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Biomedical subjects

D de Zeeuw

Publications and source records attributed to D de Zeeuw.

At least 109 records · Page 6Linked to original sources
PubMed1995

Drug-induced changes in renal hippurate clearance as a measure of renal blood flow.

We studied the accuracy of the plasma 131I-hippurate clearance technique to monitor drug-induced changes in renal blood flow (RBF) by comparing it to a flow probe technique in six conscious, chronically instrumented dogs. Placebo caused no change in RBF, either established by hippurate clearance (ERPFhip) or by renal blood flow probe (RBFprobe). Enalaprilate induced a rise in ERPFhip and RBFprobe (+26 +/- 5 and 44 +/- 12%), as did dopamine (+16 +/- 4 and +33 +/- 5%). Intravenous infusion of norepinephrine induced a rise in ERPFhip (+2 +/- 6%, NS) and in RBFprobe (+18 +/- 3%), as did nitroprusside (+14 +/- 4% and +13 +/- 6%, NS). Indomethacin induced a fall in ERPFhip (-8 +/- 2%) and in RBFprobe (-7 +/- 3%, NS), as did angiotensin II (-19 +/- 1 and -26 +/- 3%). Renal hippurate extraction (Ehip) was affected by enalaprilate, dopamine, and angiotensin II (-5 +/- 2, -7 +/- 1, and +5 +/- 2%, respectively). Hematocrit (Hct) was affected by dopamine, norepinephrine, and nitroprusside (+2 +/- 1, +6 +/- 1, and -6 +/- 2%, respectively). Drug-induced changes in ERPFhip correlated well with changes in RBFprobe (r = 0.902, P < 0.01). Changes in Ehip did not independently affect this relation, whereas changes in Hct did: delta RBF(% of baseline) = 1.529 x delta ERPFhip(% of baseline) + 1.296 x delta Hct(% of baseline). These data indicate that drug-induced changes in plasma hippurate clearance can, even when changes in renal hippurate extraction are unknown, be used as a reliable indicator of changes in renal blood flow if changes in hematocrit are taken into account.

Animals↗
PubMed1995

Additive antiproteinuric effect of ACE inhibition and a low-protein diet in human renal disease.

Both ACEi and a low-protein diet (LPD) are reported to reduce urinary protein excretion in patients with stable non-diabetic renal disease. To test whether the combination of both may have an additive antiproteinuric effect, we studied the effects of single treatment with ACEi (10 mg enalapril o.d.), LPD (target, 50% reduction in protein intake), and the combination of both in 14 of such patients with stable proteinuria exceeding 3 g per day. Baseline measurements were performed while patients were on a normal protein diet (NPD). In group A (n = 7), first the effects of a LPD were investigated, whereafter the effects of addition of ACEi to LPD were studied. In group B (n = 7), first the effects of ACEi were investigated, whereafter the effects of addition of a LPD to ACEi were studied. Each treatment period lasted 2 months. LPD decreased proteinuria with 17% in patients without ACEi treatment (group A), and similarly with 19% in patients with ACEi treatment (group B). The antiproteinuric response obtained with the LPD in individual patients ranged from -63% to +1%. This variation is at least partly explained by interindividual differences in diet compliance, since the antiproteinuric effect of the LPD was found to correlate with the achieved reduction in protein intake (r = 0.58, P < 0.05). ACEi lowered proteinuria with 32% during the NPD (group B), and similarly with 43% during the LPD (group A).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Renal and systemic effects of the renin inhibitor remikiren in patients with essential hypertension.

Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. We therefore studied the effects of a single oral administration of remikiren on blood pressure and renal function in 16 patients with essential hypertension on a restricted dietary sodium intake. Remikiren induced a peak fall in mean arterial pressure of 8.5 +/- 0.8%. The glomerular filtration rate (GFR) remained stable, whereas the effective renal-plasma flow rose by 11.3 +/- 1.4%. As a consequence, the filtration fraction and the renal vascular resistance fell by 11.7 +/- 1.2% and 17.6 +/- 1.3%, respectively. These systemic and renal hemodynamic changes were more pronounced in individuals with a higher initial immunoreactive renin. Remikiren induced a significant rise in the fractional excretion of sodium [0.38% (0.24-0.52) to 0.50% (0.31-0.76)] and lithium [28.7% (25.0-32.4) to 33.2% (27-39.4)]. Moreover, remikiren induced a decrease in urinary albumin excretion [497 (268-815) to 252 (114-389) micrograms/h]. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.

