Iriane, VincentiaMaria (2015) Performa Diagnostik Kadar Transforming Growth Factor Beta 1 (uTGF-β1) dan Monocyte Chemoattractant Protein-1 (uMCP-1) Urine Sebagai Petanda Biologi Diagnosis Nefritis Lupus. Magister thesis, Universitas Brawijaya.
Abstract
Nefritis lupus (NL) merupakan manifestasi serius dari lupus eritematosus sistemik (LES). Nefritis lupus terjadi pada 60-80% kasus LES, 30-50% diantaranya dijumpai saat awal diagnosis. Orang Asia dan kulit hitam lebih sering mengalami NL dibandingkan dengan ras lainnya. Bentuk NL proliferatif yang tidak diterapi akan menyebabkan terjadinya end stage renal disease (ESRD) dalam 2 tahun setelah terdiagnosis, dengan angka kematian yang tinggi pula. Diagnosis dan pemberian terapi dini akan menghambat perkembangan menuju ESRD serta memperbaiki harapan hidup pasien. Biopsi ginjal merupakan standar emas diagnosis NL, namun pemeriksaan ini bersifat invasif. Oleh sebab itu, berbagai biomarker urine telah diteliti, seperti transforming growth factor beta 1 (uTGF-β1) dan monocyte chemoattractant protein-1 (uMCP-1). Penelitian ini bertujuan untuk mengetahui nilai diagnostik kedua biomarker tersebut dalam mendiagnosis NL. Penelitian ini dilaksanakan dalam rancang bangun penelitian observasional analitik dengan studi potong lintang (cross sectional). Penelitian dilakukan di RS Dr. Saiful Anwar Malang, Februari 2011 sampai dengan April 2013. Tujuh puluh lima subyek terlibat dalam penelitian ini, dikelompokkan menjadi 3 kelompok: pasien NL: 38 pasien dengan NL kelas III-V, kontrol LES: 12 pasien NL kelas I-II, kontrol sehat: 20 sukarelawan sehat (hasil proteinuria negatif pada pemeriksaan carik celup) dan 5 pasien sindroma nefrotik. Diagnosis LES ditegakkan berdasarkan kriteria ARA 1997. Klasifikasi NL berdasarkan ISN/RPS 2004. Kadar uTGF-β1 (laten) dan uMCP-1 ditentukan dengan ELISA, menggunakan sampel urin sewaktu. Analisis statistik dilakukan menggunakan SPSS 17.0. Pengujian normalitas data dengan uji Kolmogorov-Smirnov. Uji beda kadar uTGF-β1 dan uMCP-1 pada ketiga kelompok menggunakan uji One Way Anova/Kruskal-Wallis. Korelasi antara uTGF-β1 dengan uMCP-1 menggunakan uji korelasi Spearman. Uji diagnostik pada penelitian ini menggunakan kurva Receiver Operating Characteristic (ROC). Nilai p 0,05 menunjukkan adanya perbedaan statistik yang bermakna. Terdapat perbedaan signifikan uTGF-β1 dan uMCP-1 antara pasien NL dan kontrol sehat (p 0,000; 0,000). Tidak didapatkan perbedaan bermakna kadar uTGF-β1 antara pasien NL dan kontrol LES maupun antara kontrol LES dan kontrol sehat, dengan nilai p masing-masing sebesar 0,083 dan 0,237. Didapatkan perbedaan bermakna uMCP-1 antara kontrol LES dan kontrol sehat (p 0,000), sedangkan pada pasien NL dan kontrol LES tidak didapatkan perbedaan bermakna, dengan nilai p sebesar 0,960. Didapatkan korelasi yang signifikan antara uTGF-β1 dan uMCP-1 (p 0,000; r 0.614). Nilai AUC uTGF-β1 dan uMCP-1 berturut-turut sebesar 67,80% dan 77,80%, dengan nilai cut-off masing-masing sebesar 33,12 pg/mgCr dan 3,86 pg/mgCr. Nilai diagnostik terbaik ditunjukkan oleh variabel uMCP-1 (sensitifitas 76,92%; spesifisitas 76,00%). uTGF-β1 menunjukkan sensitifitas 71,79%; spesifisitas 64,00%. Uji ix gabungan uTGF-β1 dan uMCP-1 menunjukkan sensitifitas 61,54%; spesifisitas 80%. Uji gabungan uTGF-β1 dan/atau uMCP-1 menunjukkan sensitifitas 87,18%; spesifisitas 60%. Studi ini menunjukkan bahwa kadar uTGF-β1 dan uMCP-1 meningkat pada pasien NL. Peningkatan uTGF-β1 laten, seperti yang ditunjukkan pada penelitian ini, mungkin lebih terkait dengan kronisitas NL serta pengembangan menuju penyakit ginjal stadium akhir. Peningkatan uMCP-1 yang signifikan pada kontrol LES dibandingkan dengan kontrol sehat kemungkinan disebabkan karena pada kontrol LES (NL kelas I dan II), bisa didapatkan deposit kompleks imun yang dapat mencetuskan glomerulonefritis. Kadar uMCP-1 yang lebih tinggi pada pasien NL dibandingkan dengan kontrol menunjukkan bahwa kadar uMCP-1 pada pasien NL dengan histologi glomerulonefritis proliferatif lebih tinggi dibandingkan dengan yang nonproliferatif. Terdapat korelasi positif antara uTGF-β1 dan uMCP-1. Cross talk positif antara signaling TGF-β1 dan MCP-1 pada sel mesangial mendasari perkembangan penyakit ginjal progresif pada pasien NL. Nilai AUC pada kedua biomarker tersebut menunjukkan nilai diagnostik yang baik. Tampak bahwa uMCP-1 memiliki sensitivitas dan spesifisitas yang terbaik. Uji gabungan antara uTGF-β1 dan uMCP-1 menunjukkan peningkatan spesifisitas pemeriksaan, sedangkan uji gabungan antara uTGF-β1 dan/atau uMCP-1 menunjukkan peningkatan sensitifitas pemeriksaan.
