The American Society of Transplantation (AST) defines hypertension in adult renal transplant recipients who are not receiving antihypertensive medications as systolic BP of 140 mm Hg or higher or diastolic BP of 90 mm Hg or higher (J Am Soc Nephrol. 2000;11[Suppl 15]:S1-S86). The National Kidney Foundation recommends target BP values of 135/85 mm Hg for renal transplant recipients without proteinuria and 125/75 mm Hg for patients with proteinuria. Fewer than 30% of renal transplant recipients meet these goals.
BP may fluctuate during the early post-transplant period due to allograft dysfunction, changes in extracellular volume, administration of bolus corticosteroid therapy, and other factors. The BP target for avoiding graft ischemia during the early postoperative period is 160/90 mm Hg.
Treatment recommendations for the control of immediate post-transplant hypertension include continued use of beta blockers, the use of a nicardipene drip if hypertension is uncontrolled, and initiation of calcium channel blocker (CCB) therapy if needed.
Dihydropyridine CCBs have been a mainstay of therapy for long-term control of post-transplant hypertension. Compared with ACE inhibitors, these CCBs improve renal function, may reduce the incidence and severity of organ rejection, increase renal blood flow, and decrease the risk of calcineurin inhibitor-induced nephrotoxicity in renal transplant patients (Transplantation 2001;72:1787-1792).
However, the consequences of the increase in renal blood flow on the chronic progression of allograft dysfunction have not been defined. Dihydropyridine CCBs also increase the degree of proteinuria and this may have a detrimental effect on long term allograft function. Treatment with dihydropyridine CCBs is associated with higher risks of peripheral edema, but less impairment of the hepatic cyto-chrome P-450 enzyme system, than is treatment with other types of CCBs.
This is important because the pharmacokinetics of calcineurin inhibitors will be affected by drugs that alter the P-450 system, which in turn affects the degree of immunosuppression and toxicity of these agents. Treatment with ACE inhibitors has traditionally been avoided during the early post-transplant period until serum creatinine levels have stabilized.
However, recent studies have shown that these drugs can be introduced safely as early as four days post-transplant without affect-ing graft function. Compared with CCBs, ACE inhibitors are more often associated with graft rejection and hyperkalemia. Hypertension control is similar with both drug classes, but post-transplant renal function at two-year follow-up is better with CCBs than with ACE inhibitors.
Angiotensin receptor blockers (ARBs) in the early post-transplant period have also been avoided
to prevent possible detrimental effects on graft function. BP control is similar in hypertensive patients treated with CCBs or ARBs early after renal transplantation (Nephrol Dial Transplant. 2006;21:1389-1394). Hyperkalemia and anemia are more common in transplant patients treated with ARBs than in those treated with CCBs.
ACE inhibitors, CCBs and beta blockers all decrease left ventricular (LV) hypertrophy and improve LV diastolic function in renal transplant patients (Am J Cardiol. 2000;86:583-585). It appears that control of blood pressure is more important than inhibition of a specific biologic pathway. In patients with chronic allograft nephropathy, treatment with ACE inhibitors or ARBs is generally well tolerated and may slow the progression of renal insufficiency and improve allograft survival. These agents would be of particular benefit in patients with proteinuria.
Diuretic therapy is associated with an increased risk of volume depletion and worsening of calcineurin inhibitor-induced nephrotoxicity and is not a major initial component of the management of post-transplant hypertension.
In summary, hypertension is ubiquitous in renal transplant patients and similar to any patient with Stage 1 or Stage 2 hypertension. These patients often require two or three medications to achieve adequate BP control.
Although subtle differences exist in side effects and benefits between the different classes of agents, most renal transplant recipients will usually benefit from a combination of a beta blocker, CCB, and ACEI/ARB. The most important post-transplant objective is to attain target blood pressure goals above all else. This will ultimately translate into improved allograft and patient survival.
Dr. Kupin is associate professor of medicine and associate director of transplant nephrology at the University of Miami Jackson Memorial Medical Center in Florida.