Hypertension after kidney transplantation

INTRODUCTION — Hypertension is present in most patients with end-stage kidney disease (ESKD)/advanced chronic kidney disease (CKD). The blood pressure (BP) frequently rises early after kidney transplantation after saline loading interacts with initial high-dose immunosuppression. Long-term BP is often easier to control after transplantation, as long as the glomerular filtration rate (GFR) improves into a good range. However, poorly controlled BP is common among kidney transplant recipients.

This topic will review the pathogenesis and risk factors, evaluation, and management of hypertension after kidney transplantation. A discussion of hypertension in nontransplant patients with acute and chronic kidney disease is presented separately. (See "Overview of hypertension in acute and chronic kidney disease".)

EPIDEMIOLOGY AND RISK FACTORS — Hypertension is common among kidney transplant recipients, occurring in up to 85 percent of patients [1-4].

The following risk factors have been associated with a higher incidence of posttransplant hypertension [1,4,5]:

●Pretransplant hypertension

●Elevated body mass index

●Male sex

●Older donor age

●Presence of native kidneys

●Delayed and/or chronic allograft dysfunction

●Cyclosporine, tacrolimus, and/or glucocorticoid therapy

●Acute rejection

●Recurrence of primary kidney disease in the allograft

PATHOGENESIS — Several factors may contribute to the pathogenesis of posttransplant hypertension among kidney transplant recipients, as discussed below.

Allograft dysfunction — Both acute and chronic injury to the kidney allograft can lead to posttransplant hypertension:

●Delayed graft function (DGF), defined as the need for dialysis within the first week posttransplant, can lead to volume overload and an acute elevation in blood pressure (BP) in the immediate posttransplant period. Removal of excess fluid with diuretics or dialysis will lower the BP in many cases. (See "Kidney transplantation in adults: Timing of transplantation and issues related to dialysis", section on 'Dialysis immediately after transplantation'.)

●Acute rejection is frequently associated with hypertension. Hypertension in this setting is primarily due to sodium retention, increased activity of the renin-angiotensin system, and allograft dysfunction and is frequently compounded by treatment with high-dose glucocorticoids. Treatment and reversal of rejection will generally lower the BP.

●Chronic allograft injury (eg, due to chronic antibody-mediated rejection or interstitial fibrosis/tubular atrophy), thrombotic microangiopathy, or recurrent glomerular disease can also be associated with posttransplant hypertension. The mechanisms responsible for hypertension in these settings are similar to those involved in the pathogenesis of hypertension in patients with chronic kidney disease (CKD), as discussed elsewhere. (See "Overview of hypertension in acute and chronic kidney disease", section on 'Chronic kidney disease'.)

Immunosuppressive agents — Immunosuppressive agents, particularly glucocorticoids and calcineurin inhibitors (CNIs), play an important role in the development of posttransplant hypertension.

●Glucocorticoids – Glucocorticoids are an important contributing factor to hypertension in the early posttransplant period, especially when higher doses are commonly used. However, because of rapid dose reduction, glucocorticoids are usually not a major risk factor for chronic hypertension in transplant recipients. However, discontinuation of glucocorticoid therapy among kidney transplant recipients receiving CNIs (ie, glucocorticoid withdrawal) has not been shown to significantly lower BP in the long term [6]. (See "Major adverse effects of systemic glucocorticoids", section on 'Cardiovascular effects'.)

●Calcineurin inhibitors – CNIs play a predominant role in posttransplant hypertension if administered, raising the BP in almost all patients and producing overt hypertension in many cases [7]. Although BP is reportedly lower with tacrolimus than with cyclosporine [8], the combination of sirolimus and tacrolimus can exacerbate underlying hypertension [9].

Cyclosporine acts by increasing both systemic and renal vascular (primarily affecting the afferent arteriole) resistance. How this occurs is incompletely understood. Increased release of vasoconstrictors, particularly endothelin, has been thought to play an important role [10-12]. Additional factors may include increased sodium transport in the loop of Henle [13]. Tacrolimus has been shown to cause hypertension by activation of the renal sodium chloride cotransporter [14]. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Hypertension'.)