English Abstract
Lupus nephritis (LN) is a serious manifestation of systemic lupus ery matosus (SLE). Lupus nephritis occurs in 60-80% of LES cases, 30-50% of which is found at beginning of diagnosis. Asians and blacks more often had LN compared to o r races. Untreated proliferative LN will lead to end stage renal disease (ESRD) within 2 years after diagnosis, with high mortality rates. Early diagnosis and rapy will inhibit progress towards ESRD and improve patients life expectancy. Renal biopsy is gold standard for LN diagnosis, but this procedure is invasice. Thus, various urinary biomarkers has been investigated, such as transforming growth factor beta 1 (uTGF-β1) and monocyte chemoattractant protein-1 (uMCP-1). This study was aimed to determine diagnostic performance of those biomarkers in LN. This was an observational study with cross-sectional design. This study was conducted at Dr. Saiful Anwar Hospital Malang, from February 2011 until April 2013.Seventy-five participants were studied and categorized into 3 groups: severe LN: 38 class III-IV LN patients, mild LN: 12 class I-II LN patients, control: 20 healthy volunteers (negative protein on urine dipstick) and 5 nephrotic syndrome patients. Diagnosis of SLE was based on 1997 ARA criteria. Lupus nephritis was classified according to ISN/RPS 2004. Urinary (latent) TGF-β1 and uMCP-1 levels were determined by ELISA, using spot urine. Statistical analysis were performed using SPSS 17.0. normality of data was checked by Kolmogorov-Smirnov test. Comparison of uTGF-β1 and uMCP-1 levels in three groups (mild LN, severe LN, and healthy controls) was carried out using One Way Anova/Kruskal-Wallis. Correlation between uTGF-β1 and uMCP-1 was evaluated using Spearman correlation test. diagnostic performance of each biomarker was assessed using Receiver Operating Characteristic (ROC) curve. p-value less than 0.05 was considered as statistically significant. re were significant differences of uTGF-β1 and uMCP levels between patients and healthy controls (p = 0.000; 0.000). re were no significant differences of uTGF-β1 levels between severe LN and mild LN and mild LN-healthy controls, with p-values of 0.083 and 0.237, respectively. re were significant differences of uMCP-1 between mild LN and healthy controls (p = 0.000), whereas no significant difference was found between severe LN and mild LN, with a p-value of 0.960. Significant correlation was found between uTGF-β1 and uMCP-1 (p = 0.000; r = 0.614). AUC values of uTGF-β1 and uMCP-1 was 67.80% and 77.80%, with cut-off values of 33.12 pg/mgCr and 3.86 pg/mgCr, respectively. best diagnostic value was shown by uMCP-1 (sensitivity of 76.92%, specificity of 76.00%). Urinary TGF-β1 showed sensitivity of 71.79 and specificity of 64.00%. Using combination analysis, with both biomarkers above cut-off level, we obtained a sensitivity of 61.54% and a specificity of 80%, whereas with only one biomarker above cut-off level, we obtained a sensitivity of 87.18% and a specificity of 60%. xi This study showed that uTGF-β1 and uMCP-1 levels were increased in LN. Increased latent uTGF-β1 levels, as shown in this study, may be associated with LN chronicity and development towards ESRD. A significant increased in uMCP-1 levels in mild LN group compared to healthy controls was likely due to immune complex deposits in LN class I/II which could trigger a glomerulonephritis. Urinary MCP-1 levels were higher in severe LN compared with mild LN, indicating that uMCP-1 levels was higher in proliferative LN than in non-proliferative LN. re were positive correlation between uTGF-β1 and uMCP-1. Positive cross talk between TGF-β1 and MCP-1 signaling in mesangial cells was associated with development of progressive renal disease in LN patients. AUCs of those biomarkers indicating good diagnostic value. Urinary MCP-1 had best sensitivity and specificity. For combinations of two biomarkers, best sensitivity was shown by combination of uTGF-β1 and/or uMCP-1, while best specificity was shown by combination of uTGF-β1 and uMCP-1.
| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/616.772/IRI/p/041502539 |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.7 Diseases of musculoskeletal system |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | Samsul Arifin |
| Date Deposited: | 22 Apr 2015 12:30 |
| Last Modified: | 22 Apr 2015 12:30 |
| URI: | http://repository.ub.ac.id/id/eprint/158405 |
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