AMBULATORY BLOOD PRESSURE MONITORING IN RENALTRANSPLANTATION: SHOULD ABPM BE ROUTINELY

PERFORMED IN RENAL TRANSPLANT PATIENTS?

ADRIAN COVIC,1,3 LIVIU SEGALL,1 AND DAVID J. A. GOLDSMITH,2

In renal transplant recipients, hypertension is com-mon and associated with increased cardiovascularand allograft rejection risks. Ambulatory blood pres-sure monitoring is required for its accurate diagnosisand adequate treatment, as it clearly offers severaladvantages over office or casual blood pressure mea-surements. First, it correlates better with target-organdamage and with cardiovascular mortality. Second,ambulatory blood pressure monitoring can eliminatewhite coat hypertension. Most important is the iden-tification of nocturnal hypertension, an independentcardiovascular risk factor. A circadian nondippingpattern is often found in renal transplant recipients,most probably resulting from cyclosporine A and per-sistent fluid overload in the early posttransplantphase (approximately 70% prevalence), but reflectingan underlying renal (parenchymal or vascular) allo-graft disease when persistent (approximately 25%prevalence) beyond the first year posttransplant.

It has been clear for some years now that ambulatory bloodpressure monitoring (ABPM) is superior to casual (office)blood pressure (CBP) measurements as a predictor of targetorgan damage and morbid cardiovascular events (left ven-tricular hypertrophy, hypertensive cerebrovascular disease,retinopathy, renal abnormalities, and alterations in vascularcompliance) in patients with arterial hypertension (AHT) (1,2). This is the conclusion of nearly every study performed inthe past 10 years, although there may be certain limitationsto these data, including relatively small sample sizes for anoutcome trial, heterogeneous patient populations (e.g.,treated and untreated), and relatively short duration of fol-low-up. Also, patients whose nocturnal (or sleep) blood pres-sure (BP) remains high (i.e., nondipper circadian profile[NDP]) have a worse outcomean up to threefold higher rateof cardiovascular eventsthan patients whose nocturnal BPdecline is at least 10% or more (3). ABPM seems usefulespecially in patients with borderline AHT, possible white-coat AHT, and refractory AHT (2, 4).

ABPM IN NEPHROLOGY

Arterial hypertension is a major factor of progression ofglomerular diseases toward chronic renal failure and of thelatter toward end-stage renal disease. ABPM has been in-creasingly used by nephrologists in the past 10 years, allow-ing a better understanding of the relationship between AHT

and kidney diseases (1, 5). According to several studies,ABPM seems to be more useful than the casual measurementof BP, as it correlates better with target-organ damage (suchas left ventricular hypertrophy and dilatation) in prospectivestudies (6), provides a greater predictive value of cardiovas-cular morbidity and mortality (1, 7), and may be more repro-ducible (8). Both ABPM levels and the circadian variability ofBP significantly correlate with microalbuminuria, develop-ment of proteinuria, and progression of renal disease (9).

An NDPusually defined as a nocturnal decrease in BP ofless than 10% with respect to diurnal BPhas been foundmore often in patients with renovascular hypertension, au-tosomal dominant polycystic kidney disease, immunoglobu-lin A nephropathy, chronic renal failure, dialysis (both hemo-and peritoneal dialysis), and renal transplantation than inother populations (1, 5, 9). The NDP might be related tosevere AHT in some patients, but it was also found to beassociated with mild AHT or even with a normal BP (5). It isnot yet known whether the NDP is a factor contributing to ora consequence of renal disease.

AHT IN RENAL TRANSPLANT RECIPIENTS

AHT is present in 60% to 80% of renal transplant recipi-ents and it is usually associated with left ventricular hyper-trophy (LVH) (5). Several factors may contribute to post-transplant AHT: (1) allograft dysfunction resulting fromacute rejection or chronic allograft nephropathy; (2) treat-ment 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 graftfailure (11) and in the cardiovascular morbidity and mortal-ity (5), together with other risk factors frequently present inmost renal transplant patients, such as diabetes, hypercho-lesterolemia, obesity, and LVH (12). A large study includingalmost 30,000 renal transplant patients, with a 7-year fol-low-up period, clearly showed that the graft survival rate wassignificantly related to both systolic and diastolic BP (11).AHT is likely to aggravate immune lesions; it is well knownthat immune and nonimmune mechanisms contribute tochronic rejection (11).

AHT is also a strong predictor of acute rejection: of 1,641transplant recipients, acute rejection developed in 81% ofthose whose BP increased compared with 22% of those whoseBP decreased after transplantation (13). From the above, itbecomes clear that tight BP control is a key objective in renaltransplant patients, and for this purpose ABPM might be auseful tool.

ABPM VERSUS CBP MEASUREMENTS IN RENALTRANSPLANT PATIENTS

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

1 C. I. Parhon University Hospital, Dialysis and TransplantationCenter, Iasi, Romania.

2 Renal Unit, Guys Hospital, London, United Kingdom.3 Address correspondence to: Adrian Covic, M.D., Ph.D., Dialysis

Unit, C. I. Parhon University Hospital, Dialysis and TransplantationCenter, Blvd. Carol 1st, No. 50, Iasi 6600, Romania. E-mail:acovic@xnet.ro.

Received 23 December 2002. Revision requested 24 March 2003.Accepted 17 June 2003.

