Deleterious Effects of Increased Intra-Abdominal Pressure on Kidney Function

Abstract

Elevated intra-abdominal pressure (IAP) occurs in many clinical settings, including sepsis, severe acute pancreatitis, acute decompensated heart failure, hepatorenal syndrome, resuscitation with large volume, mechanical ventilation with high intrathoracic pressure, major burns, and acidosis. Although increased IAP affects several vital organs, the kidney is very susceptible to the adverse effects of elevated IAP. Kidney dysfunction is among the earliest physiological consequences of increased IAP. In the last two decades, laparoscopic surgery is rapidly replacing the open approach in many areas of surgery. Although it is superior at many aspects, laparoscopic surgery involves elevation of IAP, due to abdominal insufflation with carbonic dioxide (pneumoperitoneum). The latter has been shown to cause several deleterious effects where the most recognized one is impairment of kidney function as expressed by oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF). Despite much research in this field, the systemic physiologic consequences of elevated IAP of various etiologies and the mechanisms underlying its adverse effects on kidney excretory function and renal hemodynamics are not fully understood. The current review summarizes the reported adverse renal effects of increased IAP in edematous clinical settings and during laparoscopic surgery. In addition, it provides new insights into potential mechanisms underlying this phenomenon and therapeutic approaches to encounter renal complications of elevated IAP.

Full text

Review Article
Deleterious Effects of Increased Intra-Abdominal
Pressure on Kidney Function
Zaher Armaly1,2 and Zaid Abassi3,4
1Department of Nephrology, e Nazareth Hospital-EMMS, Nazareth, Israel
2Galilee Medical School, Bar Ilan University, Safed, Israel
3Research Unit, Rambam Health Care Campus, Haifa, Israel
4Department of Physiology & Biophysics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology,
P.O.Box9649,31096Haifa,Israel
Correspondence should be addressed to Zaid Abassi; abassi@tx.technion.ac.il
Received  June ; Revised  October ; Accepted  October ; Published  November 
Academic Editor: Dewan S. Abdul Majid
Copyright ©  Z. Armaly and Z. Abassi. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Elevated intra-abdominal pressure (IAP) occurs in many clinical settings, including sepsis, severe acute pancreatitis, acute decom-
pensated heart failure, hepatorenal syndrome, resuscitation with large volume, mechanical ventilation with high intrathoracic
pressure, major burns, and acidosis. Although increased IAP aects several vital organs, the kidney is very susceptible to the
adverse eects of elevated IAP. Kidney dysfunction is among the earliest physiological consequences of increased IAP. In the last
two decades, laparoscopic surgery is rapidly replacing the open approach in many areas of surgery. Although it is superior at many
aspects, laparoscopic surgery involves elevation of IAP, due to abdominal insuation with carbonic dioxide (pneumoperitoneum).
e latter has been shown to cause several deleterious eects wherethemostrecognizedoneisimpairmentofkidneyfunctionas
expressed by oliguria and reduced glomerular ltration rate (GFR) and renal blood ow (RBF). Despite much research in this eld,
the systemic physiologic consequences of elevated IAP of various etiologies and the mechanisms underlying its adverse eects on
kidney excretory function and renal hemodynamics are not fully understood. e current review summarizes the reported adverse
renal eects of increased IAP in edematous clinical settings and during laparoscopic surgery. In addition, it provides new insights
into potential mechanisms underlying this phenomenon and therapeutic approaches to encounter renal complications of elevated
IAP.
1. Introduction
Under normal conditions the intra-abdominal pressure (IAP)
isusuallybelowmmHgandeveninmostobesesubjectsit
does not exceed  mmHg [,]. Elevated IAP occurs when the
abdomen becomes subject to increased pressure. Sustained
or repeated elevation of IAP above  mmHg, called intra-
abdominal hypertension (IAH), is considered an important
mortality risk factor in intensive care unit (ICU). When
not treated, IAH has a series of consequences, explicitly,
leading to abdominal compartment syndrome (ACS), where
IAP increases over  mmHg, causing multisystem organ
failure,andnallydeath.ElevatedIAPcouldtakeplace
in various clinical settings including trauma, major burns,
abdominal surgery, severe heart failure, hepatorenal syn-
drome, and critically ill patients []. e latter are prone to
develop elevated IAP as a result of risk factors such as (i)
diminished abdominal wall compliance due to mechanical
ventilation, obesity, and patient position, (ii) increased intra-
and extraluminal abdominal contents, and (iii) enhanced
capillary permeability and interstitial uid accumulation due
to acidosis, sepsis, large volume resuscitation, pancreatitis,
and disturbed coagulation [,]. Additional clinical condition
characterized by elevated IAP is pneumoperitoneum during
laparoscopic surgery [–].
Although the deleterious eects of increased IAP are
known for decades, the interest in this eld has been revis-
ited recently most likely due to the increasing number of
Hindawi Publishing Corporation
Advances in Nephrology
Volume 2014, Article ID 731657, 15 pages
http://dx.doi.org/10.1155/2014/731657

