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P E de Jong

Publications and source records attributed to P E de Jong.

At least 19 recordsLinked to original sources
PubMed2006

The predictive value of renal vascular resistance for late renal allograft loss.

The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator-dependent. We investigated the predictive value of renal vascular resistance (RVR), a less operator-dependent method as assessed by mean arterial pressure divided by renal blood flow, for the prediction of recipient mortality and death-censored graft loss. RVR was compared to commonly used risk markers such as creatinine clearance (CrCl), serum creatinine (SCreat) and proteinuria (UProt) in 793 first-time cadaveric renal transplant recipients at predetermined time points after transplantation using receiver operating characteristics (ROC) and Cox survival analyses. The present study showed that RVR is a prominent risk marker for recipient mortality and death-censored graft loss. However, the predictive value of RVR for recipient mortality owed mainly to the impact of mean arterial blood pressure. In contrast, RVR constituted more than the sum of its components for death-censored graft loss, but showed less predictive value than SCreat in univariate analysis. As the assessment of RVR is expensive and time-consuming, we believe that RVR holds no clinical merit for the follow-up of renal transplant recipients.

Adult↗
PubMed2006

Obesity and renal hemodynamics.

Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile independent of these factors, and that may exert effects on renal damage as well. In animal models of obesity-associated renal damage, micro-puncture studies showed glomerular hypertension and hyperfiltration. In humans an elevated glomerular filtration rate has been demonstrated in several studies, sometimes associated with hyperperfusion as well, independent of blood pressure or the presence of diabetes. An elevated filtration fraction was found in several studies, consistent with glomerular hypertension. This renal hemodynamic profile resembles the hyperfiltration pattern in diabetes and is therefore assumed to be a pathogenetic factor in renal damage. Of note, the association between body mass index and renal hemodynamics is not limited to overt obesity or overweight, but is also present across the normal range, without a particular threshold. Multiple factors are assumed to contribute to these renal hemodynamic alterations, such as insulin resistance, the renin-angiotensin system and the tubulo-glomerular responses to increased proximal sodium reabsorption, and possibly also inappropriate activity of the sympathetic nervous system and increased leptin levels. Obesity has a high world-wide prevalence. On a population-basis, therefore, its contribution to long-term renal risk may be considerable, especially as it is usually clustered with risk factors like hypertension and insulin resistance. In short-term studies the renal hemodynamic alterations in obesity and the associated proteinuria were reversible by weight loss, and renin-angiotensin system-blockade, respectively. These interventions are therefore likely to have the potential to limit the renal risks of obesity.

Animals↗
PubMed2004

Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria?

BACKGROUND: Microalbuminuria, i.e. slightly elevated urinary albumin excretion, is associated with increased cardiovascular risk factors and cardiovascular morbidity in the general population. Microalbuminuria has been proposed to indicate increased endothelial permeability. Unknown are the mechanisms underlying this increased vascular permeability. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increases endothelial permeability. We hypothesised that plasma VEGF levels may be associated with microalbuminuria in a large sample of the general population. METHODS: Out of a large sample of the general population, we studied 189 control subjects (urinary albumin excretion (UAE): 0-30 mg/24 h) and 194 microalbuminuric subjects (UAE: 30-300 mg/24 h), matched for age, sex and the presence of ischemia on the electrocardiogram. RESULTS: Subjects with microalbuminuria had significant higher plasma levels of VEGF (p<0.05). The correlation between plasma levels of VEGF and systolic and diastolic blood pressure, cholesterol, glucose, diabetes and body mass index were statistically significant. Using logistic regression analysis, microalbuminuria was significantly associated with VEGF (odds ratio 1.62; 95% confidence interval: 1.15-2.27; p<0.01). This association was dependent on cardiovascular risk factors. CONCLUSION: This study suggests a relation between increased plasma VEGF levels and subsequent occurrence of microalbuminuria.

Albuminuria↗
PubMed2004

Sodium intake affects urinary albumin excretion especially in overweight subjects.

