The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone.

The risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk. INTRODUCTION: Vertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture. METHODS: In 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture. RESULTS: Mean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13-55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders. CONCLUSIONS: The prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO): rationale and design.

BACKGROUND: More than 6200 End Stage Renal Disease patients in the Netherlands are dependent on dialysis, either performed at home or in a dialysis centre. Visiting a dialysis centre three times a week is considered a large burden by many patients. However, recent data regarding the effects of dialysis at home on quality of life, clinical outcomes, and costs compared with in-centre haemodialysis are lacking. METHODS: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO) is a nationwide, prospective, observational cohort study that will include adult patients starting with a form of dialysis. Health-related quality of life, as the primary outcome, clinical outcomes and costs, as secondary outcomes, will be measured every 3-6 months in patients on home dialysis, and compared with a control group consisting of in-centre haemodialysis patients. During a 3-year period 800 home dialysis patients (600 peritoneal dialysis and 200 home haemodialysis patients) and a comparison group of 800 in-centre haemodialysis patients will be included from 53 Dutch dialysis centres (covering 96% of Dutch centres) and 1 Belgian dialysis centre (covering 4% of Flemish centres). DISCUSSION: DOMESTICO will prospectively investigate the effect of home dialysis therapies on health-related quality of life, clinical outcomes and costs, in comparison with in-centre haemodialysis. The findings of this study are expected to ameliorate the shared decision-making process and give more guidance to healthcare professionals, in particular to assess which type of patients may benefit most from home dialysis. TRIAL REGISTRATION: The DOMESTICO study is registered with the National Trial Register on (number: NL6519 , date of registration: 22 August 2017) and the Central Committee on Research Involving Human Subjects (CCMO) (number: NL63277.029.17).

Exploring experiences and health-related quality of life of caregivers of patients who start home dialysis: study protocol for a prospective, multicentre cohort study.

INTRODUCTION: Starting dialysis not only has a major impact on the life of patients but also on their informal caregivers. Previous research shows greater burden and lower quality of life among caregivers of dialysis patients compared with the general population. Unfortunately, the evidence on the course of both positive and negative experience in caregivers of incident dialysis patients is scarce. Furthermore, well-designed, prospective, multicentre studies comparing caregiving of home dialysis patients with in-centre dialysis patients are lacking. This paper proposes a protocol to assess the trajectory of experiences (both positive and negative) and quality of life of caregivers of home dialysis patients compared with caregivers of in-centre dialysis patients. METHODS AND ANALYSIS: This paper presents a protocol for a prospective, observational, multicentre cohort study which extends the ongoing Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). This study will include at least 200 adult caregivers of patients who start dialysis therapy and have been included in the DOMESTICO study. Positive experiences of the caregivers will be the primary outcome parameter of this study, and negative experiences and health-related quality of life the secondary outcome parameters. Required support will be investigated as an exploratory finding. Outcome parameters will be assessed at baseline, and at 6 and 12 months after start of dialysis using validated questionnaires. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the Medical Research Ethics Committee of the Amsterdam University Medical Centre. The results of this study will be disseminated by publication in a peer-reviewed journal and through presentations at conferences and seminars.

Home haemodialysis in the Netherlands: State of the art.

Home haemodialysis (HHD) has gained popularity in recent years, due to improved clinical outcomes associated with frequent or prolonged haemodialysis sessions, best achievable at home. However, several barriers to HHD are perceived by the physician and patient, among which lack of experience and education, logistic difficulties and reimbursement issues seem to be the most important ones. HHD, in particular when performed with intensified frequency or duration, is associated with improved quality of life, blood pressure control and survival. Serious adverse events are rare; however, more vascular access complications arise due to frequent needling. This emphasises the importance of comprehensive education and training. This review aims to provide the physician with a detailed state of the art overview on HHD in the Netherlands, discussing potential barriers and benefits, and offering practical advice.

The truth on current peritoneal dialysis: state of the art.