Advances in Nephrology
subjects undergoing laparoscopic surgery on one hand and
the continuous increase in decompensated heart failure and
cirrhosis prevalence on the other. Increased IAP adversely
aects several vital systems including the cardiac, pulmonary,
gastrointestinal, and the renal system, due to diminished
blood ow to these organs. e deleterious eects of elevated
intra-abdominal pressure (IAP) on the kidneys are widely
recognized in the setting of abdominal compartment syn-
drome or other surgical conditions involving visceral edema
[], as well as during laparoscopic surgery [–]. e kidney
seems to be extremely sensitive to the harmful consequences
of increased IAP even at low levels [,]. In this context,
data from patients in intensive care unit indicate that an IAP
cuto value of mmHg has the best sensitivity to specicity
ratio for predicting the development of acute kidney injury
(AKI) []. Although elevated IAP negatively aects multiple
physiological systems, the present review will focus only on
the kidney, which is preferentially vulnerable to this highly
common clinical condition. Specically, we will review the
deleterious impact of increased IAP due to decompensated
heart failure, hepatic failure, or pneumoperitoneum on kid-
ney function.
2. The Kidney in Heart Failure
CHF is the major cause of morbidity and mortality in the
western world, thus posing a major health and economic
burden []. Despite the continuous progress in our under-
standing of the pathogenesis of CHF and its management, the
mortality remains high.
Generalized edema formation, the clinical hallmark of
ECF volume expansion, represents uid accumulation in the
interstitial compartment and is invariably associated with
renal Na+and water retention. It occurs most commonly
in response to CHF and other edematous disease states
(cirrhosis and nephrotic syndrome), where the eector mech-
anisms that normally act to maintain normal Na+balance are
exaggerated and continue to preserve salt despite expansion
of ECF volume.
e syndrome of CHF encompasses pathophysiological
alterations related to a reduction of the eective blood volume
andthosethatarerelatedtoincreaseinthevolumeof
blood and the lling pressures in the atrium and great
veins, behind the failing ventricle. In response to these
changes,aseriesofadjustmentsoccurthatresultfromthe
operation of circulatory and neurohumoral compensatory
mechanisms (Figure ). e importance of vasoconstrictor
neurohormonal systems in the pathogenesis of CHF is
well recognized [–]. Numerous studies in patients and
experimental models of CHF have established the important
role of the renin-angiotensin-aldosterone system (RAAS) and
the sympathetic nervous system (SNS) in the progression
of cardiovascular and renal dysfunction in CHF (Figure ).
Prolonged activation of the SNS and RAAS enhances
Na+retention and has direct deleterious actions on the
myocardium, independent of their systemic hemodynamic
eects [–]. Specically, norepinephrine and angiotensin II
(ang II) have been shown to stimulate myocyte hypertrophy
and to enhance brosis and apoptosis, leading ultimately to
progressive remodeling and further deterioration in cardiac
performance []. e concept that CHF is also a “neurohor-
monal disorder” has led to the use of angiotensin converting
enzyme (ACE) inhibitors, ang II receptor blockers, and
aldosterone antagonists, as well as 𝛽-blockers, that are now
central to the treatment of CHF [,,]. Yet, the RAAS and
SNS comprise only two of the three major components orig-
inally proposed to link neurohormonal activation to CHF.
e third component of the neurohormonal axis in CHF
is arginine vasopressin (AVP), whose circulating levels are
also elevated in patients with CHF []. Likewise, endothelin
(ET) signaling is a common network activated during both
cardiac and renal dysfunctions []. Concomitant with the
stimulation of the vasoconstrictor neurohumoral systems,
compensatory vasodilatory/natriuretic systems are also acti-
vated in CHF, serving to counterbalance the actions of the
opposing vasoconstrictor systems. Among these vasodila-
tory/natriuretic agents, those particularly studied in both
patients and animals with heart failure are the natriuretic
peptides, primarily atrial natriuretic peptide (ANP), brain
natriuretic peptide (BNP), and the nitric oxide (NO) system
[,](Figure ). However, the lusitropic, antihypertrophic,
and natriuretic eects of ANP and BNP are signicantly
attenuated in CHF despite a considerable apparent increase
in plasma concentrations [,]. e imbalance between
the antinatriuretic vasoconstrictor systems and natriuretic
vasodilatory mechanisms in favor of the former leads to
avid Na+and water retention (Figure (b)). us, chronic
CHF entails a complex interaction between the heart and
the kidneys that represents the pathophysiological basis for
a new clinical entity called the cardiorenal syndrome [,
]. Worsening of renal function is frequently observed in
patients hospitalized for acute decompensated heart failure
(ADHF) at the time of admission []. e ability to sustain
ltration and tubular functions of the kidneys during thera-
peutic interventions in patients with ADHF is vital to success-
ful alleviation of congestion. erefore, understanding the
mechanisms involved in the deterioration of renal function
in this setting may allow targeting therapies that protect the
kidneys and improve clinical outcomes [].
Most ADHF hospitalizations stem from congestion in
patients refractory to oral diuretics [–]. Despite use of
intravenous diuretics in the overwhelming majority of these
patients, the average hospitalization for ADHF is . days,
with % of the patients discharged with unresolved symp-
toms, % losing ≤ pounds, and % gaining weight during
the hospitalization []. e unresolved congestion likely
contributes to high readmission rates and mortality among
ADHF subjects. Specically, the development of worsening
renalfunctioninthissettinghasbeenconsistentlyassociated
with greater short- and long-term all-cause and cardiovas-
cular mortality [–] and with accelerated progression to
more advanced kidney disease []. e pathophysiology of
kidney dysfunction in evolved CHF is complex. Classical
mechanisms include extrarenal hemodynamic changes such
as low cardiac output and venous congestion, neurohormonal
activation and release of vasoactive substances resulting in
low renal perfusion, intrarenal microvascular and cellular
dysregulation, and oxidative stress [,,]. However,

