Renal resistive index--a valid tool to assess renal endothelial function in humans?

<p><b>Background.</b> In humans, renal endothelial function is assessed by the vasoconstrictive response to l-NG-monomethyl arginine (l-NMMA). We hypothesized that Doppler sonographic measurements of the renal resistive index in response to inhibition of nitric oxide synthase offer a new methodological approach for testing renal endothelial function.</p> <p><b>Methods.</b> Forty-one patients without nephropathy were included. Para-aminohippurate and inulin clearance were performed under basal conditions and during l-NMMA infusion. In parallel, renal resistive index was assessed by Doppler sonography, and central blood pressure was determined.</p> <p><b>Results.</b> Following nitric oxide synthase inhibition, renal resistive index increased significantly, and 29% of our patients developed Doppler sonographic diastolic zero flow. Renal plasma flow decreased in response to l-NMMA, and conversely, renal vascular resistance increased. There was no correlation of renal vascular resistance and renal resistive index at baseline and during nitric oxide synthase inhibition. Changes in renal resistive index were not related to changes in renal perfusion or renal vascular resistance. Renal resistive index correlated with central pulse pressure at baseline and during l-NMMA infusion, whereas renal vascular resistance did not correlate with central pulse pressure.</p> <p><b>Conclusion.</b> Our data do not support the hypothesis that renal resistive index is a tool to test renal endothelial function in humans and should not be used interchangeably with renal vascular resistance.</p&gt

Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with essential hypertension

<p><b>Background:</b> It is not known whether the beneficial effects of N-acetylcysteine (NAC) in conditions associated with increased oxidative stress are caused by direct superoxide scavenging. We therefore compared the acute superoxide scavenging efficacy of NAC against vitamin C (VITC) on impaired endothelium-dependent vasodilation in subjects with essential hypertension.</p> <p><b>Methods:</b> In a cross-over randomized study, the effects of intra-arterial administration of either NAC (48 mg/min) or VITC (18 mg/min) were examined in 15 subjects with essential hypertension and in 15 normotensive control subjects. Both endothelium-dependent and endothelium-independent vasodilation were determined as forearm blood flow (FBF) response to the intra-arterial administration of acetylcholine (Ach) and sodium nitroprusside (NP) in doses of 12 and 48 g/min and 3.2 and 12.8 g/min, respectively.</p> <p><b>Results:</b> Subjects with essential hypertension had impaired responses to both doses of Ach (% FBF to higher dose of Ach: 325 146 in subjects with essential hypertension v 540 199 in control subjects; P = .02) and an impaired response to the higher dose of NP (330 108 v 500 199; P = .03). The intra-arterial administration of NAC had no effect on these responses (higher dose of Ach: 325 146 without v 338 112 with NAC, NS). In contrast, intra-arterial VITC improved both the response to Ach (320 132 without v 400 185 with VITC, P = .05) and to NP (383 162 v 447 170, P = .05).</p> <p><b>Conclusions:</b> We found that NAC showed no statistically significant effect on either endothelium-dependent or endothelium-independent vasodilation in hypertensive subjects, whereas VITC did. We conclude that NAC is therefore not an effective superoxide scavenger in vivo. Other, nonimmediate effects such as the generation of glutathione may explain the beneficial effects of NAC in conditions associated with oxidative stress.</p&gt

