Current Hypertension Reports

, Volume 14, Issue 6, pp 608–618

Ambulatory Blood Pressure Monitoring in Pediatric Renal Transplantation

Authors

    • Department of Pediatrics and Transplantation Center, University Hospital MotolCharles University Prague, 2nd Faculty of Medicine
    • Biomedical Centre, Faculty of Medicine in PlzenCharles University in Prague
Pediatric Hypertension (JT Flynn, Section Editor)

DOI: 10.1007/s11906-012-0301-8

Cite this article as:
Seeman, T. Curr Hypertens Rep (2012) 14: 608. doi:10.1007/s11906-012-0301-8

Abstract

Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and adverse cardiovascular outcomes. Blood pressure (BP) in transplanted children should be measured not only by clinic BP (cBP) measurement, but also by ambulatory blood pressure monitoring (ABPM), because ABPM has distinct advantages over cBP, specifically the ability to reveal nocturnal, masked or white-coat hypertension. These types of hypertension are common in transplanted children (nocturnal hypertension 36–71 %, masked hypertension 24–45 %). It may also reveal uncontrolled hypertension in treated children, thereby improving control of hypertension. Regular use of ABPM and ABPM-guided therapy of hypertension may help to decrease cardiovascular and renal target organ damage in transplanted children. Therefore, ABPM should be routinely performed in all transplanted children at least once a year, regardless of the values of cBP.

Keywords

HypertensionBlood pressureBPChildrenPediatricAmbulatory blood pressure monitoringABPMRenal transplantationGraft functionGraft survivalLeft ventricular hypertrophyAntihypertensive therapyControl of hypertension

Introduction

Arterial hypertension is a common and serious complication in adult and pediatric patients after renal transplantation [13]. It is an important risk factor for cardiovascular morbidity and mortality in transplanted patients, and a strong risk factor for impaired graft survival [410]. According to current recommendations, blood pressure (BP) must be measured in children with chronic kidney diseases during every outpatient visit as clinic BP (cBP) [11]. However, cBP has its disadvantages, because it measures BP in a medical facility and does not measure BP during sleep; therefore, it cannot diagnose white-coat or nocturnal hypertension. Ambulatory blood pressure monitoring (ABPM) has been shown to be a better method for BP evaluation than cBP measurement in children after renal transplantation [1222, 23•, 24, 25, 26••, 27]. Based on the results of both cBP and ABPM, the BP status can be classified as normotension (both cBP and ABPM normal), white-coat hypertension (elevated cBP but normal ABP), masked or nocturnal hypertension (normal cBP but elevated daytime or nocturnal ABP) and ambulatory hypertension (both cBP and ABP elevated).

Several studies on ABPM in pediatric renal transplant recipients have been published in the last 15 years since the first study by Lingens et al. in 1997 [15]. This review article summarizes the advantages and disadvantages of ABPM in pediatric renal transplant patients and gives recommendations on its use in clinical practice.

Advantages of ABPM over cBP

Detection of Nocturnal Hypertension

One of the main advantages of ABPM over cBP is its ability to measure the BP during sleep to reveal nocturnal hypertension. ABPM is the only method to detect nocturnal hypertension, and cannot be approximated by a single cBP measurement during the night in the hospital or by home BP measurements. Many studies have shown that nocturnal hypertension is the predominant type of hypertension in pediatric transplant patients, and is much more common than daytime hypertension (Table 1). If a child has hypertension after renal transplantation, it is mostly nocturnal hypertension, either isolated nocturnal or combined with daytime hypertension. Isolated nocturnal hypertension can be seen in 22–41 % of transplanted children (Table 1). This finding further stresses the importance of ABPM with its monitoring of BP values while asleep. On the contrary, isolated daytime hypertension has never been observed in transplanted children (0 % in all studies), and therefore it could be provocatively said, it would be enough to measure BP only while asleep to evaluate whether a transplanted child is hypertensive or not. However, without knowing the BP values during daytime, we would miss combined nocturnal and daytime hypertension and could not assess the nocturnal BP fall (dipping, see below).
Table 1

Prevalence of different forms of hypertension in children after renal transplantation using ambulatory blood pressure monitoring (ABPM)

Author [reference]

Definition of HT

Overall prevalence of HT (n)

Prevalence of nighttime HT (isolated nighttime HT) ((isolated daytime HT))

Prevalence of masked HT

Non-dipping (definition) systolic/diastolic dip

Prevalence of untreated HT

Other findings

Lingens et al. 1997 [15]

only daytime BP > 95th centile for ambulatory BP or use of drugs

70 % (n = 17/27)

n.d.

