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Dick de Zeeuw

Publications and source records attributed to Dick de Zeeuw.

At least 19 recordsLinked to original sources
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

Renal damage after myocardial infarction is prevented by renin-angiotensin-aldosterone-system intervention.

Recently, it was shown that myocardial infarction aggravates preexistent mild renal damage that is elicited by unilateral nephrectomy in rats. The mechanism behind this cardiorenal interaction likely involves the renin-angiotensin-aldosterone-system and/or vasoactive peptides that are metabolized by neutral endopeptidase (NEP). The renoprotective effect of angiotensin-converting enzyme inhibition (ACEi) as well as combined ACE/NEP inhibition with a vasopeptidase inhibitor (VPI) was investigated in the same model to clarify the underlying mechanism. At week 17 after sequential induction of unilateral nephrectomy and myocardial infarction, treatment with lisinopril (ACEi), AVE7688 (VPI), or vehicle was initiated for 6 wk. Proteinuria and systolic BP (SBP) were evaluated weekly. Renal damage was assessed primarily by proteinuria, interstitial alpha-smooth muscle actin (alpha-SMA) staining, and the incidence of focal glomerulosclerosis (FGS). At start of treatment, proteinuria had increased progressively to 167 +/- 20 mg/d in the entire cohort (n = 42). Both ACEi and VPI provided a similar reduction in proteinuria, alpha-SMA, and FGS compared with vehicle at week 23 (proteinuria 76 +/- 6 versus 77 +/- 4%; alpha-SMA 60 +/- 6 versus 77 +/- 3%; FGS 52 +/- 14 versus 61 +/- 10%). Similar reductions in systolic BP were observed in both ACEi- and VPI-treated groups (33 +/- 3 and 37 +/- 2%, respectively). Compared with ACEi, VPI-treated rats displayed a significantly larger reduction of plasma (41 +/- 5 versus 61 +/- 4%) and renal (53 +/- 6 versus 74 +/- 4%) ACE activity. It is concluded that both ACEi and VPI intervention prevent renal damage in a rat model of cardiorenal interaction. VPI treatment seemed to provide no additional renoprotection compared with sole ACEi after 6 wk of treatment in this model, despite a more pronounced ACE-inhibiting effect of VPI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Evaluation of measures of urinary albumin excretion.

Albuminuria has recently drawn much attention as a valuable risk marker for cardiovascular and renal disease progression. Albuminuria can be measured and expressed in several ways: 1) in a spot morning urine sample as urinary albumin concentration (mg/liter) or albumin:creatinine ratio (mg/mmol) and 2) in a 24-hour urine collection as urinary albumin excretion (mg/24 hours). It has not yet been clarified which measure for albuminuria is preferable in clinical practice. One of the points on which a choice should be made is which measure shows the least within-person coefficient of variation. From the perspective of their work in the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 1997-2001, the authors discuss several methodological issues that are important when interpreting studies on this topic. It is argued that fresh urine should be used, since freezing at -20 degrees C results in considerable extra variability in the albumin concentration. Furthermore, it is important to use specifically collected urine samples and not portions of a 24-hour urine sample as a surrogate for a spot morning urine sample. Albuminuria follows a circadian rhythm. Consequently, values for the within-person coefficient of variation will therefore be different when they are measured in a portion of a 24-hour urine collection in comparison with a spot morning urine sample.

Albuminuria↗
PubMed2006

Microalbuminuria as an early marker for cardiovascular disease.

Excretion of albumin in the urine is highly variable, ranging from nondetectable quantities to milligrams of albumin and even grams of albumin. Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d. Microalbuminuria is highly prevalent; in hypertensive and diabetic populations, its prevalence varies from 10 to 40%. It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals (5 to 7%). The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular (CV) disease: Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and/or hypertension but also in healthy individuals. Treatments that lower albuminuria are associated with CV protection, as demonstrated in randomized, controlled trials of patients with diabetes as well as in patients with hypertension. There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate. Differences between individuals in their level of albumin excretion are already observed at a very early age (just after birth). In fact, the interindividual variability seems to be relatively constant in the first 5 decades of life, indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age. Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in (renal and systemic) endothelial function. Experimental data show that between strains and even within strains, rats at young age show a remarkable difference in individual endothelial function, and this is strongly related to the susceptibility of that rat to organ damage. In conclusion, albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease. It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens.

Albuminuria↗
PubMed2006

Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.

BACKGROUND: Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. METHODS AND RESULTS: The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. CONCLUSIONS: Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.

Aged↗
PubMed2006

Microalbuminuria and endothelial dysfunction: emerging targets for primary prevention of end-organ damage.

