Tesis

Korelasi hepsidin dengan kelainan kardiovaskular pada anak dengan penyakit ginjal kronik = The correlation of hepcidin and cardiovascular disease in children with chronic kidney disease.

Latar belakang: Kelainan struktural dan fungsi kardiovaskular merupakan komplikasi dan penyebab kematian terbanyak pada anak penyakit ginjal kronik (PGK). Hepsidin adalah protein yang berperan dalam homeostasis besi yang berkontribusi dalam patogenesis anemia penyakit kronik. Hubungan hepsidin dan kelainan kardiovaskular pada pasien PGK dewasa telah ditunjukkan oleh beberapa penelitian, tetapi belum ada pada pasien anak PGK. Penelitian ini bertujuan untuk menilai korelasi hepsidin dan kelainan kardiovaskular pada anak PGK. Metode: Penelitian dengan metode potong lintang dilakukan pada anak PGK stadium 3–5 yang berusia 2–18 tahun di rumah sakit Cipto Mangunkusumo (RSCM). Ekokardiografi dilakukan untuk menilai left ventricular mass index (LVMI), relative wall thickness (RWT), fungsi sistolik, diastolik, dan peningkatan carotid intima media thickness (cIMT). Kadar hepsidin serum diperiksa dengan menggunakan ELISA (enzyme-linked immunosorbent assay). Hepsidin dibagi dalam kuartil berdasarkan persentil (hepsidin Q1,Q2,Q3 dan Q4). Hasil: Penelitian ini melibatkan 78 anak dengan PGK stadium 3–5. Median usia subyek adalah 13 tahun (min–maks 2–17). Penelitian ini menunjukkan korelasi hepsidin Q2 dan LVMI bermakna [adjusted b 0,37 (95% IK 0,08–0,65); p = 0,011] dan hepsidin Q4 terhadap LVMI [adjusted b 0,31 (95% IK 0,02–0,60); p = 0,036] pada analisis multivariat regresi linear. Korelasi bermakna antara hepsidin dan MV E/A yaitu kadar hepsidin Q2 [Crude b -0,16 (95% IK -0,29 – -0,02); p = 0,024] juga ditemukan. Tidak ada korelasi hepsidin dan fungsi sistolik serta peningkatan cIMT. Simpulan: Hepsidin berkorelasi terhadap LVMI dan MV E/A, tetapi tidak berkorelasi terhadap fungsi sistolik dan peningkatan cIMT. Penelitian ini merupakan penelitian awal dan tidak dapat membuktikan sebab-akibat sehingga masih membutuhkan penelitian selanjutnya dengan metode prospektif kohort untuk dapat memastikan hubungan hepsidin dan kelainan kardiovaskular.
Kata kunci: hepsidin, kelainan kardiovaskular, hipertrofi ventrikel kiri, penyakit ginjal kronik, anak


Background: Cardiovascular disease (CVD) is a common complication and an important cause of mortality in children with chronic kidney disease (CKD). Hepcidin is a protein that regulates iron metabolism and has been closely linked with the pathogenesis of anemia in chronic disease. Recent studies have shown a substantial association of hepcidin and CVD in adults with CKD, however this association has not been studied in children. This study aimed to investigate the correlation of hepcidin and CVD in children with chronic kidney disease. Methods: This was a cross sectional study that involved children aged 2–18 years with CKD in Cipto Mangunkusumo Hospital. Echocardiography was performed to describe LVMI, RWT, systolic and diastolic function as well as increase cIMT. Plasma hepcidin was obtained and analysed using ELISA (enzyme-linked immunosorbent assay). Hepcidin was divided into quartiles (hepcidin Q1, Q2, Q3 and Q4) Results: This study involved 78 patients with CKD stage 3–5. Median age was 13 years (min–max 2–17). The study showed a positive correlation of hepcidin Q2 and LVMI [adjusted b 0,37 (95% IK 0,08–0,65); p=0,011] as well as hepsidin Q4 and LVMI [adjusted b 0,31 (95% IK 0,02–0,60); p = 0,036] in the multivariate linear regression analysis. A correlation of hepcidin Q2 and MV E/A [Crude b -0.16 (95% IK -0.29 – -0.02); p = 0.024] was also observed. We did not find any correlation of hepcidin and systolic function as well as increased cIMT. Conclusions: Our study showed the correlation between hepcidin and LVMI and MV E/A, but displayed no association with systolic function or increased cIMT. Our results could not describe causal relationship; therefore further prospective cohort studies are needed to confirm our results.
Keywords: hepcidin, cardiovascular disease, left ventricle hypertrophy, chronic kidney disease, children