Administration, Oral↗
PubMed1995

Noninvasive measurement of intrarenal blood flow distribution: kinetic model of renal 123I-hippuran handling.

A new technique for noninvasive measurement of intrarenal blood flow distribution over cortex and medulla is proposed. The technique involves analysis of 123I-labeled hippuran renography, according to a kinetic model that describes the flow of 123I-hippuran from the heart (input) through the renal cortex and medulla to the bladder (output). The method is validated and compared with the standard microsphere injection technique in anesthetized dogs. Changes in intrarenal blood flow distribution were induced by infusion of placebo (n = 6), angiotensin I (n = 5), or atrial natriuretic factor (n = 5). Baseline percentage medullary blood flow in the left kidney was 12 +/- 1% of total renal blood flow measured with microspheres and 15 +/- 1% with renography. During infusion of the placebo, medullary blood flow decreased slightly compared with baseline, as measured with both methods, by 2 +/- 6 (microspheres) and 1 +/- 8% (renography). Infusion of angiotensin I caused a marked fall in medullary blood flow by 42 +/- 11 (microspheres) and 57 +/- 8% (renography). In contrast, infusion of atrial natriuretic factor caused a small rise in medullary blood flow as measured with both methods (9 +/- 3 and 12 +/- 11%, respectively). The absolute and percent changes in medullary blood flow measured with renography correlated with those measured with microspheres (left kidney: r = 0.67, P = 0.005; r = 0.71, P = 0.003, respectively; right kidney: r = 0.62, P = 0.01; r = 0.68, P = 0.004, respectively). We conclude that the proposed kinetic model of renal 123I-hippuran handling can be used to measure changes in intrarenal blood flow distribution and, because of its noninvasive character, may be of use in clinical studies.

Angiotensin I↗
PubMed1995

Losartan in patients with renal insufficiency.

A choice of many antihypertensive strategies is now offered for the treatment of the hypertensive patient with renal insufficiency. Angiotensin-converting enzyme (ACE) inhibitors appear to be the drugs of choice since they not only lower blood pressure but also reduce some important risk factors that may cause progressive loss of renal function, such as intraglomerular hypertension, angiotensin II (Ang II)-induced glomerular growth, proteinuria and hyperlipidemia. Indeed, several clinical studies now show that ACE inhibitors offer renal protection beyond the lowering of systemic blood pressure. The new class of Ang II receptor antagonists and its first representative losartan has not yet been tested clinically for its renal protective efficacy. The first signs, however, look promising, since losartan appears to induce changes in several identified risk factors to the same extent as ACE inhibitors, such as renal vasodilation, and a fall in proteinuria and serum lipids. The challenge will be to discover the differences between ACE inhibitors and Ang II receptor antagonists and to use them to the future advantage of the renal patient.

Acute Kidney Injury↗
PubMed1995

Effect of chronic ACE inhibition on the diagnostic value of renography for renovascular hypertension: a preliminary report.

We compared the effects of acute and chronic ACE inhibition (ACEi) on the 123I-hippurate in the stenotic kidney of two 2-kidney, 1-clip hypertensive dogs. In the period after clip implantation poststenotic renograms without ACEi of both dogs were normal. Acute ACEi always resulted in delayed hippurate handling. Chronic ACEi, however, induced abnormal poststenotic renograms in only 36% of the cases. Withdrawal of chronic ACEi restored the phenomenon of acute ACE-induced delayed hippurate handling within 5 months in both dogs. These data indicate that chronic ACEi or recent ACEi medication reduces the effectiveness of ACEi renography in diagnosing hypertension due to a moderate renal-artery stenosis. This phenomenon may explain why the sensitivity of ACEi renography in human studies varies more than in animal studies.

Animals↗
PubMed1995

Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials.