The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has decreased markedly in the Netherlands in the last 15 years. Consequently, the knowledge of nephrologists and nursing staff on PD has declined leading to a negative spiral in which loss of experience resulted in loss of enthusiasm to offer PD to patients and also in less interest in the new PD developments. All these changes took place while the results of PD improved and patient survival was at least similar to that on haemodialysis. The aim of this review is first to give a summary of the principles and practice of patient and staff education and to describe the role of the medical contribution in decision-making. On this basis, the second aim is to update internist-nephrologists on a number of issues that have been underexposed in the past. Recent patient and technique survival data of PD patients is reviewed, and also the new insights into dialysis adequacy. The presence of residual renal function is the main determinant of patient survival together with prevention of overhydration. Urea and creatinine removal are not important at all when patients are still passing urine. Many early problems with PD are due to the peritoneal catheter and suggestions are made for improvement of its function. The prevention and management of infections is reviewed, and also the regular assessment of peritoneal function. Free water transport is a predictor of encapsulating peritoneal sclerosis (EPS), which should be assessed regularly. The pathogenesis of EPS, treatment and the decreasing incidence are discussed.

The effect of treatment on health-related quality of life in patients with hypertension and renal artery stenosis.

The quality of life in patients with hypertension is considered to be impaired mainly by side effects of antihypertensive drug therapy. Since balloon angioplasty for renal artery stenosis has a medication-sparing effect, it may lead to an improvement in quality of life. The objective of the study is to compare the effect of antihypertensive drug therapy and balloon angioplasty on quality of life in patients with hypertension and renal artery stenosis. We compared the quality of life in 56 patients randomised to balloon angioplasty to that in 50 patients randomised to antihypertensive drug therapy after 3 and 12 months of follow-up. Quality of life was measured using a questionnaire on physical symptoms associated with hypertension and antihypertensive drugs, and two generic health questionnaires (MOS Survey and EuroQol instrument). After follow-up, the patients who underwent angioplasty used less antihypertensive drugs than the patients who were treated with antihypertensive drugs only (mean+/-s.d., 1.9+/-0.9 vs 2.5+/-1.0 drugs after 3 months, P=0.002). They reported similar physical complaints, however, and a similar quality of life. The results after 12 months of follow-up were the same. In conclusion, for patients with hypertension and renal artery stenosis, the decrease in antihypertensive medication after intervention is too small to lead to a detectable improvement in quality of life.

Long-term blood pressure monitoring and echocardiographic findings in patients with end-stage renal disease: reverse epidemiology explained?

BACKGROUND: In patients with end-stage renal disease (ESRD) hypertension is common and often leads to left ventricular (LV) hypertrophy and diastolic dysfunction, but hypotension at the onset of dialysis is associated with increased mortality. We studied blood pressure data over longer periods of time in patients on haemodialysis and related them to echocardiographic outcome, in order to elucidate these contradictory findings. METHODS: In 50 haemodialysis patients mean arterial pressure (MAP) and pulse pressure (PP) were calculated in the first three months of haemodialysis, the complete period from the start of haemodialysis until echocardiography and the last three months of haemodialysis before echocardiography. Hypertension load, pulse pressure and interdialytic weight gain were quantified and related to echocardiography. RESULTS: LV mass index was associated with MAP in all three periods, and also with the hypertension load, PP and PP load. In patients with LV dilatation, MAP and PP averaged over the complete period of dialysis were 5 to 7 mmHg higher than in patients without LV dilatation. Blood pressure parameters were the same in patients with or without LV diastolic dysfunction or systolic dysfunction. Systolic dysfunction was more frequent in patients undergoing long-term haemodialysis treatment. Interdialytic weight gain was not associated with any of the echocardiographic variables. CONCLUSION: When long-term blood pressure values are considered, hypertension is associated with parameters of early cardiac damage such as increased LV mass index and not with parameters of advanced heart failure such as systolic dysfunction. This supports the hypothesis that the presence of advanced heart failure reciprocally influences blood pressure in a negative way, thereby explaining the 'reverse epidemiology' of blood pressure and mortality in ESRD.

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.

