High protein intake associates with cardiovascular events but not with loss of renal function.

The long-term effects of higher dietary protein intake on cardiovascular and renal outcomes in the general population are not clear. We analyzed data from 8461 individuals who did not have renal disease and participated in two or three subsequent screenings (6.4-yr follow-up) in a prospective, community-based cohort study (Prevention of Renal and Vascular ENd-stage Disease [PREVEND]).

Albuminuria: what can we expect from the determination of nonimmunoreactive albumin?

Albuminuria is an early marker for diabetic nephropathy in patients with diabetes, and has a clear place in patient care. It also predicts cardiovascular events and mortality in diabetic patients and in the general population, and is slowly becoming accepted in population screening for cardiovascular disease and chronic kidney disease. Recently, investigators found that a considerable amount of albumin in urine is nonimmunoreactive and that classic immunochemical assays do not properly measure all albumin in urine.

Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.

Background: Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis.

Screening for albuminuria identifies individuals at increased renal risk.

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up.

Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design.

Background: Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-converting-enzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin I and angiotensin II levels, may thereby provide greater benefit compared to ACEi or ARB alone.

First morning voids are more reliable than spot urine samples to assess microalbuminuria.

Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives--measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)--in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample.

Selective cyclooxygenase-2 (COX-2) inhibition reduces proteinuria in renal patients.

Background: Renoprotection is predicted by the antiproteinuric efficacy of a pharmacological agent. Non-steroidal anti-inflammatory drugs (NSAIDs) interfering non-selectively in the prostaglandin system have strong antiproteinuric potency without reduction of systemic blood pressure. The effect of the selective COX-2 inhibitor rofecoxib in proteinuric patients is unknown, granted recently reported detrimental effects in non-renal patients.

Is the randomized controlled drug trial in Europe lagging behind the USA?

Aims: Performance of randomized controlled drug trials (drugRCTs) adds to the scientific output, scientific knowledge, scientific training and up-to-date status of healthcare and may drive economy. The purpose of this study was to benchmark Europe's position on drugRCTs relative to the rest of the world, and to identify factors that may drive this performance.

Methods: The number of scientific publications on drugRCTs, indexed in PubMed and Thomson Scientific/Web of Science database over the period 1995-2004, was used as a proxy measure for the quantitative drugRCT output.

Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality.

Screening for albuminuria has been advocated because it is associated with cardiovascular morbidity and all-cause mortality. The "gold standard" to assess albuminuria is 24-hour urinary albumin excretion (UAE). Because 24-hour urine collection is cumbersome, guidelines suggest measuring albuminuria in a first morning void, either as urinary albumin concentration (UAC) or adjusted for creatinine concentration, the albumin:creatinine ratio (ACR).

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage.

Background: Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal perfusion in vivo predict the severity of renal damage in a model of adriamycin-induced nephropathy.

A population-based screening for microalbuminuria among relatives of CKD patients: the Kidney Evaluation and Awareness Program in Sheffield (KEAPS).

Background: Microalbuminuria has been used to detect subjects at risk of cardiovascular disease and chronic kidney disease (CKD) in patients with diabetes, those with hypertension, and the general population. However, relatives of patients with CKD have not been investigated for microalbuminuria in the United Kingdom.

Study Design: A cross-sectional study evaluating the prevalence of microalbuminuria in relatives of patients with CKD compared with the general population of Sheffield, England.

Does the European clinical trials directive really improve clinical trial approval time?

Aims: To facilitate and improve clinical research within Europe, the European Union (EU) adopted in 2001 the Clinical Trials Directive (EUCTD). The aim of this study was to compare duration between submission of a clinical drug trial application and approval by regulatory authorities in EU countries regulated by EUCTD vs. EU countries regulated by local legislation and, second, to compare the duration of regulatory approval in Europe vs.

Renal disease: a common and a silent killer.

Cardiovascular risk profiling and therapy have traditionally been based on established risk factors, such as age, smoking, sex, hypertension, dyslipidemia, body weight, and diabetes mellitus. Despite optimum therapy, cardiovascular mortality and morbidity remain high. Attention is being devoted, therefore, to identifying new risk factors that can also be used as therapeutic targets.

Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease?

Much controversy has surrounded both the pathological basis and the clinical utility of the metabolic syndrome. Key questions still revolve around the definition of this syndrome, its utility as a predictor of cardiovascular risk, and the treatment implications of diagnosis. The metabolic syndrome is associated with increased cardiovascular risk.

Extended prognostic value of urinary albumin excretion for cardiovascular events.

Because urinary albumin excretion (UAE) is a marker of cardiovascular (CV) risk, some have proposed screening the general population; however, it is unknown how the predictive power of a single screening value changes over time. In this study, data of 8496 individuals in a community-based, prospective cohort were used to evaluate this question. For each doubling of baseline UAE, the hazard ratio (HR) for a CV event was 1.

Myocardial infarction does not further impair renal damage in 5/6 nephrectomized rats.

Background: Recent observational studies show that reduced renal function is an independent risk factor for the development of cardiovascular disease. Previously, we reported that myocardial infarction (MI) indeed enhanced mild renal function decline in rats after unilateral nephrectomy (NX) and that RAAS intervention inhibited this decline. The effects of an MI on pre-existing severe renal function loss and the effects of RAAS intervention interrupting this hypothesized cardiorenal interaction are however unknown and clinically even more relevant.

Screening and monitoring for albuminuria: the performance of the HemoCue point-of-care system.

Obtaining immediate results makes testing for albuminuria at the point of care far superior to central laboratory assays. Here we determined if a quantitative desk-top system could identify and monitor patients with microalbuminuria. Urinary albumin excretion was measured in 259 patients of a population cohort study where they collected 24-h urines and first morning void samples prior to three clinic visits at three week intervals.

Immune modulation and graft protection by gene therapy in kidney transplantation.

Kidney transplantation represents the therapy of choice for many patients with end-stage renal disease. However, the success of renal engraftment is hindered by a number of factors, the most important of which being adverse effects of systemic immunosuppressive therapy, chronic transplant dysfunction and a severe shortage of donor kidneys. Gene therapy approaches may provide valuable strategies in each of these areas.

Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan.

There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these interventions is unknown. Therefore, this randomized, double-blind, placebo-controlled trial to determine the separate and combined effects of a low-sodium diet and hydrochlorothiazide (HCT) on proteinuria and BP was performed.

ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy.

Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene predicts renal outcomes and death and influences the effect of losartan in these patients. Pharmacogenetic analyses were performed comparing losartan with placebo administered with conventional blood pressure-lowering therapy in 1435 (95%) of the 1513 RENAAL study patients.