Whether ACE inhibitors (ACEi) differ from other antihypertensives in their efficacy to lower proteinuria is controversial. We therefore performed a meta-analysis of articles on this subject. The secondary objective in our meta-analysis was to study whether there is any difference between diabetic and non-diabetic patients in antiproteinuric response to blood pressure reduction. To identify all articles we performed a computer search using the bibliographic databases. To minimize publication bias, only trials in which a direct comparison was made between an ACEi and another antihypertensive were included. Studies performed both in diabetic and in non-diabetic patients were eligible. Included were 41 studies, comprising 1124 patients, of which 558 had non-diabetic renal disease. The mean antiproteinuric effect of ACEi was significantly greater than that of their comparator drugs: -39.9% (95% confidence interval: -42.8 to 36.8%) versus -17.0% (-19.0 to -15.1%) respectively (difference 24% (19.5 to 28.6%)). The blood-pressure-lowering effect was equal: -12.0% (-12.8 to -11.2%) versus -11.4% (-11.7 to -11.1%) respectively (difference -0.8% (-1.8 to 0.2%)). Thus it may be concluded that ACEIs confer an antiproteinuric effect beyond that attributable to their blood-pressure-lowering effect. A wide interstudy variation in antiproteinuric response to non-ACEI antihypertensives was observed. Multiple variable regression analysis was performed to assess which factors may explain this heterogeneity. From the comparator drugs, the class was of no importance: calcium-channel antagonists (CCA), beta-blockers, and a rest group of other drug types showed a similar response. Patient characteristics such as initial GFR and blood pressure partly explained the variation in response, but most of it appeared dependent on the blood pressure reduction achieved. Furthermore the type of CCA is of importance, with nifedipine having the least effect. A significantly greater antiproteinuric effect of 'non-ACEI' antihypertensives was found in diabetic patients compared to non-diabetics. However, this coincided with a greater blood pressure reduction in diabetics. Adjusted for differences in blood pressure control, diabetics showed even a slightly lesser antiproteinuric response to non-ACEI antihypertensive compared to non-diabetics.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Discordant effects of enalapril and lisinopril on systemic and renal hemodynamics.

OBJECTIVE: To investigate whether there are quantitative differences between the angiotensin converting enzyme (ACE) inhibitors enalapril and lisinopril with respect to their influence on renal versus systemic hemodynamics in humans. METHODS: This was a 12-month, single-blind crossover study in which eight patients with essential hypertension were examined. The main outcome measures were blood pressure and renal hemodynamics during ACE inhibition and/or angiotensin II infusion. RESULTS: The decrease in blood pressure was dose dependent and not significantly different between both drugs. However, with the same blood pressure reduction effective renal plasma flow (ERPF) rose more and filtration fraction (FF) and renovascular resistance (RVR) decreased more after administration of enalapril (20 mg) than after administration of lisinopril (20 mg) (ERPF: 21.9% +/- 2.0% versus 4.4% +/- 2.5%, p = 0.018; FF: -16.7% +/- 2.8% versus -6.6% +/- 2.5%, p = 0.028; RVR: -28.1% +/- 3.1% versus -18.5% +/- 3.7%, p = 0.018). During angiotensin II infusion, with a similar increase in systemic blood pressure, the change in ERPF, FF, and RVR again was more pronounced during enalapril than during lisinopril (ERPF: -14.6% +/- 2.9% versus -7.8% +/- 3.3%, p = 0.018; FF: 18.3% +/- 5.9% versus 12.8% +/- 6.0%, p = 0.028; RVR: 36.7% +/- 8.1% versus 21.9% +/- 4.3%, p = 0.018). CONCLUSIONS: We conclude that in a situation of a comparable systemic blood pressure reduction, enalapril has greater effects on renal hemodynamics than lisinopril. This finding may have implications for the choice of a certain ACE inhibitor in specific disease conditions.

Adult↗
PubMed1994

Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system?

Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease.

