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Nephrol Dial Transplant (2011): Editorial Reviews
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Received for publication: 28.10.08; Accepted in revised form: 5.10.10
Nephrol Dial Transplant (2011) 26: 430–437
doi: 10.1093/ndt/gfq635
Advance Access publication 8 October 2010
Microvascular disease and its role in the brain and cardiovascular
system: a potential role for uric acid as a cardiorenal toxin
Mehmet Kanbay1, Laura-Gabriela Sánchez-Lozada2, Martha Franco2, Magdalena Madero2,
Yalcin Solak3, Bernardo Rodriguez-Iturbe4, Adrian Covic5 and Richard J. Johnson6
1
Division of Nephrology, Department of Medicine, Gulhane School of Medicine, Ankara, Turkey, 2Department of Nephrology, INC
Ignacio Chavez, Mexico City, Mexico, 3Division of Nephrology, Department of Medicine, Meram School of Medicine, Selcuk
University, Konya, Turkey, 4Servicio de Nefrología, Hospital Universitario and Universidad del Zulia, IVIC-Zulia, Maracaibo,
Venezuela, 5Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, ‘Gr. T. Popa’
University of Medicine and Pharmacy, Iasi, Romania and 6Division of Renal Diseases and Hypertension, University of
Colorado-Denver CO, USA
Correspondence and offprint requests to: Mehmet Kanbay; E-mail: [email protected]
Abstract
Arteriolosclerosis (microvascular disease) may have a
key role not only in driving salt-sensitive hypertension
but also in mediating the development of chronic kidney
disease, vascular dementia, stroke and coronary heart
disease. In this paper, we review the evidence that these
latter conditions result from the altered autoregulation
that occurs when arterioles become diseased. We also
discuss the increasing evidence that dietary intake of sugars rich in fructose may be driving the development of
microvascular disease as a consequence of raising intracellular uric acid. We hypothesize that the treatment of
microvascular disease may require a multifaceted approach by utilizing agents which aim at blocking of
the renin–angiotensin system, reducing oxidative stress,
stimulating endothelial nitric oxide production and lowering uric acid levels. Paradoxically, agents that only
stimulate nitric oxide, such as oestrogens, may increase
the risk of poor outcomes if microvascular disease is not
reversed.
Keywords: arteriolosclerosis; autoregulation; chronic kidney disease;
fructose; uric acid
Introduction
Cardiovascular and renal disease can be separated, to
some extent, by whether the disease process is driven
by large vessel disease (atherosclerosis), small vessel disease (arteriolosclerosis) or a combination of both. Typically,
atherosclerosis involves the presence of cholesterol-laden
plaques with infiltrating macrophages in large vessels, and
the disease manifests when the vessel reaches a critical degree of narrowing that causes distal ischaemia, when there is
embolic phenomenon or when local coagulation occurs resulting in vascular occlusion. In contrast, arteriolosclerosis
usually involves proliferation and matrix deposition in small
arterioles, often with luminal narrowing, and the disease
manifests either from the consequence of distal ischaemia,
or because of impaired autoregulation that can result in
markedly altered flows and pressures to the distal vascular
bed. In general, small vessel disease is what is observed with
primary hypertension, in many individuals with stroke, and
in hypertensive renal disease. In contrast, atherosclerosis
may manifest as coronary artery disease, carotid artery disease, abdominal aneurysms and renal artery stenosis. Major
risk factors for atherosclerosis include hypercholesterolaemia, smoking and family history; in contrast, major risk
factors for arteriolosclerosis appear to be hyperuricaemia,
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: [email protected]
Nephrol Dial Transplant (2011): Editorial Reviews
metabolic syndrome, fetal programming and possibly diet.
In this review, we will focus on the role of arteriolosclerosis
(microvascular disease) in the pathogenesis of chronic kidney disease (CKD). We will also focus to a lesser degree on
the role of arteriolosclerosis in the pathogenesis of stroke
and myocardial infarction.
The pathogenesis of microvascular disease
Arteriolosclerosis has been associated with hypertension,
chronic kidney disease and left ventricular hypertrophy
since the late 1800s [1,2]. While arteriolosclerosis can involve multiple organs, it is strongly associated with hypertension once the lesions are present in the kidney [3]. Here,
the lesions typically involve the afferent arteriole and interlobular artery, and can be characterized by intimal thickening,
vascular smooth muscle cell proliferation, and extracellular
matrix deposition, resulting in an increase in the mediato-lumen ratio, and later by the replacement of the vascular
smooth muscle cells by areas of fibrosis and cell loss.
