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Management of hypertension in patients developing end-stage renal failure

I. Dasgupta, R.J. Madeley, M.A.L. Pringle, J. Savill, R.P. Burden
DOI: http://dx.doi.org/10.1093/qjmed/92.9.519 519-525 First published online: 1 September 1999

Abstract

The benefits of treating hypertension include preventing or delaying the progression of chronic renal failure, and reducing the cardiovascular complications of patients with renal disease. We examined how well hypertension had been managed in all 145 patients from a single health district who started dialysis during a 3-year period. Data relating to management of hypertension, including all blood pressure readings, were obtained from their general practice and hospital case notes. The anonymized data were reviewed by two independent assessors against a set of standards based on the British Hypertension Society guidelines. There was close agreement between the assessors. Complete records were obtained in 98.5% of cases. Of the 145 patients, 107 (76.4%) were hypertensive before developing end-stage renal failure. There were departures from standards in all categories of care: 24.3% in detection/diagnosis, 29% in investigation, 22.4% in referring to a nephrologist, and 17% in follow-up. The British Hypertension Society recommended standard for diastolic blood pressure of 90 mmHg was achieved in only 45%. In 32%, the assessors independently concluded that poor blood pressure control might have affected adversely the progression of renal failure. New methods of dealing with these problems are required and possible approaches are discussed.

Introduction

In England and Wales, more than 24 500 patients are on dialysis or have working renal transplants, costing at least £300m a year; both figures are expected to almost double in the next 10–15 years.1 Of the various treatments applied to patients with chronic renal failure, control of hypertension is of major importance—aiming to minimize progressive deterioration of renal function and to reduce the high risk of cardiovascular complications associated with renal failure.2–,8 Given the high financial and human cost of renal replacement therapy, and the importance attached to hypertension in chronic renal failure, how well is hypertension actually managed in patients developing end-stage renal failure? Studies of hypertension in the community and in stroke patients have demonstrated significant shortcomings in detection, investigation, treatment, control and follow-up,9–,16 and a cross-sectional study17 of patients attending a renal clinic has demonstrated the difficulties in achieving recommended blood pressures, but to our knowledge there are no longitudinal studies of a cohort of patients who subsequently developed end-stage renal failure.

To assess the quality of hypertension management in patients who developed end-stage renal failure, we adapted the methods described by Payne et al. in their confidential enquiry into avoidable factors in deaths from stroke and hypertension.11 Accordingly, we examined all the previous records of all patients residing in a single health district who started dialysis during a 3-year period, comparing actual management against accepted standards of care for hypertension, and identifying areas in which improvements are needed.

Methods

Patients

All 145 adults who started dialysis at Nottingham City Hospital between 1 November 1994 and 31 October 1997 and who were residents of Nottingham Health District (population 650 000) were included.

Data collection

Details of all aspects of care relating to hypertension, including the detection, diagnosis, investigation, treatment, follow-up, and referral to a nephrologist, were taken from the hospital and general practice case notes, and recorded on a questionnaire which had been tested in a pilot study. All blood pressure measurements to the day of starting dialysis were included. Practices were visited by one investigator (ID) following an explanatory letter and receipt of agreement. The notes of deceased patients were requested from the Family Health Services Authority. To maintain confidentiality, no record was kept of the names of patients or doctors.

Standards of care

The standards of care were based on the 1993 British Hypertension Society (BHS) guidelines18 and are shown in Table 1.

View this table:
Table 1

Standards of care

Detection and diagnosis
1. Blood pressure above 160/90 mmHg should be taken as abnormal and followed-up.
2. Blood pressure should be checked 2–4 times over a short period before a diagnosis of hypertension is made.
Investigations
1. Urine analysis and serum urea and electrolyte measurements are essential investigations for all hypertensive individuals.
Treatment
1. All patients with renal impairment and diastolic blood pressure over 90 mmHg should receive anti-hypertensive treatment.
2. The optimum period of observation i.e. time between detection of hypertension and starting treatment is 3–6 months, unless diastolic blood pressure is ≥110 mmHg or there is evidence of target organ damage, in which case drug treatment should be started sooner.
Follow-up
1. After blood pressure stabilizes with drug treatment 3- to 6-monthly follow-up is adequate. However, before stabilization with drug treatment, blood pressure should be checked more frequently, depending on the severity of hypertension.
2. If a hypertensive individual defaults from follow-up, efforts should be made to recall them.
Referral
All patients with hypertension and abnormal urine analysis and/or raised serum creatinine must be referred for specialist advice.
Level of blood pressure control
Diastolic blood pressure should be maintained below 90 mmHg and systolic blood pressure below 160 mmHg.

