The blood pressure is commonly elevated after kidney transplant, as hypertension is commonly observed in almost 70% % of kidney transplant recipients.
Hypertension after renal transplantation
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| Renal transplantation |
The
blood pressure (BP) is commonly elevated after kidney transplantation (KTx),
as hypertension (HT) is commonly observed in almost 60-80 %
of kidney transplant recipients KTRs. The uncontrolled BP is
commonly seen among (KTRs). In certain reports, only 5 % of KTR were
normotensive considering the accepted BP < 130/80 mmHg monitored
via an ambulatory BP. The elevated BP may induce decline in allograft survival with LVH (left
ventricular hypertrophy), that’s considered an independent risk factor for
heart failure development and death in the general population as well as among KTR.
RISK FACTORS
Many
risk factors have been related to a higher incidence of hypertension after KTx:
1]
Delayed and/or chronic
graft malfunction
2]
Cadaveric donor allograft, particularly with a donor’s family
history of HT.
3]
Preservation of the native kidneys.
4]
Cyclosporin (Csp), tacrolimus , and/or steroid therapy
5]
Higher total body weight
6]
Renal artery stenosis (RAS).
The
kidney allograft may carry a pro-hypertensive or anti-hypertensive criteria. Certain
studies showed that inherited tendencies to HT reside
mainly in the kidney. Other factors that encourage HT evolution vary according to timing after
transplant. Immediately after transplantation, an acute rise in BP may be related
to:
1]
Volume overload,
2]
Ischemic events,
3]
CNI-related toxicity, or
4]
Allograft dysfunction owing to
rejection.
Management
of rejection or excess fluid deloading with diuretics or via dialysis will get
the BP down.
Role of glucocorticoids
Almost
all patients require maintenance antihypertensive therapy, particularly if
pulse or high-dose steroids, and/or CyA/tacrolimus were added. Steroids per se are
not considered a major risk factor for HT development in KTRs due to rapid
dose tapering. They may have a contributing effect; as gradual tapering of steroids
may induce a drop in BP; that’s most pronounced in patients with previous HT.
Role of calcineurin inhibitors (CNI)
Before
the era of cyclosporine (CyA) as
a maintenance therapy, post-transplant HT was mostly developed via RAAS (renin-angiotensin-aldosterone
system) activation. Calcineurin inhibitors (CNI) play
a crucial role in this issue, elevating BP in mostly
ALL cases leading frequently to apparent HT. Despite BP is
reported to be lower with tacrolimus as compared to CyA,
combined sirolimus and tacrolimus administration may augment
HT development. CyA can
induce rise in both systemic and reno-vascular resistance. Increased production
of vasoconstrictor mediators, e.g., endothelin, may also has a vital role.
RENAL ARTERY STENOSIS (RAS)
Evolution
of HT related to RAS is crucial to recognize as it’s a reversible form of HT. RAS usually
observed between 3 months and 2 years’ post-transplant. Risk factors for RAS development
may include:
1] Difficult allograft harvest (improper sutures/traumata),
2] Atherosclerotic vascular disease,
3] Cytomegalovirus (CMV) disease, and
4] Delayed graft function (DGF).
Anastomotic
RAS cannot be easily assessed. Stenosis with functional
significance can be seen in 12 % of KTRs with
HT. In bilateral RAS or unilateral RAS in a single kidney, an angiotensin converting enzyme inhibitor
(ACEi) or angiotensin II receptor blocker (ARB) may
induce a correctible drop in GFR. A rise in SCR in this situation may suggest- but not
diagnostic- of allograft reno-vascular lesion. Resistant uncontrolled HT,
flash pulmonary edema, and an acute rise in BP are
also common findings.
Diagnosis
Arteriography
is the preferable diagnostic technique, but owing to its invasive nature, MRA, magnetic
resonance arteriography or CT angiography are currently applied instead.
Arteriography
Renal
arteriography can be considered the procedure of choice to establish RAS diagnosis
in a single kidney transplant. An allograft biopsy is usually proceeds
angiography to exclude chronic rejection and other pathologies. However, given
the risk an invasive technique, several alternates have been admitted that
include: ultrasonography (U/S), magnetic resonance imaging (MRA), and, spiral
CT angiography.
Ultrasonography
Doppler
US may
be preferred in certain centre for RAS diagnoses. Despite it is highly accurate,
unfortunately it is highly operator-dependent.
Magnetic resonance imaging
Magnetic
resonance angiography (MRA) can be used for screening RAS among
KTRs. However, the utilized gadolinium during imaging procedure
has been strongly related to the nephrogenic systemic fibrosis development with
moderate to severe kidney dysfunction, particularly with dialysis therapy. So, gadolinium-based
procedures should be avoided, particularly with GFR < 30 mL/min.