Historically, most authorities have assumed that arteriolosclerosis represents the vascular response to hypertension. The original evidence supporting this hypothesis
was provided by Perera, who noted that subjects with either
more severe or longer duration hypertension also displayed
more severe renal microvascular disease [4]. Rats made
hypertensive by the administration of a high-salt diet
and the corticosteroid, DOCA, also developed progressive
microvascular disease [5]. In cell culture, increased pressure transduction can stimulate proliferation and activation of vascular smooth muscle cells [6] and endothelial
cells [7]. In the kidney, the afferent arteriole and interlobular artery represent the site where vasoconstriction
occurs in response to a rise in blood pressure; hence, this
autoregulatory response results in these locations being
the site for pressure-induced vascular injury.
While hypertension itself can cause arteriolosclerosis,
there is mounting evidence that the lesions can also be induced by a variety of other substances that act to cause
vasoconstriction. For example, the infusion of angiotensin
II can induce microvascular lesions in various vascular
beds in the rat that resemble arteriolosclerosis [8,9]. Blocking nitric oxide synthesis can also induce renal microvascular disease [10,11]. Some drugs, such as cyclosporine, can
also induce afferent arteriolar disease [12]. Certain foods,
such as fructose, the main ingredient in table sugar (sucrose)
and high-fructose corn syrup, can also induce renal vasoconstriction and microvascular disease [13]. In addition
to vasoconstrictive agents, renal disease itself can result
in the development of renal microvascular disease. For
example, the remnant kidney model in rats, in which oneand two-thirds of the kidneys are removed, will result
in the spontaneous development of afferent arteriolar thickening [14]. Models of low nephron number, such as
induced by maternal malnutrition, can also be associated
with the development of arteriolosclerosis-like lesions in
the kidney (Matt Vehaskari, personal communication).
431
Recent studies suggest that one of the more potent stimuli
for arteriolosclerosis is uric acid. Uric acid is a product of
purine metabolism that circulates in the plasma at concentrations that can vary from 2 to 10 mg/dL or higher. For
many years, it was thought that having elevated uric acid levels was only a risk for the development of gout or nephrolithiasis. In fact, the observation that uric acid can
function as an antioxidant led many experts to consider
an elevated uric acid as a beneficial host response, with
possible protection from the oxidant stresses associated
with ageing, cancer and cardiovascular disease [15–17].
However, more recent studies have shown that uric acid can
induce vascular smooth muscle cell proliferation in vitro,
with the production of pro-inflammatory, pro-oxidative
and vasoconstrictive substances [18–21]. Uric acid also inhibits endothelial cell function and migration [20,22,23].
More importantly, increasing serum uric acid in rats with
a uricase inhibitor was found to induce hypertension, renal
vasoconstriction and the development of afferent arteriolar
disease [24]. Additional studies showed that these vascular
lesions were mediated by angiotensin II, a reduction in
endothelial nitric oxide, and increased oxidative stress. Furthermore, there is some evidence that uric acid may have a
contributory role in the arteriolar lesions that are observed
in rats administered cyclosporine [25] and fructose [13]
(both of which raise uric acid levels).
One possible mechanism for uric acid effects on the vasculature may be inhibition of active vitamin D synthesis.
Previous studies have shown that uric acid could inhibit
1,25-(OH)2 vitamin D in vivo [26], and reduction of serum
uric acid levels via allopurinol administration increased
serum 1,25-(OH)2 vitamin D levels [27]. Our laboratory
is currently undertaking a study to clarify the interaction
between uric acid and vitamin D metabolism.
It remains unclear whether the arteriolosclerotic lesions
that are observed in vivo can occur in the absence of
hypertension. Certain agents such as angiotensin II and
uric acid can induce vascular smooth muscle cell proliferation in vitro. In addition, reducing blood pressure with hydralazine in angiotensin II-infused rats [28] and reducing
blood pressure in hyperuricaemic rats with thiazide diuretics [29] were both reported not to prevent the development
of the microvascular disease. This suggests that it may be
possible to induce microvascular disease in the absence of
hypertension. However, the latter two studies employed
tail-cuff blood pressure which may not accurately reflect
the blood pressure over a 24-h period. Indeed, Mori et al.
performed an elegant study in rats with angiotensin II-induced hypertension in which one kidney was maintained
with normal blood pressure by using a servocontrol apparatus. Interestingly, this kidney showed minimal vascular
injury despite being bathed in the same concentration of
angiotensin II as the opposite hypertensive kidney [30].
