Often persisting for years after transplantation, the condition increases the risk of graft failure.
Hypertension is a common clinical problem in renal transplant patients, and it has important consequences for patient and graft survival. At five years after transplantation, more than 50% of patients have Stage I or Stage II hypertension and nearly 40% of patients have prehypertension.
The proportion of patients receiving two or more antihypertensive agents after renal transplantation has increased steadily to about 55% during the past few decades (Am J Kidney Dis. 2004; 43:1071-1081). Despite the intensive clinical monitoring that follows renal transplantation, post-transplant hypertension often persists for years.
Etiologic factors
The etiology of hypertension in these patients is complex and includes a range of host, donor, allograft, and immunologic factors. Comorbidities are common in patients with end-stage renal disease awaiting transplantation, and these patients have increased rates of diabetes, hypertension, obesity, and glomerulonephritis.
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In normotensive patients, transplantation of a kidney from a donor with a family history of hypertension is associated with a 10-fold increase in the risk of post-transplant hypertension (J Am Soc Nephrol. 1996;7:1131-1138).
Similarly, pre-existing hypertension in the recipient may be reversed by transplant of a kidney from a normotensive donor. Transplantation of a kidney from a hypertensive donor can worsen pre-existing hypertension in the recipient. The expansion of donor criteria has resulted in an increasing number of patients receiving kidneys from donors with hypertension and other risk factors.
Renal artery stenosis (RAS) is an important cause of post-transplant hypertension, and it occurs more frequently with the transplant of a kidney from a living donor than from a cadaver. Other risk factors for post-transplant RAS include pre-existing atherosclerotic disease or fibromuscular dysplasia in the donor, intimal damage during procurement or perfusion, and an end-to-end surgical anastomosis.
RAS should be considered in any renal transplant patient with severe uncontrolled hypertension, an abdominal bruit over the anastomosis, and in recipients of kidneys from younger, Caucasian women.
The risk of hypertension is about 20% in patients receiving exogenous corticosteroid therapy, compared with 70% in those with Cushing’s disease (Blood Press. 1994;3:24-32). Steroid-induced hypertension is characterized by volume expansion, sodium retention, and increased sensitivity to catecholamines. In renal transplant patients receiving low-dose or alternate-day steroids, the risk of steroid-induced hypertension is minimal.
The incidence of post-transplant hypertension has increased concurrently with more widespread use of immunosuppression with calcineurin inhibitors. Nephrotoxicity is almost universal after 10 years of treatment with calcineurin inhibitors and may be accompanied by arterial hyalinosis, striped fibrosis, and tubular calcification (New Engl J Med. 2003;349:2326-2333).
The risk of hypertension is lower in transplant recipients treated with tacrolimus than in those treated with cyclosporine A. Immunosuppression with rapamycin or mycophenolate mofetil is not associated with an increased risk of posttransplant hypertension.
Another important cause of posttransplant hypertension is CKD. The majority of renal transplant recipients have stage 3 or higher CKD and the risk and severity of hypertension increases in proportion to the degree of CKD in the allograft.
Patient, graft outcomes
CVD is the major cause of death in renal transplant recipients, and hypertension is a major risk factor for new-onset CVD following transplantation. CVD accounts for about 46% of overall mortality in patients with functioning renal allografts, followed by infection, malignancy, and other causes. An elevated pulse pressure one year after transplantation is associated with an increased risk for cardiovascular morbidity and mortality in renal transplant patients.
Hypertension directly influences graft survival after renal transplantation. The yearly rate of graft loss is 1.5% in patients who remain normotensive without antihypertensive treatment following transplantation, 2.1% in those who are normotensive with antihypertensive treatment, and 2.9% in those with hypertension despite antihypertensive treatment (Clin Transplant. 2005;19:181-192). A year after transplantation, BP is an independent risk factor for graft failure during the following six years.
Post-transplant BP predicts the rate of acute rejection in renal allograft recipients independently of graft function (Kidney Int. 2001; 59:1158-1164). For every level of post-transplant hypertension, the use of antihypertensive medications decreases the risk of acute allograft rejection.
Graft survival following an episode of acute rejection is also negatively influenced by post-transplant hypertension. The mech-anisms by which post-transplant hypertension influence renal allo-graft function and survival are complex and may include direct effects on microvascular architecture and an independent effect on mediators of acute and chronic allograft nephropathy, including growth factors and major histocompatibility complex II antigens (Kidney Int. 2003;63:2302-2308).
