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2001; 4; 248 GraftRichard A. Demme

Hypertension in the Kidney Transplant Patient

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Hypertension in the Kidney TransplantPatient

REVIEW

Richard A. Demme

Hypertension is the second leading cause of end stage renal disease (ESRD) in the UnitedStates and is a major risk factor for cardiovascular disease. Cardiovascular disease is theleading cause of death in renal transplant recipients. Transplant recipients have a highprevalence of hypertension due to a number of underlying mechanisms. Disease in thenative kidneys or in donated kidney and renal artery may contribute to hypertension, ascan use of immunosuppressive agents such as glucocorticoids and calcineurin inhibitors(such as cyclosporine and tacrolimus). As the underlying mechanisms of hypertension arevaried among patients, treatment regimens may be tailored to individuals. A number ofmedications have been shown to be effective in transplant patients, and they are oftenused in combination. The diagnosis and treatment of hypertension in the kidney transplantrecipient is important for long-term patient and allograft survival.

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HYPERTENSION:

Resting blood pressure that is measuredpersistently higher than 140mmHg (systolic)or 90mmHg (diastolic).

Richard A. Demme, M.D.Assistant Professor of MedicineUniversity of Rochester Medical Center—

Nephrology Unit601 Elmwood Avenue, Box 675Rochester, New York, USA 14642Tel.: 716.275.4517Fax: 716.442.9201email: Richard_Demme@URMC.Rochester.edu

IntroductionHypertension is the second leading cause of

ESRD in the United States. Through the 1990s,the age adjusted incidence rates of renal failure dueto hypertension in African Americans has grown tomore than 200 per million population, and over18,000 Americans developed ESRD ascribed tohypertension in 1998. High blood pressure maycontribute to worsening renal function, heart disease,stroke and death. Cardiovascular disease is still theleading cause of death in the kidney transplantpopulation.1 Hypertension is a major risk factorfor cardiovascular disease, and mortality increaseswith increasing blood pressure levels.2,3 In kidneytransplant recipients, hypertension is associated withhyperlipidemia, coronary heart disease and chronicrenal graft failure.4 In one study, pretransplant hyper-tension was associated with chronic progressive graftdysfunction.5

In a recent large-scale study, Opelz et al investigatedthe influence of high blood pressure post-transplantation on long-term kidney allograft survivalin 29,751 patients over a seven year period.6 Theyobserved that higher systolic and diastolic bloodpressures were associated with worse outcomes.There was a progressive increase in risk of allograftloss if the systolic blood pressure was greaterthan 140 mmHg or the diastolic was greater than

90 mmHg. The adverse effect of elevated systolicblood pressures was present even in patients withdiastolic blood pressures less than 90 mmHg, andelevated systolic blood pressure one year aftertransplant was significantly associated with thesubsequent death rate. Another study by Mange, et aldemonstrated that systolic, diastolic and mean arterialblood pressures at one-year post-transplantationstrongly predict allograft survival.7 It is still notclear whether elevations in blood pressure are acause or a result of progressive allograft dysfunction;both are likely.

Hypertension is an important factor in theprogression of renal injury, and control of bloodpressure can delay progression of chronic renal failureof native kidneys.8 No long-term prospective clinicalstudies demonstrating reduced rates of allograftfailure with lowering of recipient blood pressure areavailable yet, but recent studies have advanced theconcept that antihypertensive therapy can slow theprogression of chronic renal graft failure.4,9 Thediagnosis and treatment of hypertension are importantfor transplant patient mortality and graft survival.

What is High Blood Pressure?Kaplan proposed the conceptual definition of

hypertension as “that level of blood pressure atwhich the benefits (minus the risks and costs) of

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REVIEW

LAPAROSCOPIC NEPHRECTOMY:

Removal of a kidney by surgical techniqueusing internal visualization and smallerincisions than in conventional kidneyremoval surgery.

action exceed the risks and costs (minus the benefits)of inaction.”10 Classification of blood pressure issomewhat arbitrary, but has been determined byconsensus. Table 1 represents the categorization ofblood pressure as designated by the Joint NationalCommittee on Prevention, Detection, Evaluationand Treatment of High Blood Pressure in their latestreport (JNC VI).11 Both systolic and diastolicblood pressure have a positive relationship withcardiovascular risk.

