Research Article
Impact of Pneumoperitoneum on the Post-Operative Renal Function and Level of Acute Kidney Injury Markers: Comparison between Laparoscopic and Open Nephrectomy
Amjad Shalabi1, Omri Nativ2*, Mustafa Sumri3, Bishara Bishara1, Wisam Khoury1, Hoda Awad2,
Ofer Nativ4 and Zaid Abassi2
1Department of General Surgery, Rambam Health Care Campus, Israel
2Department of Physiology, Bruce Rappaport Faculty of Medicine, Technion, Israel
3Department of Anesthesiology, Israel
4Departments of Urology, Bnai Zion Hospital Haifa 31096, Israel
*Corresponding author: Omri Nativ, Department of Nephrology, Bruce Rappaport Faculty of Medicine, Technion 6th HaAliya HaShniya St., Haifa, Israel
Published: 06 Jun, 2017
Cite this article as: Shalabi A, Nativ O, Sumri M, Bishara
B, Khoury W, Awad H, et al. Impact
of Pneumoperitoneum on the Post-
Operative Renal Function and Level
of Acute Kidney Injury Markers:
Comparison between Laparoscopic and
Open Nephrectomy. Clin Surg. 2017;
2: 1493.
Abstract
Purpose: As laparoscopic surgery becomes more widespread, understanding the adverse effects
of pneumoperitoneum becomes more important, especially in patients subjected to laparoscopic
unilateral nephrectomy. The purpose of the current study was to investigate the effect of
pneumoperitoneum on the remnant kidney after laparoscopic nephrectomy compared to open
surgery.
Methods: The study group included 30 patients. 22 patients underwent laparoscopic nephrectomy
whereas 8 patients underwent open nephrectomy. Serum and urine samples were collected before
surgery, 8 and 24 hours after surgery. At these time points’ urine levels of NGAL and KIM-1, two
novel biomarkers for acute kidney injury (AKI) were also determined.
Results: Following surgery serum creatinine slightly increased in both groups but then decreased
in those who had open procedure compared with the laparoscopic cases where it continued to
increase. Urinary NGAL, but not urinary KIM-1, increased in both groups after 8 and 24 hours.
The pattern of change of both urinary markers (NAGL and kim-1) after surgery was not affected by
the use of pneumoperitoneum compared to the open procedure. More patients in the laparoscopic
group developed acute kidney injury (41% vs. 12%).
Conclusions: The present study shows a negative effect of pneumoperitoneum on the kidney
function in patients undergoing laparoscopic nephrectomy compared to the open procedure.
NGAL and KIM-1 urinary levels were not affected by the increased intra-abdominal pressure.
Keywords: KIM-1; Nephrectomy; NGAL; Pneumoperitoneum; Renal function
Introduction
Minimally invasive surgery continues to gain popularity and widespread acceptance due
to its clear advantages. During laparoscopic surgery, pneumoperitoneum is mandatory to allow
adequate exposure. It is, however, may be associated with oliguria, decreased glomerular filtration
rate (GFR) and renal perfusion [1-2]. The exact mechanism of renal dysfunction secondary to
pneumoperitoneum is not fully understood. This may be related to direct compression of the
renal parenchyma and vasculature that leads to reduced renal blood flow [3]. The consequence
is an increased stimulation of the renin-angiotensin-aldosterone system (RAAS) and exertion of
antidiuretic hormone [4]. The result is salt and water retention leading to oliguria.
We have previously reported the association between pneumoperitoneum and kidney injury
in rat model [5]. Others reported similar results in human Correlation between the duration of pneumoperitoneum
and the post-operative urinary levels NGAL and KIM-1.[6,7]. These results may be of clinical
significance especially in patients remaining with a single kidney after laparoscopic nephrectomy.
Unfortunately, there is very small number of human studies in the literature addressing this
important topic. One study investigated the effect of pneumoperitoneum after laparoscopic donor
nephrectomy [8]. However, donor patients were healthy and rigorously screened for preexisting
comorbidities and the patients were not compared to open procedure.
The aim of the current study was to quantitatively document in
patients after unilateral nephrectomy the possible deleterious effect
of pneumoperitoneum on the residual kidney function by serial
measurements of serum creatinine and the urinary level of two novel
biomarker for early kidney injury, namely neutrophil gelatinaseassociated
lipocalin (NGAL) and kidney injury molecule- 1 (KIM-
1). The results were compared between two groups of patients who
underwent laparoscopic and open procedures.
Figure 1
Figure 1A and B
Correlation between the duration of pneumoperitoneum
and the post-operative urinary levels NGAL and KIM-1.
Materials and Methods
Patients
This is a non randomized prospective study that was carried
out after achieving the IRB approval and an informed consent was
obtained from all individual participants included in the study. The
study group included 30 patients who underwent nephrectomy for
various causes. 22 patients underwent laparoscopic surgery and
8 open approaches. Patients with active chronic infection were
excluded from the study.
