Download Education and counseling of renal transplant recipients

THOROUGH CRITICAL APPRAISAL
JNEPHROL 2012; 25 ( 06 ) : 879-889
DOI: 10.5301/jn.5000227
Education and counseling of renal transplant
recipients
Claudio Ponticelli, Giorgio Graziani
Department of Internal Medicine, Division of Nephrology,
Istituto Clinico Humanitas IRCCS Rozzano, Milan - Italy
Abstract
Introduction
A large number of factors can influence the clinical outcome of kidney transplant recipients, but the active role
of the patient to prevent the possible complications related to transplant and its treatment is often neglected.
Poor adherence to prescriptions is frequent in transplant
recipients and represents a major contributor to the development of graft failure, cardiovascular disease, infection and/or malignancy. Smoking can render the patient
more susceptible to cancer, cardiovascular disease
and infection, and can also impair renal allograft function. The risk of malignancy is increased in transplant
recipients. Therefore screening for cancer is of paramount importance. Measures that can enable prevention or early detection of cancer include self-exams and
screening, physical activity, avoidance of smoking and
sun exposure, and a diet rich in fruits and vegetables
but limited in fats, red meats, salt and alcohol. Regular exercise can help to prevent cardiovascular disease,
diabetes, obesity, osteoporosis and even some forms of
cancer. Thus regular exercise is recommended. Yet, too
many transplant patients remain sedentary. Weight gain
is common in renal allograft recipients and may be associated with hypertension, hyperlipidemia and/or glucose
intolerance or overt diabetes. To prevent these complications, patients should follow diet regimens based on
low fat and normal/low caloric intake. Small amounts
of alcohol may be permitted in view of its potential cardioprotective effect, but a large consumption of alcohol
can be responsible for devastating side effects. Last but
not least, abidance by hygienic measures may help in
preventing cardiovascular and infectious complications.
Key words: Adherence to prescriptions, Compliance,
Renal transplantation, Self-management, Transplant
complications, Transplant outcome
The success of kidney transplantation depends on a long list
of variables, which include the characteristics of the donor
and recipient, the skillfulness of the surgeons, the type of immunosuppressive and supportive therapy, as well as prompt
and adequate treatments for possible complications, such
as cardiovascular disease, malignancy, infection etc. A critical role for the success of transplantation is also played by
the collaboration between patients and the transplant team.
However, many patients do not realize how important is
their active participation in their medical care, while some
transplant doctors do not make sufficient efforts to inform
patients about the complications they may encounter or to
explain the importance of the drugs and exams prescribed.
In this paper we review the main risk factors that may be
prevented or attenuated by careful self-management by
renal transplant recipients.
Adherence to prescriptions
Adherence to a medication is usually defined as the extent to
which patients take medications as prescribed by their health
care provider (1). The term adherence is usually preferred to
compliance because compliance means that patient is passively following the doctor’s orders (2). Poor adherence to
therapeutic prescriptions is frequent in patients requiring
long-term therapies and represents a serious public health
issue. Actually, only 50% of patients who suffer from chronic
diseases adhere to treatment recommendations (3). The biggest stumbling block to taking medicines is the complexity
of treatment. However, poor adherence is frequent even in
patients who have to take only 1 pill per day. In a survey,
about half of patients who were prescribed a single antihypertensive drug had stopped taking it within 1 year (4).
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
879
Ponticelli and Graziani: Role of transplant recipient
The problem is of particular concern for patients who have
to take an elevated number of pills every day. In a survey of
1,130 renal transplant recipients with stable kidney function,
at a mean of 5.9 years after transplantation, each patient was
taking on average 11 pills per day – 6 immunosuppressants
and 5 nonimmunosuppressants (5). It is difficult to believe
that even an adherent subject does not make mistakes with
such a large number of pills to be taken every day. Moreover, many drugs used in organ transplantation can have a
number of adverse effects including aesthetic changes,
gastrointestinal disorders, neurologic complications, hyperglycemia, hypertension etc. Independently of the complexity and toxicity of treatment, patients with social isolation,
low belief in medications, depression, forgetfulness and/or
poor socioeconomic conditions are particularly susceptible to poor adherence to prescriptions (6-12). Another
important issue is represented by the increasing number
of immigrants from underdeveloped countries who cannot
fully understand the language and recommendations of
the medical staff.