Transplant renal artery stenosis — Kidney transplant renal artery stenosis (TRAS) is a potentially reversible cause of posttransplant hypertension, with an incidence ranging from 1 to 23 percent [15]. TRAS most commonly occurs at the site of the renal artery anastomosis but can also occur at the donor renal artery or feeding native artery. Flow limitation in the transplant renal artery can also be caused by surgical issues such as a vascular clamp, kinking, or angulation of the artery.

Although it can present at any time, TRAS usually becomes evident between three months and two years posttransplant [16]. Clinical features that should raise suspicion for the diagnosis of TRAS are similar to those that suggest renovascular disease among nontransplant patients (table 1) and include the following [17]:

●Worsening hypertension

●Hypokalemia (due to secondary hyperaldosteronism)

●Decline in kidney function in the setting of treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) (see "Renal effects of ACE inhibitors in hypertension")

●Episodes of flash pulmonary edema

●An abdominal bruit over the allograft (may or may not be present)

The risk factors for TRAS include difficulties in organ procurement and operative techniques (such as improper suturing and trauma), atherosclerotic disease, cytomegalovirus infection, and delayed allograft function [15,18,19].

The evaluation and management of TRAS are discussed below. (See 'Evaluation for transplant renal artery stenosis' below and 'Evaluation of new-onset or worsening hypertension' below and 'Management of transplant renal artery stenosis' below.)

Donor characteristics — There is suggestive evidence that the transplanted kidney may have prohypertensive or antihypertensive properties. Multiple cross-transplantation studies in experimental models of genetic hypertension have shown that the inherited tendency to hypertension resides primarily in the kidney [20]. A similar relationship may exist in humans. In one report of six transplant recipients with a prior history of end-stage kidney disease (ESKD) due to hypertensive nephrosclerosis and resistant hypertension while on dialysis, transplantation of a kidney from normotensive donors with a negative family history of hypertension led to correction of primary hypertension [21].

A larger study of 85 patients found that elevations in BP and increased antihypertensive drug requirements occurred much more frequently in recipients from "normotensive" families who received a kidney from a donor with a "hypertensive family"; a family history of hypertension in the recipient blunted the effect of a "hypertensive" kidney [22]. A follow-up study found that a "hypertensive" kidney transplanted into a recipient from a "normotensive" family had a greater hypertensive response during an acute rejection episode than did all other donor-recipient combinations [23].

EVALUATION

Routine blood pressure monitoring after transplant — Following hospital discharge, blood pressure (BP) is routinely monitored at each visit to the transplant clinic using standardized office-based BP measurements. At our centers, the initial BP measurement is obtained using an automated device; if elevated, we repeat with a manual BP measurement towards the end of the visit when the patient has been seated at rest. In patients with diabetes, on alpha blocker therapy, or with postural symptoms, we perform supine, sitting, and standing BPs to assess for orthostatic hypotension. The goal BP for kidney transplant recipients is discussed below. (See 'Blood pressure goal' below.)

We advise all kidney transplant recipients to self-measure their BP at home, at least daily for the first three months posttransplant and then, at a minimum, when they have routine laboratory monitoring. We review optimal home BP monitoring technique with patients at posttransplant clinic visits.

We do not routinely perform 24-hour ambulatory BP measurements (ABPMs) in kidney transplant recipients. However, ABPMs may be helpful for patients who have resistant hypertension or suspected white coat hypertension [24].

A more detailed discussion of in-office and out-of-office BP measurement is presented separately. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring".)

Evaluation of new-onset or worsening hypertension — All kidney transplant recipients with new-onset or worsening hypertension after transplantation should be evaluated for potentially reversible causes. We take the following approach:

●Assess volume status – We assess all patients for symptoms or signs of volume overload. Volume overload is a common cause of elevated BP in the immediate posttransplant period but may also be present later in patients with allograft dysfunction and sodium retention.

●Assess allograft function – We assess kidney allograft function by obtaining a serum creatinine level and a spot urine protein-to-creatinine ratio. Both acute and chronic allograft dysfunction can be causes of posttransplant hypertension. The evaluation and diagnosis of acute and chronic allograft dysfunction are presented in detail separately. (See 'Allograft dysfunction' above and "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction" and "Kidney transplantation in adults: Chronic allograft nephropathy".)