Advances in Nephrology 
Myocardial
damage
Vent r i c l e
dysfunction
SNS: sympathetic nervous system RAAS: renin-angiotensin-aldosterone system
AVP: arginine vasopressin
ET: endothelin
ANP: atrial natriuretic peptide
Neurohormonal
activation of
SNS, RAAS,
AVP, ET, ANP
↑
↑ Intra-abdominal
pressure and
venous
congestion
Cardiac output
↑
∙
Real perfusion
↑
∙
Cardiac lling
pressure
↑∙
Systemic vascular resistance
Wall stress (aerload)
Ventricular lling pressure and
blood volume (preload)
↑∙
↑∙
↑∙
Pathophysiology of edema formation and elevated intra-abdominal
pressure in patients with congestive heart failure
(a)
Neuroendocrine imbalance in heart failure
Antinatriuretic
Angiotensin II
Aldosterone
Symp. nervous system
Endothelin
ADH
Natriuretic
Natriuretic peptides
Bradykinin
Nitric oxide
Adrenomedullin
(b)
F : (a) Pathophysiology of edema formation and elevated intra-abdominal pressure in patients with congestive heart failure and
(b) imbalance between natriuretic and antinatriuretic neurohormonal systems in congestive heart failure, in favor of the former.
recent evidence suggests that the abdominal compartment
might contribute signicantly to renal dysfunction in ADHF
[]. Similarly, vigorous uid overload and resultant visceral
edema are a risk factor for increased IAP, which has increas-
ingly been associated with acute kidney injury (AKI) in criti-
cally ill patients[,]. e normal intra-abdominal pressure
(IAP) ranges from  to  mmHg. However, in a study of 
patients with ADHF, Mullens et al. reported that  (%)
of patients admitted with advanced heart failure had elevated
IAP (≥ mmHg) and  (%) demonstrated intra-abdominal
hypertension (IAP > mmHg) []. In patients with evolved
heart failure, already small increases in IAP, in the range of 
tommHg,areassociatedwithimpairedrenalfunction[].
Patients with IAP ≥ mmHg had higher serum creatinine
levels (2.3± 1.0mg% versus 1.5± 0.8mg%) as compared with
patients with normal IAP []. e mechanism underlying
theelevatedIAP-inducedkidneydysfunctioninpatients
with ADHF is not fully characterized. However, some of the
adverse eects overlap with those of venous congestion. For
instance, there is a direct compression of abdominal contents
ontherenalparenchymaandrenalvein[,]. is results
in prominent reduction in renal plasma ow and elevation in
renal parenchymal and renal vein pressures. Under normal
physiological condition, the hydrostatic pressure in Bowman
space is low (∼ mmHg) promoting glomerular ltration.
However, elevated IAP increases the pressure in bowman
space and proximal tubule resulting in reduced GFR [,
,]. Moreover, it has been shown that increased IAP
was associated with activation of the RAAS [], which is
known for its deleterious eects on kidney function and renal
hemodynamics. Specically, angiotensin II via AT recep-
tors exerts multiple direct intrarenal inuences, including