1 %

30 % (MAP < 5.5 %) 6 % / 10 %

n.d.

Non-dipping associated with chronic rejection or renal artery stenosis

Matteucci et al. 1999 [16]

any value > 95th percentile regardless of drugs

36 % (n = 10/28)

36 % (29 %) ((0 %))

n.d.

n.d. systolic dip 3 % diastolic dip 10 %

11 %

mean 24-hr systolic BP correlates with LVMI

Giordano 2000 [17]

daytime, nighttime or 24 hr BP > 95th centile regardless of drugs

62 % (n = 23/37)

n.d.

29 %

n.d.

41 %

ABPM is more sensitive than casual BP

Sorof et al. 2000 [18]

daytime and 24 hr systolic BP load > 35 % or diastolic BP load > 25 % (95th centile for clinic BP) regardless of drugs

71/57 % for daytime syst./diast. HT (n = 30/24 of 42) 69/78 % for 24 hr syst./diast.

n.d.

n.d.

72 % for systolic 49 % for diastolic (< 10 % systolic or diastolic dip) 5 % / 9 %

n.d.

Boys had greater BP loads than girls

Morgan et al. 2001 [19]

daytime BP > 95th centile for clinic BP or nighttime BP > 95th centile for clinic BP minus 10 % regardless of drugs

64 % (n = 29/45)

64 % (22 %) ((0 %))

n.d.

58 % (< 10 % systolic or diastolic dip) 9 % / 14 %

48 %

No significant relationship between ABPM data and LVM

Mitsnefes et al. 2004 [51]

24-hr, daytime and nighttime mean BP >95th percentile regardless of drugs

29/21 % for daytime syst./diast. HT (n = 9/7 of 31) 68/71 % for nighttime syst./diast. HT

68/71 % for syst./diast. HT (n.d.) ((n.d.))

n.d.

82 % for systolic 50 % for diastolic (< 10 % systolic or diastolic dip) 6 % / 9 %

n.d.

Daytime systolic BP was superior in predicting carotid artery distensibility and stiffness than CBP

Kitzmueller et al. 2004 [50]

24-hr, daytime or nighttime mean BP >95th percentile regardless of drugs

59 % at initial and 40 % at repeat assessment (n = 23/39 and 8/20)

n.d.

n.d.

70 % for systolic and 54 % for diastolic at initial 75 % for systolic and 60 % for diastolic at repeat assessment (< 10 % systolic or diastolic dip) n.d.

n.d.

Changes of ABP correlate with changes of LVMI at repeat assessment

Serdaroglu et al. 2005 [20]

daytime or nighttime BP > 95th centile for ABPM and BP load >30 % regardless of drugs

73 % (n = 19/26)

n.d.

45 % together with nighttime HT

85 % (< 10 % systolic or diastolic dip) 4 % / 7 %

20 %

HT was related to less antihypertensive medication, higher CyA levels and shorter time after Tx

Seeman et al. 2006 [22]

daytime or nighttime BP ≥ 95th centile or use of drugs

89 % (n = 32/36)

60 % (40 %) ((0 %))

n.d.

64 % (< 10 % systolic or diastolic dip) 7 % / 13 %

3 %

Better control of HT with ACEI and lower CyA/Tac dose/level

McGlothan et al. 2006 [23•]

24-hr, daytime and nighttime mean BP > 95th percentile or systolic load > 35 % and diastolic load > 25 % regardless of drugs

21/7 % for daytime syst./diast. HT (n = 6/2 of 29) 48/41 % for nighttime syst./diast. HT

51 % (41 %) ((n.d.))

n.d.

