Effects of low versus standard pressure pneumoperitoneum on renal syndecan-1 shedding and VEGF receptor-2 expression in living-donor nephrectomy: a randomized controlled study

Abstract

Background Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation. Methods We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO2, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded. Results The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders. Conclusion The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy. Trial registration ClinicalTrials.gov NCT:03219398, prospectively registered on July 17th, 2017.

Effect of Low-pressure Pneumoperitoneum on Pain and Inflammation in Laparoscopic Cholecystectomy: A Randomized Controlled Clinical Trial

“…34 In laparoscopic nephrectomy, Dita Aditianingsih et.al demonstrated an attenuation of the in ammatory response, including IL-6, in the low-pressure pneumoperitoneum group (8 mmHg) compared to standardpressure (12 mmHg). 35 In conclusion, this clinical trial demonstrated a reduction of pain and in ammatory markers post laparoscopic cholecystectomy in patients operated at a low-pressure (8-10 mmHg) compared to a standard-pressure (12-14 mmHg), although the difference was not signi cant except for the 6-hour postop pain scores. No signi cant difference could be observed between the two groups regarding total surgery time, also the di culty of surgery was not signi cant even in the hands of non-experienced surgeons.…”

Clinical outcomes of low-pressure pneumoperitoneum in minimally invasive urological surgery

“…The anaesthetic and physiological implications of lower pressure pneumoperitoneum have been demonstrated by multiple studies. These include reduced lactate levels and more favourable cytokine responses [ 17 – 21 ]. These findings have a presumptive benefit, however, how they translate to reduced complication rates and reduced morbidity and mortality is to date undemonstrated.…”

Effects of pneumoperitoneum on kidney injury biomarkers: A randomized clinical trial

“…Renal circulation is greatly affected by increased intra-abdominal pressure, and measurement of kidney injury biomarkers shows significant changes during pneumoperitoneum with a positive correlation with pressure levels [ 8 ]. A change in renal blood flow was suggested in a meta-analysis conducted by Wever et al, although the authors highlight the low quality of the evidence, the need for further studies to clarify the issue, and the fact that only animal studies were included [ 9 ].…”