Two systematic reviews in adult renal transplant recipients
reported that 22% (6) and 28% (7) of patients were nonadherent. The poor compliance may in part be explained by the
complexity of treatment (5). Poor adherence is even higher
in adolescents. A search of the literature showed a weighted
prevalence of nonadherence in 32% of adolescents younger than 21 years (13). Some investigators found that poor
adherence occurred more frequently in living transplant
recipients (14), while others reported a similar prevalence of
poor adherence in patients who received their kidney from
living donors or from deceased donors (15). As expected,
transplant patients are more adherent to immunosuppressive therapy in comparison with supportive treatments. In
1 study, 18% of kidney transplant recipients were nonadherent to immunosuppressive drugs, whereas 45% of patients
were nonadherent to antihypertensive, antidiabetic and/
or lipid-lowering agents (11).
Poor adherence contributes substantially to graft loss. In
a systematic review, a median of 36% of graft losses were
associated with prior nonadherence, and a meta-analysis
showed that the odds of graft failure increased sevenfold in
nonadherent patients compared with adherent subjects (6).
Another review reported that nonadherence contributed to
20% of late rejection episodes and 16% of the graft losses
(7). In a progressive study of 56 grafts that progressed to failure, 36 were caused by antibody-mediated rejection, and 17
of them occurred in nonadherent recipients (12). Also, poor
adherence to clinical visits and/or to nonimmunosuppressive
medications may favor the occurrence of infection, tumor
and cardiovascular disease (16).
880
In summary, the available data clearly show that optimizing
adherence to medications and prescriptions is an important
opportunity to improve outcomes in renal transplant recipients. The collaboration between caretakers and patient is
of paramount importance. The transplant staff should provide clear instructions about prescriptions and check that
the patient has fully understood the prescriptions, taking into
account that about 60% of patients cannot correctly report
what their physicians told them about medication use 10
to 80 minutes after receiving the information (17). Regular
contact with the patient should be established, and the adherence to prescriptions should be verified during follow-up
visits. Moreover, some measures should be suggested to the
patients to facilitate their adherence, including the following:
– Patients should be aware of the importance of prescriptions and should ask for further explanations if they have
any doubts;
– Patients should make certain they have the telephone and
e-mail details of members of the transplant team to freely
communicate any problem that may arise;
– A pill box should be used to prepare the medications
every day;
– A daily checklist of drugs should be used;
– A beeping watch or timer may be used to remind the
patient when a dose is due;
– Patients should inform doctors about any adverse events
potentially referable to medications, before stopping the
suspected drug;
– Patients should communicate in the due time if they have
to change the date/time of a prescribed visit.
Smoking
Cigarettes contain more than 4,000 chemical compounds
and at least 400 toxic substances, including tar, which can
be responsible for respiratory tumors; nicotine and reactive aldehydes, which mediate endothelial dysfunction and
atherosclerosis; and carbon monoxide, which can cause
chronic obstructive pulmonary disorder. The association of
smoking with vascular, neoplastic and respiratory disease is
well established (18-25). Smoking can also exert nephrotoxic effects. A large study showed that urinary albumin excretion rate correlated to the number of cigarettes smoked every day (26). Other epidemiologic studies have documented
a marked risk of irreversible proteinuria in smokers (27-29).
Smoking can also accelerate the progression of renal failure
in patients with diabetic nephropathy and arterial hypertension (30, 31). In patients with glomerulonephritis, smokers
showed a more rapid decline of glomerular filtration rate in
comparison with nonsmokers (29). Not only active smoking
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2012; 25 ( 06 ) : 879-889
but also second-hand smoke can be responsible for cancer
and cardiovascular complications (32, 33).
It has been demonstrated that smoking decreases patient
survival after transplantation. In a retrospective cohort of
41,705 adult renal transplant recipients, incident smoking
after transplant was associated with a risk of death more
than double that of never smokers (34). The magnitude of
the negative impact of smoking in renal transplant recipients
has been estimated to be quantitatively similar to that of diabetes (35). The main cause of death in transplant patients
who continue to smoke is represented by cardiovascular
disease (36, 37), but there is also evidence that smoking
can increase the risk of malignancy (38) and infection (39).
