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Pengaruh Tekanan Intraadomen yang Lebih Rendah terhadap Cedera Endotel dan Tubulus pada Laparoskopi Nefrektomi Donor Ginjal Hidup: Kajian terhadap Interleukin-6, Syndecan-1, VEGFR-2, Occludin, dan KIM-1 = The Effects of Lower Pressure Pneumoperitoneum on Renal Endothelial and Tubulus Injury in Living-Donor Laparoscopic Nephrectomy: Study on Interleukin-6, Syndecan-1, VEGFR-2, Occludin, and KIM-1.

Laparoskopi nefrektomi adalah teknik yang lebih baik dibandingkan nefrektomi terbuka untuk operasi donor ginjal hidup. Namun tekanan pneumoperitoneum memiliki efek yang kurang baik pada ginjal pasien donor karena menimbulkan penurunan perfusi ginjal, peningkatan inflamasi sistemik, dan respons stres tubular ginjal. Data dan uji klinis mengenai masalah tersebut masih sangat terbatas. Tujuan penelitian ini adalah untuk mengevaluasi apakah menggunakan tekanan pneumoperitoneum yang lebih rendah menurunkan resistive index ginjal (RI), kadar interleukin-6 (IL-6), mencegah peluruhan lapisan Syndecan-1 glikokaliks tubulus, pelepasan soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) dan ekspresinya pada jaringan ginjal, serta menghasilkan kadar Occludin plasma dan KIM-1 urin yang lebih rendah sebagai penanda awal cedera sel endotel dan tubulus, dibandingkan dengan tekanan standar. Telah dilakukan penelitian prospektif acak tersamar tunggal pada 44 pasien donor yang menjalani laparoskopi nefrektomi antara Juli 2017 hingga Februari 2018, yang dialokasikan ke dalam kelompok tekanan standar (12–14 mmHg) atau kelompok tekanan lebih rendah (8–10 mmHg). Pemeriksaan serial RI, IL-6, Syndecan-1, s VEGFR-2, Occludin plasma, dan KIM-1 urin dikumpulkan pada awal, intra dan pascaoperasi, dan dianalisis dengan uji yang sesuai. Imunohistokimia ekspresi Syndecan-1 dan VEGFR-2, serta gambaran ultrastruktur menggunakan transmission electron microscope juga dianalisis pada jaringan korteks ginjal. Empat puluh empat pasien dianalisis, karakteristik demografi dan nilai baseline pasien sebanding antar kelompok. Pada kelompok tekanan 8–10 mmHg dibandingkan dengan kelompok tekanan 12–14 mmHg didapatkan parameter hemodinamik perioperatif tidak berbeda antar kelompok, kecuali denyut jantung intra-dan pascaoperasi lebih rendah secara bermakna pada kelompok 8–10 mmHg. Nilai RI ginjal perioperatif keseluruhan meningkat secara bermakna (p = 0,001), tetapi perbandingan antara kedua kelompok tidak berbeda secara bermakna (p = 0,746). Kadar IL-6 plasma intraoperatif (p = 0,003) lebih rendah secara bermakna pada kelompok tekanan 8–10 mmHg. Kadar sVEGFR intraoperatif dan pascaoperatif lebih rendah secara bermakna pada kelompok tekanan 8–10 mmHg (p = 0,032, p = 0,044). Kadar Syndecan-1 plasma lebih rendah pada kelompok tekanan 8–10 mmHg meskipun tidak bermakna. H-score ekspresi Syndecan-1 pada tubulus proksimal lebih tinggi secara bermakna pada kelompok tekanan 8– 10 mmHg (p = 0,030). H-score ekspresi VEGFR-2 pada tubulus proksimal and distal lebih tinggi secara bermakna pada kelompok tekanan 8–10 mmHg (p = 0,005, p = 0,024). Persentase dan skoring ekspresi VEGFR-2 pada tubulus proksimal dan distal, podosit, endotel kapiler glomerulus dan peritubulus lebih rendah secara bermakna pada kelompok tekanan 8–10 mmHg (p < 0,05). Gambaran ultrastruktur tubulus ginjal, glomerulus, dan kapiler peritubulus lebih baik pada kelompok tekanan 8–10 mmHg. Output urin perioperatif, kreatinin serum, BUN, kadar Occludin plasma dan KIM-1 urin tidak berbeda secara bermakna antar kelompok. Pneumoperitoneum tekanan yang lebih rendah terbukti mengurangi kadar IL-6 plasma sebagai penanda respons inflamasi, menurunkan ekspresi Syndecan-1 dalam darah dan meningkatkan ekspresinya di jaringan, menurunkan ekspresi sVEGFR-2 dalam darah dan VEGFR2 pada jaringan, sebagai penanda dini cedera endotel dan tubulus pada pasien yang menjalani laparoskopi nefrektomi.