Anticoagulation with dalteparin and nadroparin in nocturnal haemodialysis.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are increasingly used as anticoagulant during haemodialysis. The aim of this study is to establish the efficiency and duration of anticoagulation with dalteparin and nadroparin administration in patients treated with nocturnal haemodialysis. METHODS: All patients were treated with nocturnal in-centre haemodialysis, 3-4 times a week. Anticoagulation was obtained with dalteparin (n = 15) or nadroparin (n = 10). Anti-factor- Xa activity was measured during a midweek dialysis session at t = 0, 4 and 8 hours. RESULTS: The LMWH dose necessary to prevent extracorporeal circuit clotting was higher for dalteparin than for nadroparin. In the dalteparin group, anti-Xa activity was almost negligible at the start of dialysis whereas most patients on nadroparin still had anti-Xa activity at the start of dialysis (0.08 (IQR 0.05-0.11) IU÷ml), reflecting the effect of previous LMWH administration. After eight hours of dialysis, median anti-factor-Xa activity was 0.49 (IQR 0.22-0.57) after dalteparin and 0.69 (IQR 0.55- .83) after nadroparin (p = 0.01). When a target range of 0.2-0.6 IU÷ml was applied, the present dosing method led to over-anticoagulation in more than half of the patients. CONCLUSION: Administration of two doses of LMWH is an effective method of anticoagulation in nocturnal, eight-hour haemodialysis. With two doses of dalteparin, a larger proportion of patients reached but did not exceed target levels of anticoagulation, compared with two doses of nadroparin. Nadroparin caused prolonged anti-Xa activity with measurable anticoagulation up to the next dialysis session. The measurement of anti-Xa activity is advocated for dose assessment of LMWH, when LMWH is used as anticoagulant during nocturnal haemodialysis.

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.

In-vitro validation, with histology, of intravascular ultrasound in renal arteries.

OBJECTIVE: To investigate the feasibility of using intravascular ultrasound to characterize normal and diseased renal arteries. MATERIALS AND METHODS: Forty-four renal artery specimens from 21 humans, removed at autopsy, were studied with intravascular ultrasound in vitro. From each vascular specimen, two to four sets of corresponding intravascular ultrasound images and histologic sections were subjected to qualitative analysis. The renal arterial wall was considered normal by intravascular ultrasound when the wall thickness (intima and media) was 0.5 mm or less. On intravascular ultrasound imaging, a distinction was made between bright lesions with or without peripheral shadowing (i.e. calcification). Histological sections were examined and fibromuscular lesions were scored with or without calcifications. Quantitative analysis of a multitude of intravascular ultrasound cross-sections (interval 5 mm) included assessment of the lumen area, vessel area, plaque area and percentage area obstructed. The target site (smallest lumen area) was compared with a reference site (largest lumen area before the first major side branch). RESULTS: Of the 130 corresponding intravascular ultrasound images and histologic sections analysed, 55 were normal and 75 presented a bright lesion on ultrasound; in 31 lesions, peripheral shadowing was involved. The sensitivity of the intravascular ultrasound in detecting calcifications was 87%, and the specificity was 89%. Lumen area reduction at the target site was associated with vessel and plaque area enlargement in eight specimens, with plaque area enlargement in 12 specimens and with a vessel area reduction in 21 specimens. CONCLUSIONS: Intravascular ultrasound is a reliable technique for distinguishing renal arteries with or without a lesion. Both plaque development and local vessel narrowing may result in renal artery stenosis.

Inter-observer variability in the angiographic assessment of renal artery stenosis. DRASTIC study group. Dutch Renal Artery Stenosis Intervention Cooperative.