Pre and post-operative renal function of the studied patients was
assessed either by serum creatinine level or by estimated glomerular
filtration rate (eGFR) using the MDRD equation. AKI was considered
either when SCr level increased by more than 50% or by 0.3 mg/dL
from baseline [9,10].
All patients have been approved by the appropriate ethics
committee and have therefore been performed in accordance with
the ethical standards laid down in the 1964 Declaration of Helsinki
and its later amendments.
Surgical technique
Open technique: All open nephrectomies (ON) were performed
through a subcostal incision approximately 2.0 cm bellow the
costal margin. The rectus abdominis muscle was divided as were
the ipsilateral external and internal obliques and the transversus
abdominis muscles. The peritoneum was entered and an Omni
retractor was positioned to expose the operative field. The white line
of Toldt was incised and the colon reflected medially to expose the
renal vessels. The kidney was then bluntly mobilized posteriorly and
laterally in the avascular plane between Gerota's fascia and quadratus
lumborum and psoas muscles. At the inferior portion of the kidney
the ureter was identified ligated and divided. The renal artery and
vein were identified, cleaned of surrounding fibrofatty tissue, doubly
ligated and divided. The superior portion of the Gerota's fascia was
freed and the whole surgical specimen was removed.
Laparoscopic technique: All laparoscopic procedures were
performed via a transperitoneal approach in the modified lateral
decubitus position. The Veress needle was used for insufflation and
the 10 mm laparoscope port was inserted in the midclavicular line 2
to 3 cm at or just above the umbilicus. A 12 mm port was inserted in
the anterior axillary line 2 cm below the costal margin, and a 10 mm
port was placed on the anterior axillary line at the level of the anterior
iliac crest. A 5 mm port was placed in the midline for liver retraction
on right-sided nephrectomies. The colon was mobilized medially
after incision along Toldt’s line, and the gonadal vein was located
and traced to the renal vein or inferior vena cava. The hilum was
dissected and the artery was secured with vascular clips and the vein
was stapled with the vascular endo-GIA stapler. The intact specimen
was placed in an endocatch bag and removed through an extension
incision at the level of the 12 mm port site. Port sites were closed with
sutures and skin clips.
Samples collection
Voided urine samples were collected for all patients before
surgery, 8 and 24 hours following nephrectomy. The collected urine
samples were stored at -80°C until analysis.
Determination of urinary NGAL and KIM-1
NGAL and KIM-1 were determined from a single 10μl specimen
of urine and were measured with commercially available ELISA kits
(NGAL Rapid ELISA Kit; Bio Porto Diagnostics, Gentofte, Denmark)
and (Wuhan EIAab Science Co. Wuhan, China), respectively.
Statistical analysis
Data are presented as mean±S.E.M (standard error of the mean).
One-way analysis of variance (ANOVA) for repeated measures,
followed by Dunnett’s test, was used for comparison of values from
the different post ischemia periods with baseline values. P value of
p< 0.05 was considered statistically significant.
Results
A total of 30 patients (19 males and 11 females) who underwent
unilateral laparoscopic nephrectomy (n=22) or open nephrectomy
(n=8) were included in the current study. The baseline characteristics
of the laparoscopic and open groups were similar in term of age,
comorbidities, tumor characteristics, preoperative baseline serum
creatinine and estimated GFR. With respect to urine biomarker
levels, while KIM-1 urine concentration did not differ significantly
between the studied groups, the urinary NGAL level was lower in the
open group (Table 1).
Table 2 summarizes the pattern of post-operative changes of the
studied biomarkers as well as serum creatinine. Assessment of urinary
level of NGAL 8 and 24 hours after nephrectomy demonstrated
gradual elevation compared with the pre-operative values in both
groups.
When urinary level of KIM-1 was studied at the same time points
before and after surgery a different pattern was observed, i.e. the
urinary concentration of the marker gradually decreased regardless
of the operative method used. The patterns of change of the studied
markers were not affected by the pneumoperitoneum.
Evaluation of post nephrectomy serum creatinine demonstrated
early (8 hours) similar increase in both groups of 0.23 mg% and 0.31
mg% for laparoscopic and open groups respectively (p=0.83). Further
measurements revealed continuous elevation of the creatinine
in the patients managed by laparoscopy (up to 1.45 mg %) but
decreased level in the open surgery cases (up to 1.18 mg %). Such
pneumoperitoneum related decrease in the laparoscopic group is
statistically significant (P=0.01).
Additionally, we examined the impact of pneumoperitoneum
duration in patients treated by laparoscopic procedures on the urinary
levels of NGAL and KIM-1. As presented in Figure 1A and 1B, there
was no correlation between the duration of pneumoperitoneum and
the post-operative urinary levels of the studied markers.
