AMBULATORY BLOOD PRESSURE MONITORING

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Vol. 76, No. 11

AMBULATORY BLOOD PRESSURE MONITORING IN RENAL
TRANSPLANTATION: SHOULD ABPM BE ROUTINELY
PERFORMED IN RENAL TRANSPLANT PATIENTS?
ADRIAN COVIC,1,3 LIVIU SEGALL,1
In renal transplant recipients, hypertension is common and associated with increased cardiovascular
and allograft rejection risks. Ambulatory blood pressure monitoring is required for its accurate diagnosis
and adequate treatment, as it clearly offers several
advantages over office or casual blood pressure measurements. First, it correlates better with target-organ
damage and with cardiovascular mortality. Second,
ambulatory blood pressure monitoring can eliminate
“white coat” hypertension. Most important is the identification of nocturnal hypertension, an independent
cardiovascular risk factor. A circadian nondipping
pattern is often found in renal transplant recipients,
most probably resulting from cyclosporine A and persistent fluid overload in the early posttransplant
phase (approximately 70% prevalence), but reflecting
an underlying renal (parenchymal or vascular) allograft disease when persistent (approximately 25%
prevalence) beyond the first year posttransplant.
It has been clear for some years now that ambulatory blood
pressure monitoring (ABPM) is superior to casual (office)
blood pressure (CBP) measurements as a predictor of target
organ damage and morbid cardiovascular events (left ventricular hypertrophy, hypertensive cerebrovascular disease,
retinopathy, renal abnormalities, and alterations in vascular
compliance) in patients with arterial hypertension (AHT) (1,
2). This is the conclusion of nearly every study performed in
the past 10 years, although there may be certain limitations
to these data, including relatively small sample sizes for an
outcome trial, heterogeneous patient populations (e.g.,
treated and untreated), and relatively short duration of follow-up. Also, patients whose nocturnal (or sleep) blood pressure (BP) remains high (i.e., nondipper circadian profile
[NDP]) have a worse outcome—an up to threefold higher rate
of cardiovascular events—than patients whose nocturnal BP
decline is at least 10% or more (3). ABPM seems useful
especially in patients with borderline AHT, possible “whitecoat” AHT, and refractory AHT (2, 4).
ABPM IN NEPHROLOGY

Arterial hypertension is a major factor of progression of
glomerular diseases toward chronic renal failure and of the
latter toward end-stage renal disease. ABPM has been increasingly used by nephrologists in the past 10 years, allowing a better understanding of the relationship between AHT
1
C. I. Parhon University Hospital, Dialysis and Transplantation
Center, Iasi, Romania.
2
Renal Unit, Guy’s Hospital, London, United Kingdom.
3
Address correspondence to: Adrian Covic, M.D., Ph.D., Dialysis
Unit, C. I. Parhon University Hospital, Dialysis and Transplantation
Center, Blvd. Carol 1st, No. 50, Iasi 6600, Romania. E-mail:
[email protected].
Received 23 December 2002. Revision requested 24 March 2003.
Accepted 17 June 2003.

DOI: 10.1097/01.TP.0000091288.19441.E2

AND

DAVID J. A. GOLDSMITH,2

and kidney diseases (1, 5). According to several studies,
ABPM seems to be more useful than the casual measurement
of BP, as it correlates better with target-organ damage (such
as left ventricular hypertrophy and dilatation) in prospective
studies (6), provides a greater predictive value of cardiovascular morbidity and mortality (1, 7), and may be more reproducible (8). Both ABPM levels and the circadian variability of
BP significantly correlate with microalbuminuria, development of proteinuria, and progression of renal disease (9).
An NDP— usually defined as a nocturnal decrease in BP of
less than 10% with respect to diurnal BP— has been found
more often in patients with renovascular hypertension, autosomal dominant polycystic kidney disease, immunoglobulin A nephropathy, chronic renal failure, dialysis (both hemoand peritoneal dialysis), and renal transplantation than in
other populations (1, 5, 9). The NDP might be related to
severe AHT in some patients, but it was also found to be
associated with mild AHT or even with a normal BP (5). It is
not yet known whether the NDP is a factor contributing to or
a consequence of renal disease.
AHT IN RENAL TRANSPLANT RECIPIENTS

AHT is present in 60% to 80% of renal transplant recipients and it is usually associated with left ventricular hypertrophy (LVH) (5). Several factors may contribute to posttransplant AHT: (1) allograft dysfunction resulting from
acute rejection or chronic allograft nephropathy; (2) treatment with corticosteroids, calcineurin inhibitors, or both; (3)
diseased native kidneys; (4) renal artery stenosis; and (5)
essential hypertension (10).
AHT plays a major role in the progression of kidney graft
failure (11) and in the cardiovascular morbidity and mortality (5), together with other risk factors frequently present in
most renal transplant patients, such as diabetes, hypercholesterolemia, obesity, and LVH (12). A large study including
almost 30,000 renal transplant patients, with a 7-year follow-up period, clearly showed that the graft survival rate was
significantly related to both systolic and diastolic BP (11).
AHT is likely to aggravate immune lesions; it is well known
that immune and nonimmune mechanisms contribute to
chronic rejection (11).
AHT is also a strong predictor of acute rejection: of 1,641
transplant recipients, acute rejection developed in 81% of
those whose BP increased compared with 22% of those whose
BP decreased after transplantation (13). From the above, it
becomes clear that tight BP control is a key objective in renal
transplant patients, and for this purpose ABPM might be a
useful tool.
ABPM VERSUS CBP MEASUREMENTS IN RENAL
TRANSPLANT PATIENTS

The few existing studies indicate large differences between
casual and 24-hr BP measurements. Only 63% of 27 renal
transplant pediatric patients were found to be in the same

