which may account for up to 50% death rate in patients with severe sepsis. Aminoglycoside antibiotics, especially amikacin, are the most commonly used antibiotics in the septic patients with Gram-negative bacterial infections, despite these drugs may induce nephrotoxicity in 10-25%

patients. Hence, it is essential to monitor amikacin trough plasma concentration and to detect nephrotoxicity as early as possible. The aim of this study is to find out the correlation between amikacin trough plasma concentration with normalized KIM-1 concentration in the urine as a sensitive and specific biomarker.

Methods:

This is a pilot study conducted in 12 septic patients treated with amikacin 1000 mg/day from May, 2015 to September, 2015. The correlation between amikacin

trough plasma concentrations measured at the third doses with the elevation of urine normalized KIM-1 concentrations measured at the first/second and the third doses were evaluated.

Results:

We observed 3 patients with amikacin trough plasma concentration above the safe level (>10 g/mL), while 9 patients had amikacin concentrations within the safe

plasma level (<10 g/mL). Furthermore, we observed 8 out of 12 patients with higher normalized KIM-1 concentrations measured at third doses compared to normalized KIM-1 concentrations measured at first/second doses. There was no correlation between amikacin trough concentration with elevated urine normalized KIM-1

concentration (p=0,16; r=0,43).

Conclusion:

Septic patients treated with amikacin 1000 mg/day hospitalized in ICU RSCM for 3 days have amikacin safe trough plasma concentration."

"Gangguan fungsi ginjal merupakan salah satu komplikasi yang sering terjadi pada pasien diabetes melitus tipe 2. Pendeteksian dini dengan menggunakan senyawa 8-iso-Prostaglandin F2α dan KIM-1 diperlukan untuk mencegah progresifitasnya. Dalam penelitian ini dilakukan analisis hubungan antara kadar 8-iso-Prostaglandin F2α dan KIM-1 urin dengan estimasi laju filtrasi glomerulus (eLFG). Sampel yang dianalisis adalah 40 orang pasien diabetes melitus tipe 2 di Puskesmas Pasar Minggu, dengan teknik total sampling. Nilai eLFG diperoleh berdasarkan nilai kreatinin serum yang diukur menggunakan metode kinetik Jaffe, sedangkan kadar 8-iso-Prostaglandin F2α dan KIM-1 diukur dengan menggunakan metode ELISA (Enzyme Linked Immunosorbent Assay). Kadar 8-iso-Prostaglandin F2α diperoleh 6633,87 ± 1292,62 pg/mg kreatinin, kadar KIM-1 diperoleh 8,23 ± 3,23 ng/mL dan nilai eLFG diperoleh 99,65 ± 41,12 (Cockroft-Gault); 96,59 ± 41,90 (MDRD study); dan 100,79 ± 40,07 (CKD-EPI). Hubungan antara kadar 8-iso-Prostaglandin F2α dengan nilai eLFG berdasarkan persamaan Cockroft-Gault (r = 0,520; p = 0,001), MDRD (r = 0,477; p = 0,004) dan CKD-EPI (r = 0,403; p = 0,013), serta setelah perokok dieksklusi, berdasarkan ketiga persamaan, yaitu Cockroft-Gault (r = 0,595; p = 0,001), MDRD (r = 0,554; p = 0,003) dan CKD-EPI (r = 0,559; p = 0,003). Hubungan antara kadar KIM-1 dengan nilai eLFG berdasarkan persamaan Cockroft-Gault (r = -0,155; p = 0,339), MDRD (r = -0,173; p =0,285) dan CKD-EPI (r = -0,024; p = 0,883). Sehingga diketahui terdapat hubungan yang bermakna antara kadar 8-iso-Prostaglandin F2α dengan nilai eLFG dan tidak terdapat hubungan yang bermakna antara KIM-1 dengan nilai eLFG.

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Renal dysfunction is one of complication that most common in type 2 diabetes mellitus patients. The earlier detection is needed to prevent its progression with 8-iso-Prostaglandin F2α and KIM-1. The aim of this study was to analyze concentration of 8-iso-Prostaglandin F2α and KIM-1urine and its correlation with estimated glomerular filtration rate (eGFR). Samples analyzed were 40 type 2 diabetes mellitus patients at Pasar Minggu Local Government Clinic, used total sampling method.

eGFR was obtained based on the measurement of serum creatinine on kinetic Jaffe method, 8-iso-Prostaglandin F2α and KIM-1 was measured by ELISA (Enzyme Linked Immunosorbent Assay) method. Concentration of 8-iso-Prostaglandin F2α was 6633,87 ± 1292,62 pg/mg creatinine, concentration of KIM-1 was 8,23 ± 3,23 ng/mL and the eGFR values were 99,65 ± 41,12 (Cockroft-Gault); 96,59 ± 41,90 (MDRD study); and 100,79 ± 40,07 (CKD-EPI).