A schema for the development of microvascular disease
is shown in Figure 1. While a variety of mechanisms may
be involved, it appears that the best milieu for inducing
microvascular disease is when there is a combination of
elevated pressure associated with high angiotensin II or a
lack of nitric oxide.
Nephrol Dial Transplant (2011): Editorial Reviews
→
Fructose
Cyclosporin
Uric acid
→
→
432
Ang II
→
→
Renal mass
→
NO
→→
NADPH oxidase
Oxidative stress
Blood pressure
Endothelium
Vascular Smooth Muscle Cells
→
cell proliferation,
pro-inflammatory factors,
vasoconstrictors
collagen
NO
apoptosis
Arteriosclerosis
Impaired autoregulation
Fig. 1. A variety of insults act to cause the induction of prosclerosing factors (uric acid and angiotensin II), reduce nitric oxide bioavailability, and
increase oxidative stress and blood pressure. Those stimuli contribute to endothelial cell dysfunction and apoptosis, whereas in VSMC, they have
proliferative and pro-inflammatory effects which induce a phenotypic switch with increased intracellular collagen deposition and diminished
contractile capacity. Thickened and stiffened microvessels have a poor autoregulatory capacity, allowing the transmission of increased blood
pressure to target organs, such as the kidney and the brain.
Microvascular disease as a cause of hypertension
While arteriolosclerosis-like lesions can be induced by
hypertension, there is also growing evidence to the contrary stating that renal microvascular disease can cause
hypertension. This hypothesis was first championed by
Harry Goldblatt in the 1930s [31]. Subsequently, our group
and others have shown that the development of afferent arteriolopathy and peritubular capillary rarefaction can result
in renal ischaemia with an interstitial infiltration of T cells
and macrophages. This inflammatory cell infiltration then
leads to intrarenal oxidative stress with activation of the
local renin–angiotensin system that exacerbates renal
vasoconstriction and mediates salt-sensitive hypertension.
Furthermore, blocking the vascular changes, or inhibiting
the interstitial inflammation, could ameliorate the development of hypertension [32–37]. Similarly, we have also
shown that acutely elevating uric acid could induce hypertension by acutely stimulating renin and oxidative stress
and by inhibiting endothelial nitric oxide [29,38,39], but
once renal microvascular disease occurs, the hypertension
becomes salt-sensitive, renal-dependent and uric acidindependent [40]. These studies suggest that the pathogen-
esis of primary hypertension may be initiated by various
stimuli that acutely cause renal vasoconstriction or hypertension, but with time, the development of renal microvascular disease results in persistent salt-sensitive and
volume-dependent hypertension. These data are in fact consistent with the observation that prevalence of renal microvascular disease and salt-sensitive hypertension increases
with age [41].
In this regard, we have previously suggested that uric
acid may have had a significant role in mediating the
marked rise in hypertension prevalence that has occurred
worldwide [42]. Over the last century, there has been a dramatic increase in the ingestion of added sugars which contain fructose, and the increased consumption of added
sugars correlates both with higher serum uric acid levels
and with elevated blood pressure [43,44]. Administering
high doses of fructose to humans raises uric acid levels
and blood pressure, and preventing the rise in uric acid
with allopurinol prevents the increase in blood pressure
[45]. Diets restricting fructose also lower uric acid levels
and blood pressure (M. Madero, submitted). Mean serum
uric acid levels are also increasing in our population in association with the rise in fructose ingestion and increasing
Nephrol Dial Transplant (2011): Editorial Reviews
prevalence of hypertension, and numerous studies have
found that elevated uric acid could predict the development
of hypertension [46,47]. Additionally, several small clinical trials have reported that lowering uric acid could reduce
blood pressure in humans, including a recent prospective
double-blind trial in obese adolescents [48–50]. Clearly,
additional studies are required to confirm these findings.
