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F H Derkx

Publications and source records attributed to F H Derkx.

At least 37 records · Page 2Linked to original sources
PubMed1998

Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME.

Experimental evidence indicates that the renal circulation is more sensitive to the effects of nitric oxide (NO) synthesis inhibition than other vascular beds. To explore whether in men the NO-mediated vasodilator tone is greater in the renal than in the systemic circulation, the effects of three different intravenous infusions of NG-nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 microg. kg-1. min-1 for 30 min) or placebo on mean arterial pressure (MAP), systemic vascular resistance (SVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and fractional sodium and lithium excretion (FENa and FELi) were studied in 12 healthy subjects, each receiving randomly two of the four treatments on two different occasions. MAP was measured continuously by means of the Finapres device, and stroke volume was calculated by a model flow method. GFR and RBF were estimated from the clearances of radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were followed for 2 h after start of infusions. During placebo, renal and systemic hemodynamics and FENa and FELi remained stable. With the low and intermediate L-NAME doses, maximal increments in SVR and RVR were similar: 20.4 +/- 19.6 and 23.5 +/- 16.0%, respectively, with the low dose and 31.4 +/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose (means +/- SD). With the high L-NAME dose, the increment in RVR was greater than the increment in SVR. Despite a decrease in RBF, FENa and FELi did not change with the low L-NAME dose, but they decreased by 31.2 +/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose, respectively. It is concluded that in men the renal circulation is not more sensitive to the effects of NO synthesis inhibition than the systemic circulation and that the threshold for NO synthesis inhibition to produce antinatriuresis is higher than the threshold level to cause renal vasoconstriction.

Adult↗
PubMed1997

Prorenin, renin, angiotensinogen, and angiotensin-converting enzyme in normal and failing human hearts. Evidence for renin binding.

BACKGROUND: A local renin-angiotensin system in the heart is often invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions. METHODS AND RESULTS: We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin. CONCLUSIONS: These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.

Adolescent↗
PubMed1997

The place of renal scintigraphy in the diagnosis of renal artery stenosis. Fifteen years of clinical experience.

BACKGROUND: Renal scintigraphy with radiolabeled pentetic acid (diethylenetriamine pentaacetic acid [DTPA]) or, more recently, mertiatide (mercaptoacetyltriglycine [MAG3]), with or without captopril challenge, is widely recommended as a diagnostic test for renal artery stenosis. OBJECTIVES: To address (1) whether the diagnostic accuracy has been improved by the use of captopril and the introduction of mertiatide and (2) whether a renal scan that shows abnormalities is a useful criterion to select patients for renal arteriography. PATIENTS AND METHODS: A standard diagnostic protocol, using both scintigraphy and arteriography, was followed in 505 consecutive high-risk hypertensive patients who were evaluated for renovascular hypertension at the University Hospital Dijkzigt, Rotterdam, the Netherlands, from 1978 to 1992. RESULTS: Renal artery stenosis (> or = 50%) was present in 263 patients. When the single-kidney fractional uptake was used as a diagnostic criterion, a specificity of 0.90 was obtained at a cutoff value of 35% for the worst kidney in scintigraphy using pentetic acid without captopril challenge (n = 225) and at a cutoff value of 37% after captopril challenge (n = 280). This was associated with sensitivity levels of 0.65 and 0.68, respectively. The difference between the uptake of pentetic acid with and without captopril challenge in the 85 patients who were studied under both circumstances was no more accurate as a predictor of renal artery stenosis. In the 93 patients who were studied with mertiatide as well as with pentetic acid, both after captopril challenge, the diagnostic accuracy was no better with mertiatide than with pentetic acid; mertiatide failed to offer any advantage not only when the single-kidney fractional uptake was used as a criterion, but also with the use of other scintigraphic parameters (eg, time to peak, time to pyelum, overall shape of renographic curve, and kidney size). CONCLUSIONS: The diagnostic accuracy of renal scintigraphy has not been improved by the introduction of mertiatide or by the use of captopril. The usefulness of scintigraphy as a diagnostic test for the presence of renal artery stenosis remains questionable. The physician will always confront either a substantial number of arteriograms that do not show abnormalities when renal scintigraphy is omitted as a screening step or a substantial number of missed diagnoses when a renal scan that shows abnormalities is used as a prerequisite for arteriography.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women.

