Renal Artery Resistance Research Articles

Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography.

Diabetes and hypertension are complex and serious diseases that may ultimately lead to renal complications. Adequate control of blood glucose and blood pressure contributes to decreased renal risks, but may not be sufficient for certain patients. The current study was undertaken to investigate the renoprotective effects of berberine as an adjuvant therapy to standard hypotensive and hypoglycemic treatment in hypertensive patients with type 2 diabetes mellitus (T2DM). In this 2-year clinical study, 69 hypertensive patients with T2DM, whose blood pressure and fasting plasma glucose (FPG) were adequately controlled by hypotensive and oral hypoglycemic agents prior to the study, were enrolled and randomly assigned into control (33 cases) and add-on (36 cases) groups. Berberine was orally administrated to the patients in the add-on group concomitantly with standard hypotensive and hypoglycemic treatment. Baseline characteristics, including the levels of FPG, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, serum creatinine, urinary albumin-to-creatine ratio (UACR), urinary osteopontin and kidney injury molecule-1 (KIM-1) were determined. Furthermore, the oxidative stress markers malondialdehyde, urinary 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, glutathione peroxidase and total-antioxidant capacity, and the inflammatory parameters vascular adhesion molecule-1, C-reactive protein and high molecular weight-adiponectin were evaluated. In addition, ultrasonographic parameters, including peak systolic velocity, end diastolic velocity and renal arterial resistance index were determined. After treatment, it was observed that the control and add-on treatments were able to adequately control blood pressure and blood glucose. Patients in the add-on group exhibited significant reductions in renal damage biochemical markers (UACR, urinary osteopontin and KIM-1) and improved renal hemodynamics, in addition to reduced inflammation and oxidative stress. The present results suggest that berberine is beneficial for hypertensive patients with T2DM as add-on therapy to standard hypotensive and hypoglycemic agents.

Sympathetic Denervation Facilitates L‐Type Ca 2+ Channel Activation in Renal Resistance Arteries by Depolarization of Vascular Smooth Muscle Cells (VSMCs)

Sympathetic denervation sensitizes renal resistance arteries (RA) to norepinephrine (NE) as well as to Rho kinase (Rock) and L-type Ca2+ channel inhibition. Since Rock-dependent Ca2+ sensitization and Ca2+ entry mutually interact in VSMCs, we tested if sympathetic denervation enhances Rock activation or L-type Ca2+ channel-dependent signaling. RA from sympathectomized rats showed higher pD2 values for NE than control RA (pD2 6.61±0.16 vs. 6.10±0.09, respectively, p<0.01). Nifedipine lowered pD2 and Emax for NE to similar values in both groups. Additional Rock inhibition did not affect pD2 but reduced Emax for NE by further 20% in both groups. NE did not significantly increase Rock substrate phosphorylation in RA of both groups. There was no evidence for group differences in IP3- and RyR-dependent Ca2+ release. While L-Type Ca2+ channel protein expression was similar in RA of both groups, the L-type Ca2+ channel activator S-(-)-BayK8644 contracted RA from sympathectomized but not from control rats. Rock inhibition or KATP channel activation blocked and depolarization enhanced S-(-)-BayK8644-induced contractions in RA from sympathectomized rats. Depolarization also gave rise to S-(-)-BayK8644-induced contractions in control RA. Resting membrane potential in VSMC from RA was lower in sympathectomized rats than in controls (-57.5 ± 2.0 mV vs. -64.3 ± 0.3 mV, p < 0.01). Sympathetic denervation depolarizes VSMC resting potential in RA thereby enhancing L-type Ca2+ channel activation and NE sensitivity. Sympathetic innervation supports hyperpolarizing currents in RA VSMCs.

