Showing papers by "Lars Christian Rump published in 2013"
TL;DR: RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.
Abstract: Background—Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. Methods and Results—A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (−10.1/−10...
338 citations
Baker IDI Heart and Diabetes Institute1, University of Erlangen-Nuremberg2, University of Chicago3, Utrecht University4, University of Southern California5, Imperial College London6, University of Milano-Bicocca7, University of Oslo8, Monash University9, Columbia University10, Gdańsk Medical University11, University of Düsseldorf12, Virginia Commonwealth University13, Ohio State University14, National and Kapodistrian University of Athens15, SUNY Downstate Medical Center16, University College London17
TL;DR: Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent.
153 citations
TL;DR: Plasma metanephrine provides a superior analyte compared with cortisol in assessing the selectivity of adrenal vein sampling during procedures without cosyntropin stimulation.
Abstract: Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative parameter. The objective of our study was to determine the use of plasma metanephrine concentrations to establish correct catheter positioning during adrenal vein sampling with and without cosyntropin stimulation. We included 52 cosyntropin-stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and metanephrine concentrations were measured in adrenal and peripheral venous samples. Success rates of sampling, using an adrenal to peripheral cortisol selectivity index of 3.0, were compared with success rates of metanephrine using a selectivity index determined by receiver operating characteristic curve analysis. Among procedures assessed as selective using cortisol, the adrenal to peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol (94.0 versus 15.5; P<0.0001). There were significant positive relationships between adrenal to peripheral vein ratios of cortisol and metanephrine for cosyntropin-stimulated samplings but not for nonstimulated samplings. Receiver operating characteristic curve analysis indicated a plasma metanephrine selectivity index cutoff of 12. Using this cutoff, concordance in sampling success rates determined by cortisol and metanephrine was substantially higher in cosyntropin-stimulated than in nonstimulated samplings (98% versus 59%). For the latter procedures, sampling success rates determined by metanephrine were higher (P<0.01) than those determined by cortisol (91% versus 56%). In conclusion, metanephrine provides a superior analyte compared with cortisol in assessing the selectivity of adrenal vein sampling during procedures without cosyntropin stimulation.
63 citations
TL;DR: In disagreement with several other studies, the authors report no significant overall blood BP lowering effect after RDN in a small group of 12 patients, and not surprisingly did not observe any changes in muscle sympathetic nerve activity.
Abstract: The recently published article by Brinkmann et al1 attempted to investigate the effect of catheter-based renal denervation (RDN) on blood pressure (BP) and muscle sympathetic nerve activity. The article is of interest; however, some aspects require clarification.
In disagreement with several other studies, the authors report no significant overall blood BP lowering effect after RDN in a small group of 12 patients, and not surprisingly did not observe any changes in muscle sympathetic nerve activity. As shown in larger series, procedural success is clearly observed in patients with high BP as a surrogate of increased sympathetic activity. In contrast to the Symplicity trials, the baseline BP herein was 157/85 mm …
51 citations
TL;DR: Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry to emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.
Abstract: Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn’s Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn’s Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p
27 citations
TL;DR: The data suggest that within renovascular hypertension, cGMP-based PDE5 activation terminates NO/cGMP signaling thereby providing a new molecular basis for further pharmacological interventions.
Abstract: 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.
26 citations
TL;DR: Deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice, and higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease.
Abstract: Purinergic signaling is involved in a variety of physiological states. P2 receptors are mainly activated by adenosine triphosphate (ATP). Activation of specific P2Y receptor subtypes might influence progression of kidney disease. To investigate the in vivo effect of a particular P2 receptor subtype on chronic kidney disease progression, subtotal nephrectomy was performed on wild type (WT) and P2Y2 receptor knockout (KO) mice. During the observational period of 56 ± 2 days, survival of KO mice was inferior compared to WT mice after SNX. Subtotal nephrectomy reduced creatinine clearance in both groups of mice, but the decrease was significantly more pronounced in KO compared to WT mice (53.9 ± 7.7 vs. 84.3 ± 8.7μl/min at day 56). The KO mice also sustained a greater increase in systolic blood pressure after SNX compared to WT mice (177 ± 2 vs. 156 ± 7 mmHg) and a 2.5-fold increase in albuminuria compared to WT. In addition, WT kidneys showed a significant increase in remnant kidney mass 56 days after SNX, but significant attenuation of hypertrophy in KO mice was observed. In line with the observed hypertrophy in WT SNX mice, a significant dose-dependent increase in DNA synthesis, a marker of proliferation, was present in cultured WT glomerular epithelial cells upon ATP stimulation. Markers for tissue damage (TGF-β 1, PAI-1) and proinflammatory target genes (MCP1) were significantly upregulated in KO mice after SNX compared to WT SNX mice. In summary, deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice. Higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease.
22 citations
01 Apr 2013
15 citations
TL;DR: Trends to improve quality metrics for hemodialysis have been established in Germany even after introduction of flat rate reimbursement, and analysis of facility practice patterns is needed to maintain quality of care in a cost-containment environment.
14 citations
TL;DR: The criteria for certification of renal denervation centers, in addition to personnel and facility requirements, proper patient selection as well as pre- and post-procedural follow-up examinations are discussed.
Abstract: Dieses Positionspapier ist eine Stellungnahme der Deutschen Gesellschaft fur Kardiologie – Herz- und Kreislaufforschung e.V., der Deutschen Gesellschaft fur Nephrologie e.V. sowie der Deutschen Hochdruckliga und fasst die Kriterien zur Zertifizierung von „Renale-Denervations-Zentren (RDZ)“ zusammen. Neben den personellen, apparativen und raumlichen Voraussetzungen werden auch die Patientenselektion, die notwendigen Vor- und Nachsorgeuntersuchungen sowie der Zertifizierungsprozess diskutiert. Die Zertifizierung soll Arzten, Patienten und Kostentragern bei der Identifikation geeigneter Zentren und der Etablierung des neuen Therapieverfahrens helfen.
5 citations
TL;DR: Renal denervation as a catheter-based procedure, introduced new challenges and requirements for hypertension centres in offering optimal patient care, and needs to be met by a multidisciplinary team of doctors who can provide excellent evaluation, treatment and follow-up of these patients.
Abstract: Renal denervation (RDN) as a catheter-based procedure was introduced in 2009. As a reinvention of an old concept this approach in treating resistant hypertension has been gathering an unprecedented momentum in the world of hypertension. The incredible success in introducing this technique, followed by its quick and wide distribution, introduced new challenges and requirements for hypertension centres in offering optimal patient care. The challenges of these new parameters and requirements have to be met not only by a multidisciplinary team of doctors who can provide excellent evaluation, treatment and follow-up of these patients, but also by the hypertension centres themselves, who wish to provide this treatment option to their patients.