Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Background

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

Methods

More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.

Conclusion

Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.     

Radiology services for remote communities: cost minimisation study of telemedicine.

OBJECTIVES--To determine the social costs of providing a rural population with radiology services under three different systems: the existing system (a small x ray unit at the remote site and all other examinations at the nearest radiology department (the host site)); a teleradiology system (most examinations at the remote site and more advanced examinations at the host site); and all examinations at the host site. DESIGN--Cost minimisation study. SETTING--Primary health care in a remote community in Norway. SUBJECTS--A randomly selected sample (n = 597) of all patients (n = 1793) having radiological examinations in 1993. MAIN OUTCOME MEASURES--Annual direct medical costs, direct non-medical (travel) costs, and indirect costs (lost production) of the three options. RESULTS--After exclusion of costs common to the three systems the direct medical, direct non-medical, and indirect costs of the three options were, respectively, 9000 pounds, 51,000 pounds, and 31,500 pounds (total 91,500 pounds) for the existing system; 108,000 pounds, 2,000 pounds, and 13,500 pounds (total 123,500 pounds) for the teleradiology option; and 0 pounds, 75,000 pounds, and 42,000 pounds (117,000 pounds in total) for the "all at host" option. Sensitivity analyses indicated that the existing system is the least costly option except when lost leisure is valued as highly as lost production. CONCLUSION--The teleradiology option did not seem to be cost saving in the study community. Such systems, however, may be justified on the grounds of equity of access and quality of care.     

Altruism, Altruistic Punishment and Social Investment

The concept of altruism is used in very different forms by computer scientists,economists, philosophers, social scientists, psychologists and biologists. Yet, in order to be useful in social simulations, the concept "altruism" requires a more precise meaning. A quantitative formulation is proposed here, based on the cost/benefit analysis of the altruist and of society at large. This formulation is applied in the analysis of the social dynamic working of behaviors that have been called "altruistic punishments", using the agent based computer model Sociodynamica. The simulations suggest that "altruistic punishment" on its own cannot maintain altruistic behaviors. "Altruistic behavior" is sustainable in the long term only if these behaviors trigger synergetic forces in society that eventually make them produce benefits to most individuals. The simulations suggest however that "altruistic punishment" may work as a "social investment", and is thus better called "decentralized social punishment". This behavior is very efficient in enforcing social norms. The efficiency of decentralized social punishment in enforcing norms was dependent on the type of labor structured of the virtual society. I conclude that what is called "altruistic punishment" emerges as a type of social investment that can evolve either through individual and/or group selection, as a successful device for changing or enforcing norms in a society. Social simulations will help us in better understanding the underlying dynamic working of such devices.     

Greenhouse tomato nutrition — A growth analysis study

Summary Chemical determination of the mineral content of a mature, healthy, high-yielding greenhouse tomato plant has shown that the total nutrient absorption is equivalent to 345 pounds per acre of nitrogen, 74 pounds per acre of phosphorus, 716 pounds per acre of potassium, 295 pounds per acre of calcium and 43 pounds per acre of magnesium. These figures form the basis for a more intelligent estimate of the fertilizer requirements of this crop than can be obtained from the more common empirical methods. The analysis of individual tissues of a whole plant harvested at mid-growth gives a clear picture of the distribution of nutrients throughout the plant.     

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE--To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN--Three year retrospective study. SETTING--Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS--60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES--Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS--All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION--Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.     

Costs and cost effectiveness of cardiovascular screening and intervention: the British family heart study.

