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Abstrak :
ABSTRAK Latar belakang: Sepsis merupakan masalah kesehatan penting yang dapat menyebabkan insidens kematian sampai 50% pada pasien dengan sepsis berat. Antibiotik aminoglikosida terutama amikasin semakin banyak digunakan untuk mengobati infeksi kuman Gram negatif pada pasien sepsis di ICU, meskipun penggunaan obat tersebut pada dosis terapi 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 dengan peningkatan 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.

Abstrak :
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 hal proteksi 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 cisplatin toxicity. 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 using Nanocurcumin Conculsion: The expression of both KIM-1 and NGAL are repressed by nanocurcumin, although it is statistically not significant.

Abstrak :
Menurut hasil Riset Kesehatan Dasar yang dilakukan pada tahun 2018, prevalensi prediabetes adalah 57,1%. Prediabetes merupakan faktor risiko hiperfiltrasi ginjal yang dapat memicu kerusakan ginjal. Meskipun vitamin D umumnya tidak digunakan dalam tatalaksana hiperglikemia, efek anti-inflamasi, anti fibrotik dan mekanisme umpan balik pada sistem renin-angiotensin vitamin D dapat bermanfaat dalam tatalaksana prediabetes. Efek protektif terapi vitamin D terhadap kerusakan ginjal akut pada kondisi prediabetes perlu diteliti lebih lanjut. Penelitian ini adalah penelitian eksperimental pada model hewan yang menggunakan sampel urin tersimpan dari penelitian sebelumnya. Tikus dikelompokan dalam kelompok sehat, kelompok prediabetes, kelompok prediabetes dengan pemberian vitamin D 100 IU/kg BB/hari atau kelompok prediabetes dengan pemberian vitamin D 1000 IU/kg BB/hari. Sebanyak 6 ekor tikus dalam setiap kelompok diteliti selama 12 minggu. KIM-1 diukur dengan metode ELISA dan dianalisis menggunakan analisis uji One-way ANOVA. Terdapat peningkatan kadar KIM1 pada tikus prediabetes. Pemberian terapi vitamin D3 dosis 100 IU/kg BB/hari dan 1,000 IU/kg BB/hari menurunkan kadar KIM-1 jika dibandingkan dengan tikus model prediabetes yang tidak mendapatkan terapi vitamin D3. Namun, hanya vitamin D3 dosis 1,000 IU/kg BB/hari yang menurunkan kadar KIM-1 pada tikus model prediabetes secara bermakna (p = 0,043). ......According to the Riset Kesehatan Dasar in 2018, the prevalence of prediabetes was 57.1%. Prediabetes is a risk factor for renal hyperfiltration that can lead to kidney damage. Although vitamin D is not generally used to treat hyperglycemia, its anti-inflammatory effect, anti-fibrotic effect and feedback mechanisms on the renin-angiotensin system may be useful in the management of prediabetes. Therefore, the protective effect of vitamin D therapy against acute kidney damage in prediabetes conditions is worthy of investigation. This study is an experimental study using stored urine samples from a previous study. Rats were grouped into the healthy group, the prediabetes group, the prediabetes group which received 100 IU/kg BW/day of vitamin D or the prediabetes group which received 1000 IU/kg BW/day of vitamin D. Each group had 6 rats and were studied for 12 weeks. KIM-1 was measured by ELISA and analyzed using the One-way ANOVA test. There was an increase in KIM-1 levels in prediabetic rats. Administration of vitamin D3 therapy at doses of 100 IU/kg BW/day and 1000 IU/kg BW/day reduced KIM-1 levels when compared to prediabetic rats which did not receive vitamin D3 therapy. However, only 1000 IU/kg BW/day of vitamin D significantly (p=0.043) reduced KIM-1 levels in prediabetic rats.

