Rapid adjustment of antihypertensive drugs produces a durable improvement in blood pressure.

Antihypertensive drugs are often initiated and adjusted over a period of weeks to months. It is not clear whether the time and inconvenience of this approach is necessary. We studied whether or not drug adjustment over several days in the context of a physician-nurse team could produce a durable blood pressure benefit according to home blood pressure measurements. Sixty-eight patients (aged 65 +/- 1 years, 47% men) were referred for management of hypertension. Indications for referral were new hypertension (13%), known/controlled hypertension (30%), or known/uncontrolled hypertension (57%). Patients had one to three brief nurse visits/day and were provided with an accurate semiautomated device for self-blood pressure (BP) measurement. Sixty patients provided follow-up data. Group 1 (n = 16) required no change in their preexisting drug regimen during clinic visits, whereas group 2 (n = 44) had drug therapy initiated or adjusted over 4 +/- 1 days. Patients were evaluated at baseline, at dismissal from the clinic, and at latest follow-up (mailed-in report of 42 readings taken over 7 days at 1- to 3-month intervals). Mean follow-up was 11 +/- 0.5 months. Mean BP at baseline, dismissal, and latest follow-up for group 1 were 132 +/- 4/73 +/- 2, 130 +/- 6/70 +/- 2, and 125 +/- 3/73 +/- 3 mm Hg (P = not significant). Mean BP for group 2 at the same intervals were 150 +/- 4/80 +/- 2, 139 +/- 3 (P < .01 v baseline)/75 +/- 2, 133 +/- 2 (P < .01 v baseline and < .05 v dismissal)/74 +/- 1 (P < .01 v baseline). The BP control rate (blood pressures less than 140/90 mm Hg) was 75% in group 2. Drug number/dose remained the same or lower in 87% and 91% of patients during follow-up in groups 1 and 2, respectively. These results suggest that a clinically significant lowering of blood pressure can often be achieved over several days and maintained for up to 1 year. Increased use of rapid drug titration, a physician-nurse team approach, and self-BP measurement at prescribed intervals have the potential to improve BP control rates and reduce the expense and inconvenience associated with the treatment of hypertension.

Are aneroid sphygmomanometers accurate in hospital and clinic settings?

BACKGROUND: The aneroid sphygmomanometer is commonly used for the indirect measurement of blood pressure despite significant concerns about its accuracy. Although the mercury sphygmomanometer is highly accurate, there are concerns about the environmental toxicity of mercury. In response to various external pressures to become essentially mercury free, the Mayo Clinic, Rochester, Minn, has replaced many mercury sphygmomanometers with aneroid devices. Since 1993, a maintenance protocol has been in place to ensure proper function and accuracy of these devices. METHODS: We assessed the accuracy of 283 aneroid devices using as the reference standard a digital pressure and vacuum meter that was calibrated using a mercury sphygmomanometer. RESULTS: The mean +/- SD values from the aneroid device in millimeters of mercury at each reference point (at 20-mm Hg intervals from 60 to 240 mm Hg defined by the reference device) were 59.9 +/- 1.9 at 60; 79.9 +/- 1.9 at 80; 100.0 +/- 1.8 at 100; 120.3 +/- 1.8 at 120; 140.7 +/- 1.4 at 140; 160.7 +/- 1.7 at 160; 180.9 +/- 1.3 at 180; 200.7 +/- 5.0 at 200; 221.0 +/- 1.3 at 220; and 240.8 +/- 1.6 at 240 (r = 0.99; P<.001). The values from the aneroid device underestimated those of the reference device by a mean of 0.5 mm Hg (95% confidence interval, 0.3-0.7). Virtually 100% of the values from the aneroid device were within the 4-mm Hg range recommended by the Association for the Advancement of Medical Instrumentation. CONCLUSION: Aneroid sphygmomanometers provide accurate pressure measurements when a proper maintenance protocol is followed.

Posttransplantation hypertension related to calcineurin inhibitors.

Calcineurin inhibitors are a mainstay of transplant immunosuppression and commonly induce hypertension. They are highly lipid soluble and penetrate vascular smooth muscle cell membranes readily. Changes in vascular tone are universally observed during administration of these agents, particularly within the kidney, leading to diminished glomerular filtration and enhanced sodium retention. Disturbances of endothelial function are prevalent in many tissues, including stimulation of endothelin and impaired nitric oxide synthesis. Multiple additional pathways produce increased vasoconstriction, leading to an increase in arterial pressure. Clinical manifestations include disturbances in circadian blood pressure patterns, left ventricular hypertrophy, and acceleration of atherosclerotic and renal injury. Rapid increases in pressure occasionally produce accelerated hypertension and microangiopathic tissue damage. Principles of therapy require recognition of hazards of changing arterial pressures during calcineurin use and preferential use of vasodilating drugs, particularly dihydropyridine calcium channel blocking agents. Attention must be paid to interactions between antihypertensive agents and calcineurin inhibitor blood levels.