OBJECTIVE: To assess inter-observer agreement in the interpretation of renal angiograms. DESIGN: Comparison of the assessment of renal angiograms by three experienced radiologists, who evaluated the number of renal arteries and the presence, location, aspect and severity of a renal artery stenosis. SETTING: General hospital and university hospital serving urban and rural populations. PATIENTS: Patients with difficult-to-treat hypertension referred for diagnostic work-up; 312 angiograms with the intra-arterial digital subtraction technique were obtained from 289 consecutive patients. MAIN OUTCOME MEASURES: Inter-observer agreement was tested for the following parameters: number of arteries per kidney, presence of stenosis, location of stenosis (truncal, ostial), aspect of stenosis (concentric, eccentric, post-stenotic dilatation), severity of stenosis (reduction of lumen diameter in categories of 30%, 40%, etc. to 100%), and overall quality of the angiographic images. Kappa (kappa) values and weighted kappa between the three pairs of radiologists were used as estimates of inter-observer agreement RESULTS: Agreement about the number of renal arteries was reasonable (kappa = 0.50-0.72), as was agreement about the presence of stenosis (kappa = 0.68-0.86). Agreement about stenosis location and aspect was poor (kappa = 0.26-0.47 and kappa = 0.15-0.26, respectively). There was general agreement about the severity of stenosis (weighted kappa = 0.65-0.70), but it was not possible to distinguish between 50 and 60% stenosis or between 60 and 70% stenosis (kappa < 0.40). No correlation was found between agreement on severity of stenosis and the quality of the images. CONCLUSIONS: It is not realistic to make statements about what degree of renal artery stenosis is clinically significant, as long as the intra-arterial angiogram with digital subtraction remains the gold standard. It is likewise risky to rely too strongly on stenosis morphology as visualized by renal angiography in choosing between balloon angioplasty and stent deployment.

Prospective studies of diagnosis and intervention: the Dutch experience.

This prospective multicenter study included 1,205 patients, who were referred for difficult-to-treat hypertension or analysis of possible secondary hypertension. After a standardized selection protocol based on sharply defined drug-resistant hypertension or renal function impairment during angiotensin-converting enzyme inhibition, patients underwent renal scintigraphy and a captopril-renin challenge test. A set of clinical characteristics was also recorded. Sensitivity and specificity of renal scintigraphy for diagnosing renal artery stenosis were 0.72 and 0.90 and of the captopril-renin test 0.77 to 0.91 and 0.69 to 0.75 depending on the criterion used. The clinical characteristics were used to construct a clinical prediction rule for renal artery stenosis, which had a sensitivity of 0.68 and a specificity of 0.87 at a cut-off level of 30% predicted probability. However, with the prediction rule a sensitivity of 0.90 could be reached by performing arteriography only in patients with a predicted probability of stenosis of > or =10%, resulting in a considerable reduction of the number of arteriograms to be made. A diagnostic strategy is advocated starting with drug-resistant hypertension and continuing to renal arteriography only in patients with increased probability of stenosis. Patients with atherosclerotic renal artery stenosis were then randomized to balloon angioplasty (n = 56) versus antihypertensive medication (n = 50). Three months after randomization 22 patients from the medication group underwent balloon angioplasty in second instance. In an intention-to-treat analysis, no difference in blood pressure was found between the groups after 3 months, nor after 12 months of follow-up, although there was a small medication-sparing effect of balloon angioplasty. The lack of a beneficial effect of balloon angioplasty compared with medication could not be attributed to the high stenosis recurrence rate after angioplasty, nor to the fact that the inclusion criterion was set at a stenosis level of > or =50% so that patients with relatively mild stenosis were also included. Renal function after angioplasty was slightly better in the angioplasty group than in the medication group, and improvement of the renal scintigram occurred more often after angioplasty. Apart from the treatment of patients with specific characteristics, the presented therapeutic approach starts with extending the antihypertensive drug therapy to control blood pressure. Only if blood pressure cannot be controlled or if renal function deteriorates, balloon angioplasty (with stent placement) is indicated.

Which patients with hypertension and atherosclerotic renal artery stenosis benefit from immediate intervention?

The objective was to identify subgroups of patients with hypertension and atherosclerotic renal artery stenosis who may benefit from immediate intervention. In the DRASTIC study, patients with hypertension, significant atherosclerotic renal artery stenosis, and a normal or mildly impaired renal function were randomized between immediate balloon angioplasty (PTRA; n=56) and drug therapy followed by angioplasty after 3 months, if needed (Med-PTRA; n=50). In this secondary analysis of the data, changes in the renal function and blood pressure after 1 year were studied by analysis of covariance in the following subgroups: patients with positive captopril-renin challenge test, abnormal captopril renogram, recently developed hypertension, bilateral stenosis, and severe stenosis. We found a benefit of immediate angioplasty only for patients with bilateral stenosis. Their creatinine clearance had decreased (mean+/-s.d.: -4.2+/-13.5 ml/min) in the Med-PTRA group, whereas it had improved substantially (+10.0+/-15.7 ml/min) in the PTRA group (P=0.02). For patients with unilateral stenosis, the change in creatinine clearance did not differ between PTRA and Med-PTRA (+4.3+/-15.5 and +1.3+/-12.5 ml/min, respectively). The patients with bilateral stenosis also seemed to benefit most from immediate intervention with regard to blood pressure control. None of the other subgroups had a clear benefit of immediate intervention regarding renal function or blood pressure control. In conclusion, intervention should not be postponed in patients with bilateral stenosis, even if renal function is normal. Other hypertensive patients with atherosclerotic renal artery disease could initially well be treated by aggressive multidrug therapy alone unless hypertension persists or renal function deteriorates.