Advances in Nephrology
renal vasoconstriction, stimulation of tubular epithelial Na+
reabsorption, augmentation of tubular-glomerular feedback
(TGF) sensitivity, modulation of pressure natriuresis, and
stimulation of mitogenic pathways. erefore activation of
theRAASduringelevatedIAPmaycontributetothereduced
GFR obtained in this setting.
Since higher IAP is characterized with worse impaired
renal function, reduction of IAP resulted in improvement in
renal function aer medical therapy. In a small prospective
study of diuretic resistant ADHF patients with mild intra-
abdominal hypertension, Mullens et al. showed that ultra-
ltration or paracentesis (if ascites was present) produced
a signicant reduction in IAP and serum creatinine with
an increase in urine output [], suggesting that IAH may
be responsible for diuretics resistance. e improvement in
kidney function following reduction of IAP could also be
attributed to relief in venous return and enhanced cardiac
output [,–].
Collectively, treating the signs and symptoms of heart
failure while preserving or improving renal function is a
crucial therapeutic goal. is could be achieved at least
partially by reducing IAP, which without a doubt contributes
to kidney dysfunction in advanced CHF.
3. Hepatorenal Syndrome
Avi d Na+and water retention are very common in cirrhosis
and may lead to ascites, a common complication of this
disease and a major cause of morbidity and mortality, with
the occurrence of spontaneous bacterial peritonitis, variceal
bleeding, and development of the hepatorenal syndrome
[–]. In CHF and cirrhosis with ascites, the primary
disturbance leading to Na+retention does not originate
within the kidney, but from extrarenal mechanisms that
regulate renal Na+and water handling.
Several formulations have been proposed over the years
to explain the mechanism(s) by which patients with cirrhosis
develop positive Na+balance and ascites formation. Two
major theories put forward to explain the mechanisms of
Na+and water retention in cirrhosis are the “overow” and
the “underlling” theories of ascites formation []. While
the occurrence of primary renal Na+and water retention
and plasma volume expansion prior to ascites formation was
favored by the “overow” hypothesis, the classical “underll-
ing” theory posits that ascites formation causes hypovolemia
that further initiated secondary renal Na+and water retention
[]. e importance of NO as a cardinal player in the
hemodynamic abnormalities that mediate vasodilation and
salt and water retention in cirrhosis became increasingly
evident [].DecreasesinRBFandGFRareamongthe
most common pathophysiological alterations in clinical and
experimental cirrhosis [,]. Kidney hypoperfusion in
decompensated hepatic failure is attributed to intense renal
vasoconstriction caused by imbalance between the vasodila-
tory/diuretic mechanisms and vasconstrictory retaining sys-
tem in favor of the latter []. e increase in Na+and water
retention along enhanced permeability of the abdominal
capillaries contributes to the elevation in IAP. Increased IAP
in liver disease aggravates the impaired kidney function. is
concept is further supported by the nding that reduction in
IAP from mmHg to  mmHg following the placement of
LeVeen shunt resulted in improvement of kidney function at
theexcretoryandhemodynamiclevels[]. Umgelter et al.
[] have shown that the improvement in kidney function in
patients with hepatorenal and tense ascites following reduc-
tion of IAP via paracentesis and albumin substitution stems
from enhanced renal blood ow as reected by decreasing
renal resistive index in Doppler ultrasound. Collectively,
cirrhotic patients with ascites display an exaggerated renal
vulnerability to increased IAP. Relief of the latter results in
prompt reversal of kidney dysfunction.
4. Pneumoperitoneum and Kidney Function
Laparoscopic surgery is rapidly replacing the open approach
in many areas of surgery, owing to its advantages includ-
ing lesser pain and shorter postoperative hospital stay [].
Moreover, laparoscopic donor nephrectomy has the poten-
tial to increase the number of living kidney donations by
reducing donor morbidity and therefore lower the threshold
of donating a kidney []. However, laparoscopic procedure
requires induction of pneumoperitoneum, an increased IAP,
which adversely aects kidney function []. For instance,
pneumoperitoneum at a pressure above mmHg has been
shown to produce transient oliguria and deterioration in
glomerular ltration rate (GFR) [,–]. Likewise, most
of the studies identied a decrease in renal blood ow
(RBF)andrenalcorticalperfusion[,–]. Elevated IAP
secondary to pneumoperitoneum (– mmHg) causes sig-
nicant renal hypoxia in association with decreased RBF [].
e most prominent consequence of pneumoperitoneum is
transient oliguria []. Despite much research in this eld,
the systemic physiologic consequences of CO2pneumoperi-
toneum and the mechanisms underlying its adverse eects
on renal excretory function and hemodynamics are not
fully understood. Nevertheless, it is well hypothesized that
pneumoperitoneum-induced renal dysfunction is a mul-
tifactorial phenomenon. For instance, the severity of the
reduction in renal function following pneumoperitoneum is
aected by the level of IAP [], baseline volume status [],
degree of hypercarbia [], positioning [], and individual
hemodynamic and renal reserve. Contradictory results have
been reported in studies of cardiac output and release of vaso-
pressin and endothelin in combination with pneumoperi-
toneum [–], whereas compression of the urethra has now
been ruled out as a factor contributing to the oliguria [,,
]. Additional factors that may aect renal function during
pneumoperitoneum include direct compression of the renal
parenchyma and renal vein [,], increased resistance in
the renal vasculature [], neurohormonal responses due to
increases in hormones release such as vasopressin, endothe-
lin, hormones of the renin-angiotensin-aldosterone system
(RAAS), and catecholamines [], and, to a lesser extent, the
negative eects of absorbed CO2on cardiac contractility [].
In the last few years, there is an increasing body of evidence,
mainly from animal studies, that the pneumoperitoneum-
induced decrease in splanchnic perfusion is associated with