During the postoperative period, 10 patients (33%) developed
acute kidney injury (AKI). Only one (12%) among the open surgery
group compared with nine cases (40%) in patients subjected to
pneumoperitoneum. (Table 3) presents the baseline and post operative
urinary levels of NGAL and KIM-1 normalized to urine creatinine
among patients with and without AKI in the laparoscopic group. As
shown these biomarkers did not demonstrate a different pattern in
terms of urinary concentration changes among the two sub-groups
(AKI vs. Non-AKI). We further looked at clinical variables and their
association with peri-operative functional outcome that define the
two categories. As demonstrated in Table 4 the basal renal function
was statistically significantly lower in patients who developed AKI,
i.e. before surgery eGFR of 50.43 vs. 82.70 (P< 0.0001) and serum
creatinine 1.205 vs. 1.005 (P=0.0004) for AKI and Non-AKI patients
respectively. Patients in the AKI group were on average 10 year older,
had slightly smaller lesions (mean size 5.65 cm vs. 6.63 cm) and
their surgical procedure was associated with reduced blood loss. By
contrast no difference in rate of relevant comorbidities or duration of
pneumoperitoneum was observed between the two sub-groups.
Table 1
Table 2
Table 2
Post-operative changes of urinary NGAL and KIM-1 as well as serum
creatinine in patients treated by laparoscopic and open nephrectomy.
Discussion
The expansion of minimally invasive laparoscopic surgery
emphasizes the essential need to understand the adverse effects of
pneumoperitoneum which is an essential part of this therapeutic
modality. This is particularly important in cases of laparoscopic
nephrectomy, because maintaining the function of the remnant
kidney is critical. Increased intra-abdominal pressure associated with
pneumoperitoneum leads to compression of the kidney parenchyma,
reduced cardiac output and systemic hormonal effects, which result
in decreased glomerular filtration rate (GFR) and urinary output [1-
5]. In a review of five animal studies, Shafer et al. demonstrated a
decrease in renal perfusion ranged from 12% to 14% [11]. Miki et
al. [12] reported a decreased urine output and GFR in patients after
laparoscopic cholecystectomy, whereas no significant changes in
these parameters were observed when an abdominal lift device was
used.
The present study shows a negative effect of pneumoperitoneum
on the post- operative kidney function in patients undergoing
laparoscopic nephrectomy. This is evident by the further decrease
of serum creatinine (beyond 8 hours) after surgery which was not
observed in the open nephrectomy group. Moreover, the rate of AKI
after laparoscopic surgery was 3.4-fold higher compared with those treated by the open approach. Our results suggest that older age and
decreased baseline renal function may contribute to the development
of AKI in patients managed by laparoscopic nephrectomy. One may
assume that kidneys in elderly patients and compromised renal
function are more vulnerable to the deleterious effect of increased
intra-abdominal pressure. In a study by Cho A et al. [13] who
evaluated 519 patients they found that age and GFR were predictors
of post nephrectomy AKI. In their report patients who experienced
post-operative AKI had a 4.24-fold higher risk of new onset CKD,
P< 0.001.
The duration of pneumoperitonum during surgery by itself or
amount of intra-operative blood loss were not predictors of AKI.
Santos LS et al. [14] who studied the effects of pneumoperitoneum
(15mmHg) during two and four hours in rats, reported no histologic
changes of the kidneys. They used the same magnitude of intraabdominal
pressure that we have used during our laparoscopic
procedures (12-14 mmHg). By contrast in a study published by
Ben-Haim M et al. [15] that used higher pressure (20-25 mmHg)
significant microscopic ischemic changes were observed. These data
suggest that the magnitude of intra-abdominal pressure elevation
may be important in causing renal injury.
We expected to find correlation between two novel biomarkers for
AKI, namely NGAL and KIM-1 that were found to increase following
kidney injury for various reasons. [16,17]. Such elevation could
serve as a marker and may indicate the need to consider different post-operative management such crystalloid support or use of
nephroprotective agents. Our data indicate that pneumoperitoneum
or the occurrence of AKI did not result in increased urinary level
or different pattern concentration of these markers. Micali et al.
[18] reported similar results. They compared laparoscopic and
open procedure using N-acetyl-beta-D-glucosaminidase as a
marker for kidney injury. No differences were noted in the urinary
level of the marker between both groups. They concluded, that
pneumoperitoneum is not associated with renal tubular injury.
Others claim that after the release of pneumoperitoneum, renal
function has recovered early and there were no signs of microscopic
renal tubular damage [19].
Our study has several limitations including: 1-Small number of
patients, especially in the open surgery; 2- A non-randomized study;
3- A single center study; 4- Some patients suffers from comorbidities
(Diabetes, hypertension, peripheral vascular disease ect) that cannot
be quantitated adequately; 5- We focused only on two biomarkers,
based on previous literature and our own experience.
Table 3
Table 3
Relationship between urinary NGAL and KIM-1 levels in patients with and without AKI in patients treated by laparoscopic nephrectomy.
Table 4
Conclusion
In the current study we were able to demonstrate that pneumoperitoneum used during laparoscopic nephrectomy affects immediate post-operative serum creatinine. The increased intaabdominal pressure may result in higher rate of AKI compared with open procedure especially in elderly patients with compromised renal function. NGAL and KIM-1 urinary level were not affected by the increased intra-abdominal pressure. To confirm these findings, a prospective randomized study with greater number of patients is needed.
Compliance with Ethical Standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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