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 ClinicalTrial.gov NCT:03219398, July 17th 2017. Keywords: pneumoperitoneum, renal resistive index, interleukin-6, syndecan-1, sVEGFR-2, laparoscopic nephrectomy

Pneumoperitoneum and Acute Kidney Injury—An Integrative Clinical Concept Review

“…Syndecan-1, the cellular surface proteoglycan serving as a binding site for several growth factors and cytokines, signals the damage and promotes the repair of tubular cells and predictive of AKI. 35,90 Significantly lower serum syndecan-1 levels were detected at an 8 mmHg pneumoperitoneum when compared with the 12 mmHg pneumoperitoneum insufflation during laparoscopic nephrectomy, with an identical median length of insufflation of 260 minutes in both groups. 35 Further, the vascular endothelial growth factor receptor type 2 expression, which reflects angiogenesis and microvascular permeability, was lower in the peritubular capillaries at the 8 mmHg-pneumoperitoneum group.…”

“…35,90 Significantly lower serum syndecan-1 levels were detected at an 8 mmHg pneumoperitoneum when compared with the 12 mmHg pneumoperitoneum insufflation during laparoscopic nephrectomy, with an identical median length of insufflation of 260 minutes in both groups. 35 Further, the vascular endothelial growth factor receptor type 2 expression, which reflects angiogenesis and microvascular permeability, was lower in the peritubular capillaries at the 8 mmHg-pneumoperitoneum group. The ultrastructure morphology of both proximal and distal tubules-including the number of cells with intact membranes, clear cell boundaries, intact brush borders, and basement membranes with no swollen nuclei and no vacuolization-also favored the lower pressure; however, this was to come at the price of more frequent collapses of the pneumoperitoneum.…”

“…The ultrastructure morphology of both proximal and distal tubules—including the number of cells with intact membranes, clear cell boundaries, intact brush borders, and basement membranes with no swollen nuclei and no vacuolization—also favored the lower pressure; however, this was to come at the price of more frequent collapses of the pneumoperitoneum. 35…”

“…82 Laparoscopic nephrectomy in living-donor transplantation of the kidney is an exceptionally special field with a growing impact. 35 The goal is tremendously challenging, with the aim of minimizing harm to the donor while recovering the grafted organ functionally intact. 36,37 During the procedure, several histological, immunological, and other humoral changes have been investigated to date, significantly advancing our understanding.…”

“…A significant part of clinical data comparing laparoscopic and open techniques is derived from the surgeries of the genitourinary system. 4,5,[32][33][34][35][36][37] The diagnosis of AKI may depend, however, on 1) the criteria used at the time of study (individual definition, RIFLE, AKIN, or KDIGO); 2) the method determining the baseline creatinine level; and 3) the anatomical loss of nephrons due to intervention itself (e.g., partial or full nephrectomy). [38][39][40][41][42][43] Accordingly, all of these factors can profoundly impact the case definition-whether AKI exists or not-and the perceived severity of AKI.…”