OBJECTIVE--To measure costs and cost effectiveness of the British family heart study cardiovascular screening and intervention programme. DESIGN--Cost effectiveness analysis of randomised controlled trial. Clinical and resource use data taken from trial and unit cost data from external estimates. SETTING--13 general practices across Britain. SUBJECTS--4185 men aged 40-59 and their 2827 partners. INTERVENTION--Nurse led programme using a family centered approach, with follow up according to degree of risk. MAIN OUTCOME MEASURES--Cost of the programme it self; overall short term cost to NHS; cost per 1% reduction in coronary risk at one year. RESULTS--Estimated cost of putting the programme into practice for one year was 63 pounds per person (95% confidence interval 60 pounds to 65 pounds). The overall short term cost to the health service was 77 pounds per man (29 pounds to 124 pounds) but only 13 pounds per woman (-48 pounds to 74 pounds), owing to differences in utilisation of other health service resources. The cost per 1% reduction in risk was 5.08 pounds per man (5.92 pounds including broader health service costs) and 5.78 pounds per woman (1.28 pounds taking into account wider health service savings). CONCLUSIONS--The direct cost of the programme to a four partner practice of 7500 patients would be approximately 58,000 pounds. Annually, 8300 pounds would currently be paid to a practice of this size working to the maximum target on the health promotion bands, plus any additional reimbursement of practice staff salaries for which the practice qualified. The broader short term costs to the NHS may augment these costs for men but offset them considerably for women.     

Cost implications of the British Pacing and Electrophysiology Group's recommendations for pacing.

OBJECTIVE--To compare present pacing practice with the recommendations recently published by the British Pacing and Electrophysiology Group and to assess the increase in annual budget required to implement these recommendations in a regional cardiothoracic unit. DESIGN--Retrospective analysis of pacemaker implantation for 1991 with calculation of the costs required to implement the group''s recommendations based on average 1991 costs of the types of pacing generators and electrode leads used. SETTING--Regional cardiothoracic unit for South West Thames Health Authority. PATIENTS--433 consecutive patients receiving permanent pacemaker generators: 76 (18%) with sinus node disease; 270 (62%) with atrioventricular block; 25 (6%) with both sinus node disease and atrioventricular block; 59 (14%) with chronic atrial fibrillation and atrioventricular block; and 3 (1%) with carotid sinus or malignant vasovagal syndromes. RESULTS--Only 102 (24%) patients received pacemaker generators recommended by the British Pacing and Electrophysiology Group; however, 355 (82%) patients were older than 65 years, and 264 (61%) were aged 75 or over. The cost of hardware for pacing was 462,885 pounds. Using generators as recommended would have cost 810,525 pounds for "optimal" systems (an increase of 75%) and 710,750 pounds for "alternative" systems (an increase of 54%). These increases would have been considerably reduced by limiting the use of sophisticated pacing to younger patients (aged under 75). Further savings could be made by using the least expensive pacing models available. CONCLUSIONS--Implementing these recommendations should reduce morbidity related to bradyarrhythmia but will lead to major increases in pacing costs. Age and patients'' expected activity may be used to select simple pacing systems and thus to contain cost. More research is needed to determine which patient groups will benefit most from complex pacing systems.     

Cost effectiveness of day and inpatient psychiatric treatment: results of a randomised controlled trial.

OBJECTIVE: To compare direct and indirect costs of day and inpatient treatment of acute psychiatric illness. DESIGN: Randomised controlled trial with outcome and costs assessed over 12 months after the date of admission. SETTING: Teaching hospital in an inner city area. SUBJECTS: 179 patients with acute psychiatric illness referred for admission who were suitable for random allocation to day hospital or inpatient treatment. 77 (43%) patients had schizophrenia. INTERVENTIONS: Routine inpatient or day hospital treatment. MAIN OUTCOME MEASURES: Direct and indirect costs over 12 months, clinical symptoms, social functioning, and burden on relatives over the follow up period. RESULTS: Clinical and social outcomes were similar at 12 months, except that inpatients improved significantly faster than day patients and burden on relatives was significantly less in the day hospital group at one year. Median direct costs to the hospital were 1923 pounds (95% confidence interval 750 pounds to 3174 pounds) per patient less for day hospital treatment than inpatient treatment. Indirect costs were greater for day patients; when these were included, overall day hospital treatment was 2165 pounds cheaper than inpatient treatment (95% confidence interval of median difference 737 pounds to 3593 pounds). Including costs to informants when appropriate meant that day hospital treatment was 1994 pounds per patient cheaper (95% confidence interval 600 pounds to 3543 pounds). CONCLUSIONS: Day patient treatment is cheaper for the 30-40% of potential admissions that can be treated in this way. Carers of day hospital patients may bear additional costs. Carers of all patients with acute psychiatric illness are often themselves severely distressed at the time of admission, but day hospital treatment leads to less burden on carers in the long term.     

