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Biomedical subjects

H A Koomans

Publications and source records attributed to H A Koomans.

At least 91 records · Page 5Linked to original sources
PubMed1997

Endothelial function and the kidney. An emerging target for cardiovascular therapy.

Endothelial dysfunction is emerging as an important factor in the early development of acute and chronic renal disease. Drugs aimed specifically at rectifying this aberration are being developed, although other established agents such as calcium antagonists, angiotensin converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors also have beneficial effects in this setting. Calcium antagonists are particularly effective at ameliorating acute renal ischaemia associated with endothelial dysfunction. Combination therapy with a calcium antagonist and an ACE inhibitor might optimise the beneficial effects of calcium channel blockade on the sequelae of endothelial dysfunction in chronic renal failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Causes of edema in the intensive care unit.

Patients in emergencies necessitating treatment in the intensive care unit (ICU) often develop generalized gross edema. The usual scenario is that in the emergency situation characterized by hypotension and (impending) organ failure, large amounts of fluids are administered that subsequently cannot be excreted adequately, even if the emergency situation subsides to a more stable condition. Three main factors underlie the inadequate restoration of volume balance: (1) impaired edema mobilization, due to the negative influence on lymphatic flow of reduced muscle activity and increased central venous pressure by mechanical ventilation; (2) secondary renal sodium retention by circulatory impairment and hypotension caused by mechanical ventilation and by the cardiodepressant and vasodilatory effects of (endo-)toxemia; and (3) primary renal sodium retention by renal vasoconstriction and filtration impediment, due to a complex of systemic and intrarenal vasomodulator activation and intrarenal endothelitis, or acute renal failure. Edema itself, as far as impeding organ function and necessitating mechanical ventilation, may further perpetuate this difficult to handle and vicious circle.

Edema↗
PubMed1996

New insights into mechanisms of blood pressure regulation in patients with uraemia.

There is no doubt that in patients with endstage renal failure sodium/water retention and (often unrecognized) hypervolaemia is the single most important determinant for elevated blood pressure. More detailed analysis reveals that in the renal patient susceptibility to hypervolaemia is increased due to inappropriately elevated activity of pressor systems (and/or decreased activity of depressor systems). These abnormalities comprise inappropriately activated renin-angiotensin system (RAS) (circulating and local) as well as sympathetic activity, but more hypothetical possibilities must also be considered, e.g. abnormalities of renal vasodilators (medullipin), L-arginine-derived agmatin, endothelin and NO.

Blood Pressure↗
PubMed1996

Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms.

We studied renal sodium handling during water diuresis in children in the early phase of relapse of minimal lesion nephrotic syndrome (MLNS). Findings were related to presence or absence of symptoms suggestive of hypovolaemia, and to neurohumoral factors, and were compared to results of similar studies in the same children in remission. Nine children (aged 7.8 +/- 3.1 years) presented with hypovolaemic symptoms, and 10 (7.4 +/- 4.3 years) without such symptoms. Both groups displayed severe proteinuria, hypoproteinaemia and oedema. Symptomatic patients showed tendency for a low glomerular filtration rate, and significantly impaired urine dilution, decreased fractional sodium and lithium excretions, and elevated diluting segment reabsorption [CH2O/(CH2O + CNa)] and sodium/potassium exchange [UK/(UK + UNa)]. In the non-symptomatic patients these parameters were normal. Plasma renin and aldosterone were significantly elevated in the symptomatic children, and strongly correlated with all parameters of tubule sodium reabsorption. Weaker associations were found for plasma noradrenaline and atrial natriuretic peptide. Vasopressin was also relatively high in the symptomatic group, but showed no association with impaired urine dilution. The diffusely stimulated tubular sodium reabsorption in the symptomatic children, in association with stimulated neurohumoral factors, indicates that secondary sodium retention contributes to oedema formation in at least a subset of children developing a nephrotic relapse. This may be limited to the early stage, and be more pronounced in some patients than in others. The tubular defect responsible for maintenance of oedema in stabilized MLNS remains unclear.

Adolescent↗
PubMed1996

No change in automatic function tests during uncomplicated haemodialysis.