Patients who continue to smoke after transplantation also
run an increased risk of graft failure (40, 41). Even if the risk of
death and graft failure may be attenuated by stopping smoking after transplantation (37), a history of smoking before
kidney transplantation can also contribute significantly to
allograft loss (42, 43). The pathogenesis of smoking-related
renal damage is largely unknown. There is no evidence that
smoking can favor rejection. Rather the histologic picture
in smokers is characterized by interstitial fibrosis (40) or
nodular glomerulosclerosis (44). The intermittent increase
in blood pressure during smoking might play a major role
in causing renal damage (45). Increased sympathetic activity, increased renal vascular resistance, oxidative stress,
increased intraglomerular pressure and/or renal artery arteriosclerosis may probably contribute to the deleterious
effects of smoking (29).
Patients on the waiting list for a transplant should be informed
that stopping smoking represents the single most important
step that they can take to enhance the length and quality
of their lives. However, the prevalence of smokers in transplant candidates ranges around 35% in European patients
(46) and 25% in North American patients (47). After kidney
transplantation, only 28% of patients stop smoking (48).
Tumors
Cancer represents a major cause of morbidity and mortality
for renal transplant recipients. Organ transplant recipients
have a threefold excess risk of cancer relative to the ageand sex-matched general population (49). In Europe, the
overall prevalence of cancer after renal transplantation can
reach 40% at 20 years (50). In the United States, the adjusted death rate from cancer for renal transplant patients is
1.4 per 1,000 person-years (51). In Australia and New
Zealand, the cumulative risk of tumors other than those of
the skin is 40% at 30 years after transplantation, whereas
75% of renal allograft recipients have skin cancer (52).
Some types of cancer are particularly frequent after transplantation. Kaposi sarcoma is 400-1,000 times more frequent after transplantation in comparison with the general
population. Skin and genitourinary carcinomas are 100
times more frequent than in the general population. NonHodgkin’s lymphoma, hepatic carcinoma, labial carcinoma
and renal carcinoma also have a higher incidence after
transplantation (53, 54). Although the risk of cancer is mainly
related to the intensity of immunosuppression (55, 56), viral
infection (57, 58) and duration of transplantation (59), patients may take measures that can prevent the occurrence
of tumors or at least may allow an early diagnosis.
Screening is of paramount importance, but transplant recipients have a limited awareness of the importance of cancer screening (60). A number of measures are helpful for an
early detection of malignancy (Tab. I).
Lifestyle can help to prevent cancer. The main measures to
prevent malignancy include physical activity, weight control,
avoiding cigarettes, limited sun exposure and appropriate
diet regimen.
The evidence for decreased risk with increased physical activity is classified as convincing for breast and colon cancer, probable for prostate cancer, and possible for lung and
endometrial cancer (59). Weight control is of particular importance since a link between obesity and cancer is well
established (61). Based on existing evidence, health organizations recommend regular physical activity of 30 minutes
per day for at least 5 days every week (62). Smoking is the
main cause of lung cancer and can also cause tumors of the
oral cavity, pharynx, larynx, esophagus, bladder, stomach,
cervix, kidney and pancreas, as well as acute myeloid leu-
TABLE I
SUGGESTED SCREENING FOR CANCER IN KIDNEY
TRANSPLANT RECIPIENTS
Cancer
Type and time of screening
Breast
Frequent self-examination
Mammography every year
Cervix (women >21 years) Pap smear every year
Colorectal
Fecal occult blood every year
Colonoscopy every 3 years
Prostate
PSA test and digital rectal
exam every year
Skin
Frequent self-examination
Dermatological evaluation
every year
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
881
Ponticelli and Graziani: Role of transplant recipient
kemia. Therefore transplant recipients should stop smoking
and try to avoid passive smoking.
Patients should also try to minimize sun exposure, through
avoidance of sun and UV light exposure; use of appropriate
clothes, sunglasses, wide-brimmed hat and sun-protective
creams; avoidance of smoking (risk of lip cancer); frequent
self-examination; and a regular dermatological evaluation.