The correlation between 8-iso-Prostaglandin F2α concentration and eGFR is based on Cockroft-Gault (r = 0,520; p = 0,001), MDRD (r = 0,477; p = 0,004) and CKD-EPI (r = 0,403; p = 0,013), and the correlation between 8-iso-Prostaglandin F2α concentration after smoker exclution and eGFR based on Cockroft-Gault (r = 0,595; p = 0,001), MDRD (r = 0,554; p = 0,003) and CKD-EPI (r = 0,559; p = 0,003). But the correlation between KIM-1 concentration and eGFR based on Cockroft-Gault (r = -0,155; p = 0,339), MDRD (r = -0,173; p =0,285) and CKD-EPI (r = -0,024; p = 0,883). So there was a significant correlation between 8-iso-Prostaglandin F2α concentration and eGFR, and also there were no significant correlation between KIM-1 concentration and eGFR."

"Latar Belakang: Cisplatin merupakan salah satu obat kemoterapi yang biasa digunakan untuk mengobati berbagai jenis kanker. Namun, meskipun kemampuannya sangat baik dalam mengatasi kanker, cisplatin dapat menyebabkan nefrotoksisitas. Curcumin memiliki efek antioxidan dan anti inflamasi yang diperkirakan dapat melindungi ginjal dari toksisitas cisplatin. Namun, bioavailabilitas curcumin yang rendah menjadi perhatian utama. Pada percobaan ini, kami akan membandingkan efektivitas kurkumin dan nanokurkumin dalam halproteksi terhadap ginjal pada tikus yang diberikan cisplatin injeksi diperiksa menggunakan KIM-1 dan NGAL sebagai biomarker nefrotoksisitas akut. Metode: Tikus Sprague-dawley jantan dipilih secara acak dan dikelompokkan ke dalam 5 grup (n = 5 tikus/grup) dengan perlakuan yang berbeda; normal, cisplatin, cisplatin + curcumin, cisplatin + nanocurcumin 50 mg/kgBB, dan cisplatin + nanocurcumin 100 mg/kgBB. Dosis cisplatin yang digunakan sebesar 7 mg/kgBB. Pada hari ke 10, tikus dikorbankan dan ginjal diambil untuk dianalisis. Ekspresi KIM-1 dan NGAL pada ginjal dianalisa menggunakan RT-PCR. Hasil: Tidak ada perbedaan diantara seluruh kelompok (p>0.05). Namun, ekspresi kedua gen lebih rendah pada grup yang diberikan nanocurcumin. Konklusi: Ekspresi KIM-1 dan NGAL menurun setelah administrasi nanocurcumin, meskipun tidak signifikan.Background: Cisplatin is one of the chemotherapy drugs that is commonly used to treat many kinds of cancer. However, despite its great effect, cisplatin can trigger nephrotoxicity due to its usage. Curcumin, has antioxidant and anti-inflammatory effect that has been suggested to be able to protect the kidney from cisplatintoxicity. Nevertheless, its low bioavailability has become one of the major concern. In this experiment, we will compare the effectivity of curcumin and nanocurcumin in protecting the kidney from cisplatin-induced nephrotoxicity using KIM-1 and NGAL as the biomarker of acute kidney failure Method: Sprague Dawley rats are randomly divided into 5 groups (n = 5 rats/group) with different treatment; normal, cisplatin, cisplatin+curcumin, cisplatin+nanocurcumin 50 mg/kgBW, cisplatin+nanocurcumin 100mg/kgBW. The dose of cisplatin used in this research is 7mg/kgBW. On the 10th day of experiment, the rat is sacrified and the kidneys are taken for analysis. Then, KIM and NGAL expression in the kidney is analyzed using qRT-PCR. Results: There are no statistical significancy between all group (p>0.05). However,expression of both KIM-1 and NGAL decrease in group treated usingNanocurcumin Conculsion: The expression of both KIM-1 and NGAL are repressed by nanocurcumin, although it is statistically not significant."

