Abstract
Background and objectives: Data are limited regarding BP distribution and the prevalence of hypertension in pediatric long-term dialysis patients. This study aimed to examine BP distribution in U.S. pediatric long-term hemodialysis patients.
Design, setting, participants, & measurements: This cross-sectional study of all U.S. pediatric (aged 0-< 18 yr, n = 624) long-term hemodialysis patients was performed as part of the Centers for Medicare & Medicaid Services End-Stage Renal Disease (ESRD) Clinical Performance Measures Project. BP and clinical information were collected monthly in October, November, and December 2001. Hypertension was defined as the mean of pre- and postdialysis systolic or diastolic BP above the 95th percentile for age, height, and sex, or antihypertensive medication use. Results were calculated by age, sex, race, ethnicity, ESRD duration, body mass index percentile, primary cause of ESRD, and laboratory data.
Results: Hypertension was present in 79% of patients; 62% used antihypertensive medication. Five percent of patients were prehypertensive (mean BP at 90th to 95th percentile). Hypertension was uncontrolled in 74% of treated patients. Characteristics associated with hypertension included acquired kidney disease, shorter duration of ESRD, and lower mean hemoglobin and calcium values. Characteristics associated with uncontrolled hypertension were younger age and shorter duration of ESRD.
Conclusions: Hypertension is common in U.S. pediatric long-term hemodialysis patients, uncontrolled in 74% of treated patients, and untreated in 21% of hypertensive patients. It is concluded that a more aggressive approach to treatment of hypertension is warranted in pediatric long-term hemodialysis patients.
Hypertension is present in 50% to 90% of adults receiving long-term dialysis therapy and is a risk factor for cardiovascular morbidity and mortality in this population (1–3). Although cardiovascular disease is increasingly identified as a cause of morbidity and mortality in pediatric long-term dialysis patients, few data are available regarding the distribution of BP and the prevalence of hypertension in a large pediatric long-term dialysis population, or regarding whether treated hypertension is adequately controlled (4–10).
The end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project is a national quality assurance program led by the Centers for Medicare & Medicaid Services (CMS) and the 18 ESRD Networks in an effort to improve patient care for long-term dialysis patients (11). In 2002, the ESRD CPM Project collected data on all pediatric (aged 0-< 18 yr) in-center long-term hemodialysis patients in the United States who were alive on December 31, 2001. For the first time, ESRD CPM data were collected on children aged <12 yr as well as adolescents. Data were collected as part of a special study by the Cardiovascular Special Studies Center of the United States Renal Data System (USRDS). Using these data, the goals of the present study are to report distribution of BP and prevalence of hypertension in the entire U.S. pediatric in-center long-term hemodialysis population (n = 624), and to provide new data regarding factors associated with hypertension in this population.
Materials and Methods
Data and Sources
For this USRDS CMS ESRD CPM special study, BP measurements were obtained for the entire U.S. population of pediatric long-term hemodialysis patients receiving therapy during the fourth quarter of 2001. Methods used to conduct the 2002 ESRD CPM Project and to assure data quality have been described (11). Briefly, in May 2002, a three-page in-center hemodialysis form and a one-page USRDS Cardiovascular Special Studies Center pediatric in-center hemodialysis supplemental form were distributed to ESRD facilities. The use of these forms was approved through the National Institutes of Health clinical exemption process. Facility staff abstracted clinical information in the patients' medical records for all pediatric in-center hemodialysis patients (n = 710) who received in-center hemodialysis during October, November, and December of 2001. Completed forms were sent to the appropriate ESRD Network for data verification and entry and then electronically submitted to CMS for analysis and reporting. These data were later merged with the USRDS database, which includes ESRD registration and billing information. Patients with incomplete forms or birth date information not in agreement with USRDS data were excluded (n = 70). Sixteen patients on BP medication with incomplete BP data were excluded. The remaining 624 pediatric patients make up the study population included in this report.