Skin cancers are by far the most frequent tumors in transplant recipients. Squamous cell carcinoma and particularly
basal cell carcinoma are the most frequent types of skin
tumors. These tumors are rare in blacks, while they are particularly frequent in transplant patients with blond or red hair
(63). Although ethnicity and genetic factors may be involved
in the pathogenesis of skin tumors, a major role is played by
the oncogenic effect of ultraviolet B (UVB) light. Preventive
measures include diligent UV protection, avoiding or minimizing sun exposure. Tanning beds and sunscreens should
be prohibited. The use of protective clothing, sunglasses,
wide-brimmed hat is recommended. Sun-protective creams
may reduce the effects of UVA and UVB radiation (64).
Frequent self-examination of the skin and regular dermatologic evaluation are also recommended. Unfortunately the
use of sun protective measures is often neglected by transplant patients (65). Transplant patients should keep in mind
that intermittent but intense exposure to sun can cause a
malignant melanoma (66).
Appropriate dietetic measures may prevent the development of some cancers. Fruit and vegetables may have a
protective role in some types of cancer (67, 68). Although
the relationship between fat intake and cancer is controversial, high-fat foods, particularly those from animal sources,
should be limited as they tend to be higher in calories and
may increase the risk of becoming overweight or of obesity.
Protective effects of soy for both hormone- and non-hormone-related cancers have been documented, although a
definitive statement that soy reduces cancer risk cannot be
made. A reduced intake of red meat, particularly processed
meat, might decrease the risk of colorectal and prostate cancer and may have beneficial effects on breast cancer as well,
although the evidence for this is less compelling (69). Experimental studies and clinical trials showed a beneficial role of
n-3 polyunsaturated fatty acids in preventing colorectal cancer and suggest that a consumption of dietary fish oil might
help in preventing colon cancer (70). The molecular basis
of this effect is still unclear, but it has been hypothesized
that the antineoplastic activity of fatty acids is related to their
antiproliferative and antiangiogenic effects (71). Cohort studies suggest a moderate direct association between salt intake and gastric cancer. Salt might cause stomach cancer
by damaging gastric mucus, improving temporary epithelial
882
proliferation and inducing hypergastrinemia that leads to
eventual parietal cell loss (72). Alcohol should be used with
moderation. Chronic alcohol consumption is a strong risk
factor for cancer in the upper aerodigestive tract and in colorectum; moreover, excessive alcohol consumption is also a
major etiologic factor in hepatocarcinogenesis (73).
In summary, due to the increased risk of cancer, renal transplant recipients should take a number of preventive measures that include physical activity, avoidance of smoking
and sun exposure, and a diet rich in fruit and vegetables but
limited in fats, red meat and salt.
Physical activity
Regular exercise can help to prevent some forms of cancer,
cardiovascular disease (74), diabetes (75), obesity (76) and
osteoporosis (77); can normalize large artery compliance
(78); and can lead to beneficial effects on physical fitness,
cardiovascular health, quality of life and nutritional parameters in adults with chronic kidney diseases (79). Moreover,
serotonin and endorphins released during exercise may improve mood, increase self-esteem and reduce depressive
symptoms among patients with chronic illness (80).
Poor levels of physical activity at the time of kidney transplantation is a strong predictor of all-cause mortality (81) particularly in older recipients (82), smokers and diabetics (83).
However, in spite of the risk connected to physical inactivity, most transplant candidates, in particular elderly subjects
and children, are sedentary. Older people referred for renal
transplantation usually have poorer physical performance
than older adults with other chronic diseases and are at
risk for disability while awaiting transplantation (84). Most
pediatric patients with chronic kidney disease have a low
exercise capacity and are physically inactive (85). Even after
successful renal transplantation, many patients still believe
themselves to be disabled, as they did when they were on
dialysis (86) and remain sedentary, with only a quarter of
them practicing physical exercise (87).
