Korelasi antara Ekspresi Nefrin dengan Cedera Tubulus dan Kadar Kreatinin Serum pada Model Gagal Ginjal yang Diinduksi dengan 5/6 Nefrektomi Subtotal pada Mencit

RIKY SETYAWAN, dr. Muhammad Mansyur Romi, SU, PA(K); dr. Nur Arfian, Ph.D.

2015 | Skripsi | S1 PENDIDIKAN DOKTER

LATAR BELAKANG: Gagal ginjal merupakan penyakit dengan prevalensi dan insidensi meningkat. Gagal ginjal kronis ditandai dengan glomerulosklerosis, cedera tubulus, dan proteinuria. Nefrin termasuk protein penting dalam proses filtrasi glomerulus. Belum diketahui mekanisme ekspresi nefrin terhadap kejadian gagal ginjal kronis. TUJUAN: Menelaah hubungan ekspresi nefrin dengan cedera tubulus ginjal dan kadar kreatin serum. METODE: Mencit jantan galur Swiss diberi perlakuan 5/6 nefrektomi subtotal untuk merangsang gagal ginjal kronis. Mencit diterminasi pada hari ke-7 (SN7; n=8) dan hari ke-28 (SN28; n=8)setelah operasi. Kadar kreatinin serum diukur untuk menilai fungsi ginjal. Skor cedera tubulus dihitung berdasarkan pewarnaan menggunakan Periodic Acid Schiff (PAS). Ekspresi nefrin diperiksa dengan Reverse Transcriptase-PCR (RT-PCR). HASIL: Perlakuan 5/6 nefrektomi subtotal menyebabkan kenaikan kadar kreatinin serum pada SN7 dan SN28 (p<0,01 vs SO), diikuti kenaikan skor cedera tubulus pada SN7 dan SN28(p<0,01 vs SO). Terdapat penurunan ekspresi nefrin pada SN28 (p<0,01 vs SO). Terdapat korelasi negatif antara ekspresi nefrin dengan cedera tubulus, korelasi positif tinggi antara cedera tubulus dan kadar kreatinin serum. Namun, tidak terdapat korelasi signifikan antara ekspresi nefrin dengan kadar kreatinin serum. KESIMPULAN: Penurunan ekspresi nefrin berkorelasi negatif dengan cedera tubulus, namun tidak berkorelasi dengan kadar kreatinin serum. Hal ini menunjukkan bahwa nefrin dapat menjadi marker yag baik untuk cedera ginjal.

BACKGROUND: Chronic kidney failure is marked by glomerulosclerosis, tubular injury, and proteinuria. Neprin is the one of the important protein involved in glomerular filtration but mechanism of nephrin expression in chronic kidney failure is not well understood. PURPOSE: To elucidate the correlation between nephrin expression with tubular injury and serum creatinine level. METHOD: We performed 5/6 subtotal nephrectomy (SN) in male strain Swiss mices to induce CKD. Sham operation was performed to control group (SO) (n=8). Mices were sacrificed in day 7 (SN7; n=8) and day 28 (SN28; n=8) after operation. We measured creatinine serum level to assess renal function. Tubular injury score was quantified based on Periodic Acid Schiff (PAS) staining. We performed reverse transcriptase PCR (RT-PCR) to examine nephrin expression. RESULT: 5/6 subtotal nephrectomy induced an increased of serum creatinine level in SN7 and SN28 (p<0,01 vs SO), that was followed by increased of tubular injury score in SN7 and SN28 (p<0,01 vs SO). We confirmed reduction of nephrin expression in SN28 (p<0,01 vs SO). There were negative correlation between nephrin and tubular injury, high-positive correlation between tubular injury and serum creatinine level. However, we did not find any significant correlation between nephrin expression and serum creatinine level. CONCLUSION: We revealed that reduction of nephrin expression has negative correlation with tubular injury, however no correlation with tubular injury. It showed that nephrin might be a good marker of kidney injury.

Kata Kunci : nefrin, 5/6 nefrektomi subtotal, remnant kidney, mencit, kreatinin serum, cedera tubulus, Sham Operation