A minor increase in urinary albumin excretion (microalbuminuria) is known to predict adverse renal and cardiovascular events in diabetic and hypertensive patients. Recent intriguing findings show that microalbuminuria is an early and sensitive marker of future cardiovascular events even in healthy subjects. The mechanisms linking microalbuminuria with end-organ damage have not been fully explained yet; however, generalized endothelial dysfunction might play an important role. Prevailing experimental and clinical data suggest that generalized endothelial dysfunction, frequently characterized by decreased nitric oxide bioavailability, actually precedes the development of microalbuminuria. This review summarizes the current knowledge about the intricate relationship between microalbuminuria and endothelial dysfunction. On the basis of the current evidence, we propose that microalbuminuria and endothelial dysfunction are an emerging target for primary prevention strategies in cardiovascular disease. In near future, dietary components improving nitric oxide bioavailability, such as cocoa-derived flavanols may play important role in these preventive strategies.

Albuminuria↗
PubMed2006

The role of angiotensin(1-7) in renal vasculature of the rat.

OBJECTIVE: Angiotensin(1-7) is an active component of the renin-angiotensin-aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1-7) on the renal vasculature in vitro and in vivo. METHODS: Isolated small renal arteries were studied in an arteriograph system by constructing concentration-response curves to angiotensin II, without and with angiotensin(1-7). In isolated perfused kidneys, the response of angiotensin II on renal vascular resistance was measured without and with angiotensin(1-7). The influence of angiotensin(1-7) on angiotensin II-induced glomerular afferent and efferent constriction was assessed with intravital microscopy in vivo under anaesthesia. In freely moving rats, we studied the effect of angiotensin(1-7) on angiotensin II-induced reduction of renal blood flow with an electromagnetic flow probe. RESULTS: Angiotensin(1-7) alone had no effect on the renal vasculature in any of the experiments. In vitro, angiotensin(1-7) antagonized angiotensin-II-induced constriction of isolated renal arteries (9.71 +/- 1.21 and 3.20 +/- 0.57%, for control and angiotensin(1-7) pre-treated arteries, respectively; P < 0.0005). In isolated perfused kidneys, angiotensin(1-7) reduced the angiotensin II response (100 +/- 16.6 versus 72.6 +/- 15.6%, P < 0.05) and shifted the angiotensin II dose-response curve rightward (pEC50, 6.69 +/- 0.19 and 6.26 +/- 0.12 for control and angiotensin(1-7) pre-treated kidneys, respectively; P < 0.05). Angiotensin(1-7), however, was devoid of effects on angiotensin-II-induced constriction of glomerular afferent and efferent arterioles and on angiotensin-II-induced renal blood flow reduction in freely moving rats in vivo. CONCLUSION: Angiotensin(1-7) antagonizes angiotensin II in renal vessels in vitro, but does not appear to have a major function in normal physiological regulation of renal vascular function in vivo.

Anesthesia↗
PubMed2006

Altered myogenic constriction and endothelium-derived hyperpolarizing factor-mediated relaxation in small mesenteric arteries of hypertensive subtotally nephrectomized rats.

OBJECTIVES: Chronic renal failure (CRF) is associated with altered systemic arterial tone and hypertension. Myogenic constriction and endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation represent major vasoregulatory mechanisms in small systemic arteries. Elevated myogenic response and impaired EDHF might participate in the development of essential hypertension; however, their role in CRF-related hypertension is unknown. We investigated whether myogenic response and EDHF are altered in subtotally nephrectomized (sNX) rats and whether these changes are modifiable by chronic treatment with angiotensin-converting enzyme (ACE) inhibitor. METHODS: In a pressure arteriograph, myogenic constriction and EDHF-mediated relaxation were evaluated in small mesenteric arteries isolated from male Wistar rats 15 weeks after either sham operation (n = 7) (SHAM), sNX (n = 12) or sNX followed by 9 weeks of treatment with lisinopril (sNX + LIS, 2.5 mg/kg, n = 13). RESULTS: Surprisingly, myogenic response was reduced in hypertensive CRF rats (maximal myogenic tone: 37 +/- 2 and 18 +/- 4%, P < 0.01; peak myogenic index: -0.80 +/- 0.08 and -0.40 +/- 0.12%/mmHg, P < 0.05 in SHAM and sNX respectively). At the same time EDHF-mediated relaxation was also impaired (maximal response: 92 +/- 2 and 77 +/- 5%, P < 0.01; pD2: 6.5 +/- 0.1 and 5.9 +/- 0.1, P < 0.05). Both myogenic response and EDHF were inversely related to the severity of renal failure and restored by treatment with lisinopril to levels found in SHAM animals. CONCLUSION: Major constrictive (myogenic) and dilatory (EDHF) mechanisms of small systemic arteries are impaired in hypertensive CRF rats. These alterations do not seem to participate in the development of hypertension, being rather directly related to the severity of renal impairment. Both systemic vascular changes might be restored by renoprotective treatment with ACE inhibitor.

Angiography↗
PubMed2006

Update on microalbuminuria as a biomarker in renal and cardiovascular disease.