Advances in Nephrology 
oxidative stress. e contribution of pneumoperitoneum-
associated oxidative stress to the pathogenesis of kidney
dysfunctionduringthisclinicalprocedureisstillawaiting
further research.
Although the transient renal dysfunction during lapar-
oscopyhasnotbeenshowntohaveanypermanenteects
on the donor [,], concerns have been raised that these
negative renal eects may predispose to altered allogra
function in the recipient [].
erefore, some suggestions were oered to overcome
the negative renal eects of pneumoperitoneum such as
avoidance of treatment inhibiting the RAAS and aggressive
hydration [,]. Preconditioning consisting of  min of
pneumoperitoneum followed by  min of deation decreases
the oxidative stress induced by sustained pneumoperitoneum
in the plasma, liver, and kidney and other organs []. Never-
theless, the precise consequences of pneumoperitoneum on
renal perfusion and function require further studies, espe-
cially developing new approaches to minimize the adverse
eects of the laparoscopic surgical procedure.
Experimental evidence has accumulated in recent years
suggesting that locally produced vasoactive substances, such
as nitric oxide (NO), play a fundamental role in the reg-
ulation of systemic and intrarenal hemodynamics, pressure
natriuresis, release of sympathetic neurotransmitters and
renin, and tubular solute and water transport [,,]. e
involvement of NO system in the adverse eects of pneu-
moperitoneum on renal perfusion and function was studied
by our group where we have used an experimental model
of pneumoperitoneum. e latter was induced via a small
incision in the lower third between the xiphoid and pubis
of normal rats, through which a regular Veress needle was
inserted into the abdominal cavity. A pneumoperitoneum of 
or  mmHg was established with CO2gas supply to maintain
IAP at the desired level using a special insuator connected
to the Veress needle. e muscle layer and skin layer of the
abdominal wall were closed separately by silk sutures in an
airtight manner.
As depicted in Figures (a) and (b), there were no signif-
icant changes in GFR and RPF during  mmHg insuation.
However, substantial reductions in these parameters were
observed when  mmHg was applied: GFR decreased from
1.6±0.12to 0.9±0.09 mL/min and RPF from 8.15±0.87to 3.8±
0.16mL/min, 𝑃 < 0.05. When the animals were pretreated
with NTG, the adverse eects of IAP of  mmHg on GFR
and RPF were improved by ∼% (Figures (c) and (d)). In
line with this notion, pretreatment with L-NAME remarkably
aggravated the hypoperfusion/hypoltration associated with
pneumoperitoneum (Figures (e) and (f)). ese results
clearly show that elevated IAP pressure to , but not
 mmHg, decreased kidney function and perfusion. ese
eects are most likely related to impairment of NO system
and could be partially ameliorated by pretreatment with
nitroglycerine. Support for this concept came from experi-
mental study in swine, where some of the animals were sub-
ject to insuation with CO2alone or CO2containing xed
amounts of ethyl nitrite (– ppm) []. Insuation with
CO2aloneproduceddeclinesinsplanchnicorganbloodows
and it reduced circulating levels of S-nitrosohemoglobin (i.e.,
nitric oxide bioactivity); these reductions were obviated by
ethyl nitrite. Moreover, preservation of kidney blood ow
with ethyl nitrite kept serum creatinine and blood urea
nitrogen concentrations constant whereas in the CO2alone
group both increased as kidney blood ow declined. e data
indicate ethyl nitrite can eectively attenuate insuation-
induced decreases in organ blood ow and nitric oxide
bioactivity leading to reductions in markers of acute tissue
injury. is simple intervention provides a method for con-
trolling a major source of laparoscopic-related morbidity and
mortality: tissue ischemia and altered postoperative organ
function [].
An additional unmet concern is whether pneumope-
ritoneum-induced kidney dysfunction is inuenced by the
presence of background diseases. is issue is of particular
importance since a considerable portion of the patients
who undergo laparoscopic surgery suer from cardiovascular
and metabolic diseases, including diabetes, heart failure,
jaundice, and cirrhosis. Interestingly, decreases in RBF and
GFR are among the most common pathophysiological alter-
ations in clinical and experimental CHF []. Previously,
we demonstrated that rats with aortocaval stula (ACF),
an experimental model of volume-overload CHF, closely
mimic the neurohumoral, renal, and cardiac manifestations
of patients with CHF [,]. ese include increased
activity of neurohormonal systems such as renin angiotensin
aldosterone system (RAAS), sympathetic nervous system
(SNS), antidiuretic hormone (ADH), and atrial natriuretic
peptide (ANP); decreases in RBF and GFR with sodium
retention; and a marked degree of cardiac hypertrophy [–
].
e importance of locally released vasoactive substances
in the regulation of RBF and systemic hemodynamics,
in particular the endothelial nitric oxide (NO) synthase
(eNOS) pathway under normal conditions and during CHF,
has been extensively studied [,]. Several studies have
clearly documented an impaired endothelium-dependent
vascular response in CHF, such as a markedly attenuated
response to acetylcholine [,]. Since the adverse renal and
hemodynamic consequences of increased IAP were studied
extensively under normal conditions [,], but not in the
presence of background diseases such as CHF. We examined
whether rats with CHF of various severities are vulnerable to
the adverse renal eects of increased IAP and the potential
involvement of the NO system in this susceptibility. Basal
renal function and hemodynamics were lower in CHF rats in
correlation with disease severity. Decompensated CHF rats
that were subjected to  and  mmHg exhibited aggravated
declines in urine ow, urinary sodium excretion, GFR, and
RPF (Figure ). In contrast, no adverse renal eects were
observed in compensated CHF under identical IAP condi-
tions. When compensated CHF rats were pretreated with the
NO synthase inhibitor L-NAME, they exhibited worsened
renal function in response to pneumoperitoneum (Figure ).
ese ndings indicate that decompensated CHF rats are sus-
ceptible to the adverse renal eects of pneumoperitoneum,
a phenomenon which may involve alterations in the renal
NO/cGMP system. To explore in depth this possibility we
examined whether phosphodiesterase  (PDE) inhibition