Vitamin C augments the renal response to L-arginine in smokers

<p>Background: In the coronary and the forearm circulations, endothelium-dependent vasomotion is impaired in smokers, but can be augmented by l-arginine or vitamin C. We examined whether smoking similarly affects the renal circulation.</p> <p>Methods: In 20 smokers (age 26 ± 4 years) and in 20 non-smokers (age 28 ± 3 years) changes of renal plasma flow (RPF), glomerular filtration rate (GFR), blood pressure and heart rate in response to the subsequent intravenous infusions of NG-monomethyl-l-arginine (L-NMMA), l-arginine and l-arginine plus vitamin C were studied by use of a constant infusion input clearance technique.</p> <p>Results: Systemic haemodynamic parameters did not differ between smokers and non-smokers during each experimental phase. At baseline, RPF and GFR were similar between the groups. The infusion of L-NMMA led to a similar decrease of RPF, while GFR did not change in either group. During the infusion of l-arginine RPF increased similarly. Finally, the co-infusion of l-arginine plus vitamin C led to a significantly greater increase of RPF (+277 ± 395 vs +79 ± 76 ml/min, P = 0.03) and GFR (+12.1 ± 10.6 vs +3.4 ± 11.2 ml/min, P = 0.02) in smokers as compared to non-smokers.</p> <p>Conclusions: L-NMMA-induced vasoconstriction of the renal vasculature was similar in smokers compared to non-smokers. l-arginine alone induced a similar increase of RPF. The co-infusion of vitamin C and l-arginine led to a greater increase of RPF and GFR in smokers. This might suggest that oxidative stress is increased in the renal vasculature of smokers.</p&gt

Effects of nitric oxide synthase inhibition and L-arginine on renal haemodynamics in young patients at high cardiovascular risk

<p><b>Background:</b> Aging and a variety of cardiovascular risk factors are associated with oxidative stress and impaired endothelial function. Whether such an association is already evident in the renal vascular bed in young patients at high cardiovascular risk has not yet been determined.</p> <p><b>Methods:</b> We compared renal haemodynamics in 23 young (age 30 ± 5 years) male patients at high cardiovascular risk with impaired lipid metabolism and elevated blood pressure with 23 matched, healthy control subjects (age 28 ± 3 years) without cardiovascular risk factors at baseline and following infusions of the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine (l-NMMA: 4.25 mg/kg), the substrate of NO synthase l-arginine (100 mg/kg) and the antioxidant Vitamin C (3 g, co-infused with l-arginine 100 mg/kg).</p> <p><b>Results:</b> Baseline renal haemodynamics did not differ between the two groups. Infusion of l-NMMA decreased renal plasma flow (RPF) in both groups to a similar extent (−113 ± 95 ml/min versus −128 ± 133 ml/min, p = NS). The response of RPF to infusion of l-arginine was more pronounced in high risk patients than in control subjects (+123 ± 64.4 ml/min versus +75.6 ± 60.2 ml/min, p = 0.012) and further exaggerated during co-infusion of l-arginine and Vitamin C (+299 ± 164 ml/min versus +175 ± 148 ml/min, p = 0.003).</p> <p><b>Conclusions:</b> Basal NO activity of the renal vasculature appears to be unaltered in young patients at high cardiovascular risk. However, the greater response of RPF to l-arginine and to Vitamin C co-infused with l-arginine in these young patients suggests that decreased substrate availability for NO synthase and oxidative stress are key factors for alterations in endothelium-dependent vasodilation of the renal vasculature in this young high risk group of patients.</p&gt

Early Effects of Renal Replacement Therapy on Cardiovascular Comorbidity in Children with End-Stage Kidney Disease: Findings from the 4C-T Study

PubMedID: 28926375Background The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective cardiovascular comorbidity in children with chronic kidney disease study and focuses on the early effects of renal replacement therapy (RRT) modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis. Methods We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n = 76 transplantation, n = 90 dialysis). Results RRT modality had a significant impact on the change in arterial structure and function: compared to dialysis treatment, transplantation was independently associated with decreases in pulse wave velocity (ß = -0.67; P < 0.001) and intima media thickness (ß = -0.40; P = 0.008). Independent of RRT modality, an increase in pulse wave velocity was associated with an increase in diastolic blood pressure (ß = 0.31; P < 0.001). Increasing intima media thickness was associated with a larger increase in body mass index (ß = 0.26; P = 0.003) and the use of antihypertensive agents after RRT (ß = 0.41; P = 0.007). Changes in left ventricular mass index were associated with changes in systolic blood pressure (ß = 1.47; P = 0.01). Conclusions In comparison with initiating dialysis, preemptive transplantation prevented further deterioration of the subclinical vascular organ damage early after transplantation. Classic cardiovascular risk factors, such as hypertension and obesity are of major importance for the development of cardiovascular organ damage after renal transplantation. © 2017 Wolters Kluwer Health, Inc. All rights reserved.Roche Organ Transplant Research Foundation 01EO0802This study has been made possible by grants of the German Federal Ministry of Education and Research (reference number: 01EO0802), the European Renal Association - European Dialysis and Transplant Association (www.era-edta.org), the KfH Foundation for Preventive Medicine and the Roche Organ Transplantation Research Foundation (ROTRF)