PURPOSE OF REVIEW: To discuss recently published papers on the potential use of albuminuria as a predictor of cardiovascular and renal disease. RECENT FINDINGS: Recent studies indicate that screening for microalbuminuria may not only be beneficial for detection and prevention of cardiovascular and renal disease in patients with diabetes, but also in the general population. The best method for this, however, is not yet clear. Findings indicate that it is preferable to assess albumin concentration in fresh urine samples rather than in samples that have been frozen. Furthermore, a new assay for albumin assessment has become available, which detects previously undetectable immuno-unreactive albumin above and beyond immunoreactive albumin detected by classic immunochemical assays. The pros and cons of this assay are considered. SUMMARY: Urinary albumin is a cheap, noninvasive, and easily assessable risk marker, that does not per se require a visit to a physician or health center. As such, it is a promising candidate for screening to identify subjects at high risk of cardiovascular and renal disease, even if albuminuria is not shown to be independent of other risk markers.

Albumins↗
PubMed2006

A French cost-consequence analysis of the renoprotective benefits of irbesartan in patients with type 2 diabetes and hypertension.

OBJECTIVES: We performed a cost-consequence analysis in a French setting of the renoprotective benefit of irbesartan in hypertensive type 2 diabetes patients over a 25-year period. RESEARCH DESIGN AND METHODS: A previously published Markov model simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease and death. Three treatment strategies with analogous blood pressure control were compared: (A) control--conventionally medicated antihypertensive therapy (excluding angiotensin converting enzyme inhibitors, other angiotensin-2-receptor antagonists and dihydropyridine calcium channel blockers) initiated at microalbuminuria; (B) early irbesartan--(300 mg daily added to control, initiated with microalbuminuria) and (C) late irbesartan--(300 mg daily, initiated with overt nephropathy). Probabilities came from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other sources. Clinical and economic outcomes were projected over 25 years. Annual discount rates were 3%. RESULTS: Compared to control, early use of irbesartan added (mean +/- standard deviation) 1.51 +/- 0.08 undiscounted life years (discounted: 0.94 +/- 0.05 years), while late irbesartan added 0.07 +/- 0.01 (0.04 +/- 0.01) years/patient. Early irbesartan added 1.03 +/- 0.06 discounted quality-adjusted life years (QALYs), while late irbesartan added 0.06 +/- 0.01 QALYs. Early and late irbesartan treatments were projected to save 22,314 +/- 1273 euro and 6619 +/- 820 euro/patient, respectively versus control. Sensitivity analysis showed that even over short time horizons both irbesartan treatments were superior to the control group. CONCLUSIONS: In France, early irbesartan treatment improved quality and length of life and reduced costs in hypertensive patients with type 2 diabetes and microalbuminuria. Late irbesartan therapy is beneficial, but earlier irbesartan leads to better outcomes.

Albuminuria↗
PubMed2006

Urinary albumin excretion as a predictor of the development of hypertension in the general population.

The hypothesis that high urinary albumin excretion (UAE; indicating mild renal damage) may precede development of hypertension was tested, and the relation among UAE, GFR, and development of hypertension was investigated. Data of 4635 patients of a prospective cohort study who participated in an extensive screening in 1997 to 1998 and 2001 to 2003 at our outpatient unit and were normotensive at baseline were used. Hypertension was defined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, UAE was measured in two consecutive 24-h urine samples, and GFR was calculated with the modified Modification of Diet in Renal Disease formula. Mean follow-up was 4.3 yr. Baseline UAE was significantly associated with the risk for developing hypertension (odds ratio 2.29; 95% confidence interval 1.77 to 2.95 per 10-fold increase of UAE). This association was independent of potential confounders. An interaction between UAE and GFR was found (P = 0.030), indicating that with elevated UAE and lowered GFR, but still within the normal range, the risk for developing hypertension was highest. In conclusion, these findings support the hypothesis that mild renal damage may precede the development of hypertension.

Adult↗
PubMed2006

Endothelial function predicts the development of renal damage after combined nephrectomy and myocardial infarction.

It was demonstrated that individual renal endothelial dilatory function of the healthy rat predicts susceptibility to subsequent renal damage induced by 5/6 nephrectomy. In addition, it is reported that myocardial infarction (MI) that was performed upon unilateral nephrectomy (UNx) induced highly variable renal damage. Therefore, whether the variability in renal damage after MI could be explained by the variation in individual renal endothelial function before the induction of injury was studied. Endothelium-dependent relaxation to acetylcholine was investigated in vitro in small arteries that were isolated from the extirpated kidney at UNx. MI was induced 1 wk after UNx by ligation of the left coronary artery. Proteinuria and systolic BP were evaluated weekly for 16 wk thereafter using metabolic cages and the tail-cuff method, respectively. Upon termination of the study, focal glomerulosclerosis was evaluated by histology as an additional marker of renal damage. After MI, nephrectomized male Wistar rats (n = 15) gradually developed variable proteinuria, ranging from 20 to 507 mg/24 h at week 16, with an average systolic BP of 131 +/- 7 mmHg. The individual renal endothelial function of the healthy rats predicted the extent of renal damage in terms of proteinuria (r = -0.62, P = 0.008) and focal glomerulosclerosis (r = -0.70, P = 0.003). The individual level of renal endothelial function in the healthy rat is able to predict the severity of renal damage that is induced by MI. Further exploration of the underlying mechanisms may lead to discovery of preventive renoprotective therapies.

Acetylcholine↗