Advances in Nephrology
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(d)
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(e)
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2
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Recovery
U3U2Baseline
IAP =14mmHg
Control
Control +L-NAME
∗/#
∗/#
∗
∗
(f)
F : Eects of  and mmHg insuations with CO2on glomerular ltration rate (GFR) (a) and renal plasma ow (RPF) (b). Note
that only IAP of  mmHg was eective in attenuating IAP-induced renal hemodynamics alterations. (∗)𝑃 < 0.05 versus baseline, (#)
𝑃 < 0.05 versus U- mmHg, () 𝑃 < 0.05 versus U- mmHg, Eects of nitroglycerine on pneumoperitoneum- (IAP =  mmHg)
induced renal hemodynamic alterations. Glomerular ltration rate (GFR) (c) and renal plasma ow (RPF) (d) in nitroglycerine treated
rats as compared with untreated animals (controls). Note that nitroglycerine was eective in attenuating the pneumoperitoneum-induced
reduction in renal hemodynamic alterations. (∗)𝑃 < 0.05 versus baseline; (#) 𝑃 < 0.05 versus untreated pneumoperitoneum. Eects of
L-NAME on pneumoperitoneum- (IAP = mmHg) induced renal hemodynamic alterations. Glomerular ltration rate (GFR) (e) and renal
plasma ow (RPF) (f) in L-NAME treated rats as compared with untreated animals (controls). Note that L-NAME treatment aggravated the
pneumoperitoneum-induced reductions in GFR and RPF. (∗)𝑃 < 0.05 versus baseline; (#) 𝑃 < 0.05 versus untreated pneumoperitoneum
[,].

