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Abstrak


Pengaruh pemberian vitamin d3 (calcitriol) terhadap kadar tgf-?1 dan il-6 pada pasien penyakit ginjal kronik stadium v


Oleh :
Rahma Anindita - S501008004 - Sekolah Pascasarjana

Penyakit ginjal kronik (PGK) merupakan permasalahan bidang nefrologi dengan angka kejadiannya yang masih cukup tinggi, etiologinya yang luas dan komplek, sering tanpa keluhan maupun gejala klinik. Pasien PGK yang menjalani dialisis mempunyai resiko 10-30 kali lebih besar terjadi kematian karena penyakit jantung vaskuler.
Sitokin di dalam glomerulus mempunyai peran dalam meningkatkan permeabilitas membran basalis, sehingga menyebabkan proteinuria. Selanjutnya berbagai penelitian invivo maupun invitro menunjukkan peran berbagai jenis sitokin, seperti interleukin (IL)-1, tumor necrosis factor (TNF)-, IL-6, platelet derived growth factor (PDGF), dan transforming growth factor (TGF-β1).
TGF-β1 mempunyai kapasitas untuk mengaktivasi fibroblas interstisial, menginduksi apoptosis (yang menyebabkan sel intrinsik ginjal hilang, digantikan dengan jaringan fibrotik), dan diferensiasi sel tubulus menjadi miofibroblas, sehingga terjadi pembentukan jaringan parut ginjal       Berbagai macam rangsangan inflamasi termasuk reactive oxygen species (ROS) dapat mengaktivasi pelepasan TNF-α, IL-1 dan IL-6 yang kemudian merangsang pelepasan CRP dan berbagai mediator inflamasi seperti monocyte derived macrophage, sel endotelial, tissue factor dan berbagai adhesion molecule yang berperan dalam pembentukan plak aterosklerotik.            
Penurunan fungsi ginjal pada PGK akan disertai dengan penurunan produksi 1,25- dihydroxyvitamin D. Rendahnya kadar 1,25- hydroxyvitamin D berhubungan dengan meningkatnya resiko penyakit jantung vaskuler. Vitamin D dapat memodulasi respon imun dan diferensiasi sel. Karena efek tersebut, diharapkan vitamin D dapat mengontrol status inflamasi pada pasien PGK dan pemberian vitamin D dapat menekan mortalitas pada pasien PGK.
Penelitian ini bertujuan untuk mengetahui pengaruh suplementasi calcitriol terhadap kadar TGF-β1 dan IL-6 pada pasien PGK stadium V yang menjalani hemodialisa.
       Metode penelitian ini merupakan penelitianeksperimen dengan randomisasi, sampel 30 orang, dibagi menjadi kelompok kontrol diberikan plasebo dan perlakuan diberikan calcitriol 1x0,5 µg peroral selama 4 minggu. Karakteristik penelitian yang berupa variabel kualitatif, uji homogenitas dilakukan menggunakan uji Chi Square. Uji beda dua rerata menggunakan uji parametrik (uji t) jika data variabel berdistribusi normal atau uji non parametrik (Mann-Whitney / Wilcoxon Signed Rank Test).
 Hasil penelitian menunjukkan pada kelompok plasebo (n=13) ; Kadar TGF-β1sebelum dan sesudah perlakuan (28741,13±4824,42 pg/mL vs 30413,77±6913,25 pg/mL ; p=0,122) dan IL-6 (12,40±4,51 pg/mL vs 13,85±3,97 pg/mL; p=0,178). Pada kelompok perlakuan (n=13) ; Kadar TGF-β1 sebelum dan sesudah perlakuan(29967,54±11326,44 pg/mL vs  22427,59±11970,94 pg/mL; p = 0,001) dan kadar IL-6; (12,42±5,64pg/mL vs 8,22±8,22 pg/mL; p = 0,001). Terdapat perbedaan yang bermakna pada selisih rata-rata kadar TGF-β1 (Delta-tgfb1) sebelum dan sesudah perlakuan pada kelompok Placebo (1672,64±4217,61 pg/mL vs  (-7539,95)±6435,86 pg/mL;p=0,001), dan selisih rata-rata kadar IL-6 (Delta-IL6) sebelum dan sesudah perlakuan pada kelompok placebo vs kelompok perlakuan (1,45±3,14 pg/mL vs (-4,20) ±2,83 pg/mL; p=0,001)
Penelitian ini menyimpulkan bahwa pemberian suplementasi vitamin D3 (calcitriol) dapat menurunkan kadar TGF-β1 dan kadar IL-6 pada pasien penyakit ginjal kronik stadium V  yang menjalani hemodialisis secara signifikan.

Chronic kidney disease (CKD) is a problem field of nephrology with the number of events that are still quite high, wide and complex etiology, often with no complaints or clinical symptoms unless already entered into the terminal stage. Increased oksifatif stress and chronic inflammation in patients with chronic kidney disease (CKD) undergoing dialysis has been widely documented. Patients with CKD on dialysis have a 10-30 times greater risk of deaths due to heart disease vascular, they have a high risk for heart disease. Arterial Vascular Disease and cardiomyopathy is the leading cause of death.
Cytokines in having a role in increasing the glomerular basement membrane permeability, resulting in proteinuria. Furthermore, in vivo and in vitro studies demonstrate the role of various types of cytokines, such as interleukin (IL-1), tumor necrosis factor (TNF-α) IL-6, platelet derived growth factor (PDGF), and transforming growth factor (TGF-β1).
TGF-β1 has the capacity to activate fibroblast interstitial, induces apoptosis (which cause cell intrinsic renal gone, replaced with a network of fibrotic), and cell differentiation tubules become miofibroblas, resulting in the formation of renal scarring wide variety of inflammatory stimuli including reactive oxygen species (ROS) can activate the release of TNF-α, IL-1 and IL-6 which then stimulates the release of CRP and other inflammatory mediators such as the monocyte derived macrophages, endothelial cells, tissue factor, and various adhesion molecules that play a role in the formation of atherosclerotic plaques. The decline in kidney function in CKD will be accompanied by a decrease in the production of 1,25- dihydroxyvitamin D. Epidemiologic studies mention that low levels of 1,25- hydroxyvitamin D are associated with increased risk of vascular heart disease. And research shows that low levels of vitamin D in patients with CKD either pre-dialysis dialisiss or closely associated with increased mortality and cardiovascular events. Vitamin D can modulate the immune response and cell differentiation. Because of these effects, the expected vitamin D may control the inflammatory status in patients with CKD and vitamin D can reduce mortality in patients with CKD.
This study aims to determine the effect of calcitriol supplementation on levels of TGF-β1 and IL-6 in patients with stage V CKD undergoing hemodialysis.
This research method is a randomized experimental study, a sample of 30 people, divided into a control group given a placebo and the treatment given calcitriol 1x0,5 mg orally for 4 weeks. Statistical analysis using SPSS 22 for windows. Characteristics of research in the form of qualitative variables, homogeneity test was performed using Chi Square test. Two different test mean using parametric tests (t test) if the data is normally distributed variable or non-parametric tests (Mann-Whitney / Wilcoxon Signed Rank Test).
The study concluded that vitamin D supplementation significantly can reduce levels of TGF-β1 and lower levels of IL-6 in patients with stage V chronic kidney disease who undergo hemodialysis.