OBJECTIVE: To study the effects of the angiotensin II antagonist losartan in hypertensive patients with renal disease. DESIGN: A single-blind longitudinal study was performed, lasting 4 months. Patients were treated once a day with placebo, 50 mg losartan, 100 mg losartan and placebo, each for 1 month, in sequence. Measurements were taken at the end of each treatment period. PATIENTS: The study subjects comprised 13 patients with biopsy-proven renal disease, a diastolic blood pressure of > 90 mmHg, creatinine clearance of > 60 ml/min and stable proteinuria of > 2.0 g/day. RESULTS: Mean arterial pressure, measured 4 h after the dose, fell from 113.8 +/- 2.1 mmHg (placebo) to 99.2 +/- 2.4 mmHg (50-mg dose) and 96.5 +/- 2.4 mmHg (100-mg dose). This blood pressure lowering effect was sustained for 24 h 116.3 +/- 2.3 mmHg (placebo) versus 105.5 +/- 1.8 mmHg (50-mg dose) and 103.3 +/- 1.9 mmHg (100-mg dose)]. The glomerular filtration rate remained stable, while the effective renal plasma flow increased by 12.5 +/- 2.9% (100-mg dose). The systemic and renal hemodynamic effects were similar at the 50- and 100-mg doses. Urinary excretion of total protein, albumin and immunoglobulin G decreased dose-dependently by a maximum of +/- 50% (100-mg dose). With the high dose, serum uric acid fell from 0.43 +/- 0.02 mmol/l to 0.39 +/- 0.02 mmol/l, and potassium increased from 4.2 +/- 0.1 to 4.6 +/- 0.1 mmol/l. CONCLUSIONS: The angiotensin II antagonist losartan lowers blood pressure and displays a favorable renal profile in hypertensive patients with renal disease.

Albuminuria↗
PubMed1994

Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria.

Elevated serum levels of the atherogenic and thrombogenic lipoprotein (a) (Lp(a)) have been recognized as a feature of the nephrotic syndrome associated hyperlipidaemia. To examine a possible relationship between serum Lp(a) concentration and proteinuria, serum albumin, or blood pressure, we studied nine patients with nephrotic-range proteinuria both at baseline and after various forms of antihypertensive and antiproteinuric treatment. In fixed order, patients received conventional antihypertensive treatment (either alpha-methyldopa or clonidine), subsequently ACE-inhibition therapy (lisinopril), ACE inhibition combined with an NSAID (indomethacin), and finally NSAID plus conventional antihypertensive therapy. Measurements were performed at the end of each 2-month study period. When compared to controls (n = 29), proteinuric patients before treatment showed increased levels of total cholesterol, very-low and low-density lipoprotein (VLDL+LDL) cholesterol, triglycerides and apolipoprotein B (apoB), while high-density lipoprotein (HDL) HDL cholesterol was lower. Lp(a) was significantly higher in patients (107 (95% CI: 55-208) mg/l) as compared to controls (25 (13-49) mg/l, P < 0.01). Conventional antihypertensive treatment did not reduce proteinuria, while Lp(a) remained unaffected. ACE-inhibitor treatment lowered proteinuria, raised serum albumin, while La(a) tended to fall (-11 +/- 8%). Addition of an NSAID induced a further fall in proteinuria and a rise in serum albumin. Lp(a) now fell by 40 +/- 5% from baseline values (P < 0.01). Both serum total, HDL and VLDL+LDL cholesterol fell significantly. Finally, during subsequent single therapy with NSAID most parameters, including proteinuria and Lp(a), returned towards values obtained during single therapy with ACE inhibiton.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Renal tubular sensitivity to atrial natriuretic factor in essential hypertension.