BACKGROUND: Oral estrogen replacement therapy (ERT) is known to stimulate the synthesis of angiotensinogen. The effects of such therapy on renin, ACE, and aldosterone are less clear. This seems noteworthy, however, since further activation of the system could be disadvantageous to postmenopausal women who replace estrogen in the context of heart failure, coronary artery disease, or hypertension. METHODS AND RESULTS: Estrogen status and components of the renin-angiotensin system were examined in a population-based sample of postmenopausal women and age-matched men. Renin was quantified immunoradiometrically, ie, independent of substrate abundance; aldosterone, angiotensinogen, and ACE activity were determined by standard methods. Renin levels were lower in women with ERT (n = 107; 12.0 +/- 0.7 mU/L) compared with women without ERT (n = 223; 16.6 +/- 0.9 mU/L; P = .001) or men (n = 342, 20.5 +/- 1.5 mU/L, P < .0001). In contrast, angiotensinogen was higher in women with ERT (1.36 +/- 0.08 mg/L) compared with women without ERT (1.03 +/- 0.02 mg/L; P < .0001) or compared with men (0.97 +/- 0.01 mg/L; P < .0001). Renin suppression was seen with either oral or transdermal estrogen replacement (-30% and -31%, respectively; both P < .001). In contrast, the increase of angiotensinogen was limited to women taking oral estrogens (+58%, P < .001). Multivariate analysis revealed that these estrogen effects were independent of age, body mass index, blood pressure, and/or antihypertensive medication. Finally, only marginal differences between groups were observed for serum ACE activity and aldosterone. CONCLUSIONS: Aside from a well-documented induction of angiotensinogen, ERT is related to a substantial suppression of renin, a phenomenon that might have received little attention because of widely used indirect measurements of the hormone.

Aged↗
PubMed1997

High renin and prorenin in plasma and pleural exudate of a patient with the ovarian hyperstimulation syndrome.

We present the case of a 35-year-old woman with a severe ovarian hyperstimulation syndrome (OHSS) as a complication of ovulation induction for primary infertility. The clinical picture showed massively enlarged ovaries, pleural effusion and haemoconcentration. She needed a thoracentesis for evacuation of the large pleural effusion. High levels of renin and prorenin were observed in plasma and pleural exudate.

Abortion, Spontaneous↗
PubMed1997

Endothelin and active renin levels in essential hypertension and hypertension with renal artery stenosis before and after percutaneous transluminal renal angioplasty.

OBJECTIVE: To determine whether active renin and endothelin levels in venous plasma differ between patients with renal artery stenosis and patients with primary hypertension. Among the patients with renal artery stenosis we also compared active renin and endothelin levels between subjects who had been cured or whose blood pressure had improved after treatment of the stenosis and those without a beneficial reaction after such treatment. METHODS: We measured immunoreactive endothelin and active renin levels in peripheral venous plasma before and 1 h after angiotensin converting enzyme inhibition in 25 patients with primary hypertension and in 27 patients with hypertension and renal artery stenosis. Percutaneous transluminal angioplasty was performed in 21 patients of the latter group. For 11 patients of this group, hypertension was cured or there was an improvement, whereas 10 other patients did not respond to this treatment. Baseline active renin and endothelin levels were compared between these groups, as were the clinical characteristics of the patients. RESULTS: Baseline endothelin levels were similar in members of the renal artery stenosis [median 3.6 pg/ml (range 1.4-11.7)] and in members of the no stenosis group [5.0 pg/ml (1.5-8.0)]. Also baseline endothelin levels did not differ between members of the successfully treated [3.6 pg/ml (1.8-8.9)] and unsuccessfully treated groups [3.75 pg/ml (1.4-8.3)]. Angiotensin converting enzyme (ACE) inhibition failed to cause a significant change in endothelin level in members of any of the patient groups. Although baseline renin levels differed significantly between members of the renal artery stenosis and no stenosis groups [40.2 microu/ml (0.9-543) versus 13.4 microu/ml (2.5-931), (P< 0.05)], there was no difference in baseline renin levels between the members of successful and unsuccessful groups [25.7 microu/ml (9.2-475.6) versus 65.3 microu/ml (12.3-542.6)]. ACE inhibition caused a significant increase in renin level in members of all groups except the unsuccessfully treated group. CONCLUSIONS: Circulating endothelin levels did not differ significantly among patients with essential hypertension, hypertension with renal artery stenosis and proven renovascular hypertension and, although the renin-angiotensin system was clearly activated in members of the renovascular hypertension group, ACE inhibition did not affect their endothelin levels. These results suggest that endothelin does not play a direct role in the pathophysiology of renovascular hypertension.