"Patogenesis nefropati diabetik (ND) merupakan hasil interaksi faktor hemodinamik, metabolik dan lingkungan serta faktor genetik. ND biasanya tidak terdeteksi secara klinis sampai terjadi kerusakan ginjal yang bermakna dapat berupa glomerulosklerosis, tubular atrofi dan fibrosis interstitial. KIM-1 dapat digunakan sebagai penanda adanya kerusakan tubulus ginjal. Hubungan polimorfisme gen ACE dengan nefropati diabetes masih tidak konsisten. Penelitian ini merupakan studi cross sectional komparasi antara dua kelompok penyandang DMT2 dengan atau tanpa nefropati yang bertujuan untuk mengetahui adanya kerusakan tubulus, polimorfisme gen ACE dan menganalisis hubungannya dengan kadar KIM-1 terhadap terjadinya kelainan tubulus. Didapatkan adanya peningkatan ekskresi KIM-1 urin pada 19 subjek pre-nefropati dengan median 1,3 (interquartile 1,5) ng/mL, 25 subjek nefropati insipien dengan median 1,6 (interquartile 2,3) ng/mL dan 12 subjek nefropati overt dengan rerata kadar KIM-1 3,1 ± 2,4 ng/mL. Terdapat polimorfisme gen ACE pada penyandang DMT2. Proporsi genotipe DD 9,3%, ID 33,3% dan II 57,4% pada kelompok NND, pada kelompok ND proporsi genotipe DD 4,7%, ID 34,1% dan genotipe II 61,2%. Dijumpai adanya hubungan bermakna antara alel D dengan peningkatan ekskresi KIM-1 urin pada kelompok pre-nefropati (p = 0,030). Peningkatan kadar KIM-1 urin pada kelompok pre-nefropati menunjukkan adanya kerusakan tubulus yang merupakan proses awal nefropati DM. Distribusi genotipe polimorfisme gen ACE pada penelitian ini menyerupai penelitian lain di negara-negara Asia, sedangkan di negara Eropa genotipe DD lebih banyak daripada genotipe II. Hubungan bermakna alel D dengan kadar KIM-1 hanya pada kelompok prenefropati mungkin disebabkan adanya faktor lain seperti kadar glukosa, kontrol glikemik, ureum, kreatinin dan kadar trigliserida yang memengaruhi. Simpulan: Terdapat peningkatan ekskresi KIM-1 urin pada penyandang DMT2 kelompok pre-nefropati yang meningkat secara bermakna pada penyandang DMT2 dengan nefropati overt. Peningkatan ekskresi KIM-1 urin dapat dipakai sebagai penanda kerusakan tubulus. Terdapat polimofisme gen ACE pada penyandang DMT2. Genotipe II lebih banyak dibanding genotipe ID dan DD. Dijumpai adanya hubungan alel D dengan peningkatan kadar KIM-1 urin pada penyandang DMT2 pre-nefropati.

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The pathogenesis of nephropathy diabetic (ND) is the result of the interaction of haemodynamic, metabolic, environment, and genetic factors. In general, ND was clinically undetectable until kidney has been damaged significantly, in the form of glomerulosclerosis, tubular atrophy, or interstitial fibrosis. KIM-1 can be used as the initial indicator of kidney tubules damage. The relationship between ACE gene polymorphism and diabetic nephropathy was still inconsistent.

This research was a comparative cross-sectional study on two groups of DMT2 patients with and without nephropathy diabetic. The objectives of this study were to identify the tubules damage, ACE gene polymorphism, and to analyze the relationship between the degree of KIM-1 and the tubules damage. The increase of KIM-1 urine excretion was found in 19 pre-nephropathy subject (median = 1.3 with interquartile 1.5 ng/mL), in 25 incipient nephropathy subject (median = 1.6 (2.3) ng/mL), in 12 overt nephropathy subject (Mean = 3.1 ± 2,4 ng/mL). ACE polymorphism gene was found in DMT2 patients. In the NDD group, the genotype proportion of DD = 9.3%, ID = 33.3% and II = 57.4%. Whereas, in the ND group, the figures were 4.7%, 34.1% and 61.2%, respectively.

Significant relationship was found between allele D and the increase of KIM-1 urine on pre-nephropathy group (p = 0.030). The increase of KIM-1 urine on prenephropathy group shows the tubules damage which is the initial process of nephropathy diabetic. The genotype distribution of ACE gene polymorphism in this study was similar with the studies in Asian countries; however, in European countries the genotype DD is found higher than genotype II. The significant relationship between allele D and KIM-1 level in pre-nephropathy group might be the influence of other factors, such as glucose level, glycaemic control, urea, creatinine, and triglyceride level.

Conclusion: There was KIM-1 excretion increased on DMT2 pre-nephropathy group, which increase significantly in DMT2 overt nephropathy group. The increase of KIM-1 urine excretion can be used as the indicator of tubules damage. ACE gene polymorphism was found in DMT2 group, with genotype II was higher than genotype ID and DD. A significant relationship between allele D and the increase of KIM-1 urine excretion was found in pre-nephropathy group."