A systematic review of studies showed that habitual physical
activity after renal transplantation was positively associated
with quality of life and aerobic fitness, and negatively associated with body fat (88). Zelle et al (89) reported that physical
activity was inversely associated with metabolic syndrome,
cardiovascular disease, fasting insulin and triglycerides, and
positively associated with kidney function, in renal transplant
recipients, while the risk of cardiovascular death and allcause mortality was significantly higher in patients with poor
levels of physical activity. In children with a successful kidney
transplant, a weekly physical exercise total of 3-5 hours significantly improved cardiorespiratory fitness and left ventricu-
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2012; 25 ( 06 ) : 879-889
lar mass (90). Physical exercise might also have an impact on
the immune response. It has been shown that exercise may
down-regulate proinflammatory cytokines, reduce the expression of the adhesion molecules CD80 and CD86, and increase the number of T regulators (91). Königsrainer et al (92)
found that exhaustive physical exercise caused a different
pattern of gene expression in transplant recipients compared
with healthy athletes and concluded that physical exercise
might reduce the need for immunosuppressive medication in
transplant recipients.
Counseling and encouragement for more physical activity
are warranted as a part of routine medical care for candidates to transplantation and for transplant recipients. Regular exercise and physical activity may help reduce the high
prevalence of cardiovascular risk factors, improve quality of
life and reduce the side effects of immunosuppression.
Diet
In dialysis patients waiting for transplantation, nonadherence to the prescribed regimen and excessive weight gain
between dialysis sessions is a common problem (93), which
can favor hypertension (94), left ventricular hypertrophy (95)
and congestive cardiopathy (96). Another issue is represented by a very high or very low body mass index (BMI), either
of which represents a risk factor for patient and graft survival
after transplantation (97). Thus it is important that transplant
candidates pay particular attention to avoiding excessive
fluid intake between dialysis and to taking steps to prevent
both malnutrition and obesity.
After transplantation, many patients have spontaneously
improved appetite, which is also stimulated by use of glucocorticoids. Moreover, transplant patients feel free from the
food and fluid restrictions they had to follow during dialysis.
As a consequence, many patients show weight gains, and
some of them become obese. Moreover, some 70%-90% of
kidney transplant recipients have arterial hypertension (98),
60%-80% have hyperlipidemia (99, 100) and about 20%25% develop new-onset diabetes, while 40%-45% show an
abnormal glucose tolerance (101-103). Dietary advice can
contribute to healthier eating habits and prevent metabolic
syndrome which can increase the risk of cardiovascular
morbidity and mortality (104, 105).
Although, some transplant patients may require a personalized dietetic regimen, as a general rule their diet should be
normocaloric/hypocaloric and hypolipidemic. The diet should
be varied and contain about 20% proteins (fish, lean meat
and poultry), 30% fat (olive oil, well-cooked eggs, fish oil and
dairy products) and 50% carbohydrates (cereals, vegetables,
fruit and whole grains). To reduce the caloric intake in over-
weight patients, smaller portions should be consumed, and
second helpings should be avoided. The use of soft drinks,
which account for one third of total intake of sugar in the
United States (106) and are associated with multiple metabolic risk factors (107), should be prohibited or at least minimized. To reduce the intake of fats, the consumption of fruit,
vegetables, whole grains, fish and fish oil should be encouraged. Poultry without skin, low-fat dairy products, lean meat
and eggs (no more than 3 times a week) may be consumed
in moderate doses, while fried foods and products containing
saturated or trans fats should be avoided. In summary, the
following principles should be followed:
– The ideal calorie intake should be calculated on the basis
of age, sex, BMI and level of physical activity;
– The diet should contain about 20% proteins (fish, lean
meat and poultry), 30% fat (olive oil, well-cooked eggs,
fish oil and dairy products) and 50% carbohydrates (cereals, vegetables, fruit and whole grains);
– Dietary sodium should not exceed 1,500 mg per day;
– Soft drinks with high sugar content should be prohibited
in overweight patients;
– To reduce the intake of fats, the consumption of fruit, vegetables, whole grains, fish and fish oil should be encouraged. Poultry without skin, low-fat dairy products, lean
meat and eggs (no more than 3 times a week) may be
consumed in moderate doses, while fried foods and products containing saturated or trans fats should be avoided.
– To prevent osteoporosis, a calcium-rich diet (low-fat
yogurt, cheese, nonfat milk, fortified bread and cereals,
and nuts) associated with caloric restriction is suggested. In cases of hypercholesterolemia, some food may be
replaced by oral calcium supplementation;
– Moderate intake of alcohol is permitted.