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.

Left ventricular diastolic dysfunction in patients with hypertension and preserved systolic function.

OBJECTIVE: To assess prospectively diastolic function in hypertensive patients with preserved left ventricular function, particularly focusing on the limitation of the transmitral flow velocity curve alone to detect diastolic dysfunction. PATIENTS AND METHODS: Comprehensive Doppler analysis was performed in 51 hypertensive patients with preserved left ventricular systolic function. RESULTS: The ratio of the peak early diastolic filling wave velocity to the peak velocity of filling wave at atrial contraction was less than the age-adjusted mean value minus 2 SD in 16 patients, and the other 35 patients had a "normal" transmitral Doppler signal. However, the combined transmitral and pulmonary venous Doppler analysis revealed that 12 of these 35 patients had a "pseudonormal" pattern. The prevalence of diastolic dysfunction was estimated at 31% with use of transmitral Doppler alone but increased to 55% when comprehensive Doppler analysis was used (P < .05). CONCLUSION: The presence of diastolic dysfunction has been frequently overlooked in hypertensive patients with transmitral Doppler analysis alone, and an assessment of diastolic function with a comprehensive Doppler analysis is needed in patients at risk for diastolic dysfunction.

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 prostacyclin 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.

Importance of blood pressure reduction for prevention of progression of renal disease.

Despite reduction of stroke and coronary mortality rates, progression of renal disease to end stage continues to occur with increasing frequency. Recent studies emphasize common pathways of elevated arterial pressures that produce increased glomerular capillary pressures and increase filtered proteins in the urinary space. Such proteinuria, along with activation of the intrarenal renin-angiotensin system, endothelin, and inflammatory cytokines, magnifies progressive renal injury and fibrosis. Malignant forms of hypertension with severe arteriolar injury and proteinuria can be treated effectively with current antihypertensive regimens with improved patient survival. Several recent studies indicate improved renal outcomes in proteinuric diseases, generally regardless of the specific antihypertensive agent. Recent trials of hypertensive subjects with minimal proteinuria demonstrate slower rates of disease progression than that seen in subjects with proteinuria above 1 gram per day. Reduction of arterial pressures, particularly when it leads to reduced proteinuria, can slow the progression of many renal diseases.

Late hypertension after liver transplantation: a comparison of cyclosporine and tacrolimus (FK 506).

Hypertension frequently develops early after liver transplantation when cyclosporine-based immunosuppression is used. However, initial experience with tacrolimus has suggested that its use leads to a lower early incidence of hypertension. In this study, the blood pressure status of patients treated with cyclosporine (n = 131) and those treated with tacrolimus (n = 28) was compared 24 months after liver transplantation. At this time interval, the prevalence of hypertension in the cyclosporine and tacrolimus groups were 82% and 64%, respectively (P < .05). For those patients who were hypertensive by 24 months, onset was delayed in the tacrolimus group compared with the cyclosporine group: 40% versus 71% and 73% versus 93% at 1 and 12 months, respectively (P < .05). Within the cyclosporine group, patients with hypertension were heavier than those with normal blood pressure, 84.7 +/- 1.8 versus 73.4 +/- 4.0 kg, respectively (P < .05). Within the tacrolimus group, hypertensive patients had lower glomerular filtration rates and higher renal vascular resistances compared with normotensive patients, 74 +/- 12 versus 47 +/- 6 mL/min and 15,711 +/- 2,445 versus 28,830 +/- 4,310 dyne/s/cm5/m2, respectively (P < .05). There were no within-group differences for age, gender, pretransplant history of hypertension, family history of hypertension, graft function, or daily doses of prednisone, cyclosporine, or tacrolimus. These results indicate that, compared with cyclosporine, the onset of hypertension after liver transplantation is delayed and less prevalent with tacrolimus. Additionally, hypertension is associated with increased body weight in cyclosporine-treated patients and with more severe renal dysfunction in patients receiving tacrolimus. The relationships of these findings to the development of posttransplant hypertension requires further study.

Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506).