Resistance to antihypertensive medication as predictor of renal artery stenosis: comparison of two drug regimens.

BACKGROUND: Renal artery stenosis is among the most common curable causes of hypertension. The definitive diagnosis is made by renal angiography, an invasive and costly procedure. The prevalence of renal artery stenosis is less than 1% in non-selected hypertensive patients but is higher when hypertension is resistant to drugs. OBJECTIVE: To study the usefulness of standardised two-drug regimens for identifying drug-resistant hypertension as a predictor of renal artery stenosis. DESIGN AND SETTING: Prospective cohort study carried out in 26 hospitals in The Netherlands. PATIENTS: Patients had been referred for analysis of possible secondary hypertension or because hypertension was difficult to treat. Patients < or =40 years of age were assigned to either amlodipine 10 mg or enalapril 20 mg, and patients >40 years to either amlodipine 10 mg combined with atenolol 50 mg or to enalapril 20 mg combined with hydrochlorothiazide 25 mg. Renal angiography was performed: (1) if hypertension was drug-resistant, ie if diastolic pressure remained > or =95 mm Hg at three visits 1-3 weeks apart or an extra drug was required, and/or (2) if serum creatinine rose by > or =20 micromol/L (> or =0.23 mg/dL) during ACE inhibitor treatment. RESULTS: Of the 1106 patients with complete follow-up, 1022 had been assigned to either the amlodipine- or enalapril-based regimens, 772 by randomisation. Drug-resistant hypertension, as defined above, was identified in 41% of the patients, and 20% of these had renal artery stenosis. Renal function impairment was observed in 8% of the patients on ACE inhibitor, and this was associated with a 46% prevalence of renal artery stenosis. In the randomised patients, the prevalence of renal artery stenosis did not differ between the amlodipine- and enalapril-based regimens. CONCLUSIONS: In the diagnostic work-up for renovascular hypertension the use of standardised medication regimens of maximally two drugs, to identify patients with drug-resistant hypertension, is a rational first step to increase the a priori chance of renal artery stenosis. Amlodipine- or enalapril-based regimens are equally effective for this purpose.

An improved method for the determination of islet amyloid polypeptide levels in plasma.

We describe an improved method for the determination of islet amyloid polypeptide (IAPP) levels in plasma. Plasma is first extracted with acid-acetone, followed by a specific and sensitive radioimmunoassay (RIA) for IAPP using rabbit-anti-human-IAPP serum. Recovery of synthetic IAPP from plasma was 82 +/- 6% (n = 16). Standard samples, prepared in 'hormone-free' serum, were also extracted with acid-acetone. Displacement curves of serially diluted acid-acetone extracted plasma samples were parallel to the standard curve. The lower detection limit of the RIA was 2.3 +/- 0.1 fmol/sample (n = 5). Intra-assay variations for IAPP concentrations of 4, 17 and 32 pM were 16.3% (n = 10), 9.2% (n = 10) and 6.2% (n = 10); interassay variations were 35.9% (n = 14), 19.9% (n = 15) and 15.4% (n = 15), respectively. Non-stimulated IAPP levels ranged from 2.4 to 12 pM (mean 6 +/- 4 pM, n = 10) in healthy control subjects. IAPP was not detectable in type 1 (insulin-dependent) diabetic patients before and after glucagon administration. In type 2 (non-insulin-dependent) diabetic patients basal levels ranged from 2.2 to 14.5 pM and glucagon-stimulated levels ranged from 2.2 to 38.9 pM. The increase in IAPP varied from 0 to 24.4 pM. The anti-human-IAPP serum had full cross-reactivity with rat IAPP (= mouse IAPP). Transgenic mice overexpressing the human IAPP gene showed elevated plasma IAPP levels as compared to (non-transgenic) control mice. It is concluded that the method presented for the determination of IAPP in plasma is reliable and easy to perform, yielding reproducible results.(ABSTRACT TRUNCATED AT 250 WORDS)

Reproducibility and validity of quality of life measurements in hypertensive patients on stable medication.