Ethical approval

The study was approved by the Nottingham City Hospital Ethics Committee and by the Local Medical Committee.

Assessment

For each patient, the information relating to each standard was entered onto a set of forms—including all blood pressure readings and plasma creatinines, as both tables and graphs, together with relevant clinical information. The forms were presented to two assessors, MP (Professor of General Practice) and JS (Professor of Medicine with an interest in Nephrology), neither of whom had been involved in the care of any of the patients. The assessors were asked to note all the relevant clinical circumstances, including the patient's age, initial blood pressure and whether and when it was repeated, the results of any tests that were available at the time, the state of knowledge at the time, the need to follow up particularly high readings, any adverse effects of antihypertensive drugs recorded on the forms, the presence or absence of diabetes, and the serial creatinine values. They were then asked to use all this information in assessing whether there were any departures from the standards of care for the detection/diagnosis, investigation, follow-up and specialist referral. They were also asked to categorize the quality of blood pressure control in each patient as excellent, good, fair or poor. Finally, they were asked to inspect the serial blood creatinine and blood pressure readings for each patient and identify any patients in whom, in their opinion, poor blood pressure control may have affected the course of the chronic renal failure adversely. In addition to the assessors' evaluations, the mean of all blood pressure readings was calculated for each patient from the start of antihypertensive treatment to the start of dialysis and for 1, 3 and 5 years before dialysis, and compared with recommended standards. This information was not made available to the assessors.

Statistical analysis

The level of agreement between the assessors was measured by the kappa statistic, which is the method of choice for analysis of agreement between sets of observations on the same sample, and takes account of chance agreement. Statistical Package for Social Sciences (SPSS for Windows, version 6.1.1) was used. A κ value of 0.81–1.00 suggests `almost perfect' agreement, 0.61–0.80 `substantial', 0.41–0.60 `moderate', 0.21–0.40 `fair', 0.00–0.20 `slight' and <0.00 `poor' agreement.19 The validity of the two-assessor method and of the use of kappa statistic was highlighted in the study by Payne et al. of deaths from stroke and hypertension.11 The Mann-Whitney U test and Student's t test were used to compare mean blood pressure values as appropriate. A p value of <0.05 was taken as significant.

Results

Of the 145 patients from Nottingham Health District who started dialysis in the 3 years of the study, complete records were not available in five patients, who were excluded from analysis. The median age was 60 years (range 20–82) and the male-to-female ratio was 2 : 1.

The causes of renal failure are shown in Table 2. Diabetes was the single commonest cause (25%). In 23% of patients the cause of the renal failure was unknown. Glomerulonephritis and hypertensive nephrosclerosis accounted for 10% each and polycystic kidney disease 7%. Diabetes was also the leading diagnosis in the hypertensive patients.

View this table:
Table 2

Causes of renal failure and the number (%) with hypertension

Primary renal diseaseAll cases n (%)Hypertensive n (%)
Glomerulonephritis was only diagnosed histologically. Hypertensive nephrosclerosis was diagnosed histologically in 6 cases; 8 cases were labelled as such in the notes on clinical grounds only.
* No clinically obvious primary renal disease, normal serology and small kidneys on ultrasound scanning in all but five patients whose renal biopsy showed non-specific end-stage changes only.
** Three myeloma, 2 amyloid, 2 interstitial nephritis, 2 analgesic nephropathy, 2 lupus nephritis, 2 nephrocalcinosis, 2 carcinoma kidney, 1 papillary necrosis, 1 systemic sclerosis, 1 urolithiasis, 1 megacystis, 1 haemolytic uraemic syndrome and 1 unresolved tubular necrosis.
Diabetic nephropathy35 (25)32 (23)
Unknown*32 (23)19 (14)
Hypertensive nephrosclerosis14 (10)14 (10)
Glomerulonephritis14 (10)12 (8.6)
Polycystic kidney disease10 (7)9 (6)
Renovascular disease7 (5)6 (4)
Reflux nephropathy4 (3)2 (1.4)
Post-obstructive4 (3)3 (2)
Miscellaneous**20 (14)10 (7)
Total number140107 (76)

Both assessors agreed that 107 patients (76.4%) were hypertensive and that 30 were normotensive, but disagreed about the remaining three patients (κ=0.95—almost perfect inter-assessor agreement). Further analyses are confined to the 107 hypertensive patients (see Table 2).