Adult↗
PubMed1997

Mannose 6-phosphate receptor-mediated internalization and activation of prorenin by cardiac cells.

The binding and internalization of recombinant human renin and prorenin (2500 microU/mL) and the activation of prorenin were studied in neonatal rat cardiac myocytes and fibroblasts cultured in a chemically defined medium. Surface-bound and internalized enzymes were distinguished by the addition of mannose 6-phosphate to the medium, by incubating the cells both at 37 degrees C and 4 degrees C, and by the acid-wash method. Mannose 6-phosphate inhibited the binding of renin and prorenin to the myocyte cell surface in a dose-dependent manner. At 37 degrees C, after incubation at 4 degrees C for 2 hours, 60% to 70% of cell surface-bound renin or prorenin was internalized within 5 minutes. Intracellular prorenin was activated, but extracellular prorenin was not. The half-time of activation at 37 degrees C was 25 minutes. Ammonium chloride and monensin, which interfere with the normal trafficking and recycling of internalized receptors and ligands, inhibited the activation of prorenin. Results obtained with cardiac fibroblasts were comparable to those in the myocytes. This study is the first to show experimental evidence for the internalization and activation of prorenin in extrarenal cells by a mannose 6-phosphate receptor-dependent process. Our findings may have physiological significance in light of recent experimental data indicating that angiotensin I and II are produced at cardiac and other extrarenal tissue sites by the action of renal renin and that intracellular angiotensin II can elicit important physiological responses.

Animals↗
PubMed1997

Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus.

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.

Adolescent↗
PubMed1997

Effect of long-acting somatostatin analog (Somatulin) on renal hyperfiltration in patients with IDDM.

OBJECTIVE: To investigate whether long-acting somatostatin (SMS) can suppress renal hyperfiltration in patients with IDDM. RESEARCH DESIGN AND METHODS: A double-blind, randomized treatment of nine patients with IDDM was used. Selection criteria were renal hyperfiltration (glomerular filtration rate [GFR] > or = 129 ml.min-1.1.73 m2) and absence of hypertension and macroalbuminuria. Treatment was either with a long-acting SMS analog (Somatulin, 30 mg) or with placebo, given by intramuscular injections every 10 days for 9 months. GFR, effective renal plasma flow (ERPF), IGF-I, and 24-h growth hormone (GH) profiles were used as evaluation parameters. RESULTS: Five patients were randomized to Somatulin, four patients to placebo. One of the patients treated with Somatulin stopped after 3 months because of persistent abdominal discomfort after the injections. Somatulin treatment for 3 months lowered GFR and ERPF compared with placebo (P < 0.05). After 9 months, the differences were no longer significant. After 3 months, IGF-I concentrations were decreased in all Somatulin-treated patients. GH secretion tended to increase in the placebo group. CONCLUSIONS: The administration of long-acting Somatulin to patients with IDDM and renal hyperfiltration leads to only a temporary reduction of ERPF/GFR.

Adult↗
PubMed1997

More on renin.

Explore the source record for details and available documents.

Enzyme Precursors↗
PubMed1996

The influence of dietary sodium restriction on renal and ovarian renin and prorenin production during ovarian stimulation.

In a prospective study, the effect of dietary sodium restriction on plasma and follicular fluid renin and prorenin concentrations and on fertilization measures was investigated during ovarian stimulation. In all, 18 women undergoing ovarian stimulation for in-vitro fertilization and embryo transfer were randomly divided into groups with and without sodium restriction. Plasma renin and prorenin concentrations were higher in the low sodium than in the normal sodium group. Plasma renin concentrations showed a mid-luteal rise. Plasma prorenin concentrations increased 4-fold on the day of oocyte retrieval, followed by a gradual decline to basal values. The low sodium group had more follicles than the normal sodium group. Neither follicular fluid renin and prorenin concentrations, nor the total amount of follicular fluid renin and prorenin per ovary differed significantly between the two groups. Oocyte yield and fertilization rates were similar in both groups. These rates were correlated with neither renin nor prorenin concentrations in follicular fluid. We conclude that sodium restriction did not influence cyclic plasma variation of renin or prorenin or follicular fluid renin and prorenin concentrations. In addition, fertilization rates were not affected by sodium restriction.

