Showing papers by "Roland E. Schmieder published in 2005"

Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients.

Abstract: Background Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection. This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator. Methods and results The study was a randomized, multicenter, double-blind, placebo-controlled, active-comparator 8-week trial in patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [DBP] > or =95 and Conclusions Once-daily oral treatment with aliskiren lowers blood pressure effectively, with a safety and tolerability profile comparable to that of irbesartan and placebo, in patients with mild-to-moderate hypertension. Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure.

Additional Antiproteinuric Effect of Ultrahigh Dose Candesartan: A Double-Blind, Randomized, Prospective Study

Abstract: Proteinuria indicates future renal and cardiovascular morbidity, and, conversely, its reduction is associated with improved outcome. In a randomized, double-blind trial with parallel group design, the antiproteinuric effect of candesartan at high doses was analyzed. Patients with normal or mildly impaired renal function, protein excretion rate of 1 to 10 g/d, and treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for 3 mo were eligible. After a 4-wk treatment with 16 mg/d candesartan, patients (n = 32) were allocated to double-blind therapy with either 32 or 64 mg/d candesartan for 12 wk (including 4 wk of uptitration), followed again by 4 wk of candesartan 16 mg/d. Proteinuria at study entry was similar in both groups (geometric mean [95% confidence interval (CI)]; 32 mg/d candesartan 2.14 g/d [95% CI, 1.45 to 3.17]; 64 mg/d candesartan 2.54 g/d [95% CI, 1.91 to 3.40]; NS). After the double-blind treatment phase, proteinuria was reduced to 1.42 g/d (0.85 to 2.37) in the 64-mg/d group (P = 0.017), without any change in the 32-mg/d group (2.02 g/d [95% CI, 1.26 to 3.26]). The change in proteinuria differed between the two groups in absolute (P = 0.025) and relative terms (-29 +/- 50 versus -0 +/- 26%; P = 0.012). After downtitration to 16 mg/d candesartan, proteinuria increased again to 2.38 g/d (1.57 to 3.62) in the 64-mg/d group (P = 0.001) but remained unchanged in the 32-mg/d group (2.04 g/d [95% CI, 1.17 to 3.57]; NS). No change in BP was noticed in response to the different doses of candesartan. These data indicate an additive antiproteinuric effect of ultrahigh dose of the angiotensin receptor blocker candesartan compared with standard dose.

Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study.

Abstract: OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272) Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment Reading of the echocardiograms was central and blinded for therapy, patient and sequence RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 00001 and P = 0003) The left ventricular mass index decreased by 136 +/- 239 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 00001) and 39 +/- 239 g/m(2) with enalapril (P < 0005); these decreases were significantly different (P < 00001) The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 00001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0001) Both treatments were well tolerated CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH

Enhanced levels of platelet P-selectin and circulating cytokines in young patients with mild arterial hypertension.

Abstract: BackgroundEmerging evidence links inflammation to atherosclerosis (AS). Although some studies have addressed the role of inflammation in patients with arterial hypertension (AH), its overall contribution in AH is far from being understood. Therefore, the present pilot study was designed to examine t

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Abstract: Background: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

The role of non-haemodynamic factors of the genesis of LVH

Abstract: himself, would place too much of a responsible burden on these particular patients. Our experience has shown that the establishment of a multidisciplinary team composed of psychiatrist, nephrological personnel and social workers enables the extension of chronic dialytic therapy to patients with major psychiatric illnesses. Obviously, every such patient will have to be thoroughly evaluated and his suitability for chronic dialysis individually assessed. Although this endeavour undoubtedly demands the investment of considerable time and resources by all involved, the satisfaction gained upon successful treatment is well worth the effort. It is time that both the psychiatric and nephrological communities openly address this issue.

CYP3A5 genotype is associated with elevated blood pressure.