OBJECTIVES: To examine the relationship between sodium intake and urinary albumin excretion, being an established risk marker for later cardiovascular morbidity and mortality. DESIGN: Cross-sectional cohort study using linear regression analysis. Setting. University hospital outpatient clinic. SUBJECTS: A cohort drawn from the general population, consisting of 7850 subjects 28-75 years of age, all inhabitants of the city of Groningen, the Netherlands. The cohort is enriched for the presence of subjects with elevated urinary albumin concentration. RESULTS: The results show a positive relationship between dietary sodium intake and urinary albumin excretion. The association was independent of other cardiovascular risk factors (such as sex, age, blood pressure, body mass index (BMI), waist-to-hip ratio, serum cholesterol, plasma glucose and smoking) and other food constituents (calcium, potassium and protein). The relationship between sodium intake and urinary albumin excretion was steeper in subjects with a higher BMI compared with a lower BMI. CONCLUSIONS: Sodium intake is positively related to urinary albumin excretion. This relation is more pronounced in subjects with a higher BMI. These results suggest that high sodium intake may unfavourably influences cardiovascular prognosis especially in overweight and obese subjects.

Adult↗
PubMed2003

[Clinical reasoning and decision-making in practice. A woman with hypokalaemia].

A 39-year-old woman had been investigated elsewhere due to symptomatic hypokalaemia, renal potassium wasting and metabolic alkalosis. Vomiting was considered to be the underlying cause but the patient repeatedly denied this behaviour. After extensive investigations, Bartter's syndrome was finally diagnosed. Eighteen months later the patient was readmitted due to progressive renal insufficiency. On the basis of a very low urinary chloride excretion and the aforementioned laboratory results, it was concluded that the metabolic disturbances were due to vomiting and the diagnosis of Bartter's syndrome was rejected. Upon being confronted with these findings, the patient finally admitted to vomiting, but stated that this happened involuntarily after meals. She had a stenotic ulcer in the pylorus and a gastric biopsy demonstrated the presence of Helicobacter pylori associated gastritis. Eradication therapy was given and the symptoms disappeared. The renal insufficiency was partly accounted for by hypovolaemia and partly by tubulointerstitial nephropathy (demonstrated by kidney biopsy) which was probably due to the chronic hypokalaemia. This case illustrates the difficulty of establishing the differential diagnosis of hypokalaemia, especially in the case of denied vomiting. However, it also shows that in such cases the correct diagnosis can be made if objective parameters are used.

Adult↗
PubMed2003

The reliability of different formulae to predict creatinine clearance.

OBJECTIVES: Creatinine clearance (CCR) is a commonly used tool to measure glomerular filtration rate (GFR) in clinical practice. This tool requires collection of 24-h urine, which is quite bothersome. Several different formulae have been used to estimate GFR using plasma creatinine and other easy formulae to obtain biometrical data. We examined 10 formulae and compared them with actually measured CCR in a large sample of the general population. DESIGN: Cross-sectional cohort study. SETTING: University hospital outpatient clinic, a population based study. SUBJECTS: A total of 8592 inhabitants of the city of Groningen, 28-75 years of age. The cohort is enriched for microalbuminuria. RESULTS: In general, the formulae did not give an accurate estimation of CCR, particularly not in male and in obese subjects. Six formulae, including the Cockcroft-Gault gave a fairly good estimation of CCR in the overall population and in subgroups of specific gender, body mass index and age. All formulae however, gave an underestimation of the measured CCR in higher ranges of CCR and an overestimation in the lower ranges. Moreover, the age-related decline of CCR is hard to approximate with a formula. CONCLUSIONS: We conclude that formulae to estimate CCR in the general population, although giving a fairly good estimate of mean CCR, do not offer reliable data on CCR in the upper and lower ranges and do not adequately estimate the age-related decline in CCR.

Adult↗
PubMed2002

Urinary albumin excretion is related to cardiovascular risk indicators, not to flow-mediated vasodilation, in apparently healthy subjects.