Blood Pressure↗
PubMed1996

Assessment of the role of the renin-angiotensin system in cardiac contractility utilizing the renin inhibitor remikiren.

1. The role of the renin-angiotensin system in the regulation of myocardial contractility is still debated. In order to investigate whether renin inhibition affects myocardial contractility and whether this action depends on intracardiac rather than circulating angiotensin II, the regional myocardial effects of systemic (i.v.) and intracoronary (i.c.) infusions of the renin inhibitor remikiren, were compared and related to the effects on systemic haemodynamics and circulating angiotensin II in open-chest anaesthetized pigs (25-30 kg). The specificity of the remikiren-induced effects was tested (1) by studying its i.c. effects after administration of the AT1-receptor antagonist L-158,809 and (2) by measuring its effects on contractile force of porcine isolated cardiac trabeculae. 2. Consecutive 10 min i.v. infusions of remikiren were given at 2, 5, 10 and 20 mg min-1. Mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), systemic vascular resistance (SVR), myocardial oxygen consumption (MVO2) and left ventricular (LV) dP/dtmax were not affected by remikiren at 2 and 5 mg min-1, and were lowered at higher doses. At the highest dose, MAP decreased by 48%, CO by 13%, HR by 14%, SVR by 40%, MVO2 by 28% and LV dp/dtmax by 52% (mean values; P < 0.05 for difference from baseline, n = 5). The decrease in MVO2 was accompanied by a decrease in myocardial work (MAP x CO), but the larger decline in work (55% vs. 28%; P < 0.05) implies a reduced myocardial efficiency ((MAP x CO)/MVO2). 3. Consecutive 10 min i.c. infusions of remikiren were given at 0.2, 0.5, 1, 2, 5 and 10 mg min-1. MAP, CO, MVO2 and LV dP/dtmax were not affected by remikiren at 0.2, 0.5 and 1 mg min-1, and were reduced at higher doses. At the highest dose, MAP decreased by 31%, CO by 26%, MVO2 by 46% and LV dP/dtmax by 43% (mean values; P < 0.05 for difference from baseline, n = 6). HR and SVR did not change at any dose. 4. Thirty minutes after a 10 min i.v. infusion of the AT1 receptor antagonist, L-158,809 at 1 mg min-1, consecutive 10 min i.c. infusions (n = 5) of remikiren at 2, 5 and 10 mg min-1 no longer affected CO and MVO2, and decreased LV dP/dtmax by maximally 27% (P < 0.05) and MAP by 14% (P < 0.05), which was less than without AT1-receptor blockade (P < 0.05). HR and SVR remained unaffected. 5. Plasma renin activity and angiotensin I and II were reduced to levels at or below the detection limit at doses of remikiren that were not high enough to affect systemic haemodynamics or regional myocardial function, both after i.v. and i.c. infusion. 6. Remikiren (10(-10) to 10(-4) M) did not affect contractile force of porcine isolated cardiac trabeculae precontracted with noradrenaline. In trabeculae that were not precontracted no decrease in baseline contractility was observed with remikiren in concentrations up to 10(-5) M, whereas at 10(-4) M baseline contractility decreased by 19% (P < 0.05). 7. Results show that with remikiren i.v., at the doses we used, blood pressure was lowered primarily by vasodilation and with remikiren i.c. by cardiac depression. The blood levels of remikiren required for its vasodilator action are lower than the levels affecting cardiac contractile function. A decrease in circulating angiotensin II does not appear to be the sole explanation for these haemodynamic responses. Data support the contention that myocardial contractility is increased by renin-dependent angiotensin II formation in the heart.

Angiotensin Receptor Antagonists↗
PubMed1996

Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular renin-angiotensin system.