Excess dietary sodium is a major contributor to hypertension
and a critical public health issue. In the United States, the
National Health and Nutrition Examination Survey reported a
mean daily sodium consumption of 3,266 mg, excluding salt
added at the table, instead of an ideal consumption of 2,300
mg per day (i.e., about 5.7 g of salt) (108). Reducing sodium
intake to 2,300 mg/day potentially could prevent 11 million
cases of hypertension (109). In renal transplant recipients, a
reduced salt intake is recommended by the European guidelines (50), although no indication is provided concerning the
desirable daily intake. We feel that the general recommendations of the Canadian Hypertension Education Program
(110) may be applied also to kidney transplant recipients. Dietary sodium should be restricted to 1,500 mg (65 mmol) per
day in adults ≤50 years of age and to 1,300 mg (57 mmol)
per day in adults over 51 years of age. Foods high in sodium
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
883
Ponticelli and Graziani: Role of transplant recipient
are commercial soups, processed meats, processed vegetables, salty snack foods, vegetable juices and condiments
such as pickle relish, olives, garlic or onion salt, monosodium glutamate, soy sauce and meat tenderizers.
Osteopenia and osteoporosis are frequent in renal transplant recipients (111, 112) and are mainly related to the
long-term administration of glucocorticoids (113). To prevent this complication, a diet rich in calcium (low-fat yogurt,
cheese, nonfat milk, fortified bread and cereals, and nuts)
associated with caloric restriction is suggested. In case of
contraindications to the above-mentioned foods, an oral
calcium supplement can be used. In this context, some investigations reported that a calcium intake higher than 600
mg/day reduced blood pressure and abdominal fat in hypertensive patients (114), in obese subjects (115-117) and
in kidney transplant recipients (118).
In summary, transplant candidates should try to avoid important weight gains between dialysis sessions to prevent
cardiac disease that may compromise the results of renal
transplantation. After transplantation, efforts should be
made to maintain a normal BMI, to avoid the use of saturated or trans fats and to minimize the intake of sodium.
These dietetic measures in conjunction with physical activity, multidisciplinary care and pharmacologic treatment can
lead to improvements in cardiovascular risk factors.
Alcohol consumption
Severe alcohol use is a major public health concern. The
physical health effects of alcohol may include cirrhosis, pancreatitis, epilepsy, polyneuropathy, dementia, heart disease,
nutritional deficiencies, sexual dysfunction, cancer and death
from many sources. On the other hand, a moderate alcohol consumption may reduce the risk of cardiovascular disease. A J-shaped relationship has been observed between
the level of alcohol intake and risk of cardiovascular mortality and total mortality, with a maximal protection at about
26 g/day (119). Epidemiologic studies showed that wine is
more protective than beer, and red wine is more protective
than white wine because of the higher content of polyphenols and in particular of resveratrol, which has antioxidant,
vasoprotective and antifibrotic properties (119). An increase
in high-density lipoprotein cholesterol is considered as the
most plausible mechanism of the protective effect of alcohol,
although other mechanisms including down-regulation of
blood platelet function and coagulation factors are probably
involved (120). It has also been shown that a moderate alcohol assumption is associated with arterial dilation; this effect
may represent a further mechanism explaining the protective
effect of alcohol intake on cardiovascular disease (121).
884
Alcohol use seems to be less prevalent in renal transplant
recipients than in the general population (122). The effects
of alcohol in renal transplant patients are in line with those
observed in the general population. Alcohol dependency
is associated with increased risk of death-censored graft
failure and death (123). On the other hand, moderate alcohol
consumption is associated with a low prevalence of newonset diabetes and reduced risk for mortality (124). Of interest, in an experimental model of ischemia-reperfusion injury,
resveratrol administration reduced the mortality of ischemic
rats from 50% to 10%, and also renal damage was reduced,
as shown by histology and serum creatinine level. These
protective effects are probably related to inhibited renal lipid
peroxidation induced by ischemia and reperfusion (125).
In summary, heavy alcohol intake increases the risk of some
severe diseases including cardiovascular diseases. On the
other hand, alcohol may prevent atherosclerosis and cardiovascular disease, by increasing high-density lipoprotein
cholesterol and inhibiting thrombus formation. Since a moderate use of alcohol may be beneficial, abstinence from alcohol is not recommended for kidney transplant recipients.
The maximal protective effect is reached with a daily alcohol
consumption of 25 g (126).