60 % for systolic 37 % for diastolic (<10 % syst. or diast. dip) 40 % for systolic 30 % for diastolic (< 5.5 %) 8 % / 9 %

n.d.

Isolated nocturnal HT is more common than daytime HT, children on ACEI/ARB had lower systolic BP than on CCB

Ferraris et al. 2007 [14]

daytime or nighttime BP >95th centile regardless of drugs (only treated children)

n.a. (only treated hypertensive children)

62 % (38 %) ((0 %))

38 %

36 % (< 7 % systolic or < 14 % diastolic dip) n.d.

n.a.

Office BP readings miss a substantial number of hypertensive by ABPM criteria

Seeman et al. 2007 [32]

daytime or nighttime BP ≥95th centile or use of drugs

97 % at 2 years (n = 30/31)

n.d.

n.d.

45 % at 2 years (< 10 % systolic or diastolic dip) 10 % / 14 %

0 % at 2 years

Improved control of HT can be achieved and is associated with stabilization of graft function

Paripovic et al. 2010 [24]

daytime or nighttime BP ≥95th centile regardless of drugs

44 % (n = 18/41)

68 % (36 %) ((0 %))

24 %

71 % (< 10 % systolic or diastolic dip) 6 % / 12 %

24 %

Hidden (masked) uncontrolled daytime HT in 21 % of treated children

Tangeraas et al. 2010 [25]

daytime or nighttime BP ≥95th centile or use of drugs

73 % (n = 16/22

53 % (16 %) ((0 %))

n.d.

79 % (<10 % systolic or diastolic dip) n.d.

10 %

Children with metabolic risk factors incl. HT have lower cardiorespiratory fitness

Basiratnia et al. 2011 [26••]

daytime or nighttime BP ≥95th centile or use of drugs

76 % (n = 33/66)

45 % (25 %) ((0 %))

32 %

73 % (< 10 % systolic or diastolic dip) n.d.

27 %

Inverse correlation between ABP and time after Tx, ABPM parameters correlate with LVMI

Balzano et al. 2011 [27]

daytime or nighttime BP ≥95th centile or drugs

82 % (n = 4/22) at 9 years follow-up

n.d.

n.d.

n.d.

5 %

Very low prevalence of LVH (4 %) and lack of progression of cIMT might reflect positive effect of good BP control

Median values from all studies

n.a.

71 %

60 % (33 %) ((0 %))

30 %

71 % (for all definitions) 6 % / 12 %

24 %

n.a.

HT = hypertension, BP = blood pressure, n.d. = not determined, n.a. = not applicable; LVMI = left ventricular mass index, CyA = cyclosporine A; Tac = tacrolimus; Tx = transplantation; ACEI = angiotensin converting enzyme inhibitors; ARB = angiotensin receptor blockers; CCB = calcium channel blockers

The importance of nocturnal BP in non-transplanted children is stressed by its closer correlation with left ventricular mass than daytime BP [28], and by its relationship with renal function [29]. It has been demonstrated in African-American children and adolescents that nocturnal systolic BP, but not daytime BP or cBP, negatively correlates with renal function measured as creatinine clearance. This clearly shows that nocturnal BP in non-transplanted children is at least as dangerous for the heart and kidney as daytime BP.

On the contrary, the clinical relevance of nocturnal hypertension in transplanted children is not yet clear. In adult transplant patients, it has been shown that nocturnal BP but not cBP correlates negatively with graft function at 1-year post-transplant, suggesting that nocturnal hypertension plays an important role in predicting poor renal transplant outcome [30••]. High rates of mainly nocturnal hypertension, together with a high prevalence of left ventricular hypertrophy in transplanted children, would point out to an association between nocturnal BP and hypertensive target organ damage; however, in most pediatric studies, nocturnal BP did not show any correlation with left ventricular mass index [19, 22]. The only study showing significant correlation between nocturnal BP and left ventricular mass index (LVMI) is that of Calzolari et al.; however, even in that study, daytime BP correlated better with LVMI than nocturnal BP [12]. The reason why the association between nocturnal BP and left ventricular mass is in transplanted children less pronounced than in non-transplanted children is not yet clear. It may be related to the presence of non-traditional cardiovascular risk factors such as microinflammation, uremic toxins, or treatment with corticosteroids or calcineurin inhibitors.