Advances in Nephrology 
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CHF-decompensated
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#/$
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−20
−40
−60
−80
−100
(d)
F : Eects of , , and  mmHg insuations on (a) glomerular ltration rate (GFR) and (b) percentage change in GFR from baseline.
(c) Renal plasma ow (RPF) and (d) percentage change in RPF from baseline in rats with compensated and decompensated CHF and sham
controls. (∗)𝑃 < 0.05 versus baseline; () 𝑃 < 0.05 versus sham. () 𝑃 < 0.05 versus compensated [].
via Tadalal protects against the adverse renal eects of IAP
in rats with congestive heart failure. Decompensated CHF
rats induced by ACF that were subjected to  and  mmHg
exhibited exaggerated declines in kidney function and renal
hemodynamics as compared with sham controls (Figure ).
Pretreatment of decompensated CHF rats with Tadalal
ameliorated the adverse renal eects of high IAP, supporting
a therapeutic role for PDE inhibition during laparoscopic
surgery in decompensated CHF.
Similar to rats with ACF, basal renal function and MAP
were lower in rats with MI compared with sham controls.
Application of IAP of , , or  mmHg in these rats decreased
renal hemodynamics (Figure ). e most profound adverse
renal eect was obtained when IAP of  mmHg was applied
(Figure ). e magnitudes of these deleterious eects were
more severe than those obtained in sham controls, but similar
to those observed in rats with decompensated CHF induced
by ACF. Administration of Tadalal to rats with MI prior
to the induction of IAP protected the kidney from adverse
consequences of high IAP. Specically, PDE-I completely
abolishedthereductioninGFRandRPFinducedbyIAPof
 mmHg (Figure ).
It should be emphasized that not in all clinical settings
increased IAP caused renal dysfunction. For instance, slightly
elevated IAP may improve kidney function due to enhanced
venous return and subsequently increase in CO in association
with renal hyperperfusion. Most recently, we investigated the
renal eects of pneumoperitoneum in rats with acute jaun-
dice and cirrhotic animals. Interestingly, decreases in RBF
and GFR are among the most common pathophysiological
alterations in clinical and experimental jaundice and cirrhosis
[,,], suggesting that these clinical conditions may

Advances in Nephrology
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$
RPF (% change from baseline)
∗
Control
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−20
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−60
−80
−100
CHF-compensated +L-NAME
(d)
F : Eects of , , and mmHg insuations on (a) glomerular ltration rate (GFR) and (b) percentage change in GFR from baseline.
(c) Renal plasma ow (RPF) and (d) percentage change in RPF from baseline in rats with compensated CHF pretreated with L-NAME. (∗)
𝑃 < 0.05 versus baseline; () 𝑃 < 0.05 versus sham. () 𝑃 < 0.05 versus compensated [].
display an exaggerated renal vulnerability to increased IAP.
In this context, Bostanci et al. [] have demonstrated that
 mmHg pneumoperitoneum for  min in a rat model of
obstructive jaundice resulted in moderate but nonsignicant
increases in serum liver enzymes including AST, ALT, and
total bilirubin values. However, this report did not refer to
the renal eects of increased IAP in rats with obstructive
jaundice. erefore, our study was designed to examine
the eects of pneumoperitoneum on kidney function and
renal hemodynamics in rats with either acute obstructive
jaundice or chronic liver cirrhosis. Basal renal function and
hemodynamics were lower in rats with obstructive jaundice.
In contrast to normal rats, application of elevated IAP of
 and  mmHg signicantly improved kidney excretory
function and renal hemodynamics (GFR, RPF) (Figure ).
Similarly, when identical IAP conditions were applied to
cirrhotic rats, no deleterious changes in these parameters
were observed (Figure ). ese results are at odds with the
deleterious consequences of elevated IAP observed in liver
disease with ascites. e base for these dierences between
clinical situation and experimental models requires further
investigation.
5. Additional Clinical Settings
Obesity. Obesity, a very prevalent health problem, is asso-
ciated with increased morbidity and mortality, especially
due to cardiovascular consequences []. Additionally, obe-
sity contributes to the development of other comorbidities

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RPF (% change from baseline)
∗
∗
∗
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CHF-decompensated +PDE-I
−20
−40
−60
−80
−100
(d)
F : Eects of , , and  mmHg insuations with CO2on (a) glomerular ltration rate (GFR), (b) percentage change in GFR from
baseline, (c) renal plasma ow (RPF), and (d) percentage change in RPF from baseline, in sham controls with or without Tadalal pretreatment
andinratswithuntreateddecompensatedCHFandanimalswithdecompensatedCHFpretreatedwithTadalal.(∗)𝑃 < 0.05 versus baseline
of each group; () 𝑃 < 0.05 versus sham controls [].
including diabetes, hypertension, and hyperlipidemia, which
are important risk factors for progressive chronic kidney
disease (CKD) [–]. However, morbid obesity is also
associated with increased intra-abdominal pressure (IAP)
[,]. In this context, Lambert et al. []havereported
that the mean IAP in the morbidly obese patients (mean
BMI 55 ± 2kg/m2)was12 ± 0.8 cmH2O, as compared to
controls (IAP =0±2cmH2O). Does the increased IAP of
morbid obesity contribute to kidney dysfunction? Such IAP
isknowntoinduceadverserenaleectsasshownbyusin
experimental models of pneumoperitoneum [,]. Moreover,
kidney function at both the renal hemodynamic level and
proteinuria has been improved in morbidly obese patients
who underwent bariatric surgery, a useful way of losing
weight in these subjects [–]. e mechanisms underlying
the benecial renal eects of bariatric surgery in severely
obese patients are not known; however it could be attributed
to improvement in glucose metabolism, cardiac function,
hypertension, and probably reduction of IAP following the
surgical procedure.
Pregnancy. e normal values of IAP during pregnancy, in
either healthy or complicated pregnancies, are poorly studied.
However, transrectal measurement of IAP was higher in
pregnant women compared to nonpregnant individuals, and
values increased throughout the course of pregnancy. Most