Hygienic measures
Hygienic measures can prevent infections and other complications. Accurate handwashing during hospitalization
can reduce the risk of nosocomial infections, and gown and
glove isolation have an additional protective effect in children (127). Patients should be advised to wash with antiseptic soap. Genitalia and anal areas should be washed carefully. Female patients should wipe the perineum from front to
back to prevent urethral contamination.
Frequent nystatin swish and swallow are recommended in
the first posttransplant period to prevent oral and esophageal fungal infections. Dental and medical care should be
closely integrated for kidney transplant recipients, since
there is evidence that dental infection and periodontal
disease are associated with an increased risk of cardiac
infarct (128-130) and infection. Moreover, in patients with
periodontitis, subgingival biofilms may act as reservoirs of
gram-negative bacteria and the periodontium as a reservoir
of inflammatory mediators (131). Other general measures
are also important. Patients should ventilate their rooms,
wear clean clothes and change them frequently and avoid
crowded meetings and passive smoking. Influenza vaccination is recommended in renal transplant recipients. Concerns that vaccination can trigger rejection episodes are not
confirmed by recent studies (132, 133).
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2012; 25 ( 06 ) : 879-889
Financial support: None.
Conflict of interest statement: C.P. served as a consultant of
Novartis Italy until December 2011. G.G. has no conflict of interest.
References
1.
Osterberg L, Blaschke T. Adherence to medication. N Engl J
Med. 2005;353(5):487-497.
2. Tilson HH. Adherence or compliance? Changes in terminology. Ann Pharmacother. 2004;38(1):161-162.
3. World Health Organization. Adherence to long term therapies: evidence for action. Geneva: World Health Organization; 2003.
4. Vrijens B, Vincze G, Kristanto P, Urquhart J, Burnier M.
Adherence to prescribed antihypertensive drug treatments:
longitudinal study of electronically compiled dosing histories.
BMJ. 2008;336(7653):1114-1117.
5. Ponticelli C, Colombo D, Novara M, Basilisco G. CETRA
Study Group. Gastrointestinal symptoms impair quality of life
in Italian renal transplant recipients but are under-recognized
by physicians. Transpl Int. 2010;23(11):1126-1134.
6. Butler JA, Roderick P, Mullee M, Mason JC, Peveler RC.
Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation. 2004;77(5):769-776.
7. Denhaerynck K, Dobbels F, Cleemput I, et al. Prevalence,
consequences, and determinants of nonadherence in adult
renal transplant patients: a literature review. Transpl Int.
2005;18(10):1121-1133.
8. Dobbels F, Ruppar T, De Geest S, Decorte A, Van DammeLombaerts R, Fine RN. Adherence to the immunosuppressive regimen in pediatric kidney transplant recipients: a
systematic review. Pediatr Transplant. 2010;14(5):603-613.
9. Butler JA, Peveler RC, Roderick P, Smith PW, Horne R, Mason
JC. Modifiable risk factors for non-adherence to immunosuppressants in renal transplant recipients: a cross-sectional
study. Nephrol Dial Transplant. 2004;19(12):3144-3149.
10. Schmid-Mohler G, Thut MP, Wüthrich RP, Denhaerynck K,
De Geest S. Non-adherence to immunosuppressive medication in renal transplant recipients within the scope of the
Integrative Model of Behavioral Prediction: a cross-sectional
study. Clin Transplant. 2010;24(2):213-222.
Address for correspondence:
Claudio Ponticelli, MD, FRCP
Via Ampere 126
IT-20131 Milano, Italy
[email protected]
11. Terebelo S, Markell M. Preferential adherence to immunosuppressive over nonimmunosuppressive medications in kidney
transplant recipients. Transplant Proc. 2010;42(9):3578-3585.
12. Sellarés J, de Freitas DG, Mengel M, et al. Understanding
the causes of kidney transplant failure: the dominant role
of antibody-mediated rejection and nonadherence. Am J
Transplant. 2012;12(2):388-399.
13. Shemesh E, Annunziato RA, Arnon R, Miloh T, Kerkar N.
Adherence to medical recommendations and transition to
adult services in pediatric transplant recipients. Curr Opin
Organ Transplant. 2010;15(3):288-292.