The independent association between altered renal arterial resistance and loop diuretic dose in chronic heart failure outpatients

BackgroundIn chronic heart failure (CHF) patients there is a wide variability in the minimal effective diuretic dose. The aim of this study is to evaluate whether renal resistance index (RRI) is associated to baseline diuretic dose and the changes at one year. Methods and results250 outpatients in a stable condition and in conventional therapy were enrolled. Baseline RRI was calculated by renal arterial Doppler. The total daily dose of loop diuretics was assessed at baseline and after one year. High diuretic dose (HDD) was defined as a daily furosemide equivalent dose >100mg. RRI was independently associated with baseline HDD at univariate (OR 1.39; 95% CI: 1.233–1.58; p<0.001) and multivariate analysis (OR 1.27; 95% CI: 1.09–1.49; p: 0.002) after correction for other univariate predictors (age, NYHA class, left ventricular ejection fraction, tricuspid annulus peak of systolic excursion, NT-proBNP, glomerular filtration rate by EPI formula and central venous pressure). Moreover, baseline RRI was independently associated to one year stable increase in loop diuretic dose at univariate and multivariate regression analyses. ConclusionsRRI is independently associated with high dose loop diuretics and their increase during a mid-term follow-up thus suggesting its usefulness in detecting an altered diuretic response in CHF outpatients.

Membrane Stretch and Angiotensin II type 1a Receptor: Causes and Role in the Myogenic Response

The ligand-independent activation of Angiotensin II type 1 receptors following vascular stretch plays very important (patho) physiological roles. Indeed, recent studies have implicated this mechanism in cardiac hypertrophy under conditions of pressure overload and it has shown to be indispensable in the regulation of the myogenic response in smooth muscle cells of small resistance arteries, as well as mesenteric and renal resistance arteries. The information discussed in here will highlight the involvement of the mechanoactivation of the Angiotensin II type I receptors in the development of the myogenic response and the molecular mechanisms modulating them following activation.

Prognostic value of renal resistance index in estimating the progression of chronic kidney disease

To study a relationship between main renal and intraparenchymal renal arterial resistance indices (RIs) measured by Doppler ultrasonography and clinical and laboratory parameters and to determine their prognostic value in estimating the progression of chronic kidney disease (CKD). The investigation enrolled 53 CKD patients divided into groups: glomerular and interstitial diseases. Glomerular filtration rate (GFR) calculated using the CKD-EPI formula, proteinuria (PU) severity, kidney sizes, renal parenchyma thickness, parenchyma/collecting index, and main and intrarenal vessel RIs were determined at the first hospitalization. The mean follow-up was 14 ± 2.64 months. The rate of GFR decline was estimated at the rehospitalization. Main renal and intrarenal vessel RIs depend on patient age and pulse pressure. The RIs are associated with GFR and PU in the group of glomerular diseases and with kidney sizes and structure in that of interstitial diseases. The interlobar arterial RI is the most sensitive predictor for worsening renal function with a threshold of 0.65, which is comparable to the prognostic value of PU. The main renal and intrarenal vessel RIs may be considered as a predictor for worsening renal function.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances.

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction.

0163: Renal arterial resistance index versus biomarkers for predicting acute kidney injury in acute heart failure

Acute kidney injury (AKI) is frequent during acute heart failure (AHF) and worsens the outcome. To predict AKI is important but remains challenging. The aim of this study was to analyze Doppler-derived renal arterial resistance index (RRI) during AHF as well as its determinants and its predictive value of AKI as compared to renal biomarkers comprehensive echocardiographic examination and Doppler measurement of RRI were performed on admission, at day 3 and at discharge. RRI was the ratio (peak systolic velocity – end diastolic velocity)/ peak systolic velocity of interlobar blood flow. Serial assessment of clinical parameters as well as creatinine, cystatin C, blood NGAL, urinary NGAL and electrolytes was also obtained. AKI was defined by an increase in creatinine ≥ 0.3 mg/l relative to the admission level. Exclusion criteria was eGFR < 15 ml/min/1.73m² and atrial fibrillation. among the 26 included patients, AKI occurred in 8 patients at day 3 and in 10 patients at discharge. Mean RRI values were 0.71±0.08 on admission, 0.71±0.09 at day 3 and 0.74±0.08 at discharge. RRI was related to age, creatinine and cystatin C (p≤0.05 for all) but not to other clinical or echocardiographic variables or BNP or NGAL levels. Only admission RRI was significantly associated with AKI at day 3 (table) as well as RRI at day 3 for AKI at discharge (0.77±0.07 vs 0.67±0.8; p=0.02). this pilot study describes RRI values as well as its early changes and determinants during AHF. Doppler-derived RRI measurement appears to be a relevant tool for predicting AKI. Abstract 0163 – Table Admission variables No AKI AKI p Age 60±17 69±14 0.29 LVEF 25±8 33±17 0.78 Blood Pressure 122±18 118±19 0.63 eGFR 62±24 52±20 0.35 Cystacin C 1.4±0.6 1.8±0.7 0.08 NGAL blood 125±84 147±130 0.76 NGAL urinary 13±17 9 ±4 0.79 BNP 1979±1815 1562±881 0.95 IRR 0.68±0.08 0.76±0.06 0.03