Should homosexuals be vaccinated against hepatitis B virus? Cost and benefit assessment.

The recent introduction of a vaccine against hepatitis B has raised the questions of who should be offered it and what the cost would be of a vaccination programme. An analysis was performed of the financial costs and benefits of such a programme designed to prevent acute hepatitis B in male homosexuals in the United Kingdom. Under various assumptions the total costs of screening and vaccination ranged from 2.2m pounds to 3m pounds for a five year programme and from 3.3m pounds to 4.8m pounds for a 10 year programme. The benefits over the same two periods for the programme, depending on two different assumptions of mortality prevented, ranged 3.9m pounds to 13.7m pounds and from 7m pounds to 24.4m pounds. Thus considerable savings may be made to the national economy by offering vaccination to homosexuals. These savings are obtained after consideration of only the acute aspects of hepatitis B. Had it been possible to determine the costs of the chronic sequelae of this disease the savings, compared with the costs, would have been greatly increased.     

Association of Versican Turnover with All-Cause Mortality in Patients on Haemodialysis

Objective

Cardiovascular diseases are among the most common causes of mortality in renal failure patients undergoing haemodialysis. A high turnover rate of the proteoglycan versican, represented by the increased presence of its fragmentation products in plasma, has previously been associated with cardiovascular diseases. The objective of the study was to investigate the association of versican turnover assessed in plasma with survival in haemodialysis patients.

Methods

A specific matrix metalloproteinase-generated neo-epitope fragment of versican (VCANM) was measured in plasma of 364 haemodialysis patients with a 5-years follow-up, using a robust competitive enzyme-linked immunosorbent assays. Association between VCANM plasma concentration and survival was assessed by Kaplan-Meier analysis and adjusted Cox model.

Results

Haemodialysis patients with plasma VCANM concentrations in the lowest quartile had increased risk of death (odds ratio, as compared to the highest quartile: 7.1, p<0.001), with a reduced survival of 152 days compared to 1295 days for patients with plasma VCANM in the highest quartile. Multivariate analysis showed that low VCANM (p<0.001) and older age (p<0.001) predicted death in haemodialysis patients.

Conclusions

Low concentrations of the versican fragment VCANM in plasma were associated with higher risk of death among haemodialysis patients. A possible protective role for the examined versican fragment is suggested.     

Cost effectiveness of incremental programmes for lowering serum cholesterol concentration: is individual intervention worth while?

OBJECTIVE--To evaluate the relative cost effectiveness of various cholesterol lowering programmes. DESIGN--Retrospective analysis. SETTING--Norwegian cholesterol lowering programme in Norwegian male population aged 40-49 (n = 200,000), whose interventions comprise a population based promotion of healthier eating habits, dietary treatment (subjects with serum cholesterol concentration 6.0-7.9 mmol/l), and dietary and drug treatment combined (serum cholesterol concentration greater than or equal to 8.0 mmol/l). MAIN OUTCOME MEASURE--Marginal cost effectiveness ratios--that is, the ratio of net treatment costs (cost of treatment minus savings in treatment costs for coronary heart disease) to life years gained and to quality of life years (QALYs) saved. RESULTS--The cost per life year gained over 20 years of a population based strategy was projected to be 12 pounds. For an individual strategy based on dietary treatment the cost was about 12,400 pounds per life year gained and 111,600 pounds if drugs were added for 50% of the subjects with serum cholesterol concentrations greater than or equal to 8.0 mmol/l. CONCLUSIONS--The results underline the importance of marginal cost effectiveness analyses for incremental programmes of health care. The calculations of QALYs, though speculative, indicate that individual intervention should be implemented cautiously and within more selected groups than currently recommended. Drugs should be reserved for subjects with genetic hypercholesterolaemia or who are otherwise at very high risk of arteriosclerotic disease.     

