Impact of IAH on renal function
Introduction:
Renal dysfunction is a common early presentation of elevated intra-abdominal pressure. Significant renal hypoperfusion develops at IAP levels of 8-12 mm Hg, oliguria is seen at intra-abdominal pressures over 15 mm Hg and anuria is common once pressures exceed 25-30 mm Hg.[1-4] The causes of renal dysfunction are likely multifactorial including reduced cardiac output, increased renal vascular resistance, decreased glomerular filtration gradient, higher levels of renin and aldosterone as well as significant renal injury from high circulating cytokine levels. [1, 2, 5-8]
Causes of IAH induced renal dysfunction:
Renal arterial flow is decreased for several reasons.[1, 2] The primary underlying reason for renal hypoperfusion is from lower cardiac output as a consequence of the elevated IAP. As intra-abdominal pressure rises to levels higher than central venous pressures it causes vena caval collapse and reduced blood return to the heart (preload.) The combination of reduced preload plus elevated intra-thoracic pressure (that occurs as the diaphragms are pushed cephlad) leads to reduced cardiac output with resultant increases in systemic vascular resistance and vasoconstriction of the arterial tree including the renal artery.
(Click here to see the a diagram outlining the pathophysiology of IAH/ACS and how this impacts the kidney). (For 8MB high resolution copy download click here)
There may also be some direct renal artery compression from the elevated IAP. Renal arterial blood flow reduction is further exacerbated by humoral factors such as increased antidiuretic hormone and increased plasma renin and aldosterone activity. Elevated intra-abdominal pressures also causes direct compression of the renal veins leading to reduction of venous drainage and renal congestion.
Pro-inflammatory mediators are another cause of renal insufficiency. As IAH progresses and inflammatory cytokines are released from the ischemic tissue – especially from the gut – they begin to circulate in the plasma. These cytokines are distributed throughout the body via the circulation and injure remote organs including the kidney, liver and lung.[5, 8] One of the positive effects of paracentesis of the closed abdomen and or negative pressure therapy of the open abdomen is removal of these high levels of cytokines from around the bowel, with subsequent reduction in circulating levels of cytokines.[8]
Cytokine injury to kidney:
Click on pictures for enlargements
First photo shows kidney tissue comparing passive observation to active removal of peritoneal cytokine (treatment).
Second photo shows the circulating plasma levels of IL-6 cytokine between observational and treatment group.
Understanding IAH impact on the kidney at the level of the nephron:
The combination of renal congestion, direct renal compression, reduced arterial blood flow and cytokine induced cellular injury to the kidneys all lead to a reduction in the renal filtration gradient (See Diagram that graphically outlines this). The filtration gradient is the hydrostatic pressure across the glomerulus that drives urine production and renal function. Filtration gradient (FG) equals glomerular filtration pressure minus proximal tubular pressure.[9, 10] When IAP is elevated, proximal tubular pressure is essentially the same as intra-abdominal pressure and glomerular filtration pressure is the difference between MAP and IAP. So filtration gradient = MAP-(2 x IAP). Therefore, changes in IAP will have a more profound effect on urine formation than will changes in arterial pressure.[9]
(Click here or on photo to enlarge diagram and see discussion regarding the physiology)
PTP: Proximal tubular pressure - The hydrostatic pressure within Bowman's capsule that resists filtration. The difference between the GFP and the PTP is the net filtration pressure also known as the renal filtration gradient. A normal PTP is about 15-18 mm Hg. If IAP reaches this level, the PTP equals IAP.
FG: Filtration gradient - The difference in hydrostatic pressure between the GFP and the PTP. This is the effective pressure that is causing filtration to occur and urine to be created.
MAP: Mean arterial pressure - The hydrostatic pressure head of blood flow in the arterial system.
IAP: Intra-abdominal pressure - The hydrostatic pressure within the abdominal cavity influenced by the amount of edema and swelling in the intra-abdominal and retroperitoneal space, the compliance of the abdominal wall and the pressure caused by ventilation moving the diaphragms up and down. PTP equals IAP once IAP is above 15-18 mm Hg.