Uraemic autonomic dysfunction is reckoned to participate in dialysis hypotension, but a clear relationship has not been established. However, autonomic function is usually tested at rest, and possibly autonomic dysfunction arises or worsens during dialysis. We therefore performed easily repeatable tests of efferent sympathetic function, that is static exercise test and parasympathetic function, that is heart rate variability during Valsalva manoeuvre and deep breathing, at successive stages of a standard haemodialysis session; before dialysis, 20 min after dialysis without ultrafiltration, after 3 h of dialysis combined with ultrafiltration, and 20 min after dialysis. Studies were performed in 22 patients on chronic haemodialysis on a cuprophane dialyser. The mean ultrafiltration volume was 2.2 +/- 0.61. We found that blood pressure elevation upon static exercise, and heart rate variability during Valsalva or deep breathing test remained unaltered at the various stages of dialysis. On past performance the patients were divided into hypotension prone (n = 6) or resistant (n = 16). Hypotension prone patients showed a greater blood pressure drop during dialysis, but also showed an appropriately enhanced heart rate acceleration. The occurrence of autonomic dysfunction was not elevated in this group, nor did such dysfunction develop along dialysis. Predialysis parasympathetic function tests were abnormal in 10 patients. These patients also showed an augmented intradialytic blood pressure decrease, but no enhanced acceleration in heart rate. Their parasympathetic dysfunction did not worsen during dialysis. Based upon the predialysis exercise test, low responding patients (blood pressure increase 5 +/- 2 mmHg, n = 11) were distinguished. These subjects were not characterized by a greater blood pressure decrease or different heart rate acceleration. Generally, the responses upon exercise, whether low or high, remained unaltered during dialysis. we conclude that haemodialysis has no systematic effect on autonomic function. Hypotension-prone patients are not distinguished by a disturbed predialytic or intradialytic autonomic blood pressure control.

Adult↗
PubMed1996

Renal responses to antagonism of the renin-angiotensin system.

Detailed knowledge is becoming available on the intrarenal renin-angiotensin system. This paper briefly describes some recent developments on the intrarenal formation and compartmentalization of components of the renin-angiotensin system. Furthermore, renal responses to angiotensin II are reviewed with respect to intraluminal angiotensin II concentrations, and interactions with nitric oxide on the afferent arteriole and the tubuloglomerular feedback system. A main issue is whether angiotensin-converting enzyme inhibitors can block the intrarenal renin-angiotensin system to the same extent as in other tissues. This is particularly interesting in view of the recently discovered polymorphism in the angiotensin-converting enzyme gene, which accounts for substantial variation in plasma angiotensin-converting enzyme levels. AT1 receptor antagonists are now available for clinical use. Although the AT1 receptor has been reported to mediate most, if not all, of the renal actions of angiotensin II, these compounds differ from angiotensin-converting enzyme inhibitors. Firstly, AT1 receptor blockers lack the prostaglandin- and kinin-potentiating effects of angiotensin-converting enzyme inhibitors. Furthermore, they increase angiotensin II, which can activate non-AT1 receptors. Finally, the pharmacodynamics of AT1 receptors may evoke different responses from the sympathetic nervous system than those of angiotensin-converting enzyme inhibitors. Currently, it is unclear whether renin inhibitors will have advantages over angiotensin-converting enzyme inhibitors or AT1 receptor antagonists. From the recent research, it is clear that the classical concept of the renin-angiotensin system cannot be pursued, and is being replaced by detailed schemes in which the intrarenal renin-angiotensin system has an important place.

Angiotensin II↗
PubMed1996

Mechanisms of cardiovascular injury in renal disease.

Patients with renal disease have an increased cardiovascular mortality. Hyperlipidemia, a hallmark of renal disease, is recognized as a principal cause of atherosclerosis. However, it is difficult to prove a pathogenetic role of renal dyslipidemia per se in this increased cardiovascular risk since multiple risk factors are often present in patients with progressive renal insufficiency, e.g. hypertension, diabetes and hypercoagulability. However, evidence is accumulating demonstrating detrimental effects of hyperlipidemia during both initiation and progression of the atherosclerotic process. The present review discusses this evidence in patients with renal disease, and the possible implications for treatment.

