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Biomedical subjects

Paul E de Jong

Publications and source records attributed to Paul E de Jong.

At least 19 recordsLinked to original sources
PubMed2007

Determinants of insulin resistance in renal transplant recipients.

BACKGROUND: Insulin resistance is considered to play an important role in the development of cardiovascular disease, which limits long-term renal transplant survival. Renal transplant recipients are more insulin-resistant compared with healthy controls. It is not known to date which factors relate to this excess insulin resistance. Therefore, we investigated which factors are related to insulin resistance long-term after renal transplantation. METHODS: All renal transplant recipients at our outpatient clinic with a functioning graft for more than one year were invited to participate. We excluded diabetic recipients. Recipient, donor, and transplant characteristics were collected as putative determinants. We used fasting insulin, homeostasis model assessment index, and McAuley's index as valid estimates of insulin resistance. Linear regression models were created to investigate independent determinants of all indexes. RESULTS: A total of 483 recipients (57% male, 50+/-12 years) were analyzed at a median (interquartile range) time of 6.0 (2.6-11.6) years posttransplant. The most consistent determinants across all three indices were body mass index (P<0.001), waist-to-hip ratio (P<0.001), and prednisolone dose (P<0.05). Independent associations were present for total cholesterol (P<0.001), high-density lipoprotein cholesterol (P<0.001), creatinine clearance (P<0.05), recipient age (P<0.001), and gender (P< or =0.002). No independent associations were present for transplant-related factors such as acute rejection treatment or cytomegalovirus seropositivity. CONCLUSIONS: Our results indicate that obesity, distribution of obesity, and prednisolone treatment are the predominant determinants of insulin resistance long term after transplantation. Insulin resistance after renal transplantation could be managed favorably by weight and prednisolone dose reduction, which may reduce cardiovascular disease.

Adult↗
PubMed2007

What predicts progression and regression of urinary albumin excretion in the nondiabetic population?

An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.

Albuminuria↗
PubMed2006

C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: data from the prospective PREVEND cohort.

AIMS: High sensitive-C-reactive protein (hs-CRP) is associated with coronary risk, which may be explained by an association with (unstable) coronary artery disease (CAD). Until now, histopathological and angiographic studies have failed to consistently demonstrate a strong relationship. However, most of these studies were limited by a cross-sectional design. Our aim was to prospectively evaluate the association between hs-CRP and plaque instability. Therefore, firstly, we investigated the relation between hs-CRP measured long before coronary angiography (CAG) and angiographic characteristics of stable and unstable CAD. In addition, we investigated the association with coronary events during follow up in the total PREVEND population. METHODS AND RESULTS: Of the population based Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 8139 subjects without previous documented CAD were followed for the incidence of CAG and coronary events from 1997 to 2003. For the qualitative angiographic analysis, 216 CAGs were available. Mean time to CAG was 37+/-19 months. The 864 coronary vessels were graded as follows: 436 coronary vessels as normal, 175 as non-obstructive CAD, 179 as stable obstructive CAD and 74 as unstable obstructive CAD. Multilevel ordinal regression analysis was performed to study associations between baseline clinical variables and angiographic findings. Hs-CRP contributed significantly to the multivariate model after adjustment for age, gender, smoking, lipids and blood pressure. In 8139 subjects, 201 (2.5%) first coronary events occurred during follow up. Cox survival analysis showed age- and sex-adjusted hazard ratios for hs-CRP 1-3 and >3mg/L of, respectively, 1.26 (95% CI 0.67-2.40) and 3.16 (95% CI 1.26-3.16), relative to hs-CRP <1mg/L. CONCLUSION: In the prospective PREVEND study of subjects without previous documented CAD, hs-CRP levels at baseline were associated with angiographic characteristics and clinical consequences of plaque instability during follow up. This observation supports the concept that hs-CRP significantly contributes to coronary atherogenesis.

Aged↗
PubMed2006

Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects.