Based on studies in diabetic and hypertensive populations it has been postulated that early endothelial dysfunction is the mechanism responsible for the increased cardiovascular risk in microalbuminuric subjects. We evaluated the relation between microalbuminuria and endothelial dysfunction, assessed as flow-mediated dilation of the brachial artery, in an apparently healthy population. Within the framework of the PREVEND Intervention Trial non-hypertensive and non-hypercholesterolemic subjects were recruited on the basis of reproducible microalbuminuria. Using high-resolution ultrasound, flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery was assessed to measure endothelium-dependent and endothelium-independent responses, respectively. For the current study subjects with diabetes mellitus, clinical atherosclerosis, and macroalbuminuria were excluded from the analyses. We studied 421 men and 233 women (mean age (SD) 50 (12)). Increasing levels of urinary albumin excretion were accompanied by a significant increase in age, percentage men, systolic and diastolic blood pressure, body mass index, and serum triglycerides, whereas there was no decrease of flow-mediated vasodilation or nitroglycerin-mediated vasodilation. Adjusted for age and sex, urinary albumin excretion was significantly related to systolic (r=0.19, P<0.001) and diastolic (r=0.16, P<0.001) blood pressure, body mass index (r=0.18, P<0.001), and triglycerides (r=0.13, P=0.001), but not to flow-mediated vasodilation (r=-0.01, P=0.8). In contrast to blood pressure, body mass index, and triglycerides, there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. These data suggest that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric, but otherwise healthy subjects.

Adult↗
PubMed2002

Obesity and target organ damage: the kidney.

Obesity is a risk marker for progressive renal function loss in patients with known renal disease. There is, however, increasing evidence that obesity may also damage the kidney in otherwise healthy subjects. There appears to be an intriguing parallel between the renal effects of obesity and those of diabetes. First, an increased renal blood flow and glomerular filtration rate has been described in obesity and, second, microalbuminuria is found to be related to obesity. These two events are known to predict future loss of renal function in diabetes. The mechanism responsible for the renal damage in obesity has not been established but there is evidence suggesting that this might be related to both hormonal changes as well as low-grade inflammation.

Adult↗
PubMed2002

The importance of microalbuminuria as a cardiovascular risk indicator: A review.

The present review describes the knowledge of microalbuminuria as a cardiovascular risk indicator. Microalbuminuria is usually defined as a urinary albumin excretion rate of 30 to 300 mg in a 24 h urine collection, or as a urinary albumin excretion rate of 20 to 200 mg/min in a timed overnight urine collection, although microalbuminuria was demonstrated to be a predictor for cardiovascular events at levels below these conventional cut-off values. More than one consecutive urine collection is preferred given the high day to day variability of urinary albumin excretion. Microalbuminuria is frequently present and a known cardiovascular risk indicator in diabetic populations. Also, in hypertensive and general populations, microalbuminuria is common and has been associated with an adverse atherogenic risk profile and a higher prevalence of cardiovascular disease. Moreover, evidence strongly suggests that microalbuminuria is also an independent predictor of cardiovascular disease in these populations. However, more prospective studies are needed to elucidate fully the value of microalbuminuria as a cardiovascular risk indicator in hypertensive and general populations. Generalized endothelial dysfunction has been hypothesized to be the underlying factor for microalbuminuria on one hand and the underlying factor for increased cardiovascular risk on the other. In this respect, the loss of the glycosaminoglycan heparin sulphate might be an important pathophysiological mechanism. This hypothesis needs further clarification, especially in nondiabetic populations.

Albuminuria↗
PubMed2001

Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria.

BACKGROUND: Controversy exists regarding the adverse and beneficial effects of oral contraceptive use and hormone replacement therapy. Microalbuminuria is associated with increased risk of renal and cardiovascular disease. OBJECTIVE: To examine the association between oral contraceptive use or hormone replacement therapy and microalbuminuria. METHODS: We performed a case-control study of the baseline data and historical pharmacy data of 4301 female subjects of the Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75 years, excluding women who were pregnant or had type 1 diabetes mellitus. The main outcome measure was microalbuminuria, defined as a urinary albumin excretion of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine collections). RESULTS: After adjusting for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was 1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone replacement therapy users. The point estimate increased in a dose-dependent fashion, albeit insignificantly, according to the estrogen content of the oral contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81-9.08). The OR was greater in oral contraceptives with a second-generation (OR, 2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63-3.06). The OR increased with the duration of hormone replacement therapy (< or =5 years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97). CONCLUSION: Regular and long-term oral contraceptive use and hormone replacement therapy are associated with an increased risk for microalbuminuria and cardiovascular disease.