AIMS/BACKGROUND: All components necessary for the formation of angiotensin II, the biologically active product of the renin-angiotensin system (RAS), have been demonstrated in ocular tissue or vitreous and subretinal fluid. The tissue concentrations of renin were too high to be explained by admixture of blood. This raises the possibility of an intraocular RAS, independent of the RAS in the circulation. METHODS: In the present study, gene expression of RAS components in different parts of enucleated human eyes was investigated as evidence for tissue specific production. RESULTS: By using pooled tissue samples renin mRNA could be detected with the RNAse protection assay in retinal pigment epithelium (RPE) choroid, but not in neural retina or sclera. With reverse transcription polymerase chain reaction (RT-PCR), renin mRNA was detected in individual samples of RPE choroid and neural retina, and not anterior uveal tract or sclera. Angiotensinogen and angiotensin converting enzyme (ACE) gene expression could be demonstrated by RT-PCR in individual RPE choroid and neural retina samples and marginally in sclera samples. CONCLUSIONS: These results support the concept of intraocular synthesis of angiotensin II, independent of renin, angiotensin, and ACE in the circulation. Since gene expression was highest in ocular parts, which are highly vascularised, local angiotensin II may be involved in blood supply and/or pathological vascular processes such as neovascularisation in diabetic retinopathy.

Adult↗
PubMed1996

Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity.

Newly developed IRMAs to measure the plasma concentrations of renin and prorenin were validated for clinical use and compared with a classical enzyme kinetic assay. The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that recognizes renin well but prorenin only minimally. Prorenin reactivity with the second antibody was enhanced by adding the renin inhibitor, Remikiren, to plasma. The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The linear working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained without Remikiren (i.e., renin) from the result obtained with Remikiren (i.e., renin plus prorenin). No more than 2% of prorenin present in plasma was detected as renin. The interassay CVs for renin quantification were 18%, 13%, and 8% at low, medium, and high concentrations, respectively. The interassay CV for calculated prorenin was 8% at both low and high concentrations. The IRMA results were highly correlated with those of an enzyme kinetic assay in healthy subjects; in patients with such conditions as primary hyperaldosteronism, renovascular hypertension, and low-, medium-, and high-renin essential hypertension; and in women undergoing gonadotropin stimulation.

Adult↗
PubMed1996

Renal artery stenosis towards the year 2000.

FUNCTIONAL DIAGNOSTIC TESTS FOR SELECTING PATIENTS FOR RENAL ARTERIOGRAPHY: The functional diagnostic tests now available to select patients for renal arteriography, such as captopril-renal scintigraphy and the captopril-peripheral vein renin test, have a high degree of diagnostic accuracy, 70% sensitivity at 90% specificity, but they are still not good enough to assess the large population of hypertensives for renal artery stenosis. The use of the angiotensin converting enzyme (ACE) inhibitor challenge and the introduction of a new pharmacon, technetium-labelled mercapto-triglycine, have not sufficiently increased the value of scintigraphy and further improvement in the near future seems unlikely. THE USE OF CLINICAL CRITERIA TO IDENTIFY HIGH-RISK PATIENTS: A more realistic approach to the diagnosis of renal artery stenosis is to seek simple and sensible clinical criteria to identify high-risk patients. The blood pressure response to 2 months of treatment with a standardized two-drug regimen is a suitable criterion. Interim analysis of an ongoing prospective multicentre study in the Netherlands indicates that the prevalence of renal artery stenosis is as high as 25% in patients who are resistant to the combination of 10 mg amlodipine + 50 mg atenolol, compared with 15% in patients resistant to the combination of 20 mg enalapril + 25 mg hydrochlorothiazide. When drug resistance is used as the selection criterion for arteriography, the total number of cases detected with intra-arterial digital subtraction angiography does not seem to differ according to which of these drug regimens is used. FUTURE POSSIBILITIES: The current enthusiasm for percutaneous transluminal renal angioplasty (PTRA) and stenting may be premature. With further improvement of non-invasive techniques to visualize the renal arteries, such as colour Doppler ultrasound with microparticle contrast enhancement or magnetic resonance angiography, it should become more attractive to follow patients with renal artery stenosis while they are being treated with drugs rather than automatically resorting to PTRA.

Angioplasty↗
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↗