Hypertension in Kidney Transplant RecipientsApproximately 50 million adult Americans have

high blood pressure.11 The prevalence of hypertensionin chronic renal disease is approximately 60-100%,depending on the target population, cause of renaldisease and level of kidney function.12 In the generalpopulation, most people do not have a discernibleetiology of their high blood pressure, other thanfamily history. Kidney transplant patients, however,may have a number of additional pathophysiologicfactors which contribute to hypertension. The list ofpotential factors is long (see Table 2), and individualpatients may have several of these mechanisms.

The role of retained native kidneys in systemichypertension in recipients of a well-functioningkidney transplant is not known. The benefit of bilateralnephrectomy of native kidneys is controversial, andthe procedure is certainly invasive. Since multipleclasses of potent antihypertensive agents are nowavailable, native nephrectomy is reserved for selectedpatients with uncontrollable hypertension.13

Recently, laparoscopic nephrectomy has become anoption in certain centers for removal of native kidneys.Advances in this technique allow for shorter hospitalstays and earlier return to normal activities. In onestudy of patients who had poorly controlled hyper-tension despite maximal dosages of three or moreantihypertensive drugs, 13 out of 14 had a markeddecrease in blood pressure and required significantlyfewer antihypertensive drugs after laparoscopicbilateral nephrectomy.14

Some renal diseases recur in transplanted kidneys.For example, focal segmental glomerulosclerosismay recur in kidney transplants in up to 40% of cases,and IgA nephropathy as well as diabetic renal diseasemay also develop again. Recurrence of renal diseasemay be heralded by a worsening of hypertension.15

Less commonly, de novo glomerulonephritis mayoccur after transplant, such as anti-GBM nephritisin patient’s with Alport’s syndrome, hemolytic uremic

syndrome in those on calcineurin inhibitors, ormembranous glomerulonephritis in patients with otherprimary renal disease. These glomerular diseases maycontribute to kidney dysfunction and hypertension.

The donated kidney itself may contribute tohypertension. Due to a shortage of “optimal”organs, many transplant centers are now accepting“expanded criteria” organs; kidneys from olderdonors or those with mild hypertension. Higheraverage blood pressures have been observed inpatients who received kidneys from hypertensivedonors.16 Progressive renal artery stenosis in nativekidney vessels, or transplant renal artery stenosismay cause elevated blood pressure. The incidenceof transplant artery stenosis varies between1-23%.17 Hypertension due to stenosis of thetransplant artery is important to detect, because itis potentially curable. High blood pressure of recentonset with allograft dysfunction, acute renalinsufficiency induced by ACE inhibitors, or bruitover the graft may be clues to transplant artery stenosis,but have unknown sensitivity and specificity.Evaluation of transplant artery stenosis may beperformed by doppler ultrasonography, nuclearrenogram, spiral computed tomography, magneticresonance angiogram, or renal arteriogram withiodinated or CO2 contrast, depending on centerexpertise. There are no large series comparing thesetechniques. Percutaneous transluminal angioplastymay be an option for those patients with focal arterialstenoses. In some patients, surgical correction ofallograft renal artery stenosis may be necessary, butit is a difficult procedure requiring a highly experiencedsurgical team.13 Surgery carries a risk of graft lossof 15-20%.17

Acute and/or chronic rejection may contribute tohypertension. Chronic rejection was a leadingcause of post-transplant hypertension in thepre-cyclosporine era.18 Recent studies have shownthat vascular endothelin (ET-1) expression is notedwith chronic allograft rejection, and correlates withpost-transplant hypertension.19

Erythrocytosis (measured hematocrit above 55%)occurs in 10-15% of those receiving kidney trans-plants and can exacerbate hypertension.20 ACEinhibitors and angiotensin II receptor blockers areeffective in decreasing erythrocytosis and improvingblood pressure control.21 Also, tertiary hyperpara-thyroidism as manifested by hypercalcemia mayalso contribute to post-transplant hypertension.