●Assess immunosuppression regimen – We assess the patient's maintenance immunosuppression regimen, in particular the doses and trends in levels of the calcineurin inhibitor (CNI) and oral prednisone. (See 'Immunosuppressive agents' above and 'Management of immunosuppression' below.)

●Evaluate selected patients for transplant renal artery stenosis – If the patient has clinical features that are suggestive of transplant renal artery stenosis (TRAS), we evaluate for TRAS, as discussed below. (See 'Transplant renal artery stenosis' above and 'Evaluation for transplant renal artery stenosis' below.)

Evaluation for transplant renal artery stenosis — Indications for testing for TRAS vary among transplant centers. At our centers, we perform an evaluation for TRAS in patients with new-onset or worsening hypertension who have clinical features suggestive of TRAS, as well as all patients with resistant hypertension. Some, but not all, transplant centers routinely evaluate all kidney transplant recipients for TRAS as part of posttransplant care. (See 'Evaluation of new-onset or worsening hypertension' above and 'Resistant hypertension' below.)

●Choice of test – Reasonable noninvasive modalities for initial testing include duplex Doppler ultrasonography, computed tomographic angiography (CTA), and magnetic resonance angiography (MRA). The choice of test should be based upon institutional expertise and patient factors. At many centers, including ours, duplex Doppler ultrasonography is the preferred initial diagnostic test for TRAS. If Doppler ultrasonography findings are consistent with TRAS, some centers will confirm the findings with either CTA or MRA, while others will proceed directly to renal arteriography. If the noninvasive test is inconclusive and the clinical suspicion remains high, we often proceed with arteriography. (See 'Management of transplant renal artery stenosis' below.)

●Testing options

•Duplex Doppler ultrasonography – Duplex Doppler ultrasonography is highly accurate but also highly dependent upon the experience of the ultrasonographer [25,26]. The following findings are used to establish a diagnosis of TRAS [27]:

-Peak systolic velocity in the transplant renal artery >200 cm/second

-Acceleration time in the transplant renal and intrarenal arteries ≥0.1 second

-Ratio of peak systolic velocity in the transplant renal artery to external iliac arteries >1.8

-Presence of tardus parvus waveform

Reported sensitivities of Doppler ultrasonography for the diagnosis of TRAS range from 58 to 100 percent, while specificity ranges from 87 to 100 percent [26,28-31].

•Spiral CT scan with CT angiography – Spiral CTA is another accurate noninvasive test that can be used for diagnosing TRAS [32,33]. CTA is less operator dependent than ultrasonography and uses a lower volume of intravenous contrast than arteriography. (See "Establishing the diagnosis of renovascular hypertension", section on 'Spiral CT scan with CT angiography'.)

•Magnetic resonance angiography – As in the nontransplant population, MRA can be used to evaluate for renal artery stenosis among transplant recipients [34,35]. Technical improvements have resulted in enhanced detection of significant renal artery disease. In small studies, three-dimensional gadolinium-enhanced MRA has demonstrated a sensitivity of 100 percent and specificity of 75 to 98 percent in detecting stenosis greater than 50 percent [36-41].

The administration of gadolinium during MR imaging has been strongly linked to an often-severe disease called nephrogenic systemic fibrosis among patients with moderate to severe kidney disease, particularly those requiring dialysis. In general, gadolinium-based contrast agents can be given safely without concern to patients with an estimated glomerular filtration rate (eGFR) between 30 to 59 mL/min/1.73 m². Gadolinium-based imaging should be avoided, if possible, in patients with an eGFR <30 mL/min/1.73 m², acute kidney injury, or on dialysis. The appropriate use of gadolinium-based contrast agents in patients with kidney function impairment is discussed elsewhere. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging", section on 'Approach to preventing nephrogenic systemic fibrosis'.)  

•Renal arteriography – Renal arteriography is the gold standard for establishing the diagnosis of TRAS. Given its invasive nature, it is not commonly used as an initial diagnostic test for TRAS. Its use is generally reserved for patients with inconclusive results on noninvasive testing or patients with established TRAS who require treatment. Digital subtraction angiography is generally preferred over conventional angiography because of its need for less contrast. An alternative modality is carbon dioxide (CO2) angiography, which uses CO2 as a contrast agent, enabling its use in patients with kidney function impairment.

