Lora Schwartz

Cyclosporine-induced hypertension after transplantation

OBJECTIVE To describe the features and mechanisms of posttransplantation hypertension and suggest appropriate management of the disorder. DESIGN We review our own experience and reports from the literature on hypertension in cyclosporine A (CSA)-treated transplant recipients. RESULTS Soon after immunosuppression with CSA and corticosteroids, hypertension develops in most patients who undergo transplantation. The blood pressure increases, which are usually moderate, occur universally because of increased peripheral vascular resistance. Disturbances in circadian patterns of blood pressure lead to loss of the normal nocturnal decline, a feature that magnifies hypertensive target effects. Changes in blood pressure sometimes are severe and associated with rapidly developing target injury, including intracranial hemorrhage, left ventricular hypertrophy, and microangiopathic hemolysis. The complex mechanisms that underlie this disorder include alterations in vascular reactivity that cause widespread vasoconstriction. Vascular effects in the kidney lead to reduced glomerular filtration and impaired sodium excretion. Many of these changes affect local regulation of vascular tone, including stimulation of endothelin and suppression of vasodilating prostaglandins. Effective therapy includes use of vasodilating agents, often calcium channel blocking drugs. Caution must be exercised to avoid interfering with the disposition of CSA or aggravating adverse effects relative to kidney and electrolyte homeostasis. CONCLUSION Recognition and treatment of CSA-induced hypertension and vascular injury are important elements in managing the transplant recipient.

Cyclosporin-induced hypertension. Incidence, pathogenesis and management

Blood pressure increases soon after administration of immunosuppressive regimens using cyclosporin. Characteristic vascular changes lead to systemic and renal vasoconstriction. Changes in blood pressure are commonly associated with disturbed circadian regulation and may promote the rapid development of target organ injury, including intracranial haemorrhage, left ventricular hypertrophy and microangiopathic haemolysis. The mechanisms underlying this disorder are complex and include altered vascular endothelial function. Vasodilators such as pro-stacyclin and nitric oxide are suppressed, whereas vasoconstrictors, including endothelin, are increased. Changes in the kidney include vasoconstriction, reduced glomerular filtration and sodium retention. Effective therapy depends upon rigorous blood pressure control by administration of vasodilating agents, with attention to potential interactions with cyclosporin.

Role of steroid dose in hypertension early after liver transplantation with tacrolimus (FK506) and cyclosporine.

Transplant immunosuppression using either cyclosporine (CsA) or tacrolimus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despite producing similar effects within the kidney and blood vessels, clinical hypertension occurs less frequently with tacrolimus during the first year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blood pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose (TAC-LO-P,n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 month, hypertension occurred more often with CsA (72%) than with TAC-HI-P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after transplantation, hypertension developed in nearly twice as many TAC-HI-P (63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely paralleled cumulative steroid dose in the first month in the TAC-HI-P and TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bolus steroids for treatment of rejection within the first month, compared with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 months to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These results demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus immunosuppression. Both daily dose and cumulative dosage, including bolus treatment for rejection, may impact on the development of hypertension. Since prevalence rates rise to levels comparable to CsA by 24 months regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttransplant course.

Improved Blood Pressure Control With a Physician-Nurse Team and Home Blood Pressure Measurement

OBJECTIVE To assess whether a physician-nurse team model could improve long-term hypertension control rates by active intervention and modification of antihypertensive drug regimens based on home blood pressure (BP) measurements. PATIENTS AND METHODS This study consisted of patients referred to a hypertension specialty clinic between July 1999 and June 2002 for the evaluation and management of uncontrolled hypertension. Patients were evaluated initially by a physician. A treatment plan was designed and implemented subsequently by a hypertension nurse specialist. Each patient was given an automated digital home BP monitor and requested to provide 42 BP readings taken during 7 days at intervals of 1, 3, 6, 9, and 12 months after dismissal from the clinic. The mean of these weekly values was reviewed by the physician-nurse team, and the treatment regimen was adjusted to achieve a goal BP of less than 135/85 mm Hg. RESULTS One hundred six consecutively referred patients were enrolled in the study (mean+/-SD age, 64+/-14 years; 58% female; baseline BP, 156+/-16/85+/-11 mm Hg). Ninety-four patients submitted BP data after 1 month, and 78 patients completed the entire 12-month study period. Overall, mean BP decreased to 138+/-17/78+/-8 mm Hg at 1 month and to 131+/-9/75+/-7 mm Hg at 12 months (P<.01 vs baseline). The percentage of patients who achieved BP control to less than 135/85 mm Hg increased from 0% at baseline to 63% at 12 months. Intensification of antihypertensive drug therapy was required, on average, in 24% of patients at each study interval. The mean number of drugs increased from 1.2 at baseline to 2.0 at 12 months (P<.01). CONCLUSION The use of home BP measurement by a physician-nurse team has the potential to significantly improve long-term hypertension control rates in a geographically dispersed patient population. This model should reduce both cost and inconvenience associated with the treatment of hypertension.

