The Pathophysiological Hypothesis of Kidney Damage during Intra-Abdominal Hypertension

摘要

The increase in intra-abdominal pressure (IAP) above specific levels (i.e., intra-abdominal hypertension, IAH) may lead to organ dysfunction in abdominal and extra-abdominal systems (Kirkpatrick and Roberts, 2013 ). Possible etiologies or risk factors for IAH development comprehend diminished abdominal compliance, increased intraluminal or intra-abdominal contents and capillary leak/fluid resuscitation (Kirkpatrick and Roberts, 2013 ). In this conditions, formally known as abdominal compartment syndrome, acute kidney injury (AKI) frequently develops and further worsens the patients outcome (Dalfino et al., 2008 ). Pathophysiological mechanisms leading to AKI during IAH are not completely known; nevertheless, evidence from the literature recognize the decrease in renal perfusion as the main factor responsible for development of AKI in this condition (De Waele et al., 2011 ). In particular, renal hypoperfusion might occur during an acute or progressive increase in IAP, mainly due to the reduction of both arterial inflow and venous outflow, leading to glomerular hemodynamic alterations. Beyond the subsequent activation of neuro-hormonal pathways (e.g., noradrenergic response and Renin-Angiotensin-Aldosteron system), the intrarenal hemodynamic alteration may be itself the responsible for an acute decrease of glomerular filtration gradient (FG; De Waele et al., 2011 ). The FG reflects the balance among hydrostatic and oncotic forces that support the ultrafiltration through the glomerular barrier. During IAH, the decrease of glomerular hydrostatic pressure (due to hypoperfusion) and the increase of Bowman's space hydrostatic pressure (due to IAH) may lead to acute reduction in FG (De Waele et al., 2011 ). Data from literature confirm an inverse correlation between IAP and FG (Harman et al., 1982 ). Physiologically, an acute increase in IAP narrows renal arteries and veins, reduces renal blood flow, leading to the activation of autoregulatory mechanisms. These cause a vasodilation of afferent arterioles, ensuring glomerular filtration also during the early stage of acute increase in IAP (Just, 2007 ). Probably, the activation of these mechanisms may determine an acute increase in glomerular filtration during stressful events and we hypothesized that it might be related to the patient's renal functional reserve. Moreover, the same IAP value may produce different levels of decreased renal function related to different levels of myogenic response influencing the efficiency of autoregulatory mechanisms. According to experimental data showed by Harman et al., Figure 1 represents the correlation between current renal function ( x axis ) and IAP ( y-right axis ) (Harman et al., 1982 ). In patients with effective myogenic response (patient n°1, dashed line), an acute increase in IAP is associated to a slight decrease in renal function. Whereas, in patients with a compromised myogenic response (patient n°2, solid line), and lower renal functional reserve, an acute increase in IAP is associated with a strong reduction in renal function. Figure 1 Correlation between current renal function, intra-abdominal pressure (IAP), and biomarkers of acute kidney injury (AKI) . Patient n° 1 (dashed line): in presence of effective myogenic response, an acute increase in IAP is associated to a slight decrease in renal function (tract 0–C). A further increase of IAP may lead to biomarkers increase (subclinical AKI, tract C–D). When IAP overcomes the intrarenal autoregulation, glomerular hypoperfusion occurs and a picture of clinical AKI becomes manifest (above point D). Patient n° 2 (solid line): in presence of compromised myogenic response, an acute increase in IAP is associated with a strong reduction in renal function until the development of clinical functional AKI (tract A–B). If IAP further increases, the inflammatory and ischemic insults may lead to the kidney parenchymal damage detectable by biomarkers (above point B). Although the hemodynamic issue is certainly quintessential to explain the pathophysiology of AKI during IAH, other mechanisms may further affect the kidney function (e.g., the direct parenchyma compression or the inflammatory damage; Doty et al., 2000 ; K?süm et al., 2013 ). Beyond the etiological conditions leading to the acute increase in IAP, the IAH itself may induce systemic inflammation (Rezende-Neto et al., 2002 ). Indeed, it is well known as systemic inflammation can widely sustain AKI through circulating biochemical factors inducing apoptoticecrotic damages to the renal parenchyma (Honore et al., 2011 ). Furthermore, also metabolic alterations induced locally may be recognized in the kidney during IAH. In particular, during IAP elevation a widely range of genes are up- and down-regulated in the kidney, leading to a dynamic and constantly changing metabolic response (Edil et al., 2003 ). In experimental models of IAH, high levels of locally-produced inflammatory mediators (e.g., TNF-a or IL-6) have been de