Rapid nongenomic effects of aldosterone on human forearm vasculature

The impact of aldosterone in cardiovascular disease and hypertension has recently gained new interest. Aldosterone is now suggested to be a more common cause of hypertension than previously believed and has been linked to myocardial fibrosis, independent of its hypertensive effects. Finally, rapid nongenomic aldosterone effects have been proposed to be important in hypertension, in addition to its genomic effects. Forty-eight healthy male volunteers were examined in a randomized, placebo-controlled, double-blind crossover trial to elucidate the rapid nongenomic, vascular effects of aldosterone in humans. Forearm blood flow was measured by venous occlusion plethysmography. First, aldosterone (500 ng/min) and placebo were infused into the brachial artery for 8 minutes. The volunteers then received ascending doses of acetylcholine, NG-monomethyl-l-arginine (L-NMMA), sodium nitroprusside, or phenylephrine. Aldosterone increased forearm blood flow (P&#60;0.001, ANOVA). The maximum effect was an increase in forearm blood flow with aldosterone of 7.9±2.6% compared with 0.1±1.9% with placebo treatment after 8 minutes. With aldosterone, L-NMMA induced a greater vasoconstriction (P&#60;0.05, ANOVA), sodium nitroprusside induced an attenuated vasoconstriction (P&#60;0.01, ANOVA), and phenylephrine induced an exaggerated vasoconstriction (P&#60;0.01, ANOVA) within minutes as compared with placebo. These data suggest that aldosterone acts through rapid nongenomic effects at the endothelium by increasing NO release and at the vascular smooth muscle cells by promoting vasoconstriction. This is consistent with in vitro data showing an increase in intracellular calcium in both cell types. Disturbances of these aldosterone effects on both levels might be important in promoting hypertension

Supplementary Material for: Removal Characteristics and Total Dialysate Content of Glutamine and Other Amino Acids in Critically Ill Patients with Acute Kidney Injury Undergoing Extended Dialysis

<p><b><i>Background:</i></b> Acute kidney injury in critically ill patients is associated with the activation of protein catabolism and a negative nitrogen balance. Renal replacement therapy (RRT) aggravates this problem by eliminating a substantial amount of amino acids. However, there is scarce data on the removal characteristics of modern dialysis membranes in extended dialysis. <b><i>Methods:</i></b> This is a prospective study in 10 extended dialysis sessions using a 1.8-m² polysulfone membrane (EMiC2 dialyzer or AV 1000S; FMC, Germany). Blood samples for 19 amino acids were drawn before, during, and after 10 h of extended dialysis (blood/dialysate flow 150 ml/min). In addition, samples for the calculation of dialyzer clearance and samples from the total spent dialysate were measured using a Biochrom 30 amino acid analyzer. <b><i>Results: </i></b>Despite no significant difference in pre- and postdialysis plasma amino acid levels, we found an impressive amount of amino acids in collected spent dialysate, i.e. 10.5 g/10 h of treatment. The dialyzer clearance ranged from 67.6 ml/min for phenylalanine to 140.0 ml/min for valine. The total eliminated masses of the measured amino acids had equal values for both membranes. There was a significant difference between the dialyzer clearance of the investigated membranes for glutamine (AV 1000S: 83.3 ml/min vs. EMiC2: 92.0 ml/min, p = 0.02) and serine (88.8 ml/min vs. 91.8 ml/min, p = 0.005). <b><i>Discussion:</i></b> Our data indicate that the modern forms of RRT eliminate amino acids to an extent that has not been met by our nutritional support standards. Especially the removal of glutamine, important for immune function and cell regeneration, might have detrimental effects on the recovery of critically ill patients.</p