The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean+/-standard error FMD was 4.73+/-0.49% and NID was 10.86+/-0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p<0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80+/-0.95, p=0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p=0.04), but only 1.1% in women (+0.06, p=0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p<0.01). In conclusion, after 4 years of follow-up, pravastatin treatment tended to increase FMD and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up.

Adult↗
PubMed2006

Predictors of angiotensin-converting enzyme inhibitor-induced reduction of urinary albumin excretion in nondiabetic patients.

Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1+/-11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (beta(standardized)=0.161; P=0.006), urinary sodium excretion (beta(standardized)=0.154; P=0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months (P<0.001). Fosinopril use and blood pressure reduction independently predicted the change in urinary albumin excretion. Baseline urinary albumin excretion independently predicted the antialbuminuric effect of fosinopril (beta(standardized)=-0.303; P<0.001). In conclusion, at baseline, sodium intake and blood pressure were positively associated with urinary albumin excretion. Fosinopril reduced albuminuria more than might be expected from its blood pressure-lowering effect alone, and this effect was more outspoken in subjects with higher baseline albumin excretion. Based on our data, we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure-lowering agents in subjects with higher baseline levels of albuminuria.

Albuminuria↗
PubMed2006

Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients.

BACKGROUND: Chronic transplant dysfunction is characterized by a gradual decline in renal function with slowly rising serum creatinine. The underlying mechanism is thought to include inflammation and atherosclerosis. C-reactive protein (CRP) is a well-established marker of both inflammation and atherosclerosis. In this prospective study, we investigated whether CRP could be of use as a clinical marker for early identification of renal transplant recipients at increased risk of deterioration of graft function. METHODS: In this prospective study, all participating patients (n = 606) visited the out-patient clinic at least once a year, and serum creatinine was assessed at every visit. Subjects with a follow-up of <1 year (n = 31) were excluded from analysis. RESULTS: A total of 575 patients participated at a median (interquartile range) time of 5.9 (2.6-11.3) years post-transplantation. Median time of follow-up was 3.0 (2.4-3.4) years. Changes in serum creatinine during follow-up were -0.45 (-4.83-4.76) micromol/l/year in 172 subjects with CRP <1.0 mg/l, 1.04 (-3.36-6.12) micromol/l/year in 184 subjects with CRP 1.0-3.0 mg/l and 2.34 (-3.33-9.07) micromol/l/year in 219 subjects with CRP >3.0 mg/l (P < 0.05 for comparison of the three groups). Proteinuria (P = 0.003), CMV IgG titre (P = 0.01), donor age (P = 0.01), CRP concentration (P = 0.02), recipient age (P = 0.02) and recipient gender (P = 0.047) were independently associated with change in serum creatinine during follow-up in a multivariate analysis. CONCLUSIONS: Elevated levels of CRP independently predict accelerated deterioration of graft function in renal transplant recipients >1 year post-transplantation. Further prospective studies are required to investigate whether early intervention can prevent deterioration of graft function in subjects with elevated levels of CRP.

Adult↗
PubMed2006

Clinical factors influencing participation in society after successful kidney transplantation.

BACKGROUND: Little information is available on the degree of actual social functioning after successful kidney transplantation. Moreover, information on factors that influence participation in social activities is scarce. The aim of this study was to examine the influence of clinical factors on social outcome. METHODS: A retrospective study was performed on a cohort of primary kidney transplantation patients, transplanted between 1996 and 2001. Cross-sectional data on participation in obligatory activities (i.e. employment, education, household tasks), leisure activities (i.e. volunteer work, assisting others, sports, clubs/associations, recreation, socializing, going out) and change in participation were collected by in-home interviews (n=239). Multivariate regression analysis was performed. RESULTS: Thirty-six percent of the patients scored low on obligatory participation and only 52.4% was employed. Patients were actively involved in a wide range of leisure activities. Twenty-six percent participated in sports. Multivariate analysis (age-, sex-, and education-adjusted) of participation in obligatory activities showed negative associations with advanced age (P<0.01), comorbidity (previous cardiovascular events; P<0.01) and cadaveric transplantation (P<0.01). There was a positive association with time since transplantation (P<0.01). Multivariate analysis of diversity of participation in leisure activities and perceived change in participation after transplantation showed no statistically significant associations with clinical factors. CONCLUSIONS: Besides age, clinical factors such as type of donation (cadaveric versus living), comorbidity (previous cardiovascular events), and time since transplantation were associated with participation in obligatory activities such as employment, education and household tasks. Diversity of leisure activities and change in participation was not affected by clinical factors.