The deleterious effect of nocturnal BP on renal function in non-transplanted children has been demonstrated in diabetic children, where it predicted development of microalbuminuria [31]. In transplanted children, it has been shown that significant reduction of nocturnal BP (with non-significant reduction in daytime BP) led to slower progression and even stabilization of graft dysfunction [32]. Therefore, it seems that nocturnal BP is at least as important for the development of hypertensive kidney damage as daytime BP.

Detection of Masked Hypertension

Masked hypertension (elevated daytime ambulatory BP but normal cBP) is a relatively new phenomenon [33]. It has been shown in 8–11 % children with various chronic health problems such as obesity or diabetes [3436].

In transplanted children, masked hypertension was first specifically documented by Paripovic et al. in 2010 [24]. They showed that 24 % of transplanted children have masked hypertension. In other older studies not specifically designed to investigate masked hypertension, this type of hypertension could be found in 1–38 % of investigated children (Table 1). The prevalence of masked hypertension in transplanted children is much higher than in any other previously investigated pediatric population, and therefore renal transplantation seems to be a major risk factor for the presence of masked hypertension in children.

The etiology of masked hypertension is not yet fully elucidated. Obesity or diabetes mellitus, both of which are increasingly recognized in transplanted children, are some of the risk factors that are associated with the increased prevalence of masked hypertension [34, 37]. Other risk factors associated with masked hypertension in the general population, such as increased sodium intake, salt and fluid retention, chronic kidney disease, antihypertensive drug therapy, decreased exercise or elevated BP at exercise, are also present in transplanted patients [25, 3336].

Masked hypertension in non-transplanted children is associated with increased cardiovascular morbidity (LVH) similar to hypertensive children with confirmed ambulatory hypertension (increased ambulatory and office BP) [34, 35]. There are still no studies investigating the cardiovascular risk of masked hypertension in transplanted children. In the only study focusing primarily on masked hypertension, no investigations of the cardiovascular system were performed [24]. However, it can be assumed from adult transplant and pediatric non-transplant studies that it likely contributes to the increased cardiovascular risk in this population.

Detection of White-Coat Hypertension

Contrary to nocturnal and masked hypertension, white-coat hypertension (WCH) is uncommon in transplanted children (0–24 %, see Table 1); whereas it is quite common in non-transplanted children with elevated cBP investigated for possible hypertension (30–40 %) [38]. The low frequency of white-coat hypertension in transplanted children is most likely related to the low prevalence of normal ambulatory BP in untreated patients (see above). However, a white-coat effect can be seen in some treated children (up to 24 %), further emphasizing the role of ABPM in the management of treated transplanted children: identification of a white-coat effect would prevent the unnecessary intensification of antihypertensive drug therapy.

Detection of Untreated Hypertension

Most transplanted children receive antihypertensive drugs; however, 10–50 % of patients are untreated (Table 2). In a considerable number of these children, ABPM may reveal previously unrecognized and therefore uncontrolled hypertension. The prevalence of untreated hypertension discovered by ABPM ranged from 3 to 48 % in many studies (Table 1). Most of the children with untreated hypertension have isolated nocturnal hypertension; however, some of them have also masked hypertension. This is a further argument that ABPM is more sensitive than cBP in detecting hypertension in transplanted children and that it might help to improve the management of hypertension.
Table 2

Control of hypertension in children after renal transplantation using ambulatory blood pressure monitoring (ABPM) (Adapted from Seeman [67])

Author [reference]

Definition of HT

Percentage of treated patients

Prevalence of uncontrolled HT among treated pts.

Mean number of antihypertensive drugs per treated patient

Lingens et al. 1997 [15]

only daytime BP > 95th centile for ambulatory BP or use of drugs

63 % (n = 17)

65 % (n = 11/17)

n.d.