Detection and treatment

Both assessors agreed that in 26 patients (24.3%), standards for detection/treatment had not been met; in 12 treatment was started too early (after a single blood pressure reading, and with no evidence at the time of renal disease nor of any other indication for immediate treatment) and in 14, treatment was not started until >6 months after hypertension had been confirmed, despite evidence of renal impairment at the time hypertension was diagnosed. The level of inter-assessor agreement was substantial (κ=0.72). At the start of treatment, the systolic pressure was 183±25 and the diastolic pressure 110±15 (mean±SD).

The median number of antihypertensive drugs on starting dialysis was two (range 1–5), consisting of calcium-channel blockers in 78%, diuretics in 71%, angiotensin-converting-enzyme inhibitor in 38%, beta blockers in 36% and alpha blockers in 21%.

Investigations

Both assessors found the standards had not been met in 31 patients (29%), in that there had been failure to test the urine and/or to check blood creatinine, urea and electrolytes after detection of hypertension. The level of agreement between the assessors was substantial (κ=0.80). Of those who were investigated, plasma creatinine was raised in 50 (71%) and proteinuria was present in 59 (77%); both abnormalities were present in 68%.

Follow-up

The median time from the detection of hypertension to starting dialysis was 7.4 years (range 0.2–29.6) with a mean of five blood pressure recordings per year. Both assessors found the standards for follow-up had not been met in 18 patients (17%); agreement was substantial (κ=0.80).

Referral

Taking into account the duration and severity of hypertension, and the results of initial and subsequent tests, both assessors agreed there had been a delay in referring to a specialist for investigation which may have influenced subsequent management in 24 (22.4%) patients (κ=0.70, substantial agreement).

Five years before the date of their first dialysis, 18% of patients were attending renal clinics; this increased to 37% at 3 years and 50% at 12 months before the first dialysis. The mean plasma creatinine at referral was 343±153 (mean±SD) μmol/l.

Control of blood pressure

There was substantial agreement between the assessors in their descriptive assessments of quality of blood pressure control (κ=0.65) and in their opinions on the effect of poor blood pressure control on the course of the chronic renal failure (κ=0.76) (Table 3). Both assessors concluded that control of blood pressure had been poor in 43 patients (40.2%) and that in 34 patients (32% of all 107 hypertensive patients), poor blood pressure control may have affected the course of renal failure adversely. The mean systolic and diastolic blood pressures which corresponded to the descriptive categories are shown in Table 4. There was a significant difference in the blood pressure values between the `good' and `fair' categories (p<0.05) and between the `fair' and `poor' categories (p<0.0001).

View this table:
Table 3

Inter-assessor agreement on management of hypertension (n=107)

QuestionAssessmentκ value*
Agreed, yesAgreed, noDisagreedCould not assess**
* κ=0.61–0.80 indicates `substantial' agreement. ** In these cases, both assessors agreed an assessment could not be made.
Were there departures from standards in any of the following?
Detection/diagnosis26641430.72
Investigations31641110.80
Follow-up1882700.80
Referral to nephrologist24701300.70
Was the quality of blood pressure control:
Excellent?2101400.65
Good?12761900.65
Fair?25612100.65
Poor?4358600.65
Might BP control have affected CRF adversely? (n=43) 342700.76
View this table:
Table 4

Blood pressure control: assessors' evaluations vs. mean diastolic and systolic pressures

Assessors' evaluationnMean diastolic BP (mmHg)Mean systolic BP (mmHg)
There was a significant difference in the mean diastolic and systolic blood pressures between the `good' and `fair' categories (p<0.05) and between the `fair' and `poor' categories (p<0.0001)
Excellent284.5±3.5136.5±7.8
Good1284.7±4.7153.1±8.5
Fair2589.2±4.7158.6±11.7
Poor4396.0±5.2165.0±12.2

The distribution of all the mean diastolic and systolic blood pressures from the time of diagnosis of hypertension to the start of dialysis is shown in Figure 1, allowing direct comparison against standards. Thus the British Hypertension Society diastolic target of <90 mmHg was met in only 45% and the systolic target of <160 mmHg was met in only 54%. However, there was an improvement in diastolic blood pressure control as patients approached the start of dialysis, although there was no change in the systolic pressure (Table 5).