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REVIEW

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CYCLOSPORINE:

A potent immunosuppressive drug derivedfrom a fungus, used to prevent transplantrejection. It is a calcineurin inhibitor.

The Role of Immunosuppressive Medicationsin Hypertension

Corticosteroids have been a mainstay of theimmunosuppressive regimen for renal transplantationsince the early 1960s. The presence of excess steroidscan cause hypertension as seen in Cushing’s diseaseand Conn’s syndrome. High blood pressure has longbeen associated as a major adverse drug reaction of theadministration of synthetic steroids. Steroids facilitatesodium retention and an increase in plasma volume,which may lead to an increase in cardiac output andblood pressure. A correlation between cortico-steroid dose and the use of antihypertensive drugs hasbeen demonstrated. A fall in systolic and diastolicblood pressure has been reported in studies of electivesteroid withdrawal after kidney transplantation.22

In the pre-cyclosporine era, hypertension wasreported in about 50% of transplant recipients.Since the addition of cyclosporine to the immuno-suppressive regimen, post-transplant hypertensionmay be detected in nearly 75% of kidney trans-plant recipients. In heart transplant recipients, theprevalence of hypertension has increased from 20%before cyclosporine, to 90% in the present era.23

Cyclosporine has been shown to cause an increasein blood pressure in healthy volunteers, as well asin nontransplanted patients who are prescribed itfor inflammatory conditions such as uveitis.24

Cyclosporine raises blood pressure by severalactions (see Table 3). It has been shown to causerenal vasoconstriction in animals and humans.25 Itmay cause cortical ischemia and increased tubularresorption of sodium and hypervolemia. In animals,cyclosporine increases renin production26 andinterferes with NO-mediated vascular relaxation.27

Cyclosporine also reduces vasodilatory prostacyclin,and increases vasoconstrictor thromboxane.28

More recent animal data show that the acutehypertensive response to intravenous cyclosporineis mediated by increased sympathetic nerve activity,and that synapsins may play a crucial role.23

Tacrolimus, a calcineurin inhibitor like cyclosporine,also causes hypertension, but produces less systemicvasoconstriction compared to cyclosporine. Onestudy showed that fewer antihypertensive agentswere used in a group of patients maintained ontacrolimus compared to patients on cyclosporine.29

Table 1 CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS

CATEGORY SYSTOLIC (MMHG) DIASTOLIC (MMHG)

Optimal <120 and <80 Normal <130 and <85High-normal 130-139 or 85-89Hypertension:

Stage 1 140-159 or 90-99Stage 2 160-179 or 100-109Stage 3 > 180 or >110

Adapted from JNCVI, Table 2

Table 2 SOME CAUSES OF HYPERTENSION IN RENAL TRANSPLANT RECIPIENTS

Native kidney diseaseRecurrent kidney disease in the allograftDonor kidney diseaseDe novo renal diseaseRenal artery disease in the allograft or native vesselsAcute or chronic rejectionCyclosporine and tacrolimusCorticosteroidsWeight gainErythrocytosisHypercalcemia

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LIFESTYLE MODIFICATION:

Non-medical changes in diet, exercise andother daily habits that my decrease cardio-vascular risk and improve hypertensioncontrol.

Management of Post-Transplant HypertensionSome transplant patients will have several of the

previously discussed processes contributing to theirhypertension and may require more than one anti-hypertensive agent to control their blood pressure.Since many transplant patients are required to takeimmunosuppressive medications, as well as othermedications for diabetes, hyperlipidemia, and oftenother medical conditions, it is worth recommendinglifestyle modifications to decrease the amount ofantihypertensive medications that must be added.