Adult↗
PubMed2001

Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.

PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women.

BACKGROUND: Microalbuminuria is an early predictor of cardiovascular morbidity and mortality, in both diabetic patients and hypertensive patients. Little is known about the relation of microalbuminuria to cardiovascular disease in women of the general population. METHODS AND RESULTS: We have studied the relation of urinary albumin levels to cardiovascular mortality in a cohort study of 12 239 postmenopausal women living in Utrecht, the Netherlands. The initial age was between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168 513 women-years). Albumin was determined in the urine of 561 cases and 557 controls. Data were analyzed by using a nested case-control design. The cardiovascular mortality rate (95% CI) for women who were in the highest quintile of urinary albumin levels was 13.2/1000 years (8.1 to 20.9) compared with 2.6/1000 years (2.3 to 3.1) in women without detectable urinary albumin. The age-adjusted rate ratio (95% CI) between these groups was 4.4 (2.6 to 7.6). CONCLUSIONS: This is the first large cohort study that confirms a predictive role of urinary albumin for the risk of future cardiovascular mortality independent of hypertension and diabetes. Our findings support the hypothesis that microalbuminuria is a reflection of vascular damage and a marker of early arterial disease in women from the general population.

Age Factors↗
PubMed2001

Anthropometry-based equations overestimate the urea distribution volume in hemodialysis patients.

BACKGROUND: Protein intake in hemodialysis patients can be estimated indirectly from the protein equivalent of total nitrogen appearance (PNA) during the interdialytic period. A reliable estimate of the patient's urea distribution volume (UDV) is required to assess protein intake from PNA values. UDV values are derived frequently from simple anthropometric equations. METHODS: UDV values based on anthropometric methods were compared with UDV values determined by direct dialysate quantitation (DDQ) in 54 stable chronic hemodialysis patients. The anthropometric methods included the following: the Watson equations (WAT), a fixed proportion of postdialysis body weight, 58% for males and 55% for females (% body wt), and skinfold thickness measurements (SFT). Postdialysis blood samples were drawn at 15-minutes postdialysis. RESULTS: UDV(WAT) and UDV(SFT) overestimated UDV(DDQ) by about 8 L [limits of agreement (LOA): 2.6 to 14.2 L] in males and about 6 L (LOA: -0.8 to 12.4 L) in females. The overestimation by UDV(%BW) was even larger: 10.5 L (LOA: 2.0 to 19.0 L) in males and 11.1 L (LOA: 2.1 to 20.1 L) in females. The difference between UDV(%BW) and UDV(DDQ) correlated with the percentage of body fat (r = 0.57) and body mass index (r = 0.48). In a subgroup of seven patients, UDV was also determined by dilution (DIL) of the stable isotope [(13)C]urea. UDV(WAT) and UDV(%BW) overestimated UDV(DIL) significantly. In contrast, UDV(DDQ) was significantly smaller than UDV(DIL), even after correction for incomplete postdialysis equilibration. PNA values calculated using the various UDV estimates were compared with dietary protein intake (DPI) assessed from food records. PNA(DDQ) (61 +/- 10 g/day) did not differ significantly from DPI (63 +/- 13 g/day), but the agreement in individual patients varied considerably (LOA, -24 to 20 g/day). Anthropometric-based PNA values overestimated DPI by 8 to 16 g/day. CONCLUSIONS: Anthropometry-based equations overestimate UDV values in hemodialysis patients, leading to an overestimation of PNA values. Although PNA measurements by DDQ appear to be more reliable for assessing protein intake, PNA(DDQ) values should be interpreted with caution in individual hemodialysis patients.