Matteucci et al. 1999 [16]

any value > 95th percentile regardless of drugs

68 % (n = 19)

47 % (n = 9/19)

1.0

Giordano et al. 2000 [17]

daytime, nighttime or 24 hr BP > 95th centile regardless of drugs

68 % (n = 25)

72 % (n = 18/25)

1.5

Morgan et al. 2001 [19]

daytime BP > 95th centile for clinic BP or nighttime BP > 95th centile for clinic BP minus 10 % regardless of drugs

49 % (n = 22)

82 % (n = 18/22)

1.4

Serdaroglu et al. 2005 [20]

daytime or nighttime BP > 95th centile for ABPM and BP load > 30 % regardless of drugs

62 % (n =16)

81 % (n = 13/16)

1.0

Seeman et al. 2006 [22]

daytime or nighttime BP ≥ 95th centile or use of drugs

86 % (n = 31)

45 % (n = 14/31)

2.1

Ferraris et al. 2007 [14]

daytime or nighttime BP > 95th centile regardless of drugs (only treated children)

n.a.

38 % (n = 10/26)

1.3

Seeman et al. 2007 [32]

daytime or nighttime BP ≥ 95th centile or use of drugs

97 % at 2 years (n = 30)

26 % (n = 8/30) at 2 years

2.7 at 2 years

Paripovic et al. 2010 [24]

daytime or nighttime BP ≥ 95th centile regardless of drugs

58 % (n = 24)

58 % (n = 24/41)

1.6

Tangeraas et al. 2010 [25]

daytime or nighttime BP ≥ 95th centile or use of drugs

70 % (n = 12)

75 % (n = 9/12)

1.3

Basiratnia et al. 2011 [26••]

daytime or nighttime BP ≥ 95th centile or use of drugs

50 % (n = 33)

40 % (n = 13/33)

1.3

Balzano et al. 2011 [27]

daytime or nighttime BP ≥ 95th centile or drugs

77 % (n = 17) at 9 years follow-up

18 % (n = 3/17) at 9 years follow-up

1.3

Median values from all studies

 

68 %

53 %

1.3

HT = hypertension, BP = blood pressure

Better Overall Detection of Hypertension

Due to the detection of nocturnal or masked hypertension that cannot be revealed by cBP and due to the low prevalence of WCH, the prevalence of hypertension in studies using ABPM are consistently higher than in studies using cBP. The prevalence of ambulatory hypertension ranges between 76–97 % (Table 1), whereas the prevalence of clinic hypertension always reported lower prevalence of hypertension ranging between 56–70 % [2, 3, 39, 40]. This phenomenon further clearly underlines the advantage of ABPM over cBP in the diagnosis of hypertension.

The reason for the wide range in the prevalence of ambulatory hypertension is based mainly on the different definitions of hypertension in various trials (see Table 1). Other reasons for different results can be differences in the studied population—different frequency of living and cadaver donors (living donor transplant recipients have lower prevalence of hypertension [40]), different frequencies of preemptive transplantation (preemptively transplanted children have less hypertension [40]), different times after transplantation (longer time after Tx is associated with lower prevalence of hypertension [2, 3]), different use of steroid free immunosuppression (steroid free immunosuppression is associated with lower BP and lower prevalence of hypertension [41]), or different use of calcineurin inhibitor-free immunosuppression (calcineurin inhibitor-free immunosuppression is associated with a lower prevalence of hypertension [42]).

Recategorizatíon of BP Status Based on ABPM Results

Performing ABPM in transplant children often leads to reclassification of BP status in comparison to previous classification (normotensive or hypertensive) based on cBP measurements only, and this happens in both ways (from normotension to hypertension, i.e. detection of isolated nocturnal hypertension or masked hypertension, and less frequently, vice versa from hypertension to normotension, i.e. detection of white-coat hypertension). In the first ABPM study on transplanted children done by Lingens et al. 15 years ago, ten children (37 %) were reclassified after performing ABPM from normotension to hypertension or vice versa [15]. Similarly, Ferraris et al. recategorized 30 % of children with controlled clinic BP to non-controlled BP (hypertension) by ABPM criteria [14]. Therefore, in about one third of children, performance of ABPM leads to recategorization of BP status in comparison to children being managed previously by cBP measurements.