The development of atherosclerotic cardiovascular complications is a common and serious problem for the long-term survivors of organ transplantation. Cyclosporine A plus steroid-based immuno-suppression regimens in these patients are associated with the development of hypertension, hyperlipidemia, obesity, and diabetes mellitus. Whether the new immunosuppressive agent tacrolimus (FK506) confers any advantage in terms of these cardiovascular risk factors has been less well studied. We compared serial changes in blood pressure, lipids, body weight, and glucose levels during the first 12 months after liver transplantation in patients using either cyclosporine A (n = 39) or tacrolimus (n = 24)-based immunosuppression. By 12 months, the prevalence of hypertension, hypercholesterolemia, and obesity was increased in the cyclosporine A group compared to tacrolimus: 82% versus 33%, 33% versus 0%, and 46% versus 29%, respectively (all p < .05). Triglyceride and total cholesterol levels were 196 +/- 23 versus 125 +/- 13 mg/dL and 225 +/- 9 versus 159 +/- 7 mg/dL for the cyclosporine A versus tacrolimus groups, respectively (p < .05). Cumulative posttransplant steroid dose was not related to the observed lipid changes in either group, although the increase in triglycerides was positively correlated to weight gain and diuretic use in the cyclosporine A group. The incidence of diabetes mellitus was not increased from baseline in either group. These results indicate that tacrolimus, compared to cyclosporine A, is associated with a less adverse cardiovascular risk profile in the first year after liver transplantation. Whether these differences persist and become clinically relevant to a liver transplant recipient population that is increasingly older and has more preexisting cardiovascular disease remains to be determined.

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.

Radiographic evaluation of the renal vasculature.

Renal artery stenosis is an important cause of hypertension and progressive renal insufficiency. Additionally, there is increasing concern that renovascular disease is a significant, but previously-unrecognized, cause of end-stage renal disease in certain subsets of patients. Advances in revascularization techniques offer a greater opportunity for blood pressure control and for the restoration or preservation of renal function. Accurate imaging of the renal vasculature, however, is essential for the proper selection of those individuals who might best benefit from such intervention. Although conventional or digital subtraction arteriography remains the gold standard diagnostic test, significant advances in non-invasive imaging techniques now offer the clinician several options for the accurate diagnosis of hemodynamically significant renovascular disease. These techniques include captopril renography, duplex ultrasonography, magnetic resonance angiography, and spiral/fast computed tomography. In this review, the advantages and limitations of these imaging techniques are compared and contrasted with an emphasis on their usefulness in screening for renovascular disease. Also reviewed are recent applications of these techniques for measurement of renal function, predicting outcome of revascularization, and the clinical monitoring of patients with renovascular disease managed either medically or by revascularization.

Hypertension after liver transplantation.

Hypertension developing after liver transplantation is nearly universal and likely reflects several pathogenic mechanisms. Foremost among these are altered vascular reactivity and vasoconstriction related to CSA, and probably FK506, administration, impaired GFR and sodium excretion, and the effects of steroids. This disorder is of both theoretical and practical importance in understanding blood pressure regulation in humans. Most importantly, it poses a considerable long-term cardiovascular risk for the transplant recipient. Recognition of acquired hypertension and timely intervention are among the primary management challenges for the transplant clinician.

Effect of chronic respiratory acidosis on calcium metabolism in the rat.

Chronic metabolic acidosis typically results in hypercalciuria and negative calcium balance. The impact of chronic respiratory acidosis on calcium metabolism has been less well studied. To address this issue, metabolic balance and static bone histomorphometric data were obtained during a 14-day exposure of rats to 10% CO2 (blood pH 7.33, PaCO2 83 mm Hg) and were compared with pair-fed controls. All rats were fed a 0.8% calcium diet. Urinary calcium excretion (mg/period, mean +/- SEM) was increased during both week 1 and week 2 (16 +/- 3 vs 9 +/- 1 and 16 +/- 2 vs 9 +/- 1, CO2 group vs controls, respectively [p < 0.05]). Net intestinal calcium absorption (intake minus fecal excretion) was increased throughout the period of hypercapnia (week 1, 213 +/- 19 mg vs 135 +/- 15 mg; week 2, 135 +/- 16 mg vs 43 +/- 14 mg; and cumulatively, 344 +/- 27 mg vs 178 +/- 20 mg, CO2 group vs controls [p < 0.01]). As a consequence of the marked increment in intestinal calcium absorption during hypercapnia, mean net calcium balance was more positive than that of controls throughout the study (week 1, 197 +/- 18 mg vs 126 +/- 15 mg; week 2, 120 +/- 15 mg vs 34 +/- 15 mg; and cumulatively, 317 +/- 25 mg vs 159 +/- 20 mg, CO2 group vs controls, respectively [p < 0.01]). There were no significant differences in calcium intake, plasma total calcium, immunoreactive parathyroid hormone, 25-hydroxyvitamin D, or creatinine clearance between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Loss of nocturnal blood pressure fall after liver transplantation during immunosuppressive therapy.