Intrarenal resistance index (RI) as a predictor of early renal impairment in patients with liver cirrhosis.

Despite its functional nature, hepatorenal syndrome (HRS) is associated with a poor prognosis and the only effective treatment is liver transplantation. It is very important to diagnose renal impairment in cirrhosis patients at an early stage before overt HRS develops. In patients with cirrhosis the early renal impairment or renovascular vasoconstriction can be predicted by renal arterial resistance index (RI). Our study aimed to compare RI in healthy controls versus patients with liver cirrhosis with and without ascites and assess its value for predicting subsequent renal status. Patients were divided into 2 groups with 50 patients in each group. Group 1 contained patients with cirrhosis without ascites and group 2 contained cirrhosis patients with ascites. All patients were subjected to detailed clinical examination, laboratory investigations and abdominal doppler ultrasound with renal RI measurements. Patients were followed for 6 months. RI was significantly higher in cirrhotic patients as compared to healthy controls (0.62 vs. 0.52, p< 0.01). In patients with cirrhosis, RI was significantly greater in patients with ascites than those without ascites (0.70 vs. 0.62, p < 0.01). RI >0.70 was significant independent predictor of subsequent HRS development (p = 0.006) CONCLUSIONS: Intrarenal RI measurement can be used as a predictor of HRS and may be further validated for regular monitoring of cirrhotic patients at risk of developing renal impairment.

Cystatin C serum concentration combined with renal artery resistance index determination for early diagnosis of hepatorenal syndrome value

肝肾综合征(HRS)是终末期肝病(MELD)的严重并发症,临床常分为Ⅰ型HRS:其特征为快速进行性肾功能损害2周内血清肌酐(Scr)较基线升高2倍以上并＞221μmol/L;Ⅱ型HRS:特征为稳定或非进行性肾功能损害,Scr在133 ～ 221 μmol/L之间,或血清肌酐清除率(Ccr)＜40％[1].引起HRS的机制主要是肾动脉显著收缩及体循环舒张调节功能紊乱,从而导致动脉血压降低,肾动脉灌注严重不足,肾小球滤过率(GFR)明显降低所致.肝肾综合征为功能性肾脏损害,因此早期预防、诊断及积极合理治疗有可能逆转肾功能衰竭(AKI)[2].本研究对肝肾综合征患者采用动态监测血清胱抑素C(cystian C,CyC)及肾动脉血流阻力指数(RI)在肝肾综合征的早期诊断及治疗上取得了一定的临床价值及经验,现总结如下. 关键词：肝肾综合征;肝硬化;血清胱抑素C;肾动脉血流阻力指数