 Advances in Nephrology
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∗
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Recovery
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GFR (% change from baseline)
$
∗
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MI +PDE-I
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IAP (mmHg)
Recovery
14
10
7
∗∗
∗
∗
∗
∗
∗
∗
∗
$
∗
20
0
40
60
80
100
RPF (% change from baseline)
−20
−40
−60
−80
−100
Sham
MI
MI +PDE-I
(d)
F : Eects of , , and  mmHg insuations with CO2on (a) glomerular ltration rate (GFR), (b) percentage change in GFR from
baseline, (c) renal plasma ow (RPF), and (d) percentage change in RPF from baseline, in sham controls with or without Tadalal pretreatment
andinratswithMIwithandwithoutTadalalpretreatment.(∗)𝑃 < 0.05 versus baseline of each group, () 𝑃 < 0.05 versus sham controls,
and () 𝑃 < 0.05 versus untreated decompensated CHF.
recently, Staelens et al. [] have demonstrated that IAP
is increased in the range of intra-abdominal hypertension
(> mmHg) in pregnant women and decreased to normal
values aer delivery. Moreover, few case reports have shown
elevated IAP in preeclampsia to abdominal compartment
syndrome range (> mmHg), suggesting a potential rela-
tionship between exaggerated IAP and maternal diseases
such as preeclampsia-eclampsia, proteinuria, and liver com-
plications and its potential impact on fetal development [–
]. ese ndings underlie the importance of including
IAP measurement in the dierential diagnosis in pregnant
women.
6. Conclusion
Elevated intra-abdominal pressure is a common phe-
nomenon, which can occur in many clinical settings includ-
ing decompensated heart failure, hepatorenal syndrome, and
laparoscopic surgery. Although it has deleterious eects
on various physiological systems, the kidney seems to be
the most susceptible organ to the adverse consequences of
increased IAP. IAP-induced kidney dysfunction is evident by
oliguria and renal hypoperfusion. e mechanisms underly-
ing the vulnerability of the kidney to elevated IAP are not
fully known, but it could be attributed to hemodynamic,

Advances in Nephrology 
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Acute BDL
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(b)
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#
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#∗
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Recovery1410Baseline
Sham
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10 Recovery
0
20
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#
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IAP (mmHg)
RPF (% change from baseline)
∗
∗
Sham
Acute BDL
−20
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−60
−80
(d)
0.0
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1.0
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#
GFR (mL/min)
∗
∗
∗
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Cirrhosis
IAP (mmHg)
1410 Recovery
Baseline
(e)
#
0
20
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60
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IAP (mmHg)
10 14
Recovery
GFR (% change from baseline)
∗
∗
Sham
Cirrhosis
−20
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(f)
F : Continued.

 Advances in Nephrology
0
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#
RPF (mL/min)
∗
∗
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Cirrhosis
IAP (mmHg)
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Recovery
#
14
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#
IAP (mmHg)
∗
∗
∗
Sham
Cirrhosis
0
20
40
60
80
RPF (% change from baseline)
−20
−40
−60
−80
(h)
F : Eects of  and mmHg insuations on (a) glomerular ltration rate (GFR), (b) percentage change in GFR from baseline, (c)
renal plasma ow (RPF), and (d) percentage change in RPF from baseline, in rats with acute bile duct ligation (BDL) and sham controls. (∗)
𝑃 < 0.05 versus baseline of each group; () 𝑃 < 0.05 versus sham controls. Eects of  and  mmHg insuations on (e) glomerular ltration
rate (GFR), (f) percentage change in GFR from baseline, (g) renal plasma ow (RPF), and (h) percentage change in RPF from baseline, in
rats with cirrhosis and sham controls. (∗)𝑃 < 0.05 versus baseline of each group; () 𝑃 < 0.05 versus sham controls [].
respiratory, and metabolic alterations. Due to the poor
understanding of this phenomenon, no benecial therapeutic
approaches are available to encounter the dangerous, even
fatal, complications of increased IAP.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
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