Few hypertensive transplant patients will achieveadequate blood pressure control by lifestylemodification alone, but some may require fewermedications.

JNC VI recommends several lifestyle modificationswhich may decrease cardiovascular risk. First, all patientsshould be encouraged to quit smoking. Cigarettesmoking has been associated with augmentedprogression of renal insufficiency in severe essentialhypertension.30 Nonpharmacologic lifestyle modifica-tions that can lead to better blood pressure controlmay include sodium restriction, weight loss, andexercise. Since corticosteroids and calcineurininhibitors lead to sodium retention, dietary sodiumrestriction may be useful. JNC VI recommendslimiting sodium intake to no more than 100 µmolper day.11 Some people gain a considerable amountof weight in the early months after transplant whilethey are on higher doses of steroids. Liberationfrom dialysis allows for less restrictive dietaryhabits. High dietary potassium may improve bloodpressure control, but cyclosporine and tacrolimusmay cause hyperkalemia, so potassium levels needto be monitored.

In the nontransplant population, even modestweight loss, as little as 4.5 kg, has been shown tolead to clinically significant long-term reductionsin blood pressure.31 Regular aerobic physical activitycan enhance weight loss and reduce the risk forcardiovascular disease. Moderately intense physicalactivity, such as walking briskly for 30 to 45 minutesmost days of the week, can lower blood pressure.32

Medications for Post-Transplant Hypertension

Calcium Antagonists. Calcium antagonists (CA),or calcium channel blockers, have been commonlyused to treat post-transplant hypertension. CAsdecrease renal vascular resistance, and may provideprotection from cyclosporine-induced renal vaso-constriction. The use of CAs in renal transplantpatients has been associated with improved renalplasma flow and GFR.33 Dihydropyridine CAssuch as amlodipine and long-acting nifedipine areeffective in treating blood pressure in transplantpatients.34 Although reported to inhibit themetabolism of calcineurin inhibitors, they usuallycause little significant clinical interference withcyclosporine levels.

Higher dose of dihydropyridine CA s may lead toincreased edema of the extremities. This is not anallergic reaction, but is the consequence of vaso-dilatation and may be commonly relieved with theaddition of a diuretic, which may augment bloodpressure control.

Both diltiazem and verapamil cause significantelevations in cyclosporine levels by competing forcytochrome P-450 metabolism. Some physiciansavoid their use in transplant patients to preventunintended changes in immunosuppression resultingfrom manipulation of these agents by otherproviders. If patients are taught to treat their diltiazemor verapamil as immunosuppressive agents (not tobe adjusted without monitoring by the transplantteam), they may require lower doses of cyclosporineto maintain an acceptable level and may realizesome cost savings. Verapamil and diltiazem also slowatrioventricular nodal conduction, and need to beused with caution in patients taking beta-blockerswhich also have nodal effects.13

Disadvantages of calcium antagonists includetheir contribution to gingival hypertrophy, which, alsomay be worsened by cyclosporine use. As CAs relaxsmooth muscle, they may exacerbate constipation orGERD. There is no role for the use of short actingnifedipine in long-term blood pressure control.

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Table 3 GENERAL MECHANISMS OF CYCLOSPORINE-INDUCED HYPERTENSION

VasoconstrictionSodium retentionImpaired vasorelaxationEnhanced adrenergic activity

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COMBINATION THERAPYOF HYPERTENSION:

Treatment of high blood pressure with morethan one class of antihypertensive agents,for example, a vasodilator and a diuretic.

Diuretics. Diuretics have been convincinglydemonstrated to reduce the incidence of cardio-vascular events in the non-transplant setting.11

Diuretics may be of use in transplant patients forblood pressure control in those who have sodiumretention, fluid overload, or edema. Loop diuretics,such as furosemide, may be useful in treating thehyperkalemia associated with cyclosporine andtacrolimus. Furosemide may also treat hypercalcemiafrom tertiary hyperparathyroidism, which can beseen in the transplant patient.

