Tesis

Korelasi Tumor Necrosis Factor Receptor 1 dan Transforming Growth Factor β1 dengan Parameter Fungsi Ginjal Pada Penyandang Diabetes Melitus Tipe 2 = Correlation of Tumor Necrosis Factor Receptor 1 and Transforming Growth Factor-β1 with Renal Function Parameters in Patients with Type 2 Diabetes Mellitus.

Latar Belakang: Inflamasi dan fibrosis merupakan mekanisme utama kerusakan ginjal pada PGD; dimana tumor necrosis factor receptor 1 (TNFR1) mencerminkan jalur inflamasi, sedangkan transforming growth factor-β1 (TGF-β1) namun interaksi antara kedua biomarker ini dengan fungsi ginjal belum jelas. Tujuan: Menilai hubungan TNFR1 dan TGF-β1 dengan parameter kerusakan ginjal berupa rasio albumin-kreatinin urin (UACR) dan eLFG pada penyandang DMT2. Metode: Studi potong lintang menggunakan data sekunder kohort penyakit tidak menular (PTM) Bogor follow-up ke-30 tahun 2021. Melibatkan 157 subjek DMT2 berusia > 18 tahun. Data klinis dan biokimia diperoleh dari kohort, sedangkan TNFR1 dan TGF-β1 serum diperiksa dengan metode ELISA dari sampel darah simpan pada suhu –80°C. Analisis korelasi menggunakan uji Pearson atau Spearman, dan analisis multivariat menggunakan regresi linear dengan penyesuaian usia, hipertensi, durasi diabetes, HbA1c, indeks massa tubuh, dan rasio triasilgliserol/HDL. Hasil: TNFR1 berkorelasi positif sangat lemah dengan UACR (r=0,176; p=0,027) dan negatif sedang dengan eLFG (r=–0,412; p < 0,001), sedangkan TGF-β1 berkorelasi positif lemah dengan UACR (r=0,208; p=0,009) dan sangat lemah dengan eLFG (r=0,157; p=0,050). Analisis multivariat menunjukkan bahwa TNFR1 merupakan prediktor independen eLFG dan tetap berhubungan dengan UACR meskipun dengan kontribusi yang kecil, sementara hubungan TGF-β1 dengan UACR dan eLFG menghilang setelah penyesuaian faktor perancu. Simpulan: Jalur inflamasi yang direfleksikan oleh TNFR1 berhubungan lebih kuat dan independen dengan penurunan fungsi ginjal dibandingkan jalur fibrotik yang direpresentasikan TGF-β1 pada penyandang DMT2.
Kata kunci: diabetes melitus tipe 2, penyakit ginjal diabetes, TNFR1, TGF-β1, albuminuria, eLFG


Background: Inflammation and fibrosis are recognized as key mechanisms of kidney injury in DKD; tumor necrosis factor receptor 1 (TNFR1) reflects inflammatory pathways, whereas transforming growth factor-β1 (TGF-β1) is a marker of fibrotic activity, but the interaction of these biomarkers with renal function is not fully understood. Aim: This study aimed to evaluate the associations of TNFR1 and TGF-β1 with markers of kidney damage, namely urinary albumin– creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), in individuals with T2DM. Methods: This cross-sectional study used secondary data from the 30th follow-up of the Bogor non-communicable disease cohort in 2021 and included 157 T2DM subjects aged >18 years. Clinical and biochemical data were obtained from the cohort database, while serum TNFR1 and TGF-β1 were measured using ELISA from blood samples stored at –80°C. eGFR was calculated using the CKD-EPI equation. Correlation analyses were performed using Pearson or Spearman tests, and multivariable linear regression was conducted with adjustment for age, hypertension, diabetes duration, HbA1c, body mass index, and triglyceride/HDL-cholesterol ratio. Result: TNFR1 showed a very weak positive correlation with UACR (r = 0.176; p = 0.027) and a moderate negative correlation with eGFR (r = –0.412; p < 0.001), while TGF-β1 demonstrated a weak positive correlation with UACR (r = 0.208; p = 0.009) and a very weak positive correlation with eGFR (r = 0.157; p = 0.050). In multivariable analysis, TNFR1 remained an independent predictor of eGFR and retained a modest association with UACR, whereas the associations of TGF-β1 with both UACR and eGFR disappeared after adjustment for confounders. Conclusion: Inflammation mechanism reflected by TNFR1 showed stronger and independent association with declining of kideny function compared with fibrotic pathway represented by TGF-β1in T2DM
Keywords: type 2 diabetes mellitus, diabetic kidney disease, TNFR1, TGF-β1, albuminuria, eGFR