View this table:
Table 5

Mean of serial diastolic and systolic blood pressures (I) and % of patients whose mean blood pressure met BHS targets (II), at different stages of the clinical course

Blood pressure parametersA. From diagnosis of hypertension to dialysis (n=107)B. During last 5 years before dialysis (n=62)C. During last 3 years before dialysis (n=81)D. During last 12 months before dialysis (n=93)*
* Another 14 patients presented within 12 months of needing dialysis. ** There was a significant difference between mean diastolic BP at each stage (p<0.0001). *** While there was no significant difference between columns B, C, and D they were each significantly different from column A (p<0.001). There were no significant differences in systolic BP.
Diastolic BP (mmHg)
(I) mean±SD**91.0±7.088.1±7.487.7±7.986.4±9.0
(II) n (%) mean ≤90***48 (45%)44 (69%)53 (65%)68 (73%)
Systolic BP (mmHg)
(I) mean±SD159±14158±16158±16159±14
(II) n (%) mean ≤16058 (54%)38 (61%)45 (55%)49 (53%)
Figure 1.

Cumulative frequency distribution graphs for a mean systolic and b mean diastolic blood pressures (from diagnosis of hypertension to the start of dialysis) for all 145 patients. Thus it is possible to see the percentage of patients whose mean blood pressure was below any given figure. For example, with reference to the British Hypertension Society targets, the mean of all systolic blood pressure readings during follow-up was <160 mmHg in 54% of patients and the mean diastolic blood pressure <90 mmHg in 45%.

Discussion

This study has demonstrated shortcomings in several aspects of the management of hypertension in patients who subsequently developed end-stage renal failure, consisting of failure to meet recommended standards for detection and diagnosis, investigation, follow-up, control of blood pressure, and referral. As the study included all patients developing end-stage renal failure from a single health district, and because reference to national figures1 indicates that our own dialysis population is similar to that of other Renal Units in the UK, the findings may well apply to other parts of the UK, and possibly elsewhere.

Diabetic nephropathy was the leading cause of end-stage renal failure, affecting 35 of the 140 patients (25%) with complete records; all but three of the diabetics were hypertensive. In 19 of the patients classified as `diagnosis unknown', hypertension preceded renal impairment by many years; adding these 19 to those classified as `hypertensive nephrosclerosis' and `renovascular disease' gives a total of 40 (28.6%) whose main problem may have been essential hypertension. These findings are consistent with reports from the United States Renal Data System (USRDS) and the European Dialysis and Transplantation Association/European Renal Association (EDTA/ERA) showing diabetes and essential hypertension to be the most frequent causes of end-stage renal failure.20,,21 There is, however, considerable uncertainty as to whether `benign' hypertension alone can cause chronic renal failure.23

Instead of death from stroke and hypertensive disease, the subjects of the study by Payne and colleagues11 whose methods we adapted, we took the start of dialysis as the means of identifying patients. Confidential enquiry is an established and successful method of assessing care.23,,24 The method of review by two independent assessors is inevitably subjective, but enables aspects of medical care which are not always taken into account by objective measurement to be evaluated. The validity of the findings was emphasized by `substantial' or `almost perfect' agreement between the assessors who had arrived at their opinions independently, one being a nephrologist and the other a general practitioner; neither had been involved in the care of the patients.

Our findings on the initial investigation of hypertension were similar to the stroke/hypertension study11 and to a recent interpractice audit of 740 hypertensive patients in London, in that about one-third of the patients had not had blood or urine tests—even after educational intervention.13 These relatively simple tests are necessary to establish the cause of hypertension and to detect target organ damage; their importance is emphasized by the fact that, of the patients in our study who had been investigated appropriately when hypertension was diagnosed, 71% had a raised creatinine and 77% proteinuria. Follow-up was considered inadequate in 17% of our patients, fewer than the figure of 69% from the study on deaths from stroke and hypertension,11 possibly because the development of renal impairment (and in as many as 25% of patients diabetes as well) introduced further reasons for follow-up apart from that of hypertension alone.

Delayed referral, which occurred in 22.4% of patients, limits the opportunities for identifying correctable disorders and, if progressive chronic renal failure is inevitable, for preparation for dialysis/transplantation. Moreover, delayed referral has been demonstrated to be associated with higher morbidity and mortality on dialysis at various times in the past 15 years and confirmed again recently.25–,29 The absence of any reduction in late referral over the years suggests that a different approach should be considered; an `at risk' register might help to keep track of those patients likely to develop progressive chronic renal failure.

The quality of the blood pressure control in this cohort of patients is a cause for concern. The British Hypertension Society standards for systolic and diastolic blood pressure were met in only 54% and 45% respectively for the whole period of their clinical course (Figure 1). The findings of the descriptive evaluation were similar; in the opinion of the assessors, blood pressure control had been `poor' in 43% of patients, and in 32% of all the hypertensive patients poor control may have affected the course of the renal disease adversely. Similar results on quality of blood pressure control have been reported in other settings, with inadequate blood pressure control found in 33–60% of hypertensive patients.12–,14 The results of the present study are of particular concern in view of the well-documented benefits of meticulous blood pressure control in chronic renal failure and the suggestion that the target blood pressure in these patients should be as low as 120/80.6 There was a significant improvement in the control of diastolic blood pressure (but not of systolic pressure) as patients approached dialysis, which coincided with a greater proportion of patients attending renal clinics. This is in keeping with other studies which have demonstrated the benefit of specialist referral,2,,17 although it may simply reflect a generally increased awareness of the importance of blood pressure control in recent years. At the time of starting dialysis, the median number of antihypertensive drugs prescribed per patient was only two, suggesting that better blood pressure control as a result of more intensive treatment may have been possible much earlier and could have had a favourable influence on the progression of renal failure in some patients. Only 38% of patients were taking angiotensin-converting-enzyme inhibitors at the time of starting dialysis, despite the evidence of their benefits in renal disease above and beyond those of blood pressure control.30 This may have been the result of concern about adverse effects in patients with vascular disease; in others renal impairment had not been recognized until they were close to needing dialysis.

For guidelines to be implemented successfully, medical staff need to be not only aware of them but committed to them; the guidelines must be realistic and there must be a simple method of audit to assess whether they are working or not. Enthusiasm for any long-term preventative measure is difficult to maintain (by both medical staff and patients) simply because the benefits are not easily seen. In other words, there are many possible reasons for the shortcomings this study has demonstrated. What can be done to correct them? Better education and more involvement of patients, for example with self-monitoring, may help to improve compliance. A measure of overall blood pressure control—the equivalent of glycosylated haemoglobin in diabetes—would be invaluable. More frequent use of 24-h blood pressure records together with echocardiographic measurement of left ventricular mass might meet this need, but would require vigorous assessment, including cost/benefit analysis before widespread implementation. And it has to be remembered that the simple tests of blood and urine which are already available are often omitted, or the significance of the abnormal findings is not realized. We therefore suggest that it may be helpful to introduce a checklist for initial investigation, provide written information for hypertensive patients together with home monitoring in some instances, make more extensive use of computerized records to facilitate follow-up and audit, and to investigate the role of new means of monitoring target organ damage.

This study has highlighted the need to overcome a number of shortcomings in the management of hypertension in the context of renal disease, which would be an important step in helping to contain the increasing number of people requiring treatment for end-stage renal failure.

Acknowledgments

Dr Dasgupta was in receipt of a grant from the Trent Research and Development Directorate. We thank all general practice and hospital colleagues who took part in the study. We also thank Dr Nick Gibson for designing the computer database, Dr Jim Pearson for statistical advice, Mrs Avril Pykett for secretarial assistance, Dr Nick Payne for his interest and help with the study design, and Mrs Christine Porter for help with computing.

References

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