Distal tubule diuretics, such as thiazides, may beused to maintain serum calcium levels in thosewith significant bone disease.

Both loop and distal tubule diuretics may predisposeto hypomagnesemia. Hypomagnesemia may be afrequent complication of cyclosporine and tacrolimustherapy, so magnesium levels need to be followed,and some patients taking diuretics may requiremagnesium supplementation. In addition, highdose thiazide diuretics may worsen lipid profiles orhyperglycemia.

Beta-Blockers. Beta-blockers have been shown toreduce morbidity and mortality following acutemyocardial infarction. Beta-blockers such asatenolol have been used safely and effectively intransplant patients.35 Patients with coronary heartdisease may benefit from beta-blockade in the peri-operative and post-transplant setting. As cyclosporinemay increase sympathetic activity, beta-blockersmay antagonize this action. They must be usedwith caution in those taking other AV nodal blockers,such as diltiazem and verapamil. Beta-blockersshould not be abruptly discontinued, as this mayincrease the risk of rebound hypertension anddysrhythmias.

Angiotensin Converting Enzyme (ACE) Inhibitors.Use of angiotensin converting enzyme inhibitorshas been discouraged in the early post-transplantperiod, as they may compromise effective allograftblood flow in renal artery stenosis or in those withhypovolemia or sodium depletion. In the early post-transplant period, during delayed graft function orwhen relatively high cyclosporine or tacrolimuslevels are desirable, ACE inhibitors may exacerbatehyperkalemia.

However, ACE inhibitors may be used later in thepost-transplant course.

Lisinopril has been shown to decrease proteinuriain transplant patients with chronic rejection, and

has been also shown to decrease left ventricularhypertrophy in transplant recipients.36 ACE inhibitorsmay also be useful in treating post-transplanterythrocytosis.

Stignant et al demonstrated that ACE inhibitorsand losartan can be safely used post transplant, andthey are effective. However, 25% of the studiedpatients discontinued ACE inhibitor or losartandue to hyperkalemia, anemia, hypotension, or elevatedcreatinine.21

Diabetes is the leading cause of renal failure in theUnited States, and a high proportion of transplantpatients may be diabetic. It is not known if the useof ACE inhibitors delays progression of diabeticrenal disease in kidney transplants as well as innative kidneys, but there is no compelling reason tobelieve they should not.

Angiotensin II (AII) Receptor Blockers. Losartanhas been shown to decrease blood pressure andproteinuria in transplant patients.21 Animal andhuman studies have shown that losartan may inhibitthe expression of transforming growth factor β-1(TGFβ-1), an important fibrogenic growth factorin the development of chronic rejection.37 AIIreceptor blockers are also effective in treating post-transplant erythrocytosis. In addition, AII blockersmay be useful in patients who cannot tolerate ACEinhibitors due to cough.

Combination Therapy. Single agents may notadequately control blood pressure in transplantpatients; combination therapy may be more effective.A common strategy might include initiating adihydropyridine calcium channel blocker with adiuretic and then adding a beta-blocker if necessary.Those on beta-blockers preoperatively should continuethem post-transplant and often require addition ofcalcium antagonists and diuretics. Other agentssuch as clonidine, alpha blockers, and minoxidilmay be added or substituted for patients with harderto control high blood pressure. Minoxidil maycause hirsutism and so can cyclosporine; some maybe averse to using medications that can worsen thisproblem.