DOI: 10.1097/01.TP.0000091288.19441.E2

TRANSPLANTATION1640 Vol. 76, No. 11

BP category (i.e., hypertensive or normotensive) by bothmethods (14). Unfortunately, no algorithm or regressionequation can be determined from comparative studies, be-cause ABPM is both underestimated and overestimated byCBP measurements (15). Overestimation may be attribut-able to white-coat hypertension or to a normal nocturnaldipping, whereas underestimation could be explained by thefact that the studied patients take their antihypertensivemedication 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 strongerpredictors of renal function (17) and of LVH than CBP. Leftventricular mass significantly correlated with awake systolicBP (16, 18) and with mean 24-hr systolic BP (19) much betterthan with the CBP. In only one study (20), no significantrelationship between LVH and ABPM-derived AHT wasfound. However, in this investigation, including 45 renaltransplant children (40% of them with both daytime andnighttime AHT and 22% with only nighttime AHT, with aprevalence of LVH of 72% before transplantation, 75% im-mediately after transplantation, and 54% at the time ofABPM), ABPM-derived hypertension was defined accordingto the task force criteria and not to the ABPM normative datain children, provided by the study of Soergel et al. (21).

Concerning white coat hypertension, its prevalence in re-nal transplant patients is not known; it was 12% in a per-sonal investigation including 68 renal transplant patientsand 32% in a study by Kooman et al. (15). Thus, ABPM isrequired to properly diagnose AHT and to assess BP controlin a large number of transplant patients, and we believethere is enough evidence to support the recommendation ofits regular use in these patients. We indicate two ABPMmeasurements during the first posttransplant year and oneevery year thereafter.

CIRCADIAN VARIABILITY OF BP

As in many renal and dialysis patients (22), in renal trans-plant recipients, a nondipper pattern of the nocturnal BP iscommon, with a prevalence of up to 90% (15, 16, 2325),although different studies used different definitions of non-dipping (Fig. 1). In the first months after renal transplanta-tion, it is common to find a loss of the normal circadianrhythm, which is usually recovered after 1 year, when thedose of immunosuppressives is lower and when the renalfunction is normal. In those cases where the NDP persists,the graft function is often altered (24, 26). In a study by Fariaet al., 12 cyclosporine A (CsA)-treated renal transplant pa-tients were found to have high mean 24-hr BP levels 8 to 10days after renal transplant, with a significant decrease after35 to 40 days. An NDP was found on both occasions, but witha tendency toward attenuation in the second phase, associ-ated with decrease of the fluid overload and of the doses ofimmunosuppressive drugs (27). In the study by Gatzka et al.,the prevalence of dippers increased from 27% in the earlyposttransplant phase (7 months) to 73% in the late phase(1 year), this effect being independent of the level of mean24-hr BP and of the antihypertensive and immunosuppres-sive medication (24). Large prospective studies investigatingthe posttransplant changes in the circadian BP variabilitywould be valuable.

The cause of nocturnal hypertension is unclear. However,it does not seem to be related to the degree of autonomicdysfunction (18) or the quality of BP control (5). The existingevidence supports the hypothesis that it is secondary to un-derlying parenchymal or renovascular disease or to immuno-suppressive therapy with CsA and corticosteroids (5, 28).

In normotensive renal transplant patients, Lipkin et al.found an NDP more frequently among CsA-treated patientsand associated with a higher left ventricular mass (16). Themechanism by which CsA impairs the nocturnal fall in BP isunclear and presumably is an increase in sympathetic nerveactivity or sodium retention (28).

In pediatric renal transplant patients, Lingens et al. foundin one study an NDP in 11 of 34 subjects. In the first yearposttransplant, four of seven patients had a reduced dipwithout any obvious cause, but beyond the first year the NDPwas always associated with a renal disease (26). In anotherstudy including 27 children who had undergone transplan-tation 1.5 to 8.4 years before, an NDP was found in eightpatients, all of these having a renal disease: renal arterystenosis 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 renaltransplant recipients with chronic transplant nephropathy,Kooman et al. found a significant relation between thenightly decline in mean BP and the creatinine clearance,regardless of the time after transplantation and of immuno-suppressive therapy (CsA or tacrolimus) (15).

CONCLUSION

AHT is common in renal transplant patients, is often as-sociated with other risk factors, and plays a major role in theprogression of the kidney graft failure and in cardiovascularmorbidity and mortality. Thus, BP control is a main objectivein these patients. Large differences, without any predictablerelation, are seen between casual and 24-hr BP levels, prob-ably because of the white coat effect, particular antihyper-tensive regimens, or a disturbance in the circadian profile. Inrenal transplantation, as in nephrology and dialysis, ABPM

FIGURE 1. Nondipper circadian profile pressure (NDP) in arenal transplant patient. The BP is adequately controlled formost of the daytime period (casual office blood pressureCBP) and increased during the nighttime (riser profile).

FORUMDecember 15, 2003 1641

seems a better predictor of target organ damage than CBP,but prospective trials of a large sample size and longer fol-low-up are necessary to confirm this. The NDP is common inrenal transplant patients, especially in the early transplantphase, probably because of high doses of immunosuppressivedrugs. The persistence of this NDP in the late posttransplantphase is usually associated with renal disease: renal graftartery stenosis, chronic rejection, or others. The presence ofNDP might require an adaptation of antihypertensive treat-ment, with higher evening doses. The value of ABPM in renaltransplant recipients will be adequately appreciated onlywhen a prospective trial is undertaken, with BP therapydecisions based on ABPM versus office BP measurements, inmatched cohorts, and with graft survival and major adversecardiovascular events as hard endpoints.

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