Kata Kunci: Interleukin-6, KIM-1, laparoskopi nefrektomi, Occludin, renal resistive index, sVEGFR-2, Syndecan-1, tekanan pneumoperitoneum.


Laparoscopic nephrectomy is a preferable technique for living kidney donation. Unfortunately, pneumoperitoneum pressure may have an unfavorable effect on the remaining kidney due to decreased renal perfusion, increased systemic inflammation, endothelial vascular response and renal tubular injury. However, limited data is available and shows various results from the clinical trials. Early detection of renal injury due to increased intraabdominal pressure is needed. The aim of this study was to evaluate whether using lower-pressure CO2 pneumoperitoneum reduces renal resistive index (RI), interleukin-6 (IL-6), reduces Syndecan-1 shedding and vascular endothelial growth factor receptor-2 (sVEGFR-2) expression in plasma and its expression in renal tissue, plasma Occludin level and urinary kidney injury molecule-1 (KIM-1 as the early markers of endothelial and renal tubular cell injury in comparison to the standard pressure. A prospective randomized study was conducted on 44 patients undergoing laparoscopic donor nephrectomy between July 2017 until February 2018, allocated into standard pressure (12–14 mmHg) group or lower-pressure (8–10 mmHg) group. The serial RI, plasma IL-6, syndecan-1, sVEGFR-2, occludin and urinary KIM-1 were collected at baseline, intra- and postoperative, and were quantified by enzyme-linked immunosorbent assay. Syndecan-1 and VEGFR-2 expression were also analysed in renal cortex tissue by immunostaining and examined the ultrastructure of renal tubules, peritubular capillaries, and glomerulus using transmission electron microscopy. The perioperative hemodynamic, renal function parameters serum creatinine, and blood urea nitrogen (BUN) were recorded. Forty-four patients were analyzed, the patients baseline and demographic characteristics were comparable between groups. The perioperative hemodynamic parameters were comparable, except the intra-and postoperative heart rate which were significantly lower in the 8–10 mmHg group. The overall perioperative renal RI were significantly increased (p = 0.001), but the comparison results between both groups were not significantly different (p = 0.746). Intraoperative plasma IL6 (p = 0.003), intraoperative and post operative sVEGFR (p = 0.032, p = 0.044) were significantly lower in the 8–10 mmHg group. The plasma Syndecan-1 was lower in the 8–10 mmHg group although not significant. The H-score of Syndecan-1 expression in proximal tubules were significantly higher in the 8–10 mmHg group (p = 0.030). The H-score of VEGFR-2 expression n proximal and distal tubules (p = 0.005, p = 0.024) was significantly lower in the 8–10 mmHg group. The percentage of VEGFR-2 expression in proximal and distal tubules, podocyte, glomerular and peritubular capillaries endothelium were significantly lower in the 8–10 mmHg group (p < 0.05). The ultrastructure of renal tubules and glomerulus showed better morphology in the 8–10 mmHg group. Perioperative urine output, serum creatinine, BUN, plasma Occludin and urinary KIM-1 levels were not significantly different between groups. In laparoscopic living donor nephrectomy, the lower-pressure pneumoperitoneum significantly reduced the inflammatory response plasma IL-6 that produced lower expression of VEGFR-2 in plasma and in renal tissue, less shedding of Syndecan1 into the plasma and higher expression in renal tubular epithelium as the marker for tubular and endothelial cell injury in comparison to the standard pressure.
Keywords: interleukin-6, kidney injury molecule-1, laparoscopic nephrectomy, pneumoperitoneum pressure, renal resistive index, syndecan-1, vascular endothelial growth factor.