Goals of Hypertension TherapyThe goals of hypertension therapy are to reduce

morbidity and mortality from cardiovascular andcerbrovascular events in transplant patients with-out causing untoward side effects or incurringexcess costs. Goal blood pressures have not been

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MEDICATION ADHERENCE:

How well a patient is able to comply withtaking multiple drugs as directed.

established for transplant patients. JNC VIrecommends maintaining SBP <140 and DBP <90in general patients with hypertension, if tolerated.11

For diabetic patients, intensive control of BP tolevels below 130/85 reduces the risk of cardio-vascular events.38 In patients with progressiverenal failure with hypertension, a similar goal isrecommended, if tolerated. For patients withproteinuria greater than 1 gram in 24 hrs, BP controlto 125/75mmHg is recommended by JNCVI.Whether this goal is applicable to renal transplantpatients has not been determined and in some casesmay not be achievable.

It is important to avoid relative hypotension inthe immediate postoperative period in transplantpatients, and a blood pressure goal of <160/90perioperatively is reasonable.13

More Effective Hypertension ManagementPractitioners may become frustrated with the

prevalence, severity, and multiple factors contributingto hypertension in transplant patients, as well asthe bewildering array of available pharmaceuticals.Practical tips for effective hypertension managementare listed below.

1. Measure the patient’s blood pressure at officevisits and discuss the results with the patient.Teach the patient why blood pressure controlis important. If blood pressure measurementand management are not treated as significantby the physician, it may not seem importantto the patient.

2. Engage the patient in home blood pressuremonitoring. Hypertension is frequentlyasymptomatic, and, therefore, easy forpatients to ignore. When patients obtainblood pressure readings, they receive frequentobjective evidence of whether their hyper-tension is controlled or not. If not controlled,they may inquire about further treatmentoptions. If well controlled, it may provide asense of satisfaction that they are participatingin their care, and reinforcement that theirmedications are working. Developing thehabit of checking blood pressure twice a dayserves as a strong reminder to take medicationstwice a day.

3. Aim for a simple regimen. It is not uncommonfor transplant patients to be prescribed morethan ten pills a day. Some transplant patientsrequire more than ten drugs a day, and have

to take multiple doses of several of thesemedications. This can lead to adherence orcompliance difficulties. Before adding anothermedication that will complicate the regimenfurther, ask “How many times in the pastfew weeks have you missed any of your bloodpressure pills?” (Given complex regimens,some patients may not recall the relativeimportance of each medication. They mayomit pills for immunosuppression or cardiacdisease, but remember to take their laxatives,as they perceive a more direct effect of thetherapy.) When choosing antihypertensivemedications, select medications that can betaken once or twice a day. Avoid shorter-actingmedications.

4. Employ nonpharmacologic therapy. Lifestylemodifications such as weight loss, increasingregular exercise, and sodium restriction mayall contribute to blood pressure control, anddecrease the requirements for drug therapy.

5. Ask about side effects. Many people are asymp-tomatic with hypertension. Aggressive bloodpressure control may cause symptoms. If bloodpressure medications cause unintendedsymptoms, patients will be less inclined totake them. Ask also about orthostatic symptoms,or light headedness. Orthostasis is notuncommon in the elderly or among diabeticpatients with autonomic dysregulation.

6. Ask patients about their medication costsand copayments. Transplant patients mayhave to pay several thousand dollars a year fortheir immunosuppressive medications, andsome have limited means to pay for theirother prescriptions. Where available, it maybe more cost effective to prescribe genericrather than brand name medications.Double-strength doses of some medicationsmay not cost twice as much as single strengthdoses; for some of these drugs it makes senseto prescribe the larger dose and have thepatient cut the tablets in half. Some pharmacyplans offer reduced rates for three monthsupplies of medications; this also enhancespatient convenience, as it may cut down thenumber of required trips to the pharmacy.

7. Individualize the regimen. Strive to use anti-hypertensive medications which may servedual roles, based on individual patient needs.For example, ACE Inhibitors may be useful

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DUAL-ROLE MEDICATIONS:

Choice of antihypertensive agents whichimprove blood pressure control, that alsohave a beneficial secondary effect for theindividual.

in treatment of post-transplant erythrocytosis,as well as hypertension and proteinuria.Thiazides may be useful for patients withosteoporosis, as well as hypertension. Loopdiuretics may be useful in those who haveedema, hyperkalemia, or hypercalcemia andhypertension. Alpha-blockers may be usefulfor men with BPH. Verapamil or diltiazemused for high blood pressure treatment mayresult in higher cyclosporine levels and allowfor decreased doses of cyclosporine and costsavings (Table 4).