Epidemiology of Thoracoabdominal Aortic Aneurysm Repairs in the United States from 1998 to 2011

underlying cause of both renovascular hypertension and the development of renal artery stenosis may be increased resistance in distal renal arteries and arterioles. Methods: We examined the velocity spectrum of 20 widely patent renal arteries. The contralateral renal artery was normal in 10 of these and stenotic or stented in 10. We compared the spectral broadening in these arteries by analyzing their mean to peak systolic flow velocities to see if patients prone to develop renal artery stenosis had more of their blood flow at lower velocities, which would be expected if these arteries had lower shear stress and eddy currents. We examined whether distal renal artery and arteriole resistance, which would result in decreased glomerular pressure and renovascular hypertension, would also account for blood flow effects inducing the development of proximal renal artery stenosis in a fluid dynamic model. Results: Normal renal arteries when the contralateral artery was also normal had a mean to peak systolic velocity ratio of 0.61 vs 0.40 in normal renal arteries when the contralateral renal artery had stenosis or had been previously stented (P < .001 by t-test). Similar spectral broadening, areas of low shear stress, and eddy currents were induced in the fluid dynamic model as the coefficient of resistance was varied to simulate increasing distal arterial resistance. Fig 1 shows a narrow spectrum with streamlined flow with low distal renal arterial resistance. Fig 2 shows spectral broadening with altered shear stress and flow as distal renal arterial resistance is increased (right). Conclusions: There is strong evidence that increased distal renal arterial and arteriolar resistance may a primary cause not only of renovascular hypertension but may also lead to the development of proximal renal artery stenosis. Proximal renal artery stenosis may often be an effect rather than a cause of renovascular hypertension explaining why its treatment may be ineffective. Author Disclosures: A. P. Sawchuk: None;H. Yu:None;M. C. Dalsing: None.

Application value of color Doppler ultrasound in the early diagnosis of diabetic nephropathy

Objective To investigate the clinical value of color Doppler in the early diagnosis of diabetic nephropathy （DN）.Methods 69 cases of DN Phase I,II patients （group A） and 75 cases Phase III （B group） all underwent renal artery line Doppler flow imaging inspection .Renal aorta （ MRA） ,interlobar artery （ IRA） ,renal seg-mental artery blood flow （SRA） peak systolic velocity （Vsmax）,resistance index （RI） and diastolic minimum speed （ Vdmin） and other hemodynamic parameters of two groups were analyzed .Results The Doppler spectrum renal blood flow characteristics of early renal damage were：between group A,B,the main renal artery （MRA）,the kidney arterial segment Vdmin significantly reduce ,RI was significantly higher;the interlobar artery Vsmax （t=3.562 5,P=0.000 5）,Vdmin （t=5.252,P=0.000 0） were significantly lower,RI was significantly higher （t=9.166 0,P=0.000 0）;with the severity of renal dysfunction ,kidney color flow imaging reduce ,the kidney volume was significantly reduced in patients with stage Ⅲ.Conclusion Color Doppler ultrasound can clearly show the size of the patient′s kidney and renal artery blood flow parameters ,which has certain value in the diagnosis of early DN . Key words: Diabetic nephropathies; Ultrasonography,doppler,color

Vessel Elasticity Rather Than Renal Parenchyma Determines Renovascular Resistance of Hypothermic Machine Perfusion.

Background: Renovascular resistance (RR) of hypothermic machine perfusion (MP) is most important indicator of kidney viability, but the factors that affect RR remain unknown. Method: In the control clinical trial, two groups were divided according to whether delayed graft function (DGF) occurred, and the characteristics of RR were analyzed under different clinical scenarios. Rabbit models of renal interstitial fibrosis (RIF) and acute renal failure (ARF) were established to explore the affecting factors of RR. Results: Renal interlobular artery resistance index in the first 2 days after transplantation in DGF group were higher than that in Non-DGF group (P=0.002). RR in DGF group was higher (P<0.001). There was a DCD donor of chronic glomerulonephritis, RR of the left kidney with the lower expression of α-smooth muscle actin in vascular smooth muscle reached normal after 12 hr of MP while that of the right one with arteriosclerosis obliterans shown by HE stain could not. In the basic research, the RR of both the RIF and ARF rabbit in which the morphology of renal vessel was normal reached normal range after 4 hr of MP.Figure: No Caption available.Conclusion: RR is mainly affected by the vessel elasticity instead of renal parenchyma. RR could not imply the pre-existing lesions of renal parenchyma. Whether a kidney is transplanted or discarded can not be decided by RR alone.