As mentioned, a number of epidemiologic and experimental studies have shown that increased dietary fructose
intake, particularly in the form of high-fructose corn syrup,
(HFCS) is associated with development of hyperuricaemia.
The precise mechanism by which fructose causes an increase in uric acid relates to its unique metabolism. The
initial phosphorylation of fructose to fructose-1-phosphate
by fructokinase results in adenosine triphosphate (ATP)
consumption. Unlike glucokinase, which has a negative
feedback to prevent excessive phosphorylation and ATP
depletion, the phosphorylation of fructose will proceed
until all fructose is phosphorylated. During this process,
intracellular phosphate falls, and adenosine monophosphate (AMP) deaminase is stimulated, which results in
the production of inosine monophosphate (IMP) and eventually uric acid. Intracellular uric acid rises followed by a
rise in serum uric acid that peaks at ~30 min [51,52]. With
high levels of fructose ingestion, even fasting levels of uric
acid will rise, consistent with epidemiological studies linking fructose intake with hyperuricaemia [53].
Microvascular disease and altered autoregulation:
a mechanism which increases the risk for chronic
kidney disease, stroke and heart disease
The arterioles have a major role in protecting distal organs
from the elevated pressure present in the central circulation. In the kidney, this autoregulatory vasoconstrictive response is critical in preventing transmission of pressure to
the glomeruli and peritubular capillary bed. Bidani and
Griffin have provided convincing evidence that an altered
renal autoregulatory response is commonly present in
chronic kidney disease, and that this leads to increased
transmission of systemic pressure to the glomeruli [54].
An insight into the mechanism was provided by the laboratory of the late Jaime Herrera-Acosta, who showed that the
development of afferent arteriolar disease resulted in impaired autoregulation and glomerular hypertension [14].
Importantly, this group showed that if the arteriolosclerosis
could be prevented and renal autoregulation remained intact, the progression of renal disease could be halted [14].
The mechanism is relatively logical, for the diseased arterioles have been shown to have an increase in collagen content [10] and hence are not expected to vasoconstrict or
vasodilate as quickly or as efficiently as normal arterioles.
We have suggested that the consequences of altering the
autoregulatory mechanisms of the arteriocapillary bed
may be critical as a risk factor for end-organ damage, particularly by increasing the risk for progression of renal disease [14]. This concept has also been proposed for the
impairment of brain function by Thompson and Hakim
in a recent publication [55].
433
Chronic kidney disease
As mentioned, the studies by Bidani and Griffin have provided key evidence that autoregulation is impaired in subjects with chronic kidney disease, and as a consequence,
there is greater transmission of pressure to the glomerulus
for any given systemic pressure [56]. This likely explains
why lower blood pressure targets are needed for subjects
with diabetic nephropathy and proteinuric chronic kidney
disease in which glomerular pressures are likely elevated.
Interestingly, these studies would also suggest that lower
blood pressure targets may be required for hypertensive
African Americans, with ageing and with long-standing
hypertension, since all of these groups often develop significant renal microvascular disease [57–59]. One might
also postulate that individuals with long-standing hyperuricaemia may also have defective autoregulation and require
lower blood pressure targets once kidney disease develops.
Cerebrovascular disease and stroke
The cerebral arterioles also have a key role in protecting
the brain from systemic pressures. As with the kidney,
the development of cerebral microvascular disease may
impair autoregulation and increase the risk of stroke
and vascular dementia [60]. Lowering the blood pressure
precipitously in subjects with cerebral microvascular disease may increase the risk for ischaemic stroke just as increasing the blood pressure or cerebral blood flow too
rapidly may increase the risk of haemorrhagic stroke [61].
There are a number of different imaging patterns of
cerebral microvascular disease comprising silent cerebral
infarction, white matter hyperintensities and cerebral microbleeds [62]. Interestingly, the possibility that uric acid
may have a role in cerebral microvascular disease has been
suggested. Schretlen and colleagues have found that subjects with elevated uric acid are at increased risk for vascular dementia and have evidence for increased cerebral
microvascular disease as noted by MRI scans [63,64].
Others have linked fructose intake with the development
of dementia, including in experimental animals [65]. However, another recent study showed that higher uric acid levels were associated with less dementia and a better
cognitive function but only after controlling for features
of the metabolic syndrome. This latter paper also did not
separate vascular dementia from other causes of dementia
[66]. An elevated serum uric acid is also known to increase
the risk for stroke [67,68].