ConclusionsHypertension is common in kidney transplant

recipients and is a risk factor for cardiovascular disease.Despite increased risk of morbidity from infectiousdisease and malignancy from chronic immuno-suppression, most renal transplant recipients diefrom cardiovascular events. High blood pressure isthe second leading cause of renal failure in theUnited States and may contribute to early loss oftransplant function, as well as cardiovascular disease.Both systolic and diastolic levels of blood pressurecorrelate with graft function. Compared to thegeneral population, transplant recipients may haveseveral additional factors that contribute to highblood pressure, including diseases which may affectthe transplant kidney, and certain immunosuppressiveagents. Many categories of antihypertensive agentsare useful in controlling high blood pressure afterkidney transplantation, and they often must beused in combination to achieve desired blood pressuregoals. Nonpharmacologic interventions may beuseful to decrease the number of medicationsrequired but will rarely suffice by themselves toachieve blood pressure control. No single algorithm ofantihypertensive agents can be generated appropriatefor all transplant patients. Individualized care usingdual-role medications may result in need for fewermedications and encourage compliance. Blood pressure

control may contribute to improved allograft andpatient survival.

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4. Peschke B, Scheuermann EH, Geiger H et al. Hypertension is associatedwith hyperlipidemia, coronary heart disease and chronic graft failure in kidneytransplant recipients. Clinical Nephrol 1999;51:290-295.

5. Freu U, Schindler R, Wieters D et al. Pretransplant hypertension: A majorrisk factor for chronic progressive renal allograft dysfunction? NephrolDial Transplant 1995; 10:1206-1211.

6. Opelz G, Wujciak T, Ritz E. Association of chronic kidney graft failure withrecipient blood pressure. KI 1998; 53:217-222.

7. Mange K, Cizman B, Joffe M et al. Arterial hypertension and renal allograftsurvival. JAMA 2000; 238(5):633-638.

8. Friedlander MM, Rubinger D, Poputzer MM. Improved renal function inpatients with primary renal disease after control of severe hypertension.Am J Nephrol 1982; 2:12-14.

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10. Kaplan NM. Hypertension: Prevalence, risks, and effect of therapy. AnnIntern Med1983;98:705-709.

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14. Fricke L, Doehn C, Steinhoff J et al. Treatment of post-transplant hyper-tension by laparoscopic bilateral Nephrectomy? Transplantation 1998;65:1182-1187.

15. Zeier M, Mandelbaum A, Ritz E. Hypertension in the transplanted patient.Nephron 1998; 80:257-268.

16. Guidi E, Bianchi G, Rivolta E. Hypertension in man with a kidney trans-plant: Role of familial versus other factors. Nephron 1985; 41:14-21.

17. Fervenza F, LafayetteR, Alfrey E et al. Renal artery stenosis in kidney trans-plants. Am J Kidney Dis 1998; 31(1):142-148.

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19. Chareandee C, Herman W, Hricik D et al. Elevated endothelin-1 in tubularepithelium is associated with renal allograft rejection. Am J Kidney Dis2000; 36(3):541-549.

20. Gaston RS, Julian BA, Curtis JJ. Post-transplant erythrocyosis: An enigmarevisited. Am J Kidney Dis 1994; 24:1.

Table 4 SEVEN HABITS FOR MORE EFFECTIVE HYPERTENSION MANAGEMENT

Measure the blood pressure and discuss the results with the patient.Engage the patient in monitoring their response to treatment.Aim for a simple regimen.Encourage lifestyle modification.Ask about side effects.Be conscious of medication expense.Individualize pharmacologic regimens with dual-role medications.

