C-reactive protein: a family of proteins to regulate cardiovascular function.

Based on a multitude of clinical studies, C-reactive protein (CRP) has emerged as a risk marker for the development of cardiovascular disease, leading to recently published recommendations for screening the general population for plasma CRP level as a predictor for future cardiovascular events. However, uncertainties exist in how to apply these recommendations to populations with very high serum CRP levels and a high prevalence of cardiovascular disease, such as patients with end-stage renal disease. Furthermore, in vitro results are conflicting concerning the role of CRP in the vessel wall.

Hidden population substructures in an apparently homogeneous population bias association studies.

Linkage- and association-based approaches have been applied to attempt to unravel the genetic predisposition for complex diseases. However, studies often report contradictory results even when similar population backgrounds are investigated. Unrecognized population substructures could possibly explain these inconsistencies.

Impact of oxidized low density lipoprotein on vascular cells.

Oxidized LDL (OxLDL) is a proatherogenic lipoprotein, accumulating in the vascular wall and contributing to the pathogenesis of vascular dysfunction early in the development of atherosclerosis. Enhanced serum levels of OxLDL, as well as antibodies against its epitopes, are predictive for endothelial dysfunction and coronary heart disease. While enhanced oxidative stress is one factor triggering formation of OxLDL, OxLDL itself has been identified as a potent stimulus for vascular oxygen radical formation, causing a vicious circle.

Endotoxin-induced acute renal failure in rats: effects of L-arginine and nitric oxide synthase inhibition on renal function.

Background: The regulation of renal hemodynamics is closely related to the L-arginine (L-Arg)/nitric oxide (NO) pathway. NO - metabolized from L-Arg - is capable of improving renal function in ischemic and toxic acute renal failure (ARF), while NO synthase (NOS) inhibition induces deterioration in renal function. The mortality rate in patients with septic shock is increased when treated with a non-selective NOS inhibitor, while the incidence of ARF requiring renal replacement therapy is unaffected.

Beta(2)-microglobulin removal by extracorporeal renal replacement therapies.

There is increasing evidence that end-stage renal disease patients with lower beta(2)-microglobulin plasma levels and patients on convective renal replacement therapy are at lower mortality risk. Therefore, an enhanced beta(2)-microglobulin removal by renal replacement procedures has to be regarded as a contribution to a more adequate dialysis therapy. In contrast to high-flux dialysis, low-flux hemodialysis is not qualified to eliminate substantial amounts of beta(2)-microglobulin.

Morbus Fabry of the heart. Why should cardiologists care?

Fabry Disease is an X-linked lysosomal storage disorder leading to the accumulation of glycosphingolipids, mainly globotriaosylceramides in all tissues and solid organs of the body. The disease was described by Johannes Fabry and William Anderson coevally in 1898. Beside the involvement of the central nervous system, peripheral nerves, kidneys, skin and endovascular endothelium, the heart plays a major role in the disease.

Native C-reactive protein increases whereas modified C-reactive protein reduces atherosclerosis in apolipoprotein E-knockout mice.

Background: C-reactive protein (CRP) may have proatherogenic but also vasoprotective properties. We tested the hypothesis that the configuration of CRP (pentameric, or native [nCRP], versus monomeric, or modified [mCRP]) determines these different characteristics in an in vivo model.

Methods And Results: We investigated the effects of human nCRP and mCRP on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice.

Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.

Background: Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.

Methods: We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo.

L-Arginine does not affect renal morphology and cell survival in ischemic acute renal failure in rats.

Background: L-Arginine (L-Arg), a substrate of nitric oxide synthases, improves renal function in ischemic acute renal failure (iARF). We evaluated whether L-Arg improves renal morphology and cell survival in the course of iARF.

Methods And Results: iARF was induced in rats by bilateral clamping of renal arteries for 45 min.

Sample sizes for clinical trials with time-to-event endpoints and competing risks.

We consider clinical trials where the time to occurrence of events in the presence of competing risks is the primary endpoint for treatment evaluation. The number of events with regard to the defined primary endpoint required to ensure the specified power can be calculated according to Schoenfeld's formula like in classical survival studies. However, determination of the number of patients that have to be recruited to observe the calculated number of events requires specification of the length of the accrual period, the trial duration and assumptions about the event-specific hazard functions.

Endothelin B receptor-deficient mice develop endothelial dysfunction independently of salt loading.

Background: Rodents without a functional endothelin B (ETB) receptor develop salt-sensitive hypertension. The underlying mechanisms, however, are so far unknown. The ETB receptor is involved in endothelial function by modulating the activity of the endothelial nitric oxide synthesis as well as contributing to the control of endothelial prostacyclin synthesis.

Optimal treatment of renal anaemia (OPTA): improving the efficacy and efficiency of renal anaemia therapy in haemodialysis patients receiving intravenous epoetin.

The medical care of renal anaemia has received much attention over the past decade, as nephrologists have recognized the increased therapeutic value of erythropoiesis-stimulating agents. The European Best Practice Guidelines and the US National Kidney Foundation's Kidney Disease Outcome Quality Initiative Guidelines have provided evidence-based advice on the optimal treatment of renal anaemia, and have recommended a target haemoglobin (Hb) level of 11 g/dl or 11-12 g/dl. Achieving this target Hb level has been shown to improve quality of life and reduce the rate of hospitalization; there is also good evidence to suggest that achieving adequate Hb levels reduces morbidity and mortality in patients with end-stage renal disease.

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

Aims: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease.

Methods And Results: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function.

Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics.

Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases. Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population. We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group.

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

Background: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown.

Methods: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress.

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients.

Advanced renal insufficiency in a 34-year-old man with Lowe syndrome.

Lowe syndrome, or oculocerebrorenal syndrome of Lowe (OCRL), is a rare X-chromosomal disorder characterized by renal dysfunction, congenital cataract, and, in the majority of cases, mental retardation. Although gradual loss of renal function has been seen in most patients, age of onset of deterioration in renal function and its severity and course over time in adult patients have not been documented in detail. We report a 34-year-old man with OCRL without histological changes in renal tissue at the ages of 5 and 8 years, whereas at the age of 29 years, focal and segmental glomerulosclerosis and tubular atrophy were found.

Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine.

We investigated 260 consecutive patients classified as migraine cases aged 3-69 at two tertiary headache centres, one for children and adolescents and the other for adults to evaluate the relationship between age and clinical features of migraine cross-sectionally. We only included subjects with definite migraine without or with aura and we excluded subjects with coexisting tension-type headache, medication overuse and/or other clinically relevant disorders. The percentage of males decreased markedly from childhood to adulthood and this affected the evaluation of age-related changes in male patients, as only large differences reached the level of statistical significance.

Tubular staining of modified C-reactive protein in diabetic chronic kidney disease.

Background: Serum levels of C-reactive protein (CRP) increase during various atherosclerotic as well as kidney diseases. Whether CRP plays a pathophysiological role or rather serves as a marker is unknown. Here, we investigated the role of CRP in diabetic patients with chronic kidney disease.

Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study.

Background: Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated.

Methods And Results: Sixteen patients with Fabry disease who were treated in an open-label study with 1.