Decrease in Kidney Graft Size and an Increase in Renal Arterial Resistance Index During the First Year Post-Transplant Predict Graft Outcome.

Decrease in Kidney Graft Size and an Increase in Renal Arterial Resistance Index During the First Year Post-Transplant Predict Graft Outcome.

Maternal alcohol consumption in pregnancy enhances arterial stiffness and alters vasodilator function that varies between vascular beds in fetal sheep.

While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g (kg body weight)(-1)) was infused intravenously into ewes over 1 h daily for 39 days in late pregnancy (days 95-133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dl(-1), and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain-body weight ratio were not affected by alcohol infusion. Small arteries (250-300 μm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium-dependent vasodilatation sensitivity was reduced 10-fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilatation sensitivity was enhanced 10-fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol-induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.

Abstract 170: CFTR as a Novel Target and Mechanism for High-Fructose Diet and Salt-Induced Hypertension

Objective: High fructose and salt diet (HFSD) consumption is very common in modern lifestyle. Fructose not only stimulates intestinal salt and water absorption but also decreases renal sodium (Na+) and chloride (Cl-) excretion. High fructose intake induces rapid and sustained increase in blood pressure (BP). But a Cl--free diet could block fructose-induced hypertension. The underlying mechanism for this Cl_dependence of high fructose and salt induced hypertension is not clear. This study was designed to test the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel may play a critical role in the HFSD-induced hypertension. Approach and Results: The DSI HD-X11 transmitters for telemetry recordings of both blood pressure and ECG were implanted into CFTR-knockout (CFTR-/-) mice (8-week old, male) and their age- and gender-matched wild-type (CFTR+/+) mice. The systolic (SBP), diastolic (DBP) and mean BP (MBP) and ECG of the mice before and after feeding with HFSD (%65 fructose, 2% salt) were monitored daily for 8 weeks. Continuous 8-week HFSD caused a significant increase in aortic stiffness, mesenteric and renal artery resistance, SBP, DBP, and MBP in CFTR+/+ mice. Real-time PCR and Western blot analysis revealed a significant decrease (~90%) in CFTR mRNA and protein expression in aorta and mesenteric arteries but not in the heart and brain. This HFSD-induced specific down-regulation of CFTR was highly correlated with the HFSD-induced reduction in WINK1 and WINK4 expression in aorta and mesenteric artery. In the mice fed with normal diet the aortic stiffness, mesenteric and renal artery resistance and the SDP, DBP, and MBP at either daytime or nighttime was significantly higher in CFTR-/- mice (n=8) than in CFTR+/+ mice (n=15), implicating an important functional role for CFTR in the regulation of vascular resistance and BP. Conclusions: 1) CFTR plays a pivotal functional role in the regulation of arterial resistance and BP; 2) HFSD may cause hypertension through a specific WINKs-CFTR signaling pathway. These results provide compelling evidence that diet may cause changes in expression of specific genes in the vasculature and CFTR may represent a novel molecular target and mechanism for the HFSD-induced hypertension.

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The renal arterial resistance index: a marker of renal function with an independent and incremental role in predicting heart failure progression

The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis.

Phosphodiesterase 5 Attenuates the Vasodilatory Response in Renovascular Hypertension