Some clinicians perform a kidney allograft biopsy prior to angiography to rule out chronic rejection or other forms of kidney parenchymal disease. These findings decrease the likelihood of a successful response to correction of a stenosis and may be relative contraindications to intervention [42].

MANAGEMENT OF POSTTRANSPLANT HYPERTENSION

Rationale for treatment — Posttransplant hypertension should be treated to protect against cardiovascular disease and possible hypertensive injury to the graft. Elevated blood pressure (BP) and pulse pressure can result in left ventricular hypertrophy, which is an independent risk factor for heart failure and death in the general population and kidney transplant recipients [43-47]. Posttransplant hypertension has also been associated with decreased long-term kidney allograft survival [45,46,48,49]. There is experimental evidence to support this hypothesis. In an animal model of chronic kidney allograft rejection, antihypertensive therapy improved graft survival and function, diminished glomerular injury, and reduced proteinuria [50].

There are also clinical data showing benefits with BP control. This was best shown in a study of nearly 25,000 first deceased-donor kidney recipients [51]. Among patients with systolic BPs >140 mmHg at one year posttransplant, improved long-term allograft outcome was observed among patients with systolic pressures controlled to less than 140 mmHg at three years versus those with sustained increases in systolic pressure (relative risk [RR] 0.79, 95% CI 0.73-0.86).

Patients in the immediate posttransplant period — Hypertension in the immediate posttransplant period (ie, within the first week posttransplant) is usually associated with volume overload and/or graft dysfunction due to rejection, ischemia, or calcineurin inhibitor toxicity, although pain and anxiety may also be contributing factors. Reversal of rejection or removal of excess fluid with diuretics or dialysis will lower the BP in many cases. (See 'Pathogenesis' above.)

In the immediate posttransplant period, it is important to maintain adequate organ perfusion to avoid hypotension and the risk of graft thrombosis. However, there is no evidence to guide the optimal BP target in this setting, and practice varies among transplant centers. Some UpToDate authors of this topic allow higher BP levels (ie, "permissive hypertension") and target a BP of less than 160/90 mmHg in the first one to two weeks posttransplant, whereas other authors would target a lower BP goal (eg, less than 140/90). However, there are no data to support these or any other BP thresholds for patients in the immediate posttransplant period.

In patients who had pharmacologically treated hypertension prior to transplant, we generally resume their antihypertensive medications after transplant surgery, with the exception of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). We generally hold ACE inhibitors and ARBs for the first three to six months posttransplantation since these medications can cause an increase in serum creatinine concentration, cause hyperkalemia, and prevent recovery from anemia. This is discussed in more detail below. (See 'Additional agents for uncontrolled hypertension' below.)

Patients in the later posttransplant period — Our general approach to posttransplant hypertension in patients beyond the immediate posttransplant period is discussed below.

Blood pressure goal — The optimal long-term BP goal for kidney transplant recipients is unclear. We suggest a target BP of <130/80 mmHg using properly measured BP. The following are options for properly measuring BP: standardized office-based measurement (table 2), automated oscillometric BP monitoring, home BP, and ambulatory BP monitoring (ABPM). (See "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Selecting a measurement strategy'.)

"Casual" or "routine" BP measurement, which is commonly performed in the clinical setting, provides unreliable readings and should not be used. On average, casual measurements lead to BP readings that are 5 to 10 mmHg higher than readings obtained with proper technique, although there is a large degree of interindividual variability.

Our approach is largely consistent with the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [52,53]. This BP target is higher than that recommended for nontransplant patients with chronic kidney disease (CKD). The different types of BP measurement are defined and discussed elsewhere. (See "Goal blood pressure in adults with hypertension", section on 'Patients with chronic kidney disease'.)

There is no high-quality evidence to support this or any other BP target in kidney transplant recipients. There are no data from randomized trials in kidney transplant recipients evaluating the effects of different BP targets on patient-relevant outcomes such as mortality, cardiovascular events, or allograft survival. In the absence of evidence to guide optimal BP, BP targets in kidney transplant recipients have historically been adopted from those for higher-risk populations, such as patients with CKD, diabetes mellitus, or atherosclerotic cardiovascular disease. (See "Goal blood pressure in adults with hypertension".)