Hypertension, which develops after organ transplantation during immunosuppression with cyclosporine (CSA), is often associated with a loss of nocturnal decrease in blood pressure. Few data correlate circadian blood pressure patterns before transplant with those observed at fixed time points after transplant, or address the role of alternate immunosuppressive agents such as FK506. FK506 is unrelated structurally to CSA and less often leads to hypertension early after transplant. The present study compared nocturnal blood pressure patterns in patients with end-stage liver disease (ESLD) before transplant to those of transplant recipients receiving either FK506 (0.15 mg/kg/day) plus prednisone or CSA (2 to 3 mg/kg/day) plus prednisone and azathioprine after orthotopic liver transplantation. Overnight ambulatory blood pressure profiles were studied in 13 pretransplant ESLD patients and in 34 patients (FK506: n = 13; CSA: n = 21) treated with different steroid doses (24 +/- 11 mg/day FK506; 34 +/- 3 mg/day CSA), according to protocol, 4 weeks (range, 2 to 7 weeks) after liver transplant. Mean blood pressure and heart rate values from awake and nocturnal 5-h time blocks were compared to 13 normotensive control subjects. Patients with ESLD were normotensive and maintained a normal nocturnal blood pressure fall (125 +/- 3/74 +/- 2 mm Hg awake; 109 +/- 3/60 +/- 2 mm Hg nocturnal). Awake ambulatory blood pressures were higher in CSA patients than in FK506 patients (148 +/- 3/95 +/- 2 v 128 +/- 3/78 +/- 2 mm Hg, respectively; P < .01), despite reduced glomerular filtration rates in both transplant groups. Both immunosuppressive regimens led to a loss of nocturnal blood pressure fall, as compared to ESLD patients or normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation.

Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET) in this process, we measured plasma and urinary ET before and at intervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rate and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Prednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 10.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained above normal, but not different from pre-transplant levels. Urinary ET was elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1.5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 alpha fell from 2567 +/- 338 ng/day to subnormal levels and remained suppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fell (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular resistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm-5.m-2, P < 0.01). Similar changes were observed both with CsA and FK506-based immunosuppression. No changes in ET were attributable to dihydropyridine calcium channel blockers. These results demonstrate that urinary ET changes independently from plasma ET after transplantation. Elevated ET and suppression of endothelium-derived prostacyclin persist with intense renal vasoconstriction for at least two years after transplant.

Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.

Hypertension is common after orthotopic liver transplantation and may be due, in part, to cyclosporin A-induced renal dysfunction and/or enhanced proximal tubular sodium reabsorption. To determine whether enhanced proximal tubular sodium reabsorption is central to the development of posttransplant hypertension, measurements of renal hemodynamics and fractional clearances of lithium and sodium were compared 1 month after orthotopic liver transplantation in previously normotensive patients receiving either cyclosporin A (N = 24) or FK506 (N = 18), an immunosuppressive agent that is structurally unlike cyclosporin A and that has a lower reported incidence of hypertension. Median prednisone doses were 20 and 13 mg/day in the cyclosporin A and FK506 groups, respectively (P < 0.05). At 1 month, mean arterial blood pressure was higher in the cyclosporin A versus the FK506 group: 108 +/- 2 versus 95 +/- 3 mm Hg (P < 0.05). GFR, RBF, and renal vascular resistance were not different between the two groups: 59 +/- 4 and 53 +/- 5 mL/min per 1.73 m2, 439 +/- 28 and 440 +/- 41 mL/min per 1.73 m2, and 22,429 +/- 1,822 and 22,977 +/- 3,506 dyne s/cm5 per 1.73 m2, respectively. Fractional lithium excretion was similar in the cyclosporin A and FK506 groups: 19.9 +/- 2.2 and 19.4 +/- 2.0% (P = not significant) although both values were lower than those of normal controls (25.5 +/- 1.1%) (P < 0.05). Fractional sodium excretion was 2.7 +/- 0.3 and 2.3 +/- 0.4% in the cyclosporin A and FK506 groups, respectively (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive diagnosis of renovascular disease.