Demographic data included age (0 to 4, 5 to 9, 10 to 14, or 15-< 18 yr); sex, race and ethnicity; duration of ESRD; primary cause of ESRD; and height, weight, and BP measures pre- and postdialysis. Predialysis laboratory data included hemoglobin, calcium, phosphorus, intact parathyroid hormone, blood urea nitrogen, and serum albumin. Urea reduction ratio and single pool Kt/V values were calculated and used as measures of dialysis adequacy. Evaluations were conducted separately for pre- and postdialysis systolic and diastolic BP and for the mean value of the pre- and postdialysis measurements. Hypertension was defined as BP above the 95th percentile for age, height, and sex (according to the pediatric BP Task Force report), or use of antihypertensive medication (12). Prehypertension was defined as BP above the 90th percentile but below the 95th percentile, with no antihypertensive medication (12). BP below the 90th percentile for age, height, and sex was considered normal or controlled in treated patients. BP was measured by an oscillometric method using each dialysis center's standard routine, and values obtained at the first dialysis of each month were averaged for the three consecutive monthly observation periods. Weight and laboratory values were also averaged for the three observation periods. Height and body mass index (BMI; kg/m2 of height) percentiles by age and sex were calculated from tables provided by the Centers for Disease Control and Prevention. Anemia was defined as a mean hemoglobin value <11 g/dl (13,14).
Data Analysis
Statistical analyses, including descriptive statistics, were conducted using Pearson chi-square test, t test, and logistic regression using the Statistical Analysis System (SAS) software version 9.1 (Cary, NC). Independent variables for predicting the prevalence of hypertension were age, sex, race, Hispanic ethnicity, primary cause of ESRD (acquired: glomerulonephritis, interstitial nephritis, vasculitis, chronic pyelonephritis, hypertension; congenital/cystic/hereditary: dysplasia, cystic kidney disease, urologic disease, congenital nephrotic syndrome, oxalosis, Alport syndrome; other), duration of ESRD (0 to < 6 mo, 6 to 12 mo, 1 to 2 yr, 3 to 6 yr, ≥7 yr), BMI percentile (< 5%, 5% to < 85%, 85% to < 95%, ≥ 95%), and laboratory values. Results are presented as mean ± 1 SD. Two-tailed P values <0.05 were considered statistically significant.
Results
Mean age was 13.8 ± 3.8 yr; 43% of patients were female and 49% white (Table 1). Median age was 15 yr overall and for normotensive and hypertensive patients, and 14 yr for prehypertensive patients. Mean hemodialysis duration was 38 ± 43 mo, and the most common duration was 1 to 2 yr (32%). Congenital causes of ESRD were less common than acquired causes, except in the normotensive group. BMI was in the normal range (5th to <85th percentile) for 64% of patients and at the 85th to 95th percentile for 12%; 11% of patients were overweight (≥ 95th percentile).
Patient characteristics
Predialysis BP was higher than postdialysis BP for all three BP groups, with a mean decrease of 9.4 (SD = 0.55) mmHg for systolic and 6.5 (SD = 0.48) mmHg for diastolic BP for the whole cohort. Hypertension prevalence was 85% predialysis, 79% using the mean of the pre- and postdialysis measurements, and 75% postdialysis (Table 2). Pre- and postdialysis BP were strongly correlated (systolic: r = 0.74, P < 0.0001; diastolic: r = 0.66, P < 0.0001). Only 8% (n = 49) of patients would be recategorized from hypertensive predialysis to normotensive postdialysis. The following results are thus based on the mean of the pre- and postdialysis BP measurements.
Distribution of blood pressure by blood pressure definition
Hypertension was present in 79% (n = 494) and prehypertension in 5% (n = 29) of patients. Of the hypertensive patients, 76% had systolic and 42% had diastolic hypertension. Hypertension was untreated in 21% of hypertensive patients (n = 105), and 62% (n = 389) of the population was taking antihypertensive medication. However, hypertension was uncontrolled in 74% (n = 288) of treated patients. Weight loss during dialysis weakly correlated with a change in pre- and postdialysis diastolic pressure (r = 0.09, P = 0.019), but not with a change in pre- and postdialysis systolic pressure (r = 0.03, P = 0.185).
Hypertension was present in 87% of patients on dialysis for 0 to 5 mo, in 80% of those on dialysis for 6 mo to 6 yr, and in 66% of those on dialysis for ≥7 yr. While patients on dialysis for ≥7 yr were similar to those on dialysis for 0 to 6 yr regarding race, BMI, and medication use, they were more likely to have congenital instead of acquired causes of ESRD (congenital ESRD, 32% for 0 to 6 yr on dialysis versus 47% for ≥7 yr, P = 0.0195), and to have failed kidney transplants (14% for 0 to 6 yr on dialysis versus 77% for ≥7 yr, P < 0.0001).
Mean age of patients with uncontrolled hypertension was significantly lower than mean age of those with controlled hypertension (13.6 versus 15.0 yr, P = 0.014), as was ESRD duration (2.7 versus 4.8 yr, P = 0.0015). By univariate analysis, characteristics associated with hypertension included Hispanic ethnicity, acquired kidney disease, shorter duration of ESRD, higher postdialysis weight, anemia, and lower mean hemoglobin and calcium values. By multivariate logistic regression analysis, hypertension prevalence did not differ significantly by age, sex, Hispanic ethnicity, or BMI percentile (Table 3).
Adjusted odds of being hypertensive (versus normotensive)
BP measurements by ESRD duration are shown in Table 4. Mean pre- and postdialysis BP values decreased as dialysis duration increased. Anemia was present in 41% of hypertensive and 29% of normotensive patients (P = 0.0221, Table 5). Mean hemoglobin values were significantly lower for hypertensive than for normotensive patients (11.1 ± 1.7 g/dl versus 11.4 ± 1.4 g/dl, P = 0.0422), as were mean calcium levels (9.2 ± 0.9 mg/dl versus 9.5 ± 0.9 mg/dl, P = 0.0116). The erythropoiesis-stimulating agent dose, measured as units/kilogram of body weight per week, was similar for hypertensive and normotensive patients (430 ± 539 units/kg/wk for hypertensive patients versus 443 ± 448 units/kg/wk for normotensive patients, P = 0.80).
Average blood pressure by duration of end-stage renal disease
Laboratory values by hypertension status
Discussion
This cross-sectional study of 624 pediatric (aged 0 to < 18 yr) hemodialysis patients shows an exceptionally high prevalence of hypertension; 79% of patients had BP >95th percentile based on pediatric BP Task Force criteria. This compares with an estimated hypertension prevalence of 2% to 5% in the general pediatric population, a prevalence of 54% in pediatric patients with stage 1 to 3 chronic kidney disease, and a prevalence of 65% in pediatric and young adult hemodialysis patients (10,15,16). A previous report of hypertension in pediatric dialysis patients included young adults and did not include pre- and postdialysis BP or laboratory data (10). Surprisingly, at this time of increased awareness of pediatric hypertension, only 36% of patients on antihypertensive medication achieved targeted BP values, and antihypertensive medication was not prescribed for 21% of the hypertensive patients. These data show that hypertension is frequently undertreated in pediatric long-term hemodialysis patients. These findings are similar to findings from a report that 39% of pediatric patients with chronic kidney disease and hypertension were not receiving antihypertensive medication (16).
Hypertension is a risk factor for cardiovascular disease in adult and pediatric ESRD patients (9,17–19). A study of 432 adult ESRD patients found that each 10 mmHg rise in mean arterial BP was independently associated with presence of concentric left ventricular hypertrophy, change in left ventricular mass index, change in cavity volume, and development of de novo cardiac failure and ischemic heart disease on follow-up echocardiography (17). A retrospective study of 64 pediatric long-term dialysis patients found that, by multivariate logistic regression analysis, higher systolic BP remained in the final model as an independent predictor of left ventricular hypertrophy with a borderline level of significance (18). Similarly, a recent study of 39 Turkish pediatric long-term dialysis patients found systolic hypertension to be an independent risk factor for increased left ventricular mass index, and diastolic hypertension to be a predictor of carotid intima-media thickness (19). Thus, improving BP control in pediatric long-term hemodialysis patients has great potential to retard the progression of cardiovascular disease in this population.
Which BP measurement to use warrants further study. A study of 35 adult long-term hemodialysis patients found that left ventricular mass strongly correlated with predialysis systolic BP and with 24 h systolic ambulatory BP (20). A study of 150 adult long-term hemodialysis patients showed that for the diagnosis of hypertension, use of intradialytic ambulatory BP measurement together with pre- and postdialysis measurements improved the reproducibility, bias, precision, and accuracy of BP measurements compared with pre- or postdialysis measurements (21). No similar study of pediatric long-term hemodialysis patients appears to have been done. Yet, a more precise diagnosis of hypertension would be expected if ambulatory and/or home BP measurements were available in addition to pre- and postdialysis measurements. Data on ambulatory BP monitoring in pediatric hemodialysis patients are limited. In a study of 18 pediatric hemodialysis patients, no correlation was found between ambulatory and predialysis BP measurements (22). In five patients, BP assessed by predialysis recordings was overestimated, and in three it was underestimated compared with ambulatory measurements (22). In a study of 12 pediatric hemodialysis patients, a modest correlation of approximately 0.5 was found between casual and ambulatory BP measurements for both systolic and diastolic BP (23). In a study of 118 children with pre-ESRD chronic kidney disease, the concordance of ambulatory BP monitoring, clinic BP measurements, and home BP measurements was analyzed. Home BP monitoring was found to be superior to clinic BP measurements in predicting ambulatory BP measurements, but neither clinic nor home BP measurements detected hypertension with enough sensitivity or specificity to replace ambulatory BP measurements (24). Home BP monitoring should be considered a viable alternative in assessing and treating high BP in long-term pediatric dialysis patients, as it correlates with ambulatory BP monitoring, which is less readily available.
Elevated BMI has been positively associated with BP in the general adult and pediatric populations (15,25), but no previous reports comparing BMI and BP in pediatric long-term hemodialysis patients appear to be available. Unlike the general population, in this study, BMI was not significantly associated with hypertension. This is similar to a finding from a study of adult long-term hemodialysis patients in which BMI and BP were not significantly related (26). However, an explanation for the discordance between obesity and hypertension in long-term hemodialysis patients is not readily apparent.
In this study, there was a linear downward trend in hypertension prevalence as ESRD duration increased. The trend toward improved control of hypertension in patients with longer-term ESRD has also been reported in adults (1). We speculate that patients on dialysis therapy longer may achieve better volume control or receive more aggressive hypertension treatment. Mortality may also be higher among patients with higher BP.
This study also found lower hemoglobin to be associated with hypertension, in contrast to a previous pediatric study that found no significant difference in hematocrit levels between a small group of normotensive (n = 29) and hypertensive (n = 42) dialysis patients (27). However, the results from the present study are similar to those reported by the HEMO study, a multicenter, prospective, randomized trial of dialysis adequacy in 1238 adult long-term hemodialysis patients (28). Univariate analysis showed an inverse relationship between hematocrit and both pre- and postdialysis systolic BP (P < 0.01) (28). Our study found no significant difference in weekly erythropoiesis-stimulating agent doses between hypertensive and normotensive patients. However, because the hypertensive patients were more anemic than normotensive patients on similar erythropoiesis-stimulating agent doses, they could be considered more erythropoietin resistant. Erythropoietin-stimulating agents are known to increase BP in a dose-dependent manner and appear to have the strongest hypertensive effect on hemodialysis patients (29). The mechanisms by which erythropoietin-stimulating agents induce hypertension were recently reviewed; these include increased mean arterial BP that is erythropoietin specific and independent of erythropoietin-induced changes in red cell mass or viscosity, enhanced sensitivity to norepinephrine and angiotensin II, and increased circulating levels of endothelin-1 and impaired endothelial relaxation (29).
Our study has some limitations. First, all BP was measured in the dialysis unit; this is a poor surrogate for ambulatory BP and left ventricular hypertrophy (30). Second, compliance with prescribed therapy was not documented, and poor adherence with prescribed therapy may have played a role in the high degree of uncontrolled hypertension found in patients reported to be on therapy. Third, data on the number or type of antihypertensive medications prescribed were not available. Fourth, BP measurements were not standardized across dialysis centers participating in this study. Finally, because this analysis was cross-sectional, no causal associations may be determined.
In summary, hypertension prevalence is high in U.S. pediatric long-term hemodialysis patients. It is poorly controlled in patients on antihypertensive medication, and 21% of long-term hemodialysis patients with hypertension are untreated. These data suggest that great potential exists for improving BP control in pediatric long-term hemodialysis patients.
Disclosures
None.
Acknowledgments
This study was performed as a deliverable under Contract No. HHSN267200715003C (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD). The authors have no competing financial interests. The authors thank Dr. Alan Sinaiko for comments and United States Renal Data System colleagues Beth Forrest for regulatory assistance; Shane Nygaard for manuscript preparation and submission assistance; and Nan Booth, MSW, MPH, for editorial assistance.
Footnotes
-
Published online ahead of print. Publication date available at www.cjasn.org.
-
Access to UpToDate on-line is available for additional clinical information at http://www.cjasn.org/
- Received February 25, 2009.
- Accepted May 29, 2009.
- Copyright © 2009 by the American Society of Nephrology
References
In this issue
Jump to section
More in this TOC Section
Original Articles
Cited By...
- Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKD
- Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents
- Assessment and Management of Hypertension in Patients on Dialysis
- Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis