Ambulatory blood pressure after renal transplantation

Nephrol Dial Transplant (2001) 16 wSuppl 1x: 110±113

Ambulatory blood pressure after renal transplantation Francisco Ferna ndez-Vega, Fernando Tejada, Jose Baltar, Ana Laures, Ernesto Go mez and Jaime Alvarez Servicio de NefrologõÂa 1, Hospital Central de Asturias, CuCelestino Villamil sun, 33006 Oviedo, Spain

Abstract Renal transplantation has been a usual medical practice in developed countries for several decades. A large number of studies report the excellent results obtained with such a practice. The survival of the graft, although able to be improved, is excellent and gives a great deal of hope to patients with renal insuf®ciency. The high level of investigation into immunosuppressor drugs offers, almost continuously, more ef®cient and better tolerated products. Paradoxically, the usual problems of patients with a renal transplant are not immunological but cardiovascular. Elevated serum cholesterol levels, obesity, diabetes and other cardiovascular risk factors (CVRFs) are usual in these patients, arterial hypertension (AHT) being the most frequent. Nephrologists are increasingly using ambulatory blood pressure monitoring (ABPM) on a daily basis. In the last 10 years, we have obtained highly valuable and interesting results with this technique which have allowed us to study and understand with greater precision the relationship of AHT to the kidney. Here we analyse and review the most relevant aspects of ABPM in the different stages of kidney disease, with special emphasis on renal transplantation. Keywords: ambulatory blood pressure monitoring; cardiovascular risk; hypertension; non-dipper pattern; renal transplantation

Introduction Arterial hypertension (AHT) is a key factor in the genesis and evolution of many renal diseases and is present in the different stages of chronic renal failure (CRF), dialysis and renal transplantation w1±6x. Cardiovascular disease (CVD) constitutes the most frequent cause of death in these patients, and AHT and Correspondence and offprint requests to: Dr Francisco FernaÂndezVega, Servicio de NefrologõÂa 1, Hospital Central de Asturias, CuCelestino Villamil sun, 33006 Oviedo, Spain. #

left ventricular hypertrophy (LVH) are frequent and independent risk factors of cardiovascular morbidity and mortality (CVMM) w6±8x. The prevalence of AHT in patients with a renal transplant is highly elevated, ;60±80%, and is usually associated with LVH. For this reason, AHT in renal transplantation should be the object of permanent study on the part of the clinician in order to avoid CVD and deleterious effects on graft function w3,9,10x. In recent years, ambulatory blood pressure monitoring (ABPM) has become an indispensable technique in patients in whom AHT is suspected. Several studies have demonstrated that ABPM is a useful, more advantageous and ef®cient technique than the measurement of blood pressure (BP) in the of®ce, as it is more reproducible, provides a greater predictive value of CVMM and correlates better with target organ damage w11±17x.

ABPM and kidney disease In the renal patient, different risk factors contribute to the development of CVD. In recent years, many other factors such as homocysteine, acute phase reactants, lipid peroxidation, advanced glycation end products, etc. have been added to the classic cardiovascular risk factors (CVRFs), conditioning an elevated prevalence of diffuse atherosclerosis in nephropathies w18x. In patients with renal disease, AHT is a very frequent ®nding, and essential AHT is responsible for renal failure. It is well known that AHT constitutes the second most common cause of end-stage renal disease w6x. Observational studies have demonstrated the relationship of AHT in dialysis patients to the risk of developing LVH, coronary disease and cardiac failure, and also the relationship of these entities to mortality. Thus, a correlation between AHT and mortality has been demonstrated, although not all studies are in agreement w7,8x. In short, we are talking of patients with an extremely high prevalence of CVRFs among which the most frequent are AHT and LVH, and who are carriers of the risk factors from the situation before dialysis w7,19±21x.

2001 European Renal Association±European Dialysis and Transplant Association

Ambulatory blood pressure monitoring after renal transplantation

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Fig 1. Non-dipper pattern in the ABPM registry in a renal transplant patient.

This indicates a worrying and insuf®cient control of BP in these patients, which can be among other causes interpreted as a certain lack of awareness on the part of clinicians and patients with respect to such situations w22x. Fortunately, nephrologists possess a tool that has been demonstrated to be extremely useful in clinical practice, namely that of ABPM w11x. The technique has provided advantages and has allowed nephrologists to study AHT together with different renal parameters and also its in¯uence on the progression of renal disease of diverse aetiology. The relationship between ABPM and the presence of renal damage such as microalbuminuria has been well documented, similar to the concordance between circadian variability (quotient or difference between the mean variables of diurnal and nocturnal BP) and microalbuminaria w16x. In patients with CRF due to AHT and who present a `non-dipper' pattern (NDP) (nocturnal decrease of BP -10% with respect to diurnal BP), the progression of renal failure is signi®cantly greater than that presented by patients with a `dipper' pattern (nocturnal drop of BP P10% with respect to diurnal BP). This demonstrates the prognostic value of circadian variability in the progression of renal disease w23x. On the other hand, a relationship has been described between the decrease in ambulatory BP with antihypertensive treatments and the slope of the reciprocal of serum creatinine, in patients with chronic glomerulonephritis and moderate CRF. The group with the greater decrease in BP showed a greater bene®t with respect to the slope of the reciprocal of serum creatinine w24x. ABPM has also provided considerable information on patients undergoing dialysis. The alteration in circadian rhythm showing an NDP is the clinical ®nding in dialysis patients. Ambulatory BP pre- and

post-dialysis maintains a great dependence on total body water and on dialysis ultra®ltration, respectively. Finally, ABPM in these patients has shown a correlation of BP with target organ damage, in particular with LVH. Furthermore, the parathyroid hormone levels correlate positively with ambulatory BP w25±29x.