Hypertension after liver transplantation. A predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations

Hypertension developing after liver transplantation during immunosuppression with cyclosporine A reflects an unusual hemodynamic transition from peripheral vasodilation to systemic and renal vasoconstriction. Although dihydropyridine calcium channel blockers are often administered for their efficacy in promoting vasodilation, some liver transplant recipients report marked symptomatic intolerance to these agents. In the present study we examined systemic and renal responses to isradipine using systemic (thoracic bioimpedance) and renal hemodynamic measurements in 15 liver transplant recipients studied at the time of initial diagnosis of posttransplant hypertension and after 3 months of treatment. Circadian blood pressure patterns were examined by overnight ambulatory blood pressure monitoring before and during antihypertensive therapy. During isradipine administration, blood pressure decreased from 151 +/- 3/91 +/- 2 to 130 +/-3/81 +/- 2 mm Hg (P < .01) without change in renal blood flow (406 +/- 43 to 425 +/- 52 mL/min/1.73m2, P = NS) or renal vascular resistance index (25,674 +/-3312 to 20,520 +/- 2311 dynes x sec x cm(-5)/m2, P = NS). Pre-treatment differences in systemic vascular tone persisted during treatment and predicted the tendency for symptomatic tachycardia and flushing, predominantly in those with hyperdynamic circulations. Twice daily dosing of isradipine was associated with partial and significant restoration of the nocturnal decrease in blood pressure (systolic blood pressure decreased 5.5%, normal 13%), usually absent early after transplantation. Our results demonstrate the ability of hemodynamic measurements to predict the symptomatic response to antihypertensive therapy in the posttransplant setting.

Hypertension: Role of the Nurse-Therapist*

In this article, we describe the evolution of the hypertension nurse-therapist program at the Mayo Clinic. Because of the large numbers of patients in whom hypertension is a major risk factor for cardiovascular disease, a leading cause of death in the United States and other industrialized nations, an approach was devised in which, with physician supervision, specially trained nurses managed many aspects of the acute and long-term outpatient care of hypertensive patients. Clinical trials in which nonphysician care-providers were used to treat hypertensive patients and to maintain long-term blood pressure control provided an opportunity to identify and to expand the concept of continuing care for blood pressure management in a community hypertension clinic. Currently, almost 7,000 patient visits are scheduled annually in this program, and these patients are seen by five full-time hypertension nurse-therapists.

Cyclosporine, Blood Pressure and Atherosclerosis

Blood pressure rises soon after administration of immunosuppressive regimens using cyclosporin A, These changes lead to widespread vasoconstriction and increased risk for atherosclerosis. Changes in blood pressure are commonly associated with disturbed circadian regulation and may produce rapidly developing target injury, including intracranial hemorrhage, left ventricular hypertrophy and microangiopathic hemolysis. Mechanisms underlying this disorder are complex and include altered vascular endothelial function. Vasodilators such as prostacyclin and nitric oxide are suppressed, whereas vasoconstrictors, including endothelin, are increased. Changes in the kidney include vasoconstriction, reduced glomerular filtration and sodium excretion. When blood pressure effects are combined with the effects of glucocorticoids and weight gain, changes in cholesterol and triglycerides magnify the risk for atherosclerotic disease. Effective therapy depends upon rigorous blood pressure control and administration of vasodilating agents with attention to the interactions with cyclosporin A. Effective blood pressure control and lipid management is an important component in the long-term management of transplant recipients.