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BP category (i.e., hypertensive or normotensive) by both
methods (14). Unfortunately, no algorithm or regression
equation can be determined from comparative studies, because ABPM is both underestimated and overestimated by
CBP measurements (15). Overestimation may be attributable to white-coat hypertension or to a normal nocturnal
dipping, whereas underestimation could be explained by the
fact that the studied patients take their antihypertensive
medication shortly before the CBP morning measurement
(15) or because they have a high nocturnal BP level. Possibly,
more often, mean 24-hr BP levels, as determined by ABPM,
exceed CBP levels (16).
Several studies found ABPM parameters to be stronger
predictors of renal function (17) and of LVH than CBP. Left
ventricular mass significantly correlated with awake systolic
BP (16, 18) and with mean 24-hr systolic BP (19) much better
than with the CBP. In only one study (20), no significant
relationship between LVH and ABPM-derived AHT was
found. However, in this investigation, including 45 renal
transplant children (40% of them with both daytime and
nighttime AHT and 22% with only nighttime AHT, with a
prevalence of LVH of 72% before transplantation, 75% immediately after transplantation, and 54% at the time of
ABPM), ABPM-derived hypertension was defined according
to the task force criteria and not to the ABPM normative data
in children, provided by the study of Soergel et al. (21).
Concerning white coat hypertension, its prevalence in renal transplant patients is not known; it was 12% in a personal investigation including 68 renal transplant patients
and 32% in a study by Kooman et al. (15). Thus, ABPM is
required to properly diagnose AHT and to assess BP control
in a large number of transplant patients, and we believe
there is enough evidence to support the recommendation of
its regular use in these patients. We indicate two ABPM
measurements during the first posttransplant year and one
every year thereafter.
CIRCADIAN VARIABILITY OF BP

As in many renal and dialysis patients (22), in renal transplant recipients, a nondipper pattern of the nocturnal BP is
common, with a prevalence of up to 90% (15, 16, 23–25),
although different studies used different definitions of nondipping (Fig. 1). In the first months after renal transplantation, it is common to find a loss of the normal circadian
rhythm, which is usually recovered after 1 year, when the
dose of immunosuppressives is lower and when the renal
function is normal. In those cases where the NDP persists,
the graft function is often altered (24, 26). In a study by Faria
et al., 12 cyclosporine A (CsA)-treated renal transplant patients were found to have high mean 24-hr BP levels 8 to 10
days after renal transplant, with a significant decrease after
35 to 40 days. An NDP was found on both occasions, but with
a tendency toward attenuation in the second phase, associated with decrease of the fluid overload and of the doses of
immunosuppressive drugs (27). In the study by Gatzka et al.,
the prevalence of dippers increased from 27% in the early
posttransplant phase (⬍7 months) to 73% in the late phase
(⬎1 year), this effect being independent of the level of mean
24-hr BP and of the antihypertensive and immunosuppressive medication (24). Large prospective studies investigating
the posttransplant changes in the circadian BP variability
would be valuable.

FIGURE 1. Nondipper circadian profile pressure (NDP) in a
renal transplant patient. The BP is adequately controlled for
most of the daytime period (casual office blood pressure
CBP) and increased during the nighttime (“riser” profile).

The cause of nocturnal hypertension is unclear. However,
it does not seem to be related to the degree of autonomic
dysfunction (18) or the quality of BP control (5). The existing
evidence supports the hypothesis that it is secondary to underlying parenchymal or renovascular disease or to immunosuppressive therapy with CsA and corticosteroids (5, 28).
In normotensive renal transplant patients, Lipkin et al.
found an NDP more frequently among CsA-treated patients
and associated with a higher left ventricular mass (16). The
mechanism by which CsA impairs the nocturnal fall in BP is
unclear and presumably is an increase in sympathetic nerve
activity or sodium retention (28).
In pediatric renal transplant patients, Lingens et al. found
in one study an NDP in 11 of 34 subjects. In the first year
posttransplant, four of seven patients had a reduced dip
without any obvious cause, but beyond the first year the NDP
was always associated with a renal disease (26). In another
study including 27 children who had undergone transplantation 1.5 to 8.4 years before, an NDP was found in eight
patients, all of these having a renal disease: renal artery
stenosis in three patients, chronic rejection in three patients,
recurrent focal segmental glomerulosclerosis in one patient,
and past acute rejection in one patient (14). In 36 renal
transplant recipients with chronic transplant nephropathy,
Kooman et al. found a significant relation between the
nightly decline in mean BP and the creatinine clearance,
regardless of the time after transplantation and of immunosuppressive therapy (CsA or tacrolimus) (15).
CONCLUSION

AHT is common in renal transplant patients, is often associated with other risk factors, and plays a major role in the
progression of the kidney graft failure and in cardiovascular
morbidity and mortality. Thus, BP control is a main objective
in these patients. Large differences, without any predictable
relation, are seen between casual and 24-hr BP levels, probably because of the white coat effect, particular antihypertensive regimens, or a disturbance in the circadian profile. In
renal transplantation, as in nephrology and dialysis, ABPM

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seems a better predictor of target organ damage than CBP,
but prospective trials of a large sample size and longer follow-up are necessary to confirm this. The NDP is common in
renal transplant patients, especially in the early transplant
phase, probably because of high doses of immunosuppressive
drugs. The persistence of this NDP in the late posttransplant
phase is usually associated with renal disease: renal graft
artery stenosis, chronic rejection, or others. The presence of
NDP might require an adaptation of antihypertensive treatment, with higher evening doses. The value of ABPM in renal
transplant recipients will be adequately appreciated only
when a prospective trial is undertaken, with BP therapy
decisions based on ABPM versus office BP measurements, in
matched cohorts, and with graft survival and major adverse
cardiovascular events as hard endpoints.
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