ABPM and renal transplantation It is evident that the renal transplant patient `inherits' the cardiovascular risk of previous situations; this is the period that constitutes the pre-dialysis stage of CRF and the time spent on dialysis. The prevalence of AHT in renal transplantation is ;60±80% and is usually associated with LVH, the pathogenesis of which is multifactorial. Although renal function improves in renal transplantation patients, in many transplant patients there is a component of some degree of renal failure, and immunopressive therapy can exacerbate AHT together with many other factors w30x. AHT plays a major role not only in the progression of renal damage in the renal transplant, but also in the survival of the patient. This is associated with other CVRFs such as diabetes mellitus, smoking and advanced age, all contributing to cardiovascular mortality w6,31x From the above, it is clear that the control of AHT in renal transplantation is primordial. ABPM offers considerable possibilities for the study of these patients. Although clinical trials are not yet very numerous, they do provide interesting conclusions. Similarly to patients on dialysis, the NDP is very frequent, with a prevalence as high as 90% w32±35x (Figure 1). The reasons for this frequent alteration of circadian rhythm are unclear and the subject of much

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discussion. We still do not know whether this alteration is a cause or consequence of renal damage. Throughout the nocturnal period, the decrease in the activity of the sympathetic and renin±angiotensin systems produces relaxation of the afferent arterioles, which facilitates the transmission of the elevated systemic pressure to the glomerulus, so causing renal damage. On the other hand, other authors are of the opinion that the NDP is a consequence of renal damage w36x. The underlying renal pathology and immunosuppressive therapy are, according to some authors, factors involved in the persistence of NDP, even though it is certain that the underlying mechanisms are not completely understood. Thus, in the ®rst months after renal transplant, it is common to observe a loss of circadian rhythm, which is usually recovered after 1 year, when the dose of immunosuppressors is lower and the kidney generally is functioning well. In cases where NDP persists, the function of the graft is often altered w33,37x. The increase in ambulatory BP during the nocturnal period has been related to greater target organ damage and with greater risk of CVMM. In this regard, although the studies in patients with renal transplants are few and often small in sample size, they provide interesting data. Thus, once more we can observe the link existing between the loss of circadian rhythm and LVH w38x. The possible predictive value of ABPM with respect to the dysfunction of the graft could be of considerable clinical value. In this sense, data have been published which indicate that ABPM is more closely related to renal function in patients after renal transplantation than casual BP, suggesting that ABPM is superior for the evaluation of hypertension-related renal graft dysfunction. Thus, rigorous BP control by ABPM appears to be mandatory for renal allograft survival w39x. Motivated by the increase in CVMM in the transplanted population, our group has made a transversal study to evaluate the prevalence of AHT, to test the degree of control of BP and to evaluate changes in circadian rhythm and its possible relationship to damage of target organs w40x. A total of 119 patients (68 males) mean age 49"11 years and with a serum creatinine -3 mgudl and a follow-up period after renal transplant of )6 months were analysed. All patients were studied by ABPM (Spacelabs 90202), and BP measurement was also made in the of®ce. Echocardiography was also carried out. Prior to renal transplantation, 47 patients (40%) were normotensive and 72 (60%) were hypertensive. After renal transplantation, the prevalence of AHT was higher (78%). Sixty percent of the hypertensive transplant patients were poorly controlled (of®ce BP )140u 90 mmHg and mean daytime BP )135u85 mmHg); 80 patients (86%) had NDP and 71 (76%) had LVH. No signi®cant differences were found with respect to the alteration of circadian rhythm nor in relation to LVH between the groups with well controlled and with poorly controlled BP, respectively.

F. FernaÂndez-Vega et al.

Our results are striking with respect to the poor control of BP and also to the large percentage of NDP and LVH. We believe that AHT after renal transplantation is conditioned by the previous hypertensive situation during the pre-dialysis and dialysis periods. After renal transplantation, the prevalence of AHT increases further in a signi®cant way, possibly due to the action of cyclosporin. Loss of circadian rhythm is also seen very frequently in both hypertensive and normotensive renal transplant patients, also probably in relation to the immunosuppressor therapy. We think that ABPM and echocardiography should be routinely and periodically studied in patients on dialysis and after renal transplantation since these data will provide us with more exact information allowing a more precise management of AHT.

Conclusions It is evident that ABPM is a useful tool for the nephrologist. In transplanted patients, studies which have employed ABPM for the study of AHT provide very interesting conclusions. On the other hand, it is of high interest to study whether ABPM has a predictive value for the progression of renal damage in transplanted patients, i.e. whether the NDP is related to renal damage and major cardiovascular risk. Some studies point to this, but prospective trials of large sample size and longer follow-up are necessary. In this way, the usefulness of ABPM in renal transplantation will be de®ned in a more complete way. The advantages of effective control of BP over 24 h, and the possibility of analysing the in¯uence on BP of new immunosuppressor drugs and of optimizing therapeutic strategies are well known. Thus, the possible role of prognostic markers could contribute in a de®nitive way to the achievement of a reduction in CVMM, so relevant in these patients.

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