Study On Hemodynamics And Mechanism In Septic Shock Inducded Acute Kidney Injury

Objectives To investigate systemic and renal hemodynamic effects on septic shock inducded acute kidney injury and the endothelial effect in the mechanisms during this process.Material and methods Three parts were inclouded in the study. In the first part, Eighty six septic shock patients with PiCCO(pulse indicator continuous cardiac output) monitoring admitted in Department of Critical Care Medicine in Peking Union Medical College Hospital from January,2009 to January,2011 were retrospectively studied. They were divided into two groups based on central venous pressure (CVP) at 24h after PiCCO monitoring,41 cases in low CVP group(CVP≤lOmmHg),45 cases in high CVP group(CVP>10 mmHg). Hemodynamic data, lactate concentration, ScvO2. APACHEⅡscore, Scr were obtained at the beginning and 24 hour after PiCCO monitering. The incidence rate and mortality of AKI, the outcome of these patients in ICU and 28th day after diagnosis were recorded, and the effects of CVP on incidence rate and prognosis of AKI were evaluated. In the second part,24 New Zealand rabbits were divided into 4 groups, control group, endotoxic shock with low CVP (LCVP) group, endotoxic shock with high CVP (HCVP) group and endotoxic shock with fasudil intervention(F) group, and each group had six rabbits. A central venous conduct was placed in the left external cervical vein of each rabbit, and a arterial conduct for pulse induced continous cardiac output(PiCCO) investigation was inserted in the left femoral artery;Septic shock model was constructed with endotoxin injected into the vein, and this time was defined 0 point. In F group, fasudil was pumped from-1h. To ensure CVP in HCVP 3mmHg higher than that in LCVP, PEEP in ventilator was adjusted properly, and in addition, MAP≥80mmHg and ScV02≥70%were maintained in each group. Renal risistive index(RI) and pluse index(PI) of the interlobular arteries in the upper lobe of left kidney were monitored by ultrasound. Blood and urine samples were obtained on defined time points to examine the blood gas and some other biochemical indicators related to kidney. In the end of the experiment, the left kidney was picked to make paraffin specimen for HE stain. In the third part, in the end of the experiment blood samples were obtained to examine the prothrombin activity and Flow cytometry was used to determine the concentration of serum endotheial microparticulate;the left kidney was picked to make paraffin specimen for Masson stain and ROCKI and II immunohistochemisty stain.Results In the first part:The incidences of AKI in low CVP group and high CVP group were 51.2%(21/41) and 75.6%(34/45) respectively.9 cases(22.0%) died in ICU in low CVP group, and 20 cases(44.4%) in high CVP group.12 cases (29.3%) died within 28 days in low CVP group, and 21 cases(46.7%) died in high CVP group. In the second part:In HCVP group, CVPs were higher than the other groups all the time after endotoxic shock, p<0.05; no significant differences of GEDVI, ITBVI, CI, EVLWI, HR, MAP and SVRI were found among groups. There was no relation between RI and SVRI. At Oh, RI and PI in F group were statistically different compared with control, LCVP and HCVP groups, p<0.05; at 3h, RI and PI in LCVP, HCVP and F groups were statistically different compared with control group, p<0.05; in LCVP and HCVP groups, RI and PI at 3h and 6h were higher than those at Oh, p<0.05; in F group, RI and PI at 6h were lower than those at Oh, p<0.05. Concentrations of Serum creatinine and BUN as well as urine NAG activity in LCVP and HCVP groups were higher than those in control group, p<0.05; serum Cys-C was higher in HCVP group than that in LCVP group, p<0.01, and serum Cys-C was lower in F group than that in HCVP and LCVP groups, p<0.01. Comparing with control group, lactates at 3h and 6h in HCVP group were higher, while BEs were lower; comparing with LCVP group, lactate at 6h in HCVP group was higher, while BE was lower, p<0.05. In renal tissue pathological specimen, there were leukocyte infiltrating in renal interstitium in experimental groups, but no acute renal tubular necrosis. In the third part:Prothrombin activity were statistically lower in LCVP and HCVP groups than that in control group (p<0.05). Prothrombin activity in F group was statistically higher than that in LCVP group. The concentrations of endothelial microparticles (EMPs) expressing CD62E in LCVP and HCVP groups were statistically different than those in control group(p<0.01); the concentration of endothelial microparticulate expressing CD62E in LCVP group was lower than that in HCVP group(p<0.01). In renal tissue pathological specimen, ROCKI andⅡ expressing in renal tubular epithelial cells and renal glomerular endothelial cells were increased in LCVP and HCVP groups, and were more higher in HCVP, with thickened renal glomerular endothelial tectorium; ROCKI andⅡwere reduced in F group. At 3 hours PI positively related with the concentration of CD62E+EMPs by linear mode. At the 8 hours, serum Cys-C negatively related with prothrombin activie by linear mode; the concentration of CD62E+EMPs related with serum Cys-C positively by linear mode and negatively related with prothrombin activie by linear mode.Conclusions (1)Increasing CVP raised incidence rate and morbility of septic AKI; (2) Decreasing CVP could reduce severity of AKI; (3) PEEP could increase renal injury in septic shock through elevating CVP; (4) Increasing CVP was related to endothelial injury; (5) Higher RI and PI were related to AKI; (6) septic AKI was primary in renal glomerular injury; (7) ROCKI andⅡwere expressed both in renal glomerulus and tubules in septic shock; (8) Activating Rho/ROCK pathway could produce endothelial microparticles (EMPs) through endothelial injury; (9)Block Rho/ROCK pathway could reduce AKI; (10) Increasing EMPs was related to reduction of thrombin activity.