OBJECTIVE: The reproducibility and validity of a hypertension-specific questionnaire and a genetic health questionnaire (the MOS Short-form General Health Survey) were evaluated for measuring the quality of life in a randomized controlled trial comparing balloon angioplasty and long-term medication in patients with renovascular hypertension. METHODS: The health questionnaires were filled out by 97 patients with hypertension on stable medication. The reproducibility of the questionnaires was assessed by intraclass correlation coefficients (ICCs). Pearson's correlation coefficients were calculated between the scales of the questionnaires to evaluate the validity. RESULTS: Medication had been changed to eliminate side-effects in an earlier phase of treatment. Only 7% of the patients reported non-compliance with the medication regime. Most patients suffered from physical symptoms, but the impact of long-term antihypertensive medication on the quality of life was not substantial. The reproducibility was good for most scales (ICC > 0.70), except for the role and social functioning scales. All correlations between the scales of the questionnaires were statistically significant and no contradictory correlations were found. CONCLUSIONS: The health questionnaires together form a reproducible and valid instrument for measuring the quality of life of hypertensive patients on stable medication.

[Fulminant sepsis caused by Streptococcus suis]. / Fulminante sepsis door Streptococcus suis.

A 26-year-old man, in daily contact with pigs was admitted to hospital with septic shock which appeared to be caused by Streptococcus suis type 2 infection. Despite immediate antibiotic therapy a multiple organ failure developed, with ARDS, cardiac failure, disseminated intravascular coagulation and acute renal failure. Streptococcus suis infection is a zoonosis. The bacterium can be isolated from the tonsils of a significant part of the Dutch pig population. Mainly people who are in close contact with pigs or pork become infected. Usually meningitis develops. Sepsis, as this case, is rare and often fatal.

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.

Quantifying exposure to calcium and phosphate in ESRD; predictive of atherosclerosis on top of arteriosclerosis?

BACKGROUND: Long-term exposure to hypercalcaemia and hyperphosphataemia leads to media calcification and predicts mortality in patients with end-stage renal disease (ESRD). It is debatable whether this exposure is only a risk factor for arteriosclerosis, or also for superimposed atherosclerosis. Calcium-phosphate exposure is difficult to quantify, because it is variable in time and exerts its deleterious effects only after prolonged presence. METHODS: In 90 dialysis patients, calcium and phosphate values from the complete dialysis period were collected. From three-month averages, measures for calcium-phosphate exposure were derived after exclusion of transplant periods. Calcium-phosphate exposure was then related to intima-media thickness (IMT) and to ankle-brachial index (ABI) as markers of early atherosclerosis. RESULTS: Calcium-phosphate exposure was quantified in three ways using 1670 patient-quarters (i.e. three-months periods) covering 93% of the time on dialysis: averaged calcium-phosphate exposure, percentage of time with above-reference values, and burden of hypercalcaemia/hyperphosphataemia represented by this percentage multiplied by months on dialysis. No association was found with IMT. Patients with increased, not decreased, ABI had higher calcium-phosphate exposure throughout dialysis treatment: hyperphosphataemia burden was 31 (19 to 43) months for patients with ABI between 0.90 and 1.40 and 79 (58 to 100) months for patients with ABI >1.40 or incompressible ankle arteries (p<0.001). CONCLUSION: These findings do not support the hypothesis that calcium-phosphate exposure leads to atherosclerotic changes on top of arteriosclerosis in ESRD, and confirm its role in causing arteriosclerotic damage leading to increased arterial stiffness and incompressible ankle arteries. The used tool for quantifying calcium-phosphate exposure is easy to apply and can properly weigh the complete exposure during ESRD.