There are two main reasons to explain the discrepancy between the recommended BP targets for kidney transplant recipients and nontransplant patients with CKD. First is the exclusion of kidney transplant recipients from major randomized trials (such as The Systolic Blood Pressure Intervention Trial [SPRINT]) that found lower rates of fatal and nonfatal major cardiovascular events and death from any cause in patients assigned to more intensive BP lowering. Secondly, there are concerns about the modestly higher risk of acute kidney injury (AKI) and decline in estimated glomerular filtration rate (eGFR) among patients assigned to a systolic BP of less than 120 mmHg compared with those assigned to a target of less than 140 mmHg in the SPRINT trial. Denervation of the transplanted kidney and treatment with a calcineurin inhibitor (CNI) to prevent rejection may render the allograft less capable of autoregulation and increase its susceptibility to AKI and loss of eGFR with lower BP targets. However, there are no clinical data to support this hypothesis, and studies in kidney transplant recipients have not identified a BP threshold below which there is a higher risk of graft failure or eGFR decline [54]. The SPRINT trial is discussed in detail elsewhere. (See "Goal blood pressure in adults with hypertension".)

Management of immunosuppression — For patients with posttransplant hypertension, some UpToDate contributors to this topic decrease the CNI (tacrolimus or cyclosporine) to the lowest effective dose needed to prevent acute rejection, as determined by clinical judgment, while others do not adjust immunosuppression doses in response to hypertension. We do not discontinue a CNI purely for posttransplant hypertension. (See 'Immunosuppressive agents' above.)

In patients receiving low-dose prednisone as part of their maintenance immunosuppression, we do not discontinue prednisone for posttransplant hypertension. Discontinuation of glucocorticoid therapy among kidney transplant recipients receiving CNIs has not been shown to significantly lower BP [6]. For patients in whom higher doses of prednisone (eg, for the treatment of rejection) are likely contributing to posttransplant hypertension, we adjust BP medications as needed to control hypertension while tapering prednisone as indicated.

Nonpharmacologic therapy for all patients — Similar to the treatment of hypertension in the general population, the treatment of posttransplant hypertension involves nonpharmacologic therapy (also called lifestyle modification) (table 3) alone or in concert with antihypertensive drug therapy. Although these lifestyle modifications have not been well studied in kidney transplant recipients [55-58], they have been shown to have beneficial effects on lowering BP in the general population. These measures are discussed in detail elsewhere. (See "Overview of hypertension in adults", section on 'Nonpharmacologic therapy'.)

Approach to pharmacologic therapy — Most transplant recipients with posttransplant hypertension will require pharmacologic antihypertensive therapy to achieve the goal BP.

Patients with new-onset hypertension — In patients with new-onset posttransplant hypertension who are not on antihypertensive therapy, our approach is discussed below.

Calcium channel blockers as first-line therapy — For most kidney transplant recipients, we suggest a dihydropyridine calcium channel blocker (eg, amlodipine, felodipine, nifedipine [preferably long-acting]) as first-line antihypertensive therapy rather than other antihypertensive agents. Dihydropyridine calcium channel blockers have been shown to reduce the risk of graft loss [59] and minimize CNI-induced vasoconstriction.

We generally avoid nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil) since they are potent cytochrome inhibitors (CYP3A/4) and concurrent use with CNIs (tacrolimus or cyclosporine) or mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (sirolimus or everolimus) will lead to elevated immunosuppressive drug levels. If these agents are used, frequently measuring CNI or mTOR inhibitor levels before and after such medication transitions is necessary. Some transplant centers preferentially use nondihydropyridine calcium channel blockers in recipients who are rapid CNI drug metabolizers to limit the CNI dose and control hypertension.

