Study and observation of ultrasound on hemorheology of continuous renal replacement therapy in ICU

Objective: To observe the influence of bedside ultrasound on Hemodynamics of Continuous Renal Replacement Therapy,and explore the clinical value of bedside ultrasound technique in acute kidney injury (AKI) Patients with continuous renal replacement therapy (CRRT) and capacity management. Methods 311 cases of AKI patients with CRRT were divided randomly into Observe group and Control group. the observe group was used bedside ultrasound technique, by monitoring tricuspid annular plane systolic excursion (TAPSE), internal diameter of inferior vena cava (IVC), respiratory variation index of the inferior vena cava internal diameter (RVI) and left vertical Tei index changes. Meanwhile, each parameter change was mediated by ultrasound detection from before, to 30min, 6h, 12h, 36h, 48h after of CRRT to sustain liquid balance in observe group, however, central venous pressure (CVP) change was modulated in control group. The difference of kidney length in pre-CRRT were examined to exclude, and of renal aortic diameter, renal resistance index (RRI)and renal blood flow in post-48h of CRRT were compared in two groups. Results Renal length, Renal parenchyma thickness and Echo strength of renal parenchyma weren't different statistically in pre-CRRT of two groups(P>0.05). In observe group, the RVI level was started to increase significantly and IVC internal diameter to decrease at 6h, which would tend to stable at 36h(F=27.746 and 15.446 respectively);the TAPSE level was gradual ascending and Tei index was descending at 12h with a stable tendency at 24h of CRRT(F=36.213 and 17.127 respectively), and there was difference statistical among time of obvious change in TAPSE, IVC internal diameter, RVI and Tei index(P<0.05);In control group, there was no difference statistical among each time in CVP(F=2.189, P>0.05). Compared with control group, renal aortic diameter and renal blood flow were increased significantly(t=2.356 and 2.075), RRI was decreased obviously in observe group(t=2.244), which was different in statistics (P<0.05). Conclusion the application of bedside ultrasound technique in AKI patient's capacity management with CRRT was more effective and evaluated the kidney perfusion.

Gentamicin Renal Excretion in Rats: Probing Strategies to Mitigate Drug-Induced Nephrotoxicity

The renal excretion of gentamicin, an aminoglycoside antibiotic, was studied in the isolated perfused rat kidney (IPRK) model. Dose-linearity experiments were carried out at four doses (400, 800, 1600, 3200 μg), targeting initial perfusate levels of 5, 10, 20 and 40 μg/ml. Additionally, gentamicin was co-perfused with sodium bicarbonate (0.25 mM) and/or cimetidine (2 mM) to evaluate the effect of urinary alkalization and secretory inhibition on gentamicin excretion and kidney accumulation. Gentamicin displayed net reabsorption in the IPRK, consistent with extensive luminal uptake. Kinetic analysis indicated that luminal transport of gentamicin (kidney ? urine) is the rate-determining step for gentamicin urinary excretion. Clearance and cumulative excretion decreased with increased gentamicin dose. Gentamicin kidney accumulation, estimated by mass balance, ranged from ~20% - 30%. Urinary alkalization significantly increased gentamicin excretion, with no effect on kidney accumulation. Conversely, cimetidine co-administration did not affect gentamicin clearance in the IPRK, but kidney accumulation was significantly reduced. When both sodium bicarbonate and cimetidine were administered together, gentamicin kidney accumulation decreased ~80% with corresponding increases in clearance and excretion ratio (XR) compared to gentamicin alone. A main strategy to reduce the incidence of nephrotoxicity with gentamicin therapy (up to ~25%) involves reducing kidney accumulation of the compound. The results of this research suggest that the combination of urinary alkalization and inhibition of basolateral secretion (blood → kidney) may be a viable approach to mitigate aminoglycoside toxicity, and warrants further investigation.

Aldosterone biosynthesis in extraadrenal tissues

Objective To determine whether extraadrenal tissues synthesize aldoster one in addition to vascular tissue and brain. Methods Ex vivo kidney perfusion was performed in normal Wistar rats, A CEI pretreated and adrenalectomized rats prior to the perfusion experiment. Afte r equilibration for 30 minutes, 120 ml of perfusate was collected and subjected to rever se phase HPLC and then aldosterone was measured by RIA. By RT PCR and Southern blot the expression of aldosterone synthase gene CYP11B2 mRNA was studied i n both kidney tissue and cultured renal tubular epithelial cell, lung and l iver tissues. In situ hybridization was used to identify the cell types of liver and lung expressing CYP11B2 mRNA.Results Production of aldosterone in the kidney perfusate was not chang ed in adrenalectomized rats although it was decreased in the group pretreated wi th ACEI perindopril. By RT PCR and Southern blot the expression of CYP11B2 mRNA was demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We have also identified CYP11B2 mRNA expression in liver and lung of rats. In si tu hybridization showed that CYP11B2 mRNA was localized in the endoplasm of live r fat storing cell (Ito cells) and type Ⅱ alveolar cells of lung.Conclusions These studies prove that kidney, liver and lung are able to produce aldosterone.

Effects of angiotensin Ⅱ receptor antagonist olmesartan on renal hemodynamic variables and vascular structural properties in streptozotocin-induced diabetic rats

Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus （DM）. It has been known that renin-angiotensin system （RAS） blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin Ⅱ receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin （STZ）-induced DM rats.Methods DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment （OLM＋DM） group. The normal group （non-DM） were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate （GFR） relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated： slope of flow-pressure （minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature）, slope of pressure-GFR （glomerular filtration capacity against pressure）and threshold pressure for beginning filtration at pressure-GFR （preglomerular to postglomerular vascular resistance ratio）. Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.Results The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight,urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM＋DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats （P 〈0.05）. But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats （P 〈0.05） with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan （P 〈0.05）. Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats （P 〈0.05）.The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.Conclusions Treatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.