Cohort Studies↗
PubMed2006

Screening, monitoring, and treatment of albuminuria: Public health perspectives.

Microalbuminuria is an early sign of progressive cardiovascular and renal disease in individuals with and without diabetes. Despite compelling data, at present only a minority of patients with diabetes and rarely individuals without diabetes are screened for albuminuria in a systematic way. All of the criteria to implement systematic albuminuria screening are fulfilled in diabetes, and most are nearly fulfilled for microalbuminuria screening in individuals without diabetes. Because of the growing evidence that treatment of microalbuminuria in individuals without diabetes may offer a cost-effective benefit to prevent cardiovascular disease, nephrologists and other health care providers should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria.

Albuminuria↗
PubMed2006

The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.

BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.

Adult↗
PubMed2006

An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: a population-based study.

BACKGROUND: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol. DESIGN: We determined relationships between the CETP -629C-->A promoter (n = 8141), the TaqIB (n = 8289), and the I405V (n = 8265) polymorphisms, serum lipids, C-reactive protein, and clinical factors with incident coronary heart disease (defined as death from or hospitalization for myocardial infarction, ischemic heart disease, or coronary intervention) during a median of 4.94 yr follow-up. SUBJECTS: A predominantly Caucasian general population was studied. RESULTS: HDL cholesterol was 0.08 mmol/liter higher in -629A carriers than in -629CC homozygotes (P < 0.001). The unadjusted coronary hazard was 1.26 [95% confidence interval (CI), 0.95-1.68; P = 0.11] in A carriers compared with CC homozygotes and increased to 1.46 (95% CI, 1.10-1.95; P = 0.01) after adjustment for HDL cholesterol. This effect remained after additional adjustment for apolipoprotein A-I, triglycerides, C-reactive protein, age, and gender. Likewise, the HDL-cholesterol-adjusted hazard ratio was also higher in AA than in CC homozygotes (hazard ratio, 1.72; 95% CI, 1.22-2.42; P < 0.01). Similar findings were obtained with the TaqIB polymorphism. The 405V allele was weakly associated with incident coronary heart disease after HDL cholesterol adjustment (P = 0.09). CONCLUSIONS: A common CETP promoter polymorphism, which beneficially contributes to higher HDL cholesterol, is paradoxically associated with increased incidence of coronary disease in the general population. Thus, CETP gene variation may affect coronary risk apart from the level of HDL cholesterol.

Apolipoprotein A-I↗
PubMed2006

Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients.

BACKGROUND: Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant recipients. METHODS: The AGE accumulation was assessed using a validated skin-autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57% male, aged 50+/-12 years) visiting the outpatient clinic at a median (interquartile range) time of 73 (32-143) months after transplantation. Furthermore, various transplant- and recipient-related factors of interest were collected. RESULTS: Average skin-autofluorescence of lower arm and leg was 2.7+/-0.8 a.u. Skin-autofluorescence was positively determined by recipient age, systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine clearance at baseline, and change in creatinine clearance since one year after transplantation in linear multivariate regression analysis. Together, these factors explained 41% of the variance of skin-autofluorescence. CONCLUSIONS: Skin-autofluorescence was associated with several risk factors for cardiovascular disease and chronic renal transplant dysfunction. These results are in line with the hypothesis that AGEs play a role in the pathogenesis of these conditions in renal transplant recipients. Prospective studies are required to investigate whether the AFR can be used as a simple, non-invasive tool to identify and monitor patients at risk for chronic renal transplant dysfunction and cardiovascular disease.

Adult↗
PubMed2006

Social participation and employment status after kidney transplantation: a systematic review.

OBJECTIVE: To summarize and assess literature regarding social participation of recipients after successful kidney transplantation. METHODS: A systematic review including a literature search in Medline (1980-2003) and five other databases, and assessment of methodological quality of selected studies by two reviewers applying a checklist of twelve criteria. RESULTS: Seventeen studies out of 1443 identified references were selected. Quality scores for internal validity ranged from 0% to 50% (median 20%). Employment was the most used indicator of social participation and two studies briefly reported on vacation and recreation. Employment rate ranged from 18% to 82%, however differences in defining categories of employment or lack of description were present. Study populations were heterogeneous with regard to demographic and clinical characteristics. Three studies identified pre-transplant employment status as predictor of post-transplant employment. Other potential risk factors were not consistent across studies. CONCLUSION: Measurement of social participation focuses mainly on employment status. Quality assessment revealed shortcomings in reporting and validity of studies, whereby valid conclusions regarding the degree of social participation after kidney transplantation cannot be drawn. Future research should supplement the focus on employment status by examining other aspects of social participation as well as potential risk factors.

Employment↗
PubMed2006

Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: A pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT).

OBJECTIVE: This study estimated the cost-effectiveness,from the Dutch health care perspective, of screening for albuminuria in the general Dutch population to prevent cardiovascular events (CVEs) with subsequent angiotensin-converting enzyme inhibitor treatment, using data from the Prevention of REnal and Vascular ENdstage Disease Intervention Trial (PREVEND IT). METHODS: PREVEND IT was a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design within the larger observational Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND IT study was conducted to assess the effects of fosinopril 20 mg and pravastatin 40 mg on CVEs in subjects with specific inclusion criteria: urinary albumin excretion (UAE) rate in the range from 15 to 300 mg/d, blood pressure <160/100 mm Hg, and plasma cholesterol level <8.0 mmol/L. Cost-effectiveness estimates for the Dutch population were expressed in euros (2002; 1 euro = US 1.01 dollars) as net costs per life-year gained (LYG) in the baseline and sensitivity (stochastic) analyses. RESULTS: Data were assessed for 864 subjects, with a mean (SD) follow-up of 46 (7) months. CVEs occurred in 45 (5.2%) subjects. Subjects who received fosinopril had a 40% lower incidence of CVEs than subjects in the placebo group (3.9% vs 6.5%, respectively; P = NS). The cost-effectiveness of screening for albumnuria was determined to be euro 16,700/LYG for the study population. Stochastic analysis indicated that the probability of the cost-effectiveness being below the suggested Dutch threshold of euro 20,000/LYG was 59% in the baseline analysis. The probability of cost-effectiveness below euro 20,000/LYG would increase to 91% if only subjects with UAE >50 mg/d were treated with fosinopril. Limiting the screening to subjects aged >50 years and >60 years also improved cost-effectiveness. CONCLUSIONS: The results of our study suggest that screening the general Dutch population for albuminuria and subsequently treating those found positive with fosinopril may be cost-effective compared with no screening and adopting the Dutch health care perspective. However, confirmation from larger multicenter trials is needed.

Adult↗
PubMed2006

Prevention of chronic kidney disease: the next step forward!

The incidence of end stage renal disease in patients who have not experienced a classic primary renal disease is dramatically increasing. Chronic kidney disease (CKD) in these patients is due to diabetes, mostly type 2, hypertension and generalised atherosclerosis. As these patients are frequently diagnosed as having renal function impairment only in the late phase, more effort should be undertaken to diagnose them earlier, that is, at a time when renoprotective measures can still be undertaken. For that purpose, measurement of the estimated glomerular filtration rate (GFR) might be helpful. To properly interpret those measurements, however, we need to be aware of the pros and cons of the use of formulas to estimate the GFR. Most likely, a better way to detect subjects at risk of CKD in the early phase is screening by dipstick proteinuria or preferably by testing for (micro-) albuminuria. Because microalbuminuria not only indicates increased renal but also enhanced cardiovascular risk, the benefits of such screening programmes may have a much greater affect than only preventing renal disease.

Albuminuria↗