Several studies have evaluated the efficacy of calcium channel blockers in kidney transplant patients [2,59-65]. A 2009 systematic review of 29 randomized trials with 2262 patients that compared calcium channel blockers with placebo or no treatment, as well as seven randomized trials with 405 patients that compared calcium channel blockers with ACE inhibitors, reported the following findings [59]:

●Compared with placebo or no treatment, calcium channel blockers reduced the risk of allograft loss (RR 0.75, 95% CI 0.59-0.99) and improved GFR (mean difference of 4.45 mL/min, 95% CI 2.22-6.68).

●Compared with calcium channel blockers, ACE inhibitors reduced GFR (mean difference of 11.48 mL/min, 95% CI -5.75 to -7.21) and increased the risk of hyperkalemia (RR 3.76, 95% CI 1.89-7.43).

Additional agents for uncontrolled hypertension — If BP is not controlled with a calcium channel blocker, other antihypertensive drugs can be added as necessary. There are no classes of antihypertensive medications that are contraindicated in kidney transplant recipients, and ACE inhibitors/ARBs, beta blockers, diuretics, and alpha blockers all may be effective in this setting. The choice of second-line agent is generally guided by patient comorbidities and time after transplant. Special considerations in kidney transplant recipients include the following:

●Diuretics – Thiazide-like (eg, chlorthalidone, indapamide) or thiazide-type (eg, hydrochlorothiazide) diuretics may be useful for patients with edema and hyperkalemia. A diuretic may also be necessary in patients with allograft dysfunction in whom volume expansion often contributes to the rise in BP. (See 'Allograft dysfunction' above.)

●ACE inhibitors and ARBs – ACE inhibitors and ARBs may be useful in patients with proteinuria. Some experts prefer to wait three to six months posttransplant before starting an ACE inhibitor or ARB, given the concern that concomitant use of these agents with CNIs in the early posttransplant period could cause hyperkalemia or an increase in the serum creatinine level that might confound the ability to accurately detect acute rejection. However, studies have shown that ACE inhibitors and ARBs are generally safe when used in the early posttransplant period, suggesting that initiation of these agents need not be deferred [66,67].

Several studies have evaluated the efficacy and safety of ACE inhibitors and ARBs in kidney transplant recipients [59,63,68-76]. However, clear evidence showing a kidney or mortality benefit with these agents is lacking. As examples:

•The efficacy and safety of ACE inhibitors and ARBs in kidney transplant recipients were evaluated in a 2009 systematic review of 10 trials (445 patients) that compared ACE inhibitors with placebo or no treatment and seven trials (405 patients) that compared ACE inhibitors with calcium channel blockers [59]. Compared with calcium channel blockers, ACE inhibitors were associated with a decrease in GFR (mean difference of 11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria level (mean difference of -0.28 g/24 hours, 95% CI -0.47 to -0.10), and hemoglobin value (mean difference of -1.3 g/dL, 95% CI -.57 to -1.02), and an increased incidence of hyperkalemia (RR 3.76, 95% CI 1.89-7.43). No definitive conclusions with respect to GFR and allograft loss could be reached when ACE inhibitors were compared with placebo or no treatment.

•In a subsequent trial that randomly assigned 154 kidney transplant recipients within three months of transplant to losartan 100 mg or placebo, rates of the composite outcome (graft loss due to biopsy-proven interstitial fibrosis/tubular atrophy or a doubling of the fraction of renal cortical volume occupied by interstitium at five years) were lower in the losartan group (13 versus 27 percent), but this difference was not statistically significant [73]. There was no difference in the time to end-stage kidney disease (ESKD) or death between the groups.

●Beta blockers – Beta blockers (eg, atenolol, bisoprolol, carvedilol, metoprolol) may be indicated in transplant recipients with known atherosclerotic cardiovascular disease, although data on their efficacy and safety in this patient population are limited. Although use of beta blockers in kidney transplant recipients has increased over time, it may still be suboptimal [77]. Like ACE inhibitors and ARBs, beta blockers are a common cause of hyperkalemia after transplantation [78].

●Alpha blockers – Alpha blockers (eg, doxazosin, prazosin) may be useful in patients with benign prostatic hyperplasia and lower urinary tract symptoms. However, alpha blockers should be avoided in patients with orthostatic hypotension. (See "Choice of drug therapy in primary (essential) hypertension", section on 'Patients with orthostatic hypotension'.)