OBJECTIVE: To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. DESIGN: Nine healthy volunteers and six patients with essential hypertension were studied on four test days under standard conditions, water loading and hydropenia with mannitol or saline loading. On each test day baseline, atrial natriuretic factor infusion (1 microgram/min) and recovery measurements were performed after equilibrium had been reached. The measurements included the atrial natriuretic factor (ANF) plasma levels, blood pressure, glomerular filtration rate (GFR), effective renal plasma flow, urinary osmolality and the (fractional) excretions of (free) water, sodium and potassium. METHODS: Fractional free-water excretion and free-water reabsorption (as a function of osmolar clearance) were calculated during water loading and hydropenia with mannitol or saline loading, respectively, using standard formulae. [125I]-iothalamate and [131I]-hippuran were infused continuously for the measurement of GFR and effective renal plasma flow, respectively. RESULTS: The plasma ANF concentration rose five- to eightfold during the infusion of ANF, which induced an increase in urinary sodium excretion, a small increase in GFR and a decrease in the effective renal plasma flow. Moreover, ANF induced an increase in fractional free-water excretion and a decrease in fractional free-water reabsorption. These changes did not correlate with changes in GFR. The blood pressure and potassium excretion were not affected. The effects of ANF on the plasma ANF levels, natriuresis and renal haemodynamics did not differ between the normotensive and the essential hypertensives. However, the increase in fractional free-water excretion was significantly greater in the patients with essential hypertension and correlated significantly with blood pressure (r = 0.56, P < 0.05). CONCLUSIONS: These results indicate that the infusion of ANF at a low dose induces a similar natriuretic response in normotensive subjects and in patients with essential hypertension. This natriuresis is probably the result of both a glomerular and a tubular effect of ANF. Proximal as well as distal tubular sites seem to be involved. In essential hypertension an enhanced proximal as well as an impaired distal tubular action of ANF can be hypothesized.

Absorption↗
PubMed1993

Long-term benefits of the antiproteinuric effect of angiotensin-converting enzyme inhibition in nondiabetic renal disease.

The long-term (1.5 years) effects of angiotensin-converting enzyme inhibition were evaluated in 22 mostly normotensive patients with nondiabetic renal disease and moderate to severe proteinuria. The nephrotic-range proteinuria of 7.5 g/24 hr fell to 2.9 g/24 hr (-62%) after 2 months' treatment with an angiotensin-converting enzyme inhibitor and remained relatively stable at this level during continued treatment. The antiproteinuric response varied between study days and between individuals. Of note was the fact that the best antiproteinuric response was observed on those study days when no more than the instituted daily sodium intake (50 to 100 mEq/24 hr) was excreted. The sustained reduction in urinary protein excretion was accompanied by an increase in serum albumin and a slight but significant decrease in serum cholesterol. Those patients with the most pronounced initial antiproteinuric response showed less deterioration of renal function, estimated from the slope of the inverse serum creatinine value in time. These data suggest that long-term angiotensin-converting enzyme inhibitor treatment may be beneficial in normotensive patients with nephrotic-range proteinuria, not only to reduce the symptoms of a nephrotic syndrome, but also to prevent further renal damage.

Adult↗
PubMed1993

Low molecular weight proteins as carriers for renal drug targeting: naproxen coupled to lysozyme via the spacer L-lactic acid.

Low molecular weight proteins (LMWPs) are potential carriers for targeting drugs to the kidney. To test whether ester bonds are suitable for the reversible drug conjugation, the antiinflammatory drug naproxen (Nap) was conjugated to the LMWP lysozyme (LYSO) via an ester bond using an L-lactic acid spacer (Nap-lact-LYSO, 1:1:1). The distribution and degradation of the conjugate in rats were compared to those of an equimolar mixture of free drug and LMWP and of a directly coupled conjugate without spacer (Nap-LYSO). The plasma clearance of Nap-lact-LYSO closely resembled that of Nap-LYSO and LYSO itself. Its major accumulation site appeared to be the kidney as demonstrated by extracorporal gamma-camera counting of the LMWP. Renally released naproxen was excreted in the urine as 6-desmethyl-naproxen-sulfate (6-DMN-S). Apparently the kidneys represent the main sites of demethylation and sulfation after administration of the LMWP-coupled drug. In addition, the renal excretion of naproxen (including its metabolites) was significantly delayed and sustained as compared to that after injection of uncoupled naproxen. Using the L-lactic acid spacer LMWP conjugation, the renal selectivity of Nap was increased 5.6 +/- 0.41-fold. Additional in vitro studies with Nap-lact-LYSO revealed that renal generation of the parent drug coincided with formation of low molecular weight catabolites, mainly as naproxen-L-lactic acid-lysine (Nap-lact-Lys). This indicated that in vitro the rate of cleavage of the ester bond is significantly slower than digestion of the carrier backbone itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