14. Jindal RM, Joseph JT, Morris MC, Santella RN, Baines LS.
Noncompliance after kidney transplantation: a systematic
review. Transplant Proc. 2003;35(8):2868-2872.
15. Vasquez EM, Tanzi M, Benedetti E, Pollak R. Medication
noncompliance after kidney transplantation. Am J Health
Syst Pharm. 2003;60(3):266-269.
16. Djamali A, Samaniego M, Muth B, et al. Medical care of
kidney transplant recipients after the first posttransplant
year. Clin J Am Soc Nephrol. 2006;1(4):623-640.
17. Gottlieb H. Medication Nonadherence: Finding Solutions to a
Costly Medical Problem. Drug Benefit Trends. 2000;12:57-62.
18. Njølstad I, Arnesen E, Lund-Larsen PG. Smoking, serum
lipids, blood pressure, and sex differences in myocardial infarction: a 12-year follow-up of the Finnmark Study. Circulation. 1996;93(3):450-456.
19. Boyle P. Cancer, cigarette smoking and premature death in
Europe: a review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October
1996. Lung Cancer. 1997;17(1):1-60.
20. Keil U, Liese AD, Hense HW, et al. Classical risk factors and
their impact on incident non-fatal and fatal myocardial infarction and all-cause mortality in southern Germany: results
from the MONICA Augsburg cohort study 1984-1992: Monitoring Trends and Determinants in Cardiovascular Diseases.
Eur Heart J. 1998;19(8):1197-1207.
21. Jacobs DR Jr, Adachi H, Mulder I, et al. Cigarette smoking
and mortality risk: twenty-five-year follow-up of the Seven
Countries Study. Arch Intern Med. 1999;159(7):733-740.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
885
Ponticelli and Graziani: Role of transplant recipient
22. Doll R. Fifty years of research on tobacco. J Epidemiol
Biostat. 2000;5(6):321-329.
23. Kabat GC. Fifty years’ experience of reduced-tar cigarettes:
what do we know about their health effects? Inhal Toxicol.
2003;15(11):1059-1102.
24. Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation
to smoking: 50 years’ observations on male British doctors.
BMJ. 2004;328(7455):1519.
25. Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung
Cancer. 2004;45(Suppl 2):S3-S9.
26. Hillege HL, Janssen WM, Bak AA, et al. Prevend Study
Group. Microalbuminuria is common, also in a nondiabetic,
nonhypertensive population, and an independent indicator
of cardiovascular risk factors and cardiovascular morbidity. J
Intern Med. 2001;249(6):519-526.
27. Halimi JM, Giraudeau B, Vol S, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int. 2000;58(3):
1285-1292.
28. Hogan SL, Colindres RE, Cai J, Coresh J. Association of
smoking with albuminuria in a cross-sectional probability
sample of US adults. J Am Soc Nephrol. 2001;12:209.
29. Orth SR. Cigarette smoking: an important renal risk factor: far
beyond carcinogenesis. Tob Induc Dis. 2002;1(2):137-155.
30. Samuelsson O, Attman PO. Is smoking a risk factor for progression of chronic renal failure? Kidney Int. 2000;58(6):2597.
31. Mercado C, Jaimes EA. Cigarette smoking as a risk factor for
atherosclerosis and renal disease: novel pathogenic insights.
Curr Hypertens Rep. 2007;9(1):66-72.
32. Hackshaw AK. Lung cancer and passive smoking. Stat
Methods Med Res. 1998;7(2):119-136.
33. Tong EK, Glantz SA. Tobacco industry efforts undermining
evidence linking secondhand smoke with cardiovascular disease. Circulation. 2007;116(16):1845-1854.
34. Hurst FP, Altieri M, Patel PP, et al. Effect of smoking on kidney transplant outcomes: analysis of the United States Renal
Data System. Transplantation. 2011;92(10):1101-1107.
35. Cosio FG, Falkenhain ME, Pesavento TE, et al. Patient
survival after renal transplantation: Part II: the impact of
smoking. Clin Transplant. 1999;13(4):336-341.
36. Martin JC, Hathaway DK, Egidi MF, Gaber AO. Lifestyle behaviors affect cardiovascular risk status in men 1 year after
kidney transplantation. Clin Transplant. 2001