APP: Abdominal perfusion pressure - The difference in hydrostatic pressure between the MAP and the IAP. This is the effective pressure of blood flowing to the renal artery and is equivalent to the GFP.
Double impact of IAP on renal function: Based on this understanding, renal filtration gradient is impacted by the IAP from two directions. First IAP reduces blood flow to the glomerulus by dropping the glomerular filtration pressure (GFP). Second IAP resists filtration because it contributes to the proximal filtration pressure (PTP):
FG = GFP- PTP → = APP - PTP → = (MAP-IAP)-(PTP) → = (MAP-IAP)-(IAP) → = MAP-2(IAP)
Therefore FG = MAP-(2xIAP) - it's no wonder IAP has such an impact on renal function
Literature showing IAH is a primary risk factor for acute renal failure:
Sugrue, et al, demonstrated the importance of IAP as a predictor of renal impairment.[9] These authors prospectively studied 263 ICU patients and found intra-abdominal pressure to be an independent predictor of renal impairment.[9] In their study, 40% of patients developed IAH (IAP >18 mm Hg) and one third of these developed renal impairment (compared to one eighth of patients with lower IAP, p=0.004). They also noted a lag time between development of elevated IAH and renal impairment suggesting that the effect on renal function is gradual rather than immediate. In addition to this data from Dr. Sugrue, both Dalfino et al and Li et al have found similar results: IAH is an independent risk factor (along with shock and age) for the development of acute renal insufficiency in ICU populations.[11, 12] Mullens’ group from the Cleveland clinic has identified IAP as the primary modifiable component to renal insufficiency in patients suffering from acute decompensated heart failure.[3, 4] This group has determined that reducing elevated IAP results in more improvement in renal function that does optimizing hemodynamic performance. Multiple other studies have demonstrated immediate improvement in renal function once IAH is lowered in an acute setting.[13-17] Mohmand and a group of nephrologists out of Philadelphia recommend that nephrologists need to assist intensivists in recognizing this common syndrome, especially in the less familiar setting of the MICU where sepsis and pancreatitis commonly cause IAH and ACS.[26] They recommend many of the interventional strategies outlines in this web site under IAH interventions tab.
Other authors have also found a direct correlation between IAP and renal function. DeWaele noted immediate increase in urinary output following medical interventions that lowered intra-abdominal pressure and immediate decreases in UOP when the IAP rose.[18] Biancofiore found a close relationship between renal failure, mortality and IAP in post-operative liver transplant patients.[19] Numerous publications are linking sepsis related IAH to ARF and recommending reduction in IAP as part of the therapy required in this high risk group of patients.[20-22] Recent publications in the nephrology literature validate the under-appreciation that clinicians have for IAH as a cause for renal problems and conclude that intra-abdominal hypertension should be considered (and IAP measured and monitored) in the differential diagnosis of all at risk patients with acute renal insufficiency.[10, 11, 15, 23, 24] Most recently a position paper by ATS, SCCM, ESICM and other critical care societies lists elevated intra-abdominal pressure as a major preventable cause of acute renal failure.[25] They recommend that all high risk patients should have IAP monitored and in those in whom it is rising, bedside medical therapy should be instituted followed by surgical decompression is ACS develops and surgery is appropriate for the clinical situation. De Waele and colleagues make similar recommendations in their recent review in the American Journal of Kidney Disease.[26]
IAH and fluid mobilization:
Summary:
In summary, IAH is a proven contributor to renal impairment in critically ill patients. It occurs gradually and responds to interventions that reduce IAP. The cause is multifactorial, but appears to be due to a combination of reduced renal blood flow, increased renal parenchymal pressure (impeding glomerular filtration), high levels of circulating cytokines and hormonal changes induced by intra-abdominal hypertension.
References:
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