Non-Dipping

An attenuated decrease (dip) of BP during the night (non-dipping phenomenon) is a frequent finding in transplanted children. The average dip in transplanted children is 6 % for systolic BP and 12 % for diastolic BP (Table 1), which are lower values than seen in healthy populations [43]. Therefore, Lingens et al. used a threshold of mean arterial BP dip < 5.5 %, which corresponds to the 5th percentile for dipping in healthy children, to define non-dipping [15]. In this study, the prevalence of non-dipping was 30 %, which is nevertheless six times higher than in healthy children (5 % of healthy children have dip < 5.5 %). Another study from Argentina defined non-dipping as dip < 7 % for systolic or < 14 % for diastolic BP, values that correspond to −1 SD (ca. 15th percentile) for healthy children [14]. Using this definition of non-dipping, only 36 % of children were non-dippers.

The reason for the frequent non-dipping phenomenon in transplanted patients is clearly multifactorial; the main factors are steroid treatment, calcineurin inhibitors, sodium retention, impaired renal function, chronic rejection or transplant renal artery stenosis [44•].

In adult transplant patients, non-dipping is associated with cardiovascular morbidity such as left ventricular hypertrophy [45] or graft dysfunction [46]. It has been shown that the nocturnal dip in systolic BP correlated negatively with graft function in cross-sectional as well as longitudinal studies [46, 47]. Adult transplant patients with non-dipping at 1 year post-transplant had decreased graft function 4-years post-transplant compared with patients with normal nocturnal dip. This indicates that abnormal circadian BP pattern identifies a group of graft recipients at risk for graft loss in the future.

In children, no significant difference in the left ventricular mass index or graft function between dippers and non-dippers was found [22], but similarly to adults, significant improvement in nocturnal dipping could be demonstrated in children in a 2-year interventional study, and this improvement of dipping (from 7 mmHg to 10 mmHg for systolic BP dip and from 13 mmHg to 15 mmHg for diastolic BP dip) was associated with stabilization of graft function [32], pointing out a possible positive effect of greater dipping on graft dysfunction.

Therefore, it is clear that renal transplantation is associated with lower nocturnal decline of BP that can be evaluated only by ABPM, and that can contribute to the high cardiovascular risk profile in transplanted children.

Better Reproducibility

The reproducibility of ABPM data has been tested in one Swedish study on 18 transplanted children [48]. Krmar et al. demonstrated that the long-term reproducibility of mean ABP values is superior to that of cBP measurements. However, the day-to-night BP variability and dipping status has low reproducibility, and it appears to change over time, making it questionable to classify a child as dipper based on a single ABPM study.

Better Association With Target Organ Damage

It has been shown in several adult and pediatric cross-sectional studies that ambulatory BP correlates better than cBP with signs of hypertensive target organ damage such as left ventricular hypertrophy (LVH) [16, 19, 22, 49]. Left ventricular hypertrophy is a frequent finding that occurs in 50– 82 % of transplanted children. Matteucci et al. [16] found a correlation between left ventricular mass index (LVMI) and mean 24-h systolic BP; however, other studies [19, 22, 49] did not find any correlation between LVMI and blood pressure. More interestingly, Kitzmueller et al. have found in their longitudinal study a correlation between LVMI and ABPM data at repeated measurement, but not at baseline. This finding suggests that long-term control of BP is an important determinant of myocardial target organ damage in transplanted children [50]. Furthermore, in a recent 9-year longitudinal study, ABPM-guided management of hypertension was associated with excellent control of hypertension and an exceptionally low prevalence of LVH (4.5 %) [27]. Moreover, this excellent ABPM-guided control of hypertension was associated with a lack of progression of carotid intima-media thickness (cIMT), another surrogate marker of cardiovascular morbidity and mortality. Thus, ABPM-guided treatment of hypertension might prevent progression of cIMT, thereby improving the cardiovascular risk profile in pediatric renal transplant recipients.