Abstract: The present study aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney, is associated with blood pressure in Caucasians. A homogenous group of 115 young, white male students with normal or mildly elevated, but untreated blood pressure was included. Blood pressure was recorded by ambulatory 24-h blood pressure-monitoring and compared between individuals with high (*1/*3) and low CYP3A5 expression (*3/*3). Moreover, genotype-dependent differences in parameters associated with the renin-angiotensin-aldosterone system were evaluated. Twenty-four hour diastolic blood pressure values were not significantly different between the two groups. However, individuals with the CYP3A5*3/*3 genotype had significantly higher 24-h ambulatory systolic blood pressure values compared to subjects with the CYP3A5*1/*3 genotype (129+/-10 versus 124+/-9, P < 0.05). There was no association of CYP3A5 genotype with angiotensin II plasma concentrations, renal plasma flow, glomerular filtration rate, urinary sodium excretion and parameters determined by echocardiography, but the *3/*3 group had significantly lower serum aldosterone concentrations compared to the individuals with the *1/*3 genotype (101+/-29 versus 117+/-29 pg/ml, P < 0.05). These data, as generated with a homogenous population of young Caucasians, indicate that the CYP3A5 genotype affects blood pressure in humans possibly by genotype-dependent differences in renal, CYP3A5-mediated metabolism of cortisol and/or aldosterone. We interpret the lower serum aldosterone concentration in the genotype group with the elevated systolic blood pressure as a counter-regulatory mechanism to attenuate the increased blood pressure associated with the CYP3A5*3/*3 genotype.

Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers.

Abstract: The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.

[BENEFIT Kidney--significance of a nephrology screening at intervention outset and therapy success].

Abstract: BACKGROUND AND OBJECTIVE Early specialist care of patients with renal disease, including timely and planned onset of dialysis, determine the course of the disease, quality of life, hospitalization and life expectancy. A multi-centre enquiry by standardized questionnaire was undertaken to define and analyse medical care of newly dialysis-requiring patients. PATIENTS AND METHODS Data on 551 patients in five different regions of Germany who for the first time required renal replacement treatment were prospectively collected between July 2002 and March 2003. Documentation of history, clinical findings and biochemical tests was done on consecutive patients with a standardized questionnaire, until the desired number of cases was reached. RESULTS The mean age of the patients (55.4% males) was 64.8 years. 30.7% had diabetes mellitus, 22.3% arterial hypertension/nephrosclerosis and 16.9% glomerulonephritis/vasculitis. Early predominantly nephrological care had been undertaken in 38.7% of patients. 59.0% were cared for almost exclusively by their general practitioner until the time when dialysis was started. 229 patients (41.6%) were referred to specialist (nephrologists) only when dialysis had become necessary. The onset of dialysis was at the right time in only 50.5% of this group. Comparing the care given by nephrologists with that by general practitioners, elective (i.e. planned) dialysis was begun in 81.0% vs. 48.0% (p<0.05). Hospitalization in the two groups was 54.5% vs. 83.7% (p<0.05), the duration of hospital stay 11.4 vs. 17.4 days (p<0.05). CONCLUSION Fewer than 40% of patients with chronic renal disease in preterminal renal failure (stage IV) were under the care of nephrologists. The lower the degree of nephrological care the more frequent was there a delay in the onset of dialysis treatment. The incidence and the duration of hospital stay was longer. Structured treatment pathways and incentives need to be formulated to reduce the incidence of wrong or substandard treatment of patients with impaired renal function.

Effects of sympathetic nerves and angiotensin II on renal sodium and water handling in rats with common bile duct ligature

Abstract: We tested the hypothesis that angiotensin II is likely to be mandatory for the neurogenic sodium and volume retention in cirrhotic rats with common bile duct ligature (BDL) following an acute volum...

Cardiotrophin: its importance as a pathogenetic factor and as a measure of left ventricular hypertrophy.

Abstract: Importance of left ventricular mass It is well known that increased left ventricular mass (LVM) [i.e. left ventricular hypertrophy (LVH)] is an important prognostic factor for cardiovascular mortality and morbidity [1]. This has been repeatedly shown for LVM, as assessed by electrocardiography (ECG) [2,3] and echocardiographic measures [4,5]. Reduction of LVM by antihypertensive treatment is accompanied by a decreasing risk [6–8]. For example, in the LIFE study, less severe LVH during antihypertensive therapy assessed by ECG [9] and echocardiographic [10] measures was associated with a decreasing risk of cardiovascular endpoints. Regression of LVH must be defined as one important target of antihypertensive therapy in addition to blood pressure control. Not all antihypertensives are equal in this regard [11]. Substances blocking the renin–angiotensin–aldosterone system generally are more effective in lowering LVM [11].

Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.

Abstract: Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.