Interestingly, chronic kidney disease increases the risk
of development of cerebral microvascular disease and,
once developed, it predicts survival [69–71]. More studies
are needed to determine if the link between CKD and
stroke is microvascular disease induced by a common substance such as uric acid.
Cardiovascular disease
The coronary arterioles that lie distally to the coronary arteries may not have an important role in autoregulation, but
434
their function and patency may still be important in the longterm outcome of patients suffering from myocardial infarction. For example, in subjects who undergo thrombolytic
therapy for acute coronary occlusion, the development of
poor myocardial blood flow post-intervention due to diseased distal microvasculature results in poor outcomes
[72]. Interestingly, we have found that the presence of impaired post-coronary intervention myocardial perfusion following thrombolytic therapy was independently associated
with elevated serum uric acid levels (Kanbay et al., submitted for publication). Again, these studies suggest that uric
acid, by driving microvascular disease, could act in this
manner to contribute causally to coronary heart disease.
Microvascular disease and vasodilatory agents: a
potential for toxicity?
As discussed, the presence of microvascular disease is likely to alter the ability of the arteriole to autoregulate, with
the greatest risk being to the kidney and the brain. While
the presence of microvascular disease suggests that lower
blood pressure targets may be needed to prevent progression of renal disease or stroke, this may also be the reason
that the use of vasodilators may result in enhanced perfusion of hyperperfusion syndromes. Evidence that this may
be the case can be observed in a study in which L-arginine
(a precursor for the synthesis of nitric oxide) was administered either to prevent or to treat hyperuricaemia-associated
hypertension (Figure 2) [39]. If L-arginine was administered prophylactically (chronic treatment), it prevented
the development of the arteriolopathy, reduced systemic
pressure, and maintained glomerular pressure in the normal
range. However, if it was administered after the microvascular lesions were induced (acute infusion), it lowered
systemic pressure but paradoxically increased glomerular
pressure (Figure 2).
The observation that stimulating nitric oxide paradoxically
increased glomerular pressure in the setting of renal microvascular disease could account for some apparently para-
Nephrol Dial Transplant (2011): Editorial Reviews
doxical findings in the literature, such as studies reporting
that the anti-oxidants vitamin E [10] or β-carotene [15] can
increase the risk for haemorrhagic stroke. In the Women’s
Health Initiative, the use of oestrogens (which increase NO)
was also reported to increase the risk for stroke, especially in
older women [73]. It is conceivable that this increased risk is
due to the presence of underlying microvascular disease.
Reversing microvascular disease and long-term
treatments
If microvascular disease is a true risk factor for hypertension, chronic kidney disease, stroke and vascular dementia,
and coronary heart disease, then what can be done to prevent or reverse it? In this regard, the best evidence to date
suggests a role for blockade of the renin–angiotensin system. Studies by Chatziantoniou et al. have shown that the
afferent arteriolopathy from L-NAME infusion can be reversed by a 4-week course of ACE inhibition [74,75].
Schiffrin and Ferrario have also shown that chronic ACE
inhibitor treatment can reverse microvascular disease in
hypertensive humans [76–78]. Other treatment modalities,
such as endothelin antagonists, may also be beneficial. In
any case, some intervention is likely required, as it is known
that the arteriolopathy, such as from chronic inhibition
of NO synthesis, can persist for at least 10 weeks in the
absence of treatment [79].
As mentioned, lowering uric acid can prevent the development of renal microvascular disease in response to hyperuricaemia [24,29] and/or fructose [13]. The question
whether established microvascular disease induced by hyperuricaemia is reversible remains unknown. Clinical studies do suggest that microvascular disease can be reversed
with long-term RAS blockade [76–78]. In relation to the
role of uric acid, the beneficial impact of a variety of uric
acid-lowering agents on the development of cardiovascular
end points has been considered in several studies. These
include studies suggesting an improvement with uric
acid-lowering therapies on chronic kidney disease [50,80],
Fig. 2. L-Arginine was administered either to prevent (chronic L-Arg) or to treat (acute infusion L-Arg) hyperuricaemia-associated hypertension
(induced by oxonic acid administration). When L-arginine was administered chronically, it prevented systemic hypertension, the development of the
arteriolopathy, shown as a reduced media-to-lumen (M/L) ratio, and prevented the glomerular hypertension induced by hyperuricaemia. Acute infusion
of L-Arg was able to reduce systemic hypertension; however, microvascular lesions already present, precluded the benefit of lowering blood pressure to
relief glomerular hypertension; on the contrary, increased renal perfusion induced a further increment in glomerular pressure [39].