Body mass index: risk predictor for cosmetic day surgery

Body mass index (BMI; weight per unit surface area) is the scientific yardstick by which overweight is gauged relative to the population norm. The contrary association between obesity and diabetes or hypertension is only too well known. Less appreciated is the heightened sensitivity to respiratory depressants such as sedatives and analgesics in the obese (BMI >/= 30) and the increased incidence of sleep apnea in the morbidly obese (BMI >/= 35)-either or both of which raise the risk of cosmetic surgery when sedation or anesthesia is contemplated. Guided by the BMI, a gender-independent measure of fatness, the surgeon now can inform the patient of her or his relative operative risk and offer an objective rationale for advising overnight hospitalization rather than office-based day surgery.The BMI is readily calculated when height and weight are expressed in metric units, much less so when measured in foot-pound units. In fact, the calculations are sufficiently cumbersome that the BMI remains underused in U.S. office surgery. The author's complimentary "BMI Calculator"-an Excel workbook available on-line to society members-is designed so that office staff need enter only height (in feet and inches) and weight (in pounds) to print the BMI for the patient's permanent record.The BMI places patient weight relative to height in proper perspective for aesthetic surgery, whether with sedation or under general anesthesia. The BMI ought to be as routine a part of the preoperative assessment as blood pressure or hemoglobin content.     

Autogenous arteriovenous elbow fistula for haemodialysis and upper extremity ischemia

BACKGROUND: The autogenous brachiocephalic or brachiobasilic arteriovenous elbow fistula is not considered to be only the secondary haemodialysis access. In patients with an unsuitable forearm vessel bundle, it is indicated as primary access and it is the method preferred to the fistula creation using a vascular prosthesis. Its rather rare complication is the development of upper extremity ischemia. AIM: To summarise current knowledge of this fistula type and its associated complications METHODS: Review of the literature. RESULTS: The creation and maturation of the fistula and occurrence of the steal syndrome is influenced by a number of factors. The analysis and awareness of such factors will provide for creation of a suitable fistula as well as for timely complication diagnostics and treatment. CONCLUSIONS: The autogenous elbow fistula utilising the brachial artery and the cephalic or basilic vein in the upper extremity represents a high-quality haemodialysis access. Its potential complication is the occurrence of the steal syndrome. Its occurrence and manifestations do not constitute indications for ligation of the access. The gathered information shows that a suitable surgical procedure can help meet the basic rule for haemodialysis access--resolving the ischemia and maintaining the access.     

Urine cytology: appropriate usage maximizes sensitivity and reduces cost

OBJECTIVE: Urine cytology is costly because of the skilled manpower required for analysis. Inappropriate requests are a significant drain both financially and on the cytopathologist's time. The present study aimed at identifying the extent and cause of this misuse and reduce it. METHODS: An audit of urine cytology usage was undertaken using the hospital results reporting system to identify requests. Patient case notes were then obtained to gain further clinical information. Initially a 2-week period was analysed, following which departmental guidelines for requesting urine cytology were produced and circulated. The audit loop was then closed. RESULTS: Over the initial 2-week period, 117 urine cytology requests were received. Thirty-three per cent were inappropriate, either because they were from patients with benign disease or because of duplication. Following the education programme this number fell to 6%. Expenditure on unnecessary samples thus decreased from pounds 2418 to only pounds 310, giving an annual overall saving of pounds 55,000. CONCLUSION: Significant cost and time savings can be made if urine cytology is sent appropriately. Simple guidelines and staff education are the key to reducing inefficiency. Our findings have implications not just for cytopathology costs but for laboratory and radiology requests in general.     