NO/cGMP signaling plays an important role in vascular relaxation and regulation of blood pressure. The key enzyme in the cascade, the NO-stimulated cGMP-forming guanylyl cyclase exists in two enzymatically indistinguishable isoforms (NO-GC1, NO-GC2) with NO-GC1 being the major NO-GC in the vasculature. Here, we studied the NO/cGMP pathway in renal resistance arteries of NO-GC1 KO mice and its role in renovascular hypertension induced by the 2-kidney-1-clip-operation (2K1C). In the NO-GC1 KOs, relaxation of renal vasculature as determined in isolated perfused kidneys was reduced in accordance with the marked reduction of cGMP-forming activity (80%). Noteworthy, increased eNOS-catalyzed NO formation was detected in kidneys of NO-GC1 KOs. Upon the 2K1C operation, NO-GC1 KO mice developed hypertension but the increase in blood pressures was not any higher than in WT. Conversely, operated WT mice showed a reduction of cGMP-dependent relaxation of renal vessels, which was not found in the NO-GC1 KOs. The reduced relaxation in operated WT mice was restored by sildenafil indicating that enhanced PDE5-catalyzed cGMP degradation most likely accounts for the attenuated vascular responsiveness. PDE5 activation depends on allosteric binding of cGMP. Because cGMP levels are lower, the 2K1C-induced vascular changes do not occur in the NO-GC1 KOs. In support of a higher PDE5 activity, sildenafil reduced blood pressure more efficiently in operated WT than NO-GC1 KO mice. All together our data suggest that within renovascular hypertension, cGMP-based PDE5 activation terminates NO/cGMP signaling thereby providing a new molecular basis for further pharmacological interventions.

Resistive index as a predictor of acute kidney injury caused by an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker in chronic kidney disease patients

BackgroundAngiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) may induce acute kidney injury (AKI). The aim of this study was to evaluate the role of the resistive index (RI), which reflects renal artery resistance on renal duplex ultrasonography, as a predictor of AKI in chronic kidney disease (CKD) patients who are prescribed an ACE inhibitor or ARB. MethodsWe screened 105 CKD patients evaluated with renal duplex ultrasonography from 2008 to 2012. We excluded patients not treated with ACE inhibitor or ARB and diagnosed with renal artery stenosis. Finally, we retrospectively analyzed the medical records of 54 patients. AKI was defined as increased serum creatinine by >30% compared with baseline after starting ACE inhibitor or ARB treatment. ResultsThe mean age of the patients was 60.5±13.0 years, serum creatinine level was 1.85±0.85mg/dL and 22.2% of the patients had AKI after the use of an ACE inhibitor or ARB. The RI (P=0.006) and the percentages of patients with diabetes (P=0.008) and using diuretics (P=0.046) were higher in the AKI group. The area under the receiver operating characteristics curve for the prediction of AKI was 0.736 (95% confidence interval=0.587–0.885, P=0.013), and RI≥0.80 predicted AKI with 83.3% sensitivity and 61.9% specificity. In the multivariate analysis, RI≥0.80 was an independent prognostic factor [Exp (B)=8.03, 95% confidence interval=1.14–56.74, P=0.037] for AKI. ConclusionRI≥0.80 on the renal duplex ultrasonography may be a helpful predictor for AKI in CKD patients who are prescribed an ACE inhibitor or ARB.

Endothelin-1, Oxidative Stress, and Endogenous Angiotensin II

Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (mean arterial pressure [MAP]) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared with control pregnant rats. To examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy, we examined the role of endogenous ANGII in AT1-AA–infused pregnant rats, and that of endothelin-1 and oxidative stress in AT1-AA+ANGII–treated rats. Chronic ANGII increased MAP from 95±2 in normal pregnant rats to 115±2 mm Hg; chronic AT1-AA increased MAP to 118±1 mm Hg in normal pregnant rats, which further increased to 123±2 mm Hg with AT1-AA+ANGII. Increasing ANGII from 10 −11 to 10 −8 decreased afferent arteriole diameter from 15% to 20% but sharply decreased afferent arteriole diameter to 60% in AT1-AA–pretreated vessels. Renal artery resistance index increased from 0.67 in normal pregnant rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA+ANGII–infused rats. AT1-AA–induced hypertension decreased with enalapril but was not attenuated. Both tissue endothelin-1 and reactive oxygen species increased with AT1-AA+ANGII compared with AT1-AA alone, and blockade of either of these pathways had significant effects on MAP or renal artery resistance index. These data support the hypothesis that AT1-AA, via activation of endothelin-1 and oxidative stress and interaction with endogenous ANGII, is an important mechanism whereby MAP and renal vascular responses are enhanced during preeclampsia.