Patients already on antihypertensive therapy — Patients with a history of hypertension prior to transplant generally experience an improvement in BP after transplantation that is commensurate with the degree of kidney function acquired from the allograft. However, most patients will still require antihypertensive medications for BP control. Our approach in such patients is as follows:

●Blood pressure well controlled – Patients whose BP is well controlled on their antihypertensive regimen can generally continue their regimen without any modifications. Some patients, particularly those who are younger, may require fewer or even no antihypertensive medications. If the patient is not already taking a dihydropyridine calcium channel blocker, some clinicians may choose to substitute one of their medications with this agent given its potential benefits in transplant recipients. (See 'Calcium channel blockers as first-line therapy' above.)

●Blood pressure not well controlled – For patients whose BP is not at the desired target on their antihypertensive regimen, additional antihypertensive medications can be added as necessary. Our approach to selecting an agent in such patients is similar to that for transplant recipients with new-onset hypertension, as discussed above. (See 'Patients with new-onset hypertension' above.)

Resistant hypertension — Resistant hypertension is defined as BP that remains above goal in spite of concurrent use of three antihypertensive agents or BP that is controlled with four or more medications. One of the medications should be a diuretic, if tolerated, and all should be prescribed at maximum recommended (or maximally tolerated) antihypertensive doses. (See "Definition, risk factors, and evaluation of resistant hypertension".)

Kidney transplant recipients with resistant hypertension should undergo an evaluation to exclude transplant renal artery stenosis, unless there are findings (such as kidney function impairment and an active urine sediment) suggesting possible recurrence of the primary disease (see 'Evaluation for transplant renal artery stenosis' above). Angioplasty (with or without stenting) or surgery are indicated if a significant stenosis is found. In the absence of renovascular disease, recurrent disease, or rejection, consideration should be given to removal of the native kidneys if there is no other way to control the hypertension [79,80]. (See 'Management of transplant renal artery stenosis' below.)

MANAGEMENT OF TRANSPLANT RENAL ARTERY STENOSIS — Our general approach to the management of transplant renal artery stenosis (TRAS) is as follows:

●Medical therapy – All kidney transplant recipients with an established diagnosis of TRAS should receive nonpharmacologic and pharmacologic therapy for control of hypertension, as discussed elsewhere in this topic. (See 'Nonpharmacologic therapy for all patients' above and 'Approach to pharmacologic therapy' above.)

●Indications for revascularization – In transplant recipients with established TRAS, indications for revascularization include failure of optimal medical therapy to control blood pressure (BP), intolerance to optimal medical therapy (eg, deterioration of kidney function during antihypertensive drug therapy), recurrent flash pulmonary edema, or otherwise unexplained worsening graft function. These indications are similar to those for nontransplant patients who have bilateral renal artery stenosis or unilateral stenosis to a solitary functioning kidney, as discussed elsewhere. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'General approach to therapy'.)

●Choice of intervention – In transplant recipients who are selected for revascularization, percutaneous balloon angioplasty (with or without stenting) is most commonly performed. Surgical revascularization is generally reserved for patients with resistant hypertension or with proximal recipient arteriosclerotic disease since the extensive fibrosis and scarring around the transplanted kidney make surgical correction of TRAS difficult.

Percutaneous balloon angioplasty may be technically successful in up to 80 percent of cases, although 20 percent will develop recurrent stenosis [42,81]. This technique is also less successful in the patient with arterial kinking, anastomotic structures, and long lesions [82]. Repeat angioplasty is usually not successful in such patients.

The success of stent placement used in combination with angioplasty for a wide variety of vascular lesions suggests that deployment of metallic stents may be useful [83,84], particularly in those with recurrent TRAS [85,86]. Stent deployment in six consecutive patients with recurrent stenosis was evaluated in a retrospective study [85]. At almost three years postprocedure, all arteries were patent without significant stenosis, and no additional interventions were required. (See "Treatment of bilateral atherosclerotic renal artery stenosis or stenosis to a solitary functioning kidney", section on 'Stent placement'.)