Furthermore, in another study, the results of ABPM, but not of cBP, were also associated with carotid artery distensibility and stiffness, an early sign of functional changes in the carotid artery—carotid arteriopathy in transplanted patients [51]. Mitsnefes et al. clearly showed that daytime ambulatory systolic BP load and BP index are superior in predicting carotid artery compliance/stiffness, compared to cBP.

Better Association with Graft Function, Graft Survival and Proteinuria

Hypertension is a strong predictor for graft loss. This relationship between BP and graft survival has been shown by many studies in adult and pediatric patients [3, 57, 10, 52, 53]. The results of ABPM are more closely related to renal function and proteinuria in transplanted patients than the results of casual BP in adults [54] and children [32, 55]. Jacobi et al. showed that 24-hr ABP, but not cBP, is closely related to graft function at 6 and 18 months in adults after transplantation [54]. Moreover, Paoletti et al. demonstrated that BP assessed by ABPM is a stronger predictor of graft damage than cBP and even than traditional immunological factors, such as history of acute rejection or HLA mismatches [30••].

Furthermore, in the only interventional hypertension trial in transplanted children, ABPM-guided management of hypertension not only prevented loss of graft function (stable graft function in normotensive children compared with a significant reduction in graft function in those who remained hypertensive, Fig. 1), but also significantly reduced proteinuria, another important risk factor for chronic allograft dysfunction, graft and patient survival [32, 56]. This result is consistent with the findings of Mitsnefes et al. [10], who showed in a retrospective cBP-based study that hypertension may act not only as a marker of chronic allograft dysfunction, but can also be deleterious to graft function. These data provide further evidence that elevated clinic BP, and even more significantly ambulatory hypertension, can directly impair graft function and should be appropriately diagnosed and rigorously treated.
https://static-content.springer.com/image/art%3A10.1007%2Fs11906-012-0301-8/MediaObjects/11906_2012_301_Fig1_HTML.gif
Fig. 1

Graft function in an ABPM-guided 2-years interventional trial showing that graft function was preserved in children with ambulatory normotension, in comparison to children being hypertensive at 2 years who loss significant graft function. From Seeman T, Šimková E, Kreisinger J, et al.: Improved control of hypertension in children after renal transplantation: Results of a two-yr interventional trial. Pediatr Transplantation 2007, 11:491–497, with permission

Better Control of the Treatment of Hypertension Due to Regular Use of ABPM

A retrospective study from Argentina demonstrated that cBP misses a substantial number of children who were hypertensive by ABPM criteria, leading to undertreatment of hypertension that could be avoided if ABPM were applied as an adjunct to cBP measurement [14]. Another study later demonstrated that repeated routine performance of ABPM and ABPM-guided management of hypertension leads to significantly more patients with controlled hypertension (83 %) in comparison to historical hypertensive recipients in whom the therapeutic decisions were driven only by clinic BP measurements [57].

In a prospective 2-year interventional study from the Czech Republic, ABPM-guided management of hypertension resulted in a decrease of the prevalence of uncontrolled hypertension from 42 % to 26 %. This improvement was reached by better detection of isolated nocturnal and masked hypertension associated with subsequent intensification of pharmacological treatment (significant increase in the use of diuretics and angiotensin-converting-enzyme (ACE) inhibitors), resulting in significant decrease of nocturnal BP [32].

An even more impressive result was seen in an observational long-term study from Sweden, where the regular annual use of ABPM over 9 years resulted in an improvement of the control of hypertension to 82 % [27]. These studies clearly showed that ABPM is superior to cBP, not only in better detection of hypertension, but it also leads to more successful treatment of hypertension in transplanted children, which in turn should be associated with a better cardiovascular risk profile (less hypertension, less LVH, relative decrease of cIMT) and better graft function (slower progression or even prevention of chronic graft dysfunction).