What can be concluded from the Oxcheck and British family heart studies: commentary on cost effectiveness analyses.

OBJECTIVES--To provide a commentary on the economic evaluations of the Oxcheck and British family heart studies: direct comparison of their relative effectiveness and cost effectiveness; comparisons with other interventions; and consideration of problems encountered. DESIGN--Modelling from cost and effectiveness data to estimate of cost per life year gained. SUBJECTS--Middle aged men and women. INTERVENTIONS--Screening for cardiovascular risk factors followed by appropriate lifestyle advice and drug intervention in general practice, and other primary coronary risk management strategies. MAIN OUTCOME MEASURES--Life years gained; cost per life year gained. RESULTS--Depending on the assumed duration of risk reduction, the programme cost per discounted life year gained ranged from 34,800 pounds for a 1 year duration to 1500 pounds for 20 years for the British family heart study and from 29,300 pounds to 900 pounds for Oxcheck. These figures exclude broader net clinical and cost effects and longer term clinical and cost effects other than coronary mortality. CONCLUSIONS--Despite differences in underlying methods, the estimates in the two economic analyses of the studies can be directly compared. Neither study was large enough to provide precise estimates of the overall net cost. Modelling to cost per life year gained provides more readily interpretable measures. These estimates emphasise the importance of the relatively weak evidence on duration effect. Only if the effect lasts at least five years is the Oxcheck programme likely to be cost effective. The effect must last for about 10 years to justify the extra cost associated with the British family heart study.     

Malnutrition, menarche, and marriage in rural Bangladesh

In order to assess the impact of nutritional status on the onset of menarche and the association between age at menarche and age at marriage, a survey of 1155 girls, ages 10 through 20, was conducted in a rural area of Bangladesh in March 1976. In order to obtain an estimated mean of age of menarche, probit analysis was used. The mean age of menarche using this technique is estimated at 15.65 for Muslims and 15.91 for Hindus. It was learned that in recent years the age of menarche has increased in a rural area. This increase seems to be associated with malnutrition caused by the war, postwar inflation, floods and famines during the 1971-75 period. When age is controlled for, the prominent effect of weight on menstrual status is evident. 98% of the girls whose weights were 88 pounds or greater had reached menarche compared to only 1% of those weighing less than 66 pounds. Body weight appears to be 1 of the most important factors for the determination of onset of menarche. There exists a seasonality of onset of menarche with a peak in winter. Age of marriage among this rural population has increased and may be associated with the increasing age of menarche. Since both age of menarche and age of marriage have increased, fertility among females age 15-19 may be expected to decrease in the future if this pattern continues.     

Production of the 57 kDa major surface antigen by a non-agglutinating strain of the fish pathogen Renibacterium salmoninarum

Both the prevalence and tissue titer of viral hemorrhagic septicemia virus (VHSV) increased in Pacific herring Clupea pallasi following their introduction into net pens (pounds) used in the closed pound spawn-on-kelp (SOK) fishery in Prince William Sound, Alaska. VHSV was also found in water samples from inside and outside the SOK pounds after herring had been confined for several days; however, water samples taken near wild free-ranging, spawning herring either failed to test positive or tested weakly positive for virus. Little or no virus was found in tissue samples from free-ranging, spawning herring captured from the vicinity of the pounds, nor did the prevalence of VHSV increase following spawning as it did in impounded herring. The data indicated that increased prevalences of VHSV were correlated with confinement of herring for the closed pound SOK fishery and that infection was spread within the pounds through waterborne exposure to virus particles originating from impounded fish. In addition, pounds containing predominantly young fish had higher prevalences of VHSV, suggesting that older fish may be partially immune, perhaps as a result of previous infection with the virus. Operation of SOK pounds during spawning seasons in which young herring predominate may amplify the disease and possibly exacerbate the population fluctuations observed in wild herring stocks.     

Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population.

OBJECTIVES--To estimate the cost effectiveness of statins in lowering serum cholesterol concentration in people at varying risk of fatal cardiovascular disease and to explore the implications of changing the criteria for intervention on cost and cost effectiveness for a purchasing authority. DESIGN--A life table method was used to model the effect of treatment with a statin on survival over 10 years in men and women aged 45-64. The costs of intervention were estimated from the direct costs of treatment, offset by savings associated with a reduction in coronary angiographies, non-fatal myocardial infarctions, and revascularisation procedures. The robustness of the model to various assumptions was tested in a sensitivity analysis. SETTING--Population of a typical district health authority. MAIN OUTCOME MEASURE--Cost per life year saved. RESULTS--The average cost effectiveness of treating men aged 45-64 with no history of coronary heart disease and a cholesterol concentration > 6.5 mmol/l for 10 years with a statin was 136,000 pounds per life year saved. The average cost effectiveness for patients with pre-existing coronary heart disease and a cholesterol concentration > 5.4 mmol/l was 32,000 pounds. These averages hide enormous differences in cost effectiveness between groups at different risk, ranging from 6000 pounds per life year in men aged 55-64 who have had a myocardial infarction and whose cholesterol concentration is above 7.2 mmol/l to 361,000 pounds per life year saved in women aged 45-54 with angina and a cholesterol concentration of 5.5-6.0 mmol/l. CONCLUSIONS--Lowering serum cholesterol concentration in patients with and without preexisting coronary heart disease is effective and safe, but treatment for all those in whom treatment is likely to be effective is not sustainable within current NHS resources. Data on cost effectiveness data should be taken into account when assessing who should be eligible for treatment.     

Prediction of resources needed to achieve the national target for treatment of renal failure.

A model of the treatment of end stage renal failure has been primed with observed survival statistics and used to predict the steady state that will be achieved when the present annual target of at least 40 new patients per million population is in equilibrium with the death rate. The number of patients expected to receive each type of dialysis or a transplant is given per million of population. The personnel and facilities required to care for these patients and the costs of each programme were derived using analyses of workloads and costs in the North Western Regional Health Authority. The study has documented the considerable need for "back up" beds for patients on dialysis who require temporary care as inpatients. The cost effectiveness of transplantation has been demonstrated; at steady state it is calculated that each successful graft saves the service pounds 30,000. Implementation of the minister''s minimum target requires a build up to some three times the resources currently allocated, with parallel increases in numbers of medical, nursing, and other essential staff.     

Effects of an angiotensin-converting enzyme inhibitor (captopril) on blood pressure in anephric subjects.

Randomised, double-blind cross-over trials were performed in seven anephric patients to determine the effect of the orally active angiotensin-converting enzyme inhibitor captopril on blood pressure in fluid-depleted and fluid-replete patients. Patients were given captopril, 100 mg orally, or placebo one hour after haemodialysis, when they were fluid depleted. Their mean (+/- SEM) supine blood pressure fell from 127 +/- 12/71 +/- 6 mm Hg before captopril to 106 +/- 13/54 +/- 4 mm Hg 24 hours after the drug, while on placebo it rose from 123 +/- 11/73 +/- 5 mm Hg to 134 +/- 10/82 +/- 8 mm Hg. All patients developed orthostatic hypotension after captopril. In the fluid-replete state, two days after haemodialysis, captopril had no effect on blood pressure. The plasma concentration of active renin was extremely low and did not rise after fluid withdrawal or captopril. Thus the hypotensive effect of captopril did not appear to depend on circulating renin concentrations. The concept of "renin-dependent" hypertension, which is responsive to captopril, as opposed to "volume-dependent" hypertension, which is not responsive to captopril, may therefore be invalid.