OBJECTIVE: To present the epidemiologic and clinical features of renovascular disease and discuss various diagnostic approaches. DESIGN: We describe the findings in patients with fibromuscular dysplasia or atherosclerotic disease of the renal arteries and review pertinent studies from the literature. RESULTS: Renovascular disease is an important cause of resistant hypertension and progressive renal insufficiency, particularly in the elderly population. Improved blood pressure control and renal function after revascularization have generated intense interest in identifying those patients likely to benefit from this intervention. Fibromuscular dysplasia and atherosclerotic renal artery stenosis account for most cases of renovascular disease. Both entities produce resistant hypertension; the latter is the more common cause of progressive renal insufficiency--occasionally leading to end-stage renal disease. Angiotensin-converting enzyme inhibitor-related renal dysfunction, otherwise unexplained renal insufficiency, and recurrent pulmonary edema are increasingly recognized clinical manifestations of renovascular disease. Traditional screening tests such as intravenous pyelography, intravenous digital subtraction angiography, radionuclide scintirenography, and measurement of the peripheral venous plasma renin activity have limited accuracy for diagnosing renal artery stenosis and do not accurately predict the blood pressure response to revascularization. In comparison, recently developed noninvasive tests such as captopril renography, renal artery duplex sonography, and magnetic resonance angiography seem to be more accurate and, in the case of captopril renography, may be more predictive of the blood pressure response to revascularization. CONCLUSION: Future directions in the area of renovascular disease should include a direct comparison among these new noninvasive diagnostic techniques, with a particular focus on the identification of those patients most likely to benefit from revascularization in terms of both blood pressure control and improved renal function.

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.

Resolution of posttransplant hypertension after liver transplantation despite impaired glomerular filtration.

Hypertension developing after transplantation is characterized by widespread vasoconstriction including the kidney. Late resolution (mean, 29 +/- 4 months) of posttransplant hypertension has been observed in 15 (Group I) of 278 subjects monitored after liver transplantation. These studies were undertaken to define the systemic and renal changes associated with resolution, as compared with a group matched for age, sex, and time after transplant who remained hypertensive (Group II; N = 15) or a group who never developed hypertension (Group III; N = 23). Blood pressure during resolution paralleled changes in the systemic resistance index, which fell from 3,052 +/- 548 to 1,872 +/- 205 dyne/s.cm5/m2 (P < 0.01). GFR and RBF remained low, despite the resolution of hypertension, and renal vascular resistance did not change. Circulating endothelin levels remained above normal in all transplant recipients (Group I, 11.9 +/- 3.0 versus normal subjects, 7.0 +/- 1.1 pg/mL; P < 0.05), and urinary prostacyclin excretion was suppressed (880 +/- 120 versus 2,247 +/- 187 ng/day; P < 0.01). No hormonal differences were apparent between transplant groups. These results demonstrate the capacity for systemic vasodilation to occur after transplantation, independent of vascular tone in the kidney. They further suggest that renal vasoconstriction and impaired GFR alone are not sufficient to explain de novo hypertension after transplantation.

Current role of automated ambulatory blood pressure and self-measured blood pressure determinations in clinical practice.

OBJECTIVE: To discuss the clinical indications for use of automated indirect blood pressure measurement (ABPM) and self-monitoring of blood pressure. DESIGN: Available equipment, variations in blood pressure, and settings in which ABPM may be useful are reviewed. RESULTS: Measurement of blood pressure in the physician's office may not reflect the usual blood pressure in other nonmedical environments, such as at work, at home, or during sleep. Self-measurement of blood pressure at home and work and ABPM can provide this additional information. These procedures can be useful not only for determining the presence of office or "white-coat" hypertension but also for assessing patients with both borderline hypertension in the office and target organ damage, those with drug resistance, and cases of episodic hypertension or hypotension. ABPM can also be used to assess very abrupt changes in blood pressure (hypertension or hypotension) and changes in heart rate and blood pressure during sleep. An abbreviated (6-hour) ABPM can be used to confirm increased office blood pressure measurements. Thus, a 6-hour ABPM has the potential to decrease the misclassification of subjects with hypertension or normotension and to limit costs. CONCLUSION: Accurate self-monitored blood pressure measurements can be integrated with office blood pressure determinations to assist in the management of many patients with hypertension. Both ABPM and self-monitoring of blood pressure can improve blood pressure control and practice efficiencies.