Abstrak :
Studi eksperimental hewan memperlihatkan bahwa kadar vasopresin serum yang tinggi berhubungan dengan hiperfiltrasi, albuminuria dan hipertrofi glomerulus, dan dikhawatirkan berlanjut menjadi penurunan laju filtrasi glomerulus (LFG) dalam jangka panjang. Namun, belum terdapat laporan yang membuktikan hubungan sebab-akibat antara peningkatan vasopresin serum dengan gangguan ginjal. Studi ini bertujuan untuk mengetahui hubungan peningkatan vasopresin serum dengan gangguan ginjal, beserta lokasi gangguan ginjal tersebut. Studi ini juga ditujukan untuk melihat kemampuan berat jenis (BJ) urin untuk mendeteksi gangguan ginjal. Penelitian ini adalah studi potong lintang dengan consecutive sampling di sebuah pabrik sepatu pada bulan Januari–Maret 2020. Subjek adalah pekerja terpajan panas yang dinyatakan sehat berdasarkan medical checkup tahun 2019. Sampel darah dan urin diambil lima jam setelah subjek bekerja. Subjek diperiksakan kreatinin plasma, estimasi LFG berdasarkan CKD-EPI, BJ urin, albuminuria carik-celup, albumincreatinine ratio (ACR) urin, vasopresin serum, kidney injury molecule-1 (KIM-1) urin, dan nefrin urin. Data masa kerja, dan jenis kelamin diperoleh melalui wawancara. Pada studi ini, diperoleh 119 subjek wanita dengan median usia 38 (31–51) tahun dan median masa kerja 10 (3–14) tahun. Hiperfiltrasi didapatkan pada 18 subjek, LFG tidak menurun pada 104 subjek (87,4%), dan peningkatan nefrin urin pada 104 pekerja (87,4%). Tidak terdapat hubungan antara vasopresin meningkat dengan hiperfiltrasi, penurunan LFG, albuminuria, nefrin urin, dan KIM-1 urin. Terdapat hubungan bermakna antara peningkatan nefrin urin dengan masa kerja ≥ 10 tahun (p = 0,03). Terdapat hubungan peningkatan KIM-1 urin dengan albuminuria (p = 0,008). Terdapat area under the curve (AUC) antara BJ urin dan nefrin urin sebesar 81,7% (95% CI 68,8–94,6%), dengan titik potong BJ urin ≥ 1,018 yang memiliki sensitivitas 71,2% dan spesifisitas 80% untuk kenaikan nefrin. Sebagai simpulan, peningkatan vasopresin serum tidak berhubungan dengan hiperfiltrasi, penurunan LFG, albuminuria, dan peningkatan KIM-urin. Masa kerja > 10 tahun dihubungkan dengan peningkatan nefrin urin. BJ urin ≥ 1,018 dapat dijadikan acuan untuk mendeteksi kenaikan nefrin urin pada pekerja terpajan panas.

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Animal experimental studies have shown that high serum vasopressin levels are associated with hyperfiltration, albuminuria, and glomerular hypertrophy, which may lead to decreased glomerular filtration rate (GFR) in long-term. However, there was no earlier report that has established the causal relationship between elevated serum vasopressin and renal impairment. This study aims to determine the association between increased serum vasopressin and kidney impairments, along with the location of these impairments. This study is also aimed to look at the ability of urine specific gravity to detect elevated serum vasopressin and kidney impairments. This study was a cross-sectional study with consecutive sampling in a shoe factory from January–March 2020. Subjects were heat-exposed workers who were declared healthy based on the medical checkup in 2019. Blood and urine samples were taken five hours after the subject worked. Subjects were examined for plasma creatinine, estimated GFR (eGFR) based on CKD-EPI, urine specific gravity, dipstick albuminuria, urine albumin-creatinine ratio (ACR), serum vasopressin, urine kidney injury molecule-1 (KIM-1), and urinary nephrin. Data on age, length of service, and gender were obtained through interviews. There were 119 female subjects with a median age of 38 (31–51) years and a median length of service 10 (3–14) years. eGFR was not decreased in 104 subjects (87.4%) and urinary nephrin increased in 104 workers (87.4%). There were no increase in urinary albumin excretion and urinary KIM-1. There were significant association between increased urinary nephrin with length of service ≥ 10 years (p = 0.03), normal-increased eGFR with age 30–39 years (p = 0.001), and increased urinary KIM-1 with albuminuria (p = 0.008). There was an area under the curve (AUC) of 81.7% (95% CI 68.8–94.6%) between urine specific gravity and urinary nephrin, with a cut-off point of urine specific gravity > 1.018 having a sensitivity of 71.2% and a specificity of 80% for the increase in urinary nephrin. In conclusion, increased serum vasopressin does not cause a decrease in GFR, albuminuria, and increase in urinary KIM, but does cause an increase in urinary nephrin. urine specific gravity ≥ 1.018 can be used as a cut-off for detecting increased urinary nephrin in heat-exposed workers.

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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. ...... 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.

Abstrak :
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.