Arteriosclerosis↗
PubMed1996

Contrast-enhanced dynamic magnetic resonance imaging of the rat kidney.

This study was designed to assess whether contrast-enhanced dynamic 1H magnetic resonance imaging (DMRI) can be used to detect the effects of the loop diuretic furosemide and the vasoactive peptide angiotensin II on tubular water reabsorption in the rat kidney. A bolus of gadolinium-DTPA-dimeglumine (Gd-DTPA) (0.025 or 0.1 mmol/kg) was used as a contrast agent. The signal intensity in the magnetic resonance images relative to the precontrast signal intensity (RSI) was assessed as a function of time in the cortex and medulla. In the cortex, no differences were observed between high and low bolus injection, and between different treatment groups and controls. In the medulla, RSI patterns were different between high and low bolus, with the high bolus showing lower RSI values, because of T2 shortening at high Gd-DTPA concentrations. No difference was observed between controls and angiotensin II-infused animals. This is in line with the finding that angiotensin II did not alter medullary water reabsorption, as evidenced by unchanged urine flow and osmolality compared with controls. Medullary RSI patterns during furosemide infusion differed markedly from controls, in a manner suggesting that a lower concentration of Gd-DTPA was present compared with controls. This agrees with the well-known inhibiting effect of furosemide on medullary water reabsorption. It was concluded that, with the method used, small concentration differences of Gd-DTPA in the cortex resulting from small changes of plus or minus 20% in tubular water reabsorption, previously found to be present by direct micropuncture measurements, cannot be detected in rats. However, large changes in renal concentrating ability do result in different RSI patterns in the medulla.

Angiotensin II↗
PubMed1996

Access flow measurements in hemodialysis patients: in vivo validation of an ultrasound dilution technique.

In this study, access flow in hemodialysis patients with bridge grafts was measured by a newly developed device. The technique is based on the measurement of changes in the ultrasound characteristics of blood. These changes were initiated by an injection of isotonic saline and measured in the tubes of the extra-corporeal circuit. The access flow rate (mean +/- standard variation) was 880 +/- 440 mL/min (range, 166 to 1740) (N = 46). The mean coefficient of variation was 13.4 +/- 6.8% (median, 13.0%; range 3.5 to 29.4%). Measurements correlated well (r = 0.91, N = 22, P < 0.001) with flow rates determined by magnetic resonance angiography and by a technique based on intra-access flow-pressure curves (r = 0.84, N = 14, P < 0.001). In conclusion, access flow can be measured easily, noninvasively, and reliably by the ultrasound dilution device.

Blood Pressure↗
PubMed1996

Ovariectomy decreases plasma triglyceride levels and both prevents and alleviates glomerular disease in uninephrectomized female analbuminemic rats.

Female Nagase analbuminemic rats (NAR) are profoundly hypertriglyceridemic and develop proteinuria and glomerulosclerosis when aging and after uninephrectomy (UNX). Ovariectomy (OVX) markedly decreases plasma triglyceride levels in this species. This study evaluated whether decreasing triglyceride levels by OVX could prevent renal disease or alleviate its progression in UNX female NAR. Female NAR underwent OVX at 0, 12, 24, or 36 wk after UNX. In the absence of OVX, the animals developed progressive proteinuria from 18 wk after UNX and showed extensive glomerular sclerosis, lipid deposition, and hypertrophy at euthanasia (49 wk after UNX). These changes were prevented by OVX carried out at 0 or 12 wk, and attenuated by OVX at 24 wk after UNX. If performed at 36 wk after UNX, OVX had no effect on glomerulosclerosis, although it reduced proteinuria. In 95% (20 of 21) of the rats with proteinuria over 10 mg/day, proteinuria decreased in the first 6 wk after OVX. The percentage decrease in proteinuria correlated inversely with the glomerulosclerosis score at euthanasia (r = -0.58, P < 0.01). OVX had no effect on hyperfiltration and hyperperfusion in the UNX rats. OVX consistently reduced plasma triglyceride levels in rats both with and without proteinuria, and it also reduced plasma cholesterol, but only in conjunction with reduction in proteinuria. It was concluded that OVX in UNX female NAR prevents glomerulosclerosis if performed before proteinuria and attenuates further development of established renal disease if performed in a timely manner. This study's data suggest that in UNX female NAR, the lowering of plasma triglyceride levels plays a central role in the renoprotective action of OVX.