Spiral CT angiography
A
useful non-invasive alternate to arteriography.
Treatment
The
following options may be considered:
Ø Angioplasty (with or with no stents), and,
Ø Surgery.
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| Allograft |
Angioplasty
Percutaneous
balloon angioplasty could be a successful technique in almost 80 % of patients,
despite 20 % may have recurrent stenosis. It’s also less efficacious with
arterial kink, anastomotic locations, and lengthy lesions. Repetition of
angioplasty cannot be successful in these patients. The successful application of
stent placement combined with angioplasty suggests that metallic stents may be successful,
particularly with recurrent allograft RAS lesions.
Surgery
The
presence of extensive fibrotic lesions and scarring around the allograft makes
surgical intervention of allograft RAS inapplicable. Surgery must be considered only with
Resistant HT, or
Proximal recipient arteriosclerotic
involvement.
Successful
rates may approach 60-90 %. However, recurrent stenosis may be observed in 10 %
of patients and allograft loss can be seen also in 30 % of patients.
DEFINITIONS AND GOALS OF THERAPY
The
target BP is primarily relied partially upon the presence/absence
of proteinuria and/or current comorbid diseases,
e.g., DM and/or cardiovascular comorbidities.
The K/DOQI guidelines’ target BP must
be < 130/80 mmHg. For patients with
noticeable proteinuria (total Protein-Cr ratio of 500-1000 mg/g), the K/DOQI recommended
that a lower systolic BP target should be optimized. The European best practice
guidelines also recommended a BP target of < 125/75 mmHg
for patients with proteinuria.
TREATMENT
Overview
The
presence of post-transplant HT should be managed to guard against cardiovascular Sequalea
and the possible hypertensive allograft injury. Post-transplant HT may
be inversely related to the long-term renal allograft longevity. There’re clinical evidence in favor of the
beneficial impacts of BP management.
It
also assumes that steroid dose is being decreased to the lower possible
maintenance level both to control the BP and to limit its other metabolic Sequalea, that may
negatively impact its cardiovascular effects, e.g., glucose intolerance and
hyperlipidemia.
Patient is taking a CNI
In
hypertensive KTRs on a CNI agent, dose reduction should be tried. If HT persists,
CCB (considering their drug interactions) or a diuretic (with
salt limitation) should be instituted.
Calcium channel blockers (CCB)
CCB members
are currently preferred by many clinicians, as they can limit the CyA-induced vasoconstriction in addition to its
potent anti-hypertensive effect. With CCB administration,
a drug interaction with CyA/ tacrolimus / sirolimus may occur. Verapamil , diltiazem , nicardipine ,and amlodipine , but not nifedipine or or isradipine slow CyA/tacrolimus degradation and increase plasma CyA levels. Some clinicians
currently recommend the use of nifedipine/isradipine to counteract this
interaction, while other nephrologists prefer verapamil/diltiazem as inhibition
of CyA/tacrolimus metabolism allows the use
of lower CyA doses.
ACEi /ARBs and other agents
Role
of ACEi/ARBs in KTR is fully understood. A variety of risks with ACEi/ARBs in CNI-dependent KTRs have been suggested:
v Combined ACEi and CyA-induced vascular dis cn induce a
modest decline in GFR as just happen with RAS.
v CyA/ tacrolimus tends to elevate potassium (K+)levels, due to reduction of
urinary K+ excretion, an effect that can be augmented by an ACEi. So, ACEi we don’t use ACEi with K+> 5.0 meq/L.
v ACEi may promote anemia in KTRs, by decreasing hematocrit by 5-10 %
via an effect tht may be augmented by CyA.
Given
these drawbacks, 3-6 months’ post-transplant should be elapsed before prescribing
an ACEi or an ARB. After that, risk of
rejection is minimized and anemia evolution can be managed.
Resistant hypertension
Persistent
HT necessitates the performance of renal arteriography to
exclude an underlying RAS, unless other findings supervene (e.g., renal impairment
with active urinary sediment) that may attract the attention to the possibility
of a recurrent primary disease. Angioplasty (with or with no stents) or surgery
is recommended with tight stenotic lesions. However, native nephrectomy (kidney
removal) is considered with the absence of the following:
1] Rejection.
2] Renovascular lesions,
3] Recurrence of the original disease.
N.B. This Blogger is created to declare the development of hypertension after renal transplantation
REFERENCES
2. Holgado, R, Anaya, F, Del Castillo, DD. Nephrol Dial
Transplant 2001; 16(Suppl 1):82.
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