Nephrol Dial Transplant (2011): Editorial Reviews
unstable angina [81], insulin resistance [82] and hypertension [49,83]. Further studies are necessary to determine
the effects of these therapies on microvascular structural
changes.
Conclusions
In conclusion, there is increasing evidence that arteriolosclerosis (microvascular disease) may have a key role in
cardiorenal disease. Renal microvascular disease may be
a key mechanism for inducing salt-sensitive hypertension. In addition, the development of microvascular disease results in altered autoregulatory and microvascular
functions, and may increase the risk for stroke, vascular
dementia, coronary heart disease and chronic kidney
disease. Non-specific vasodilators may not be beneficial
if microvascular disease is not actively treated with RAS
blockade. In addition, the role of dietary fructose and
uric acid in this process is likely but requires further
study.
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Received for publication: 7.7.10; Accepted in revised form: 20.9.10
Nephrol Dial Transplant (2011) 26: 437–444
doi: 10.1093/ndt/gfq628
Advance Access publication 20 October 2010
Organ donation, transplantation and religion
Michael Oliver1,*, Alexander Woywodt1,*, Aimun Ahmed1 and Imran Saif2
1
Department of Nephrology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, Lancashire, UK and 2Department of
Nephrology, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth, UK
Correspondence and offprint requests to: Alexander Woywodt; E-mail: [email protected]
*
Both authors contributed equally to this study.
Abstract
Religious concerns may be an important reason why patients decline listing for a renal transplant. These issues
may be equally, or even more, important when live donation
is discussed. There is good reason to believe that religious
concerns play a significant role much more often than clinicians and transplant teams believe. The issue is certainly
further compounded by the fact that a few, if any, patients
come forward with their religious concerns, not least because issue of transplantation is new to them anyway and
because they meet with transplant teams whom they do
not know. Health professionals, on the other hand, may wish
to avoid this sensitive issue altogether or may lack knowledge on religious issues pertaining to transplantation. Some
may be entirely unaware. We encountered a case in clinic
that revealed our remarkable lack of knowledge in this regard. Here, we aim to provide an overview on how the
different religions view transplantation and organ donation,
with an emphasis on practical points for health care professionals who are involved in transplant listing, organ donation and retrieval, and transplantation itself. Knowledge of
these facts may provide a background to deal with these
issues professionally and appropriately and to increase transplant numbers.
Keywords: organ donation; religion; transplantation
Introduction
There is good evidence that patients from indigenous and
migrant ethnic minorities are more likely to develop endstage renal failure but less likely to receive a renal transplant [1]. They are also typically less likely to receive a
well-matched kidney since they are under-represented
among deceased donors: in the UK, only 5.1% of deceased
kidney donations during the financial year 2008/2009 were
from non-white donors, although a quarter of patients on
the waiting list were non-white [2]. Unfortunately, low
rates of live donation among ethnic minorities have been
described as well [3]. Recent studies suggest that, apart
from cultural, social and educational issues and language
barriers, religious concerns may also play a role in a decision against donation [4]. However, care must be taken not
to equate ethnicity with religion, and detailed analysis is
required to dissect the various factors. There are also striking differences between countries as to the willingness to
donate (Table 1). Some of these differences may be explained by different infrastructure, law or consent system,
but religious factors may play a role as well, particularly in
countries with low deceased donation rates [5]. We recently encountered a case in our clinic that made us rethink our
approach to this issue, particularly in the large numbers of
Muslim patients we see in our catchment area in the North
West of England. In this review article, we first explore the
Islamic view of organ donation and transplantation. We
then provide an overview on how the other major religions
view this topic, starting with the two other Abrahamic
faiths (Christianity and Judaism), then moving on to the
two major religions in India (Hinduism and Sikhism)
and then to the religions of East Asia (Buddhism, Confucianism, Shintoism and Taoism). Finally, we discuss the
issue of directed donation and religion.
Case vignette
A 46-year-old Muslim female patient with IgA nephropathy was seen for an annual review on the renal transplant
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