Hypertension after kidney transplantation

Annual risk of fatal or nonfatal cardiovascular events in kidney transplant recipients is 3.5–5%, which is about 50-fold higher than in healthy individuals [1]. Among the many risk factors, a crucial role is played by hypertension, a condition affecting 80–85% of patients [2–4]. Hypertension is also an important risk factor for accelerated graft loss. A retrospective study on 277 kidney transplant recipients showed that each 10-mmHg increase in either SBP or DBP at 1 year after transplant was independently associated with an incremental reduction in graft survival [5]. Similarly, results from a registry analysis of 29 751 patients demonstrated that uncontrolled hypertension after transplant is associated with higher risk of allograft failure, irrespective of rejection episodes and antihypertensive medications [6]. Consistently, retrospective studies showed that blood pressure control improves graft survival in renal transplant recipients [7,8]. Moreover, in line with trials showing that reducing blood pressure decreases the cardiovascular risk in nontransplant patients [9,10], Opelz and Döhler [8] found that lowering SBP, even after 3 years since the onset of posttransplant hypertension, significantly prolongs both graft and patient survival. Thus, blood pressure control should have a pivotal role in the care of kidney transplant patients in order to improve long-term outcomes. Nevertheless, most kidney transplant patients still suffer uncontrolled hypertension and there is no universal agreement as to the optimal blood pressure goals [2,11]. In addition, there are no randomized, controlled trials comparing different antihypertensive drugs or optimal blood pressure goals in these patients. On the basis of clinical trials in nontransplant populations at high cardiovascular risk with and without kidney disease, the Kidney Disease Outcomes Quality Initiatives (KDOQI) guidelines recommend blood pressure goals of 125/75 and 130/80 mmHg for transplant recipients with or without proteinuria, respectively [11]. Whether these targets are in fact associated with improved outcomes in renal transplant recipients, as in the general population, have not been documented yet. In the current issue of the Journal of Hypertension, Chatzikyrkou et al.[12] reviewed data on prevalence, pathogenesis and management of hypertension after kidney transplantation. By considering the lack of controlled trials, this piece has the merit of carefully summarizing available knowledge and gives therapeutic advice for hypertension treatment in kidney transplant recipients. The strategy to reduce blood pressure after kidney transplant is largely based on results from nontransplant patients with hypertension. Consistently, treatment should start with nonpharmacologic interventions, such as weight reduction, exercise, smoking cessation and dietary sodium restriction. Still, simultaneous initiation of nonpharmacologic and pharmacologic treatment is frequently required to reach target levels [13]. Calcium channel blockers, diuretics, β-blockers, α1-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) have all been used to reduce blood pressure after renal transplantation. Because of the paucity of data favoring any particular antihypertensive class, both the KDOQI and the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines do not specify any individual class of antihypertensive medication for the treatment of posttransplant hypertension [11,14]. On the contrary, in choosing the antihypertensive treatment, it should be considered that, as demonstrated by functional and structural changes of chronic renal allograft failure, kidney graft is somehow the human equivalent of experimental models of remnant kidney in animals in which a low nephron mass promotes glomerular hyperfiltration and initiates a self-perpetuating process of progressive renal function loss [15]. Thus, the same therapeutic approaches able to retard progression of chronic kidney disease are expected to be effective in kidney transplant patients as well. Taking advantage of strategies developed to preserve renal function in patients with chronic kidney disease might be crucial to improve renal graft outcome in the long term. Despite similar blood pressure control, antiproteinuric effect of ACE inhibitors has been consistently associated with slower renal disease progression compared with other antihypertensive agents not interfering with the renin–angiotensin–aldosterone system (RAAS) in patients with chronic renal disease and proteinuria [16]. As proteinuria represents a major predictor of patient and graft survival [17], the same should apply also to kidney transplant patients. Consistently, in patients with established graft interstitial fibrosis and tubular atrophy, treatment with ACE inhibitors/ARBs significantly prolonged graft survival compared with untreated patients [18]. Intriguingly, use of ARBs may have the specific additional effect of antagonizing non-human leukocyte antigen antibodies targeting angiotensin type 1 receptor [19]. A retrospective analysis of 2031 kidney transplant patients showed that use of ACE inhibitors or ARBs was associated with a 45 and 43% lower risk of graft failure and mortality, respectively [20]. Thus, evidence concurs to suggest that RAAS inhibitors should be regarded as the first-choice treatment in kidney transplant patients with hypertension. Nonetheless, transplant physicians still have some reluctance in using these drugs, owing to the risk of renal function worsening and hyperkalemia. The review by Chatzikyrkou et al.[12] correctly pointed out the urgent need for ad-hoc designed, randomized, controlled trials comparing face-to-face the safety/efficacy profiles of different antihypertensive agents in kidney transplant patients with hypertension. Until such evidence will be provided, recommendations for patients with hypertension and chronic kidney disease should be extended to kidney transplant patients that have, by definition, an insufficient nephron mass. RAAS inhibition should be implemented with cautious uptitration with the dual aim of controlling hypertension and protecting the graft from the consequences of chronic hyperperfusion and hyperfiltration. Finally, patients should be warned of the importance of having a lifestyle that includes physical activity, salt restriction and avoidance of smoking, especially in light of their extremely high cardiovascular risk. Acknowledgements Conflicts of interest There are no conflicts of interest.