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21. Stignant C, Cohen J, Vivera M, et al. ACE Inhibitors and angiotensin IIantagonists in renal transplantation: An analysis of safety and efficacy. AmJ Kidney Dis 2000; 35(1):58-63.

22. Schulak JA, Hricik DE. Steroid withdrawal after renal transplantation. ClinTransplant 1994; 8(Pt 2):211-216.

23. Zhang W, Li J, Hosaka M, et al. Cyclosporine A-induced hypertensioninvolves synapsin in renal sensory nerve endings. PNAS 2000;97:9765-9770.

24. Deray G, Behnmida M, LeHoang P. Renal function and blood pressure inpatients receiving long-term low-dose cyclosporine therapy for idiopathicuveitis. Ann Intern Med 1992; 117:578-583.

25. Ponticelli C, Montagnino G, Aroldi A, et al. Hypertension after renal trans-plantation. Am J Kidney Dis 1993;21(5) Suppl 2:73-78.

26. Kurtz A, Della BR, Kuhn Kw. Cyclosporine A enhances renin secretion andproduction in isolated juxtaglomerular cell. Kidney Int 1988; 33:947-955.

27. Rego A, Vargas R, Wroblewska B et al. Attenuation of vascular relaxationand cyclic GMP responses by cyclosporine A. J Pharmacol Exp Ther1990; 252:165-170.

28. Perico N, Benigni A, Zoja C et al. Functional significance of the exaggeratedrenal thromboxane A2 synthesis induced by cyclosporine A. Am JPhysiol 1986; 251:F581-F587.

29. Hohage H, Bruckner D, Arlt M. Influence of cyclosporine A and FK506 on24 hr blood pressure monitoring in kidney transplant recipients. ClinNephrol 1996; 45:342-344.

30. Regalado M, Yang S, Wesson DE. Cigarette smoking is associated withaugmented progression of renal insufficiency in severe essential hypertension.Am J Kidney Dis 2000; 35(4):687-694.

31. Stevens, V, Obarzanek E, Cook N, et al. Long-term weight loss and changesin blood pressure: Results of the trials of hypertension prevention, phase II.Ann Intern Med 2001; 134:1-11.

32. U.S. Department of Health and Human Services. Physical Activity andHealth: A report of the Surgeon General. 1996. Centers for DiseaseControl and Prevention, National Center for Chronic DiseasePrevention and Health Promotion. Atlanta, Georgia.

33. Grekas D, Dioudis C, Klevrosoglou I, et al. Renal hemodynamics in hyper-tensive allograft recipients: Effects of calcium antagonists and ACEInhibitors. Kidney Int 1996; 49:S97-S100.

34. Venkat-Raman G, Feehally J, Elliot HL et al. Renal and hemodynamic effectsof amlodipine and nifedipine in hypertensive renal transplant recipients.Nephrol Dial Transplant 1998; 13(10):2612-2616.

35. Hausberg M, Barenbrock M, Hohage H et al. ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft patients.Hypertension 1999; 33:862-868.

36. Hernandez D, Lacalzada J, Salido E et al. Regression of left ventricularhypertrophy by lisinopril after renal transplantation: Role of ACE gene poly-morphism. Kidney Int 2000; 57:889-897.

37. Campistol J, Inigo P, Jimenez W et al. Losartan decreases plasma levels ofTGF-β1 in Transplant patients with chronic allograft nephropathy. KidneyInt 1999; 56:714-719.

38. Grossman E, Messerli F, Goldbourt U. High blood pressure and diabetesmellitus. Arch Intern Med 2000; 160:2447-2452.

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Done.

. . . an internet-based transplant library that provides the most current andupdatable information for surgeons, residents, fellows and students—

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Finally. . .

Visit our Web site at www.eurekah.com and view our extensive library oftransplantation handbooks. Simply download text and images directly

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it’s FREE!www.eurekah.com

For more information about ourPDA Program contact us at

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