Aging↗
PubMed1995

Transluminal vascular stent for ostial atherosclerotic renal artery stenosis.

We implanted transluminal stents in 24 hypertensive patients with a critical atherosclerotic ostial renal artery stenosis (28 arteries). Immediate revascularisation was successful in all. Follow-up angiography at 6 months, available in 18 patients, revealed restenosis twice. In another patient restenosis was suspected and confirmed by angiography at 2 months. Hence, the total restenosis rate was 3 of 19 patients (16%) and 3 of 23 arteries (13%). Two patients developed renal insufficiency due to cholesterol embolism. In the remaining 22 patients renal function improved (n = 8) or stabilised (n = 14). Although all had to resume antihypertensive treatment, blood pressure normalised in 15 patients, improved in one, remained unchanged in five and worsened in one.

Aged↗
PubMed1995

Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication.

To study whether vascular dysfunction in hypercholesterolaemia is reversible, we investigated patients without overt arterial disease who were taking maintenance treatment for hypercholesterolaemia. Medication was stopped for 2 weeks, reinstituted for 12 weeks, and again stopped for 6 weeks. During both maintenance treatment and the 12 weeks of step-up medication the lipid profile was improved but did not return to normal. Dose-response curves for serotonin-induced vasodilatation, an index of nitric oxide-dependent vasodilatation, showed a comparable and significant rightward shift after a medication-free period of 2 and 6 weeks compared with control subjects, indicating endothelial dysfunction, which was already maximum after 2 weeks. After 12 weeks of lipid-lowering medication, the difference in endothelial function between controls and patients had disappeared. Co-infusion of L-arginine, the substrate for nitric oxide synthase, returned the impaired serotonin response during hypercholesterolaemia to normal, but had no effect on this response in controls or in patients while on lipid-lowering medication. Neither endothelium-independent vasorelaxation, assessed by sodium nitroprusside infusion, nor vasoconstriction induced by the nitric oxide blocker L-NMMA, were different between controls and patients, whether the latter were on or off lipid-lowering medication. Our results show an L-arginine-sensitive, impaired nitric-oxide-mediated vascular relaxation of forearm resistance vessels in hypercholesterolaemia which is reproducible, and reversible after short-term lipid-lowering therapy. Demonstration of such changes in this readily accessible vascular bed will allow larger trials assessing vascular function during lipid-lowering therapy to be done.

Adult↗
PubMed1995

Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms.

The cause of sodium retention in nephrotic syndrome is unclear. Hypovolaemia has traditionally been labelled as the cause but there is evidence in adults of a renal disturbance as the main cause. We aimed to find out whether children with early nephrosis can be classified as hypovolaemic by objective measures. We measured blood volume, kidney function, and hormone concentrations in children with early relapse of minimal-change nephrosis. Three presentations could be defined. The first was patients with incipient proteinuria and normal plasma protein, characterised by sodium retention, increased renal plasma flow, and slightly increased aldosterone, but normal noradrenaline. The second was patients with severe proteinuria, hypoproteinaemia, and hypovolaemic symptoms, who had oedema, sodium retention, and high concentrations of plasma renin, aldosterone, and noradrenaline, low atrial natriuretic peptide, and low glomerular filtration rate. The third was patients with equally severe proteinuria and hypoproteinaemia, but without hypovolaemic symptoms; they had oedema, but no active sodium retention, and normal plasma hormones and glomerular filtration. Neither blood pressure nor blood volume discriminated patients with or without hypovolaemic symptoms. These findings show that children with early full-blown nephrosis can present both with and without hypovolaemic symptoms and laboratory signs, despite equally severe hypoproteinaemia, and also that sodium retention precedes the reduction in serum protein.

Adolescent↗