Adult↗
PubMed2001

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. METHODS: Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. RESULTS: Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. CONCLUSIONS: The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Optimal antiproteinuric dose of losartan in nondiabetic patients with nephrotic range proteinuria.

Although the antiproteinuric response to antihypertensive treatment is the main predictor of renoprotective efficacy in long-term renal disease, to date, dose-finding studies of antihypertensives have been based only on blood pressure. We aimed to find the optimal antiproteinuric dose of the angiotensin II antagonist losartan. An open-label, dose-response study using subsequent 6-week treatment periods was performed in 10 nondiabetic patients with proteinuria of 5.8 +/- 0.8 g/d and a mean arterial pressure of 103 +/- 3.7 mm Hg without antihypertensive medication. All patients had normal to moderately impaired renal function. After the baseline period, five periods followed with a daily losartan dose of 50 mg, 100 mg, 150 mg, and 50 mg and a recovery without losartan. At the end of each period, proteinuria and mean arterial pressure were measured. The consecutive doses of losartan had a similar antihypertensive response (-11.3 +/- 2.8% by the 100-mg dose). The optimal antiproteinuric response was reached at 100 mg of losartan (-30 +/- 8%). The 50-mg dose (-13 +/- 7%) was less effective, and the 150-mg dose (-28 +/- 8%) was not more effective. A 100-mg dose of losartan is optimal for reduction of proteinuria in nondiabetic patients with nephrotic range proteinuria.

Antihypertensive Agents↗
PubMed2001

Role of genetic variability in the renin-angiotensin system in diabetic and nondiabetic renal disease.

Studies on genetic variability in the renin-angiotensin system (RAS) provide intriguing data that support its possible relevance to renal pathophysiology. However, from the discrepancies between different studies it is clear that RAS polymorphisms do not provide simple markers for renal prognosis or therapy response. Rather than attempting to force a conclusion from the available discrepancies, we should attempt to develop strategies from the current state of knowledge to attack this complex issue from different angles. Unraveling their functional impact in renal pathophysiology can provide a framework for understanding that can guide further studies with the eventual purpose of improving the prognosis of renal patients. Clinical association studies should be large and prospective, to obtain the necessary robustness, with proper attention paid to the role of contextual factors. Moreover, studies elucidating the physiologic mechanisms of the genetic determinants of the disease phenotype are of prime importance. Such information is vital, not only to make sense of observed associations, but all the more so if one wants to apply the insights on the role of genetic factors into better strategies for disease intervention.

Angiotensin Receptor Antagonists↗
PubMed2001

Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM.

BACKGROUND: Interference in the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors has proven to be effective in lowering albuminuria in patients with insulin-dependent diabetes mellitus (IDDM). We studied whether angiotensin II receptor antagonism reduces urinary albumin excretion (UAE) in IDDM patients, and the relationship between the antiproteinuric effect and changes in systemic and renal haemodynamics. METHODS: Nine IDDM patients with microalbuminuria (30-300 mg/24 h) were studied. Patients were studied after a 4 week placebo period, on days 3, 7 and 28 of treatment with losartan 50 mg once daily, and after a 4 week placebo-controlled recovery period. RESULTS: Mean arterial pressure (MAP) was only slightly lowered during losartan treatment. Effective renal plasma flow (ERPF) was significantly increased on the third day of treatment and remained stable throughout the treatment period. Glomerular filtration rate (GFR) did not change throughout the study. Filtration fraction (FF) was maximally lowered on the third day of treatment and remained stable during treatment. UAE was already significantly lowered after 2 days of treatment, during both the day and night, and remained stable throughout the treatment period. The time course of the changes in UAE paralleled that of the changes in MAP, ERPF and FF. CONCLUSIONS: The angiotensin receptor antagonist losartan effectively lowers UAE in microalbuminuric IDDM patients. The changes observed in renal haemodynamics and UAE are concordant in time and maximal within only a few days of treatment. These results support the importance of the specific effects of interference in the renin angiotensin system (RAS) in microalbuminuric IDDM on blood pressure and renal haemodynamics in reducing urinary protein leakage, rather than non-haemodynamic, structural changes of the glomerular basement membrane.

Albuminuria↗