Success rates of surgical revascularization have ranged from 60 to 90 percent. However, recurrent stenosis may occur in approximately 10 percent, and graft loss has been reported in up to 30 percent of cases [82,87].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology and pathogenesis – Hypertension is common among kidney transplant recipients, occurring in up to 85 percent of patients. Several factors may contribute to the pathogenesis of posttransplant hypertension, including allograft dysfunction, immunosuppressive agents, transplant renal artery stenosis (TRAS), and certain donor characteristics. (See 'Epidemiology and risk factors' above and 'Pathogenesis' above.)

●Evaluation

•Routine monitoring after transplant – Blood pressure (BP) is routinely monitored at each visit to the transplant clinic using office-based BP measurements. We advise all kidney transplant recipients to self-measure their BP at home, at least daily for the first three months posttransplant and then, at a minimum, when they have routine laboratory monitoring. (See 'Routine blood pressure monitoring after transplant' above.)

•Evaluation of new-onset or worsening hypertension – All kidney transplant recipients with new-onset or worsening hypertension after transplantation should be evaluated for potentially reversible causes. We assess volume status, allograft function, and the immunosuppression regimen. Patients with clinical features suggestive of TRAS should be evaluated for TRAS. (See 'Evaluation of new-onset or worsening hypertension' above.)

•Evaluation for TRAS – Indications for testing for TRAS vary among transplant centers. We evaluate for TRAS in patients with new-onset or worsening hypertension who have clinical features suggestive of TRAS, as well as all patients with resistant hypertension. Reasonable noninvasive modalities for initial testing include duplex Doppler ultrasonography, computed tomographic angiography (CTA), and magnetic resonance angiography (MRA). The choice of test should be based upon institutional expertise and patient factors. (See 'Evaluation for transplant renal artery stenosis' above and 'Resistant hypertension' above.)

●Management of posttransplant hypertension – Posttransplant hypertension should be treated to protect against cardiovascular disease and possible hypertensive injury to the graft. (See 'Rationale for treatment' above.)

•Immediate posttransplant period – In the first week posttransplant, it is important to maintain adequate organ perfusion to avoid hypotension and the risk of graft thrombosis. However, there is no evidence to guide the optimal BP target in this setting, and practice varies among transplant centers. Some UpToDate authors of this topic allow higher BP levels (ie, "permissive hypertension") and target a BP of less than 160/90 mmHg in the first one to two weeks posttransplant, whereas other authors would target a lower BP goal (eg, less than 140/90). (See 'Patients in the immediate posttransplant period' above.)

•Later posttransplant period – Our general approach to posttransplant hypertension in patients beyond the immediate posttransplant period is as follows:

-BP goal – The optimal long-term BP goal for kidney transplant recipients is unclear. For kidney transplant recipients, we suggest a target BP of less than 130/80 mmHg rather than lower targets (which are recommended for other patients with chronic kidney disease [CKD]) (Grade 2C). The following are options for properly measuring BP to determine if a patient is at goal: standardized office-based measurement (table 2), automated oscillometric BP monitoring, home BP, and ambulatory BP monitoring [ABPM]). "Casual" or "routine" BP measurement, which is commonly performed in the clinical setting, provides unreliable readings. Our approach is largely consistent with the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. (See 'Blood pressure goal' above.)

-Nonpharmacologic therapy – Similar to the treatment of hypertension in the general population, the treatment of posttransplant hypertension involves nonpharmacologic therapy (also called lifestyle modification) (table 3) alone or in concert with antihypertensive drug therapy. (See 'Nonpharmacologic therapy for all patients' above.)

-Pharmacologic therapy – For most kidney transplant recipients with new-onset posttransplant hypertension who are not on antihypertensive therapy, we suggest a dihydropyridine calcium channel blocker as first-line antihypertensive therapy rather than other antihypertensive agents (Grade 2C). (See 'Approach to pharmacologic therapy' above.)

●Management of TRAS – Indications for revascularization of TRAS include failure of optimal medical therapy to control BP, intolerance to optimal medical therapy, recurrent flash pulmonary edema, or otherwise unexplained worsening graft function. In patients selected for revascularization, percutaneous balloon angioplasty (with or without stenting) is most commonly performed. Surgical revascularization is generally reserved for patients with resistant hypertension or proximal recipient arteriosclerotic disease. (See 'Management of transplant renal artery stenosis' above.)