Drawbacks to ABPM

There are a few disadvantages of ABPM in children after renal transplantation. The ABPM devices are still more expensive than devices for clinic BP measurement. However, in the general pediatric population, it has been shown that the use of ABPM in the initial evaluation of hypertensive children is cost-effective [58, 59•]. A similar cost-effectiveness study has not yet been performed in transplanted children.

A further limitation of ABPM in children is its need for cooperation of the child during the whole 24-h monitoring. Moreover, there are no normative values for toddlers < 120 cm; therefore, the interpretation of data in this age group is limited.

ABPM is time-consuming not only for the patient and his parents, but also for the physician. Furthermore, the reimbursement of ABPM in children is limited in some countries.

Another limitation of ABPM in children is the lack of normative data for non-Caucasian, non-European populations, as the most widely used normative data are derived from ABPM measurement in white, Caucasian children from central Europe [59•].

Controversial Issues in ABPM

Interpretation of ABPM

There is still no general agreement on which ABPM parameter should be used for classification of BP status in children—mean BP or BP load (i.e. percentage of BP reading > 95th percentile). The current American Heart Association recommendations for pediatric ABPM recommend using a combination of both parameters to define ambulatory hypertension [60].

Nocturnal Dip

There is still no agreement on how to define non-dipping status in children (see above). Furthermore, the reproducibility of dipping status in transplanted children is low [48], therefore repeated ABPM studies might be needed to describe a child as a non-dipper. Perhaps, rather than looking at dipping status, which is not clearly defined and poorly reproducible, we should rely on mean BP or BP load while asleep to guide the treatment of hypertension in transplanted children.

Target BP in Transplanted Children

The target BP in transplanted children is not yet known. The NKF Task Force on Cardiovascular Disease recommends a target cBP level < 130/85 for adult transplant patients and < 125/75 for proteinuric patients [61]. But there are no prospective interventional trials showing that lower BP will improve graft survival. Therefore, these recommendations are only based on retrospective studies showing that elevated BP is associated with shorter graft survival [3, 57, 10, 50, 62]. A retrospective European study in adults showed that improved BP control was independently associated with improved long-term graft survival [63]. The results from the ESCAPE trial showed that in children with chronic native kidney disease, strict BP control (ambulatory MAP < 50th percentile) lead to significantly slower progression toward end-stage renal failure [64]. Whether strict control of BP would lead to slower progression of chronic allograft dysfunction is not known. In the only prospective interventional study on control of hypertension, it was shown that hypertensive children in whom BP was lowered during a 2-year period of time to normotension had stable graft function, in contrast to children who remained hypertensive after 2 years and who lost significantly glomerular filtration rate [32]. These results provide a clinical rationale for adequately controlling BP in transplanted patients to at least < 90th percentile. However, whether target BP should be < 75th or even < 50th percentile, as it is recommended for children with chronic native kidney diseases [65•], is still unclear and needs further prospective interventional trials.

Recommendations for the Performance of ABPM in Transplanted Children

Due to the many advantages that unequivocally overcome the disadvantages of ABPM over cBP in the management of children after renal transplantation, ABPM should be routinely performed in all transplanted children, regardless of the values of cBP. This statement has been firstly used by the European Society of Hypertension (ESH) in its pediatric recommendations [65•] and has recently been recommended by other experts [66]. How often ABPM should be performed in transplanted children must still be determined, but it should be at least once a year [27, 32], and perhaps also about 6 months after each change of antihypertensive medication, to assess for improved control of hypertension.

Conclusions

Ambulatory blood pressure monitoring is currently the best method for evaluation of BP in children after renal transplantation. Clinic BP measurements should be performed at every check in the clinic, and ABPM should be routinely performed in all transplanted children at least once a year regardless of cBP, because it reveals quite often nocturnal hypertension, masked hypertension or uncontrolled hypertension.

Acknowledgments

T. Seeman is supported by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund and by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic).

Disclosure

T. Seeman has received a grant from the Internal Grant Agency of the Ministry of Health of the Czech Republic, has served as a consultant to Otsuka Pharmaceuticals, and has received payment for lectures, including service on speaker bureaus from the Pediatric Academic Societies.

Copyright information

© Springer Science+Business Media, LLC 2012