Multiple Prior Live Births Are Associated With Cardiac Remodeling and Heart Failure Risk in Women.

Objective: Greater parity has been associated with cardiovascular disease risk. We sought to find whether the effects on cardiac remodeling and heart failure risk are clear.

Methods: We examined the association of number of live births with echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression.

The STAGED-PKD 2-Stage Adaptive Study With a Patient Enrichment Strategy and Treatment Effect Modeling for Improved Study Design Efficiency in Patients With ADPKD.

Rationale & Objective: Venglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in mouse models of autosomal dominant polycystic kidney disease (ADPKD). STAGED-PKD aims to determine the safety and efficacy of venglustat and was designed using patient enrichment for progression to end-stage kidney disease and modeling from prior ADPKD trials.

Study Design: STAGED-PKD is a 2-stage, international, double-blind, randomized, placebo-controlled trial in adults with ADPKD (Mayo Class 1C-1E) and estimated glomerular filtration rate (eGFR) 45-<90 mL/min/1.

Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease.

Background: Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown.

Methods: Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m2, 2.

Serum Calcification Propensity and the Risk of Cardiovascular and All-Cause Mortality in the General Population: The PREVEND Study.

Objective: Vascular calcification contributes to the cause of cardiovascular disease. The calciprotein particle maturation time (T) in serum, a measure of calcification propensity, has been linked with adverse outcomes in patients with chronic kidney disease, but its role in the general population is unclear. We investigated whether serum T is associated with cardiovascular mortality in a large general population-based cohort.

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk.

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD.

Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention.

Background And Objectives: In the treatment of CKD, individual patients show a wide variation in their response to many drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi). To investigate whether therapy resistance to RAASi can be overcome by uptitrating the dose of drug, changing the mode of intervention (with drugs from similar or different classes), or lowering dietary sodium intake, we meta-analyzed individual responses to different modes of interventions.

Design, Setting, Participants, & Measurements: Randomized crossover trials were analyzed to assess correlation of individual responses to RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; =395 patients).

Urinary renin-angiotensin markers in polycystic kidney disease.

In autosomal dominant polycystic kidney disease (ADPKD), activation of the renin-angiotensin aldosterone system (RAAS) may contribute to hypertension and disease progression. Although previous studies have focused on circulating RAAS components, preliminary evidence suggests that APDKD may increase urinary RAAS components. Therefore, our aim was to analyze circulating and urinary RAAS components in ADPKD.

Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints.

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis.

Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial.

Background: and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline.

Design, Setting, Participants, & Measurements: In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18-50 years), with total kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo.

Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk: The PREVEND study.

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been linked with an increased risk of type 2 diabetes, but their relationships with cardiovascular disease (CVD) are uncertain. We aimed to assess the associations of ALT and AST with CVD risk and determine their potential utility for CVD risk prediction.

Methods: ALT and AST measurements were made at baseline in the PREVEND prospective cohort involving 6899 participants aged 28-75 years without pre-existing CVD.

Serum Alkaline Phosphatase and Risk of Incident Cardiovascular Disease: Interrelationship with High Sensitivity C-Reactive Protein.

Background: Alkaline phosphatase (ALP) has been suggested to be associated with cardiovascular disease (CVD) risk, however, important aspects of the association, such as shape and independence from established risk factors, have yet to be characterized in detail. We assessed the association of ALP with CVD risk and determined its utility for CVD risk prediction.

Methods: Alkaline phosphatase activity was measured at baseline in the PREVEND prospective cohort involving 6,974 participants aged 28-75 years without pre-existing CVD.

Added value of screening for CKD among the elderly or persons with low socioeconomic status.

Background And Objective: Three screening approaches were compared for their ability to detect CKD cases, and identify patients with CKD who have a higher rate of incident cardiovascular disease (CVD) events and renal function decline. Approach 1 was the traditional CKD screening approach, targeting only individuals with known diabetes, hypertension, or CVD history. Approach 2 was defined as Approach 1+elderly, and Approach 3 as Approach 1+low-socioeconomic status (SES) individuals.

Circulating total bilirubin and risk of incident cardiovascular disease in the general population.

Objective: To assess the association of circulating total bilirubin and cardiovascular disease (CVD) risk in a new prospective study and to determine whether adding information on total bilirubin values to established cardiovascular risk factors is associated with improvement in prediction of CVD risk.

Approach And Results: Circulating total bilirubin levels were measured at baseline in the PREVEND (Prevention of Renal and Vascular End-stage Disease) prospective study of 7222 participants and 773 incident CVD events. Total bilirubin was log-linearly associated with CVD risk.

Circulating gamma glutamyltransferase and prediction of cardiovascular disease.

Background: The value of measuring levels of gamma glutamyltransferase (GGT) for the prediction of first cardiovascular events is uncertain. We aimed to determine whether adding information on GGT values to conventional cardiovascular risk factors is associated with improvement in prediction of CVD risk.

Methods: Circulating GGT levels were measured at baseline in the PREVEND prospective cohort study.

Twenty-four hour urinary urea excretion and 9-year risk of hypertension: the PREVEND study.

Objectives: It is not yet clear whether dietary protein could help maintaining a healthy blood pressure (BP). We investigated the association between total protein intake, estimated from 24-h urinary urea excretion, and incident hypertension in Dutch men and women.

Methods: We analyzed data of 3997 men and women (aged 28-75 years) who participated in the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, a prospective cohort study.

Urinary vitamin D binding protein: a potential novel marker of renal interstitial inflammation and fibrosis.

Non-invasive tubulointerstitial damage markers may allow better titration and monitoring of renoprotective therapy. We investigated the value of urinary vitamin D binding protein excretion (uVDBP) as a tubulointerstitial inflammation and fibrosis marker in adriamycin rats, and tested whether uVDBP parallels renal damage and responds to therapy intensification in humans. In adriamycin (ADR) rats, uVDBP was strongly elevated vs controls (CON) already 6 wks after nephrosis induction (ADR: 727±674 [mean±SD] vs CON: 9±12 µg/d, p<0.

Screening for chronic kidney disease can be of help to prevent atherosclerotic end-organ damage.

Atherosclerotic damage to the kidney is one of the most prevalent causes of chronic kidney disease and ultimately kidney failure. It frequently coincides with atherosclerotic damage to the heart, the brain and the lower extremities. In fact, the severity of the damage in the various end organs runs in parallel.

Influence of urine creatinine on the relationship between the albumin-to-creatinine ratio and cardiovascular events.

Background And Objectives: In the albumin-to-creatinine ratio (spot-ACR), urine creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass is associated with cardiovascular disease (CVD). We hypothesized that the spot-ACR would be higher in women, lower-weight persons, and older individuals, independent of timed urine albumin excretion (24hr-UAE), and accordingly, that spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these subgroups.

Do albuminuria and hs-CRP add to the International Diabetes Federation definition of the metabolic syndrome in predicting outcome?

Background: To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic syndrome (MetS) defining criteria.

Methods: The PREVEND Study is a prospective population-based cohort study in the Netherlands, including 8592 participants. The MetS was defined according to the 2004 International Diabetes Federation criteria, elevated UAE as albuminuria ≥ 30 mg/24 h and high hs-CRP as ≥ 3 mg/L.

Development and validation of a general population renal risk score.

Background And Objectives: There is a need for prediction scores that identify individuals at increased risk for developing progressive chronic kidney disease (CKD). Therefore, this study was performed to develop and validate a "renal risk score" for the general population. Design, setting, participants, & measurements For this study we used data from the PREVEND (Prevention of Renal and Vascular ENdstage Disease) study, a prospective population-based cohort study with a median follow-up of 6.

Selection on albuminuria enhances the efficacy of screening for cardiovascular risk factors.

Background: As many subjects with a cardiovascular (CV) risk factor are undiagnosed, guidelines to prevent cardiovascular disease argue for case finding on those risk factors. Such an approach is, however, labour and cost intensive. An elevated urinary albumin loss is an early marker of vascular damage and is associated with an increased CV risk.

Comparison of the yield of different screening approaches to detect chronic kidney disease.

Background: Screening for chronic kidney disease (CKD) has been advised in high-risk populations. The present study aims to compare the yields of four approaches to select high-risk subjects for CKD screening, which are defined as follows: Approach 1, history of cardiovascular (CV) disease, diabetes mellitus or hypertension (=high CV risk); Approach 2, high CV risk or age >55 years; Approach 3, urinary albumin concentration (UAC) ≥20 mg/L; or Approach 4, UAC ≥10 mg/L at pre-screening.

Methods: The study population is a sample of the general population of Groningen, the Netherlands (n = 3398).

Changes in renal risk factors versus renal function outcome during follow-up in a population-based cohort study.

Background: Chronic kidney disease is a growing public health problem worldwide. Previous studies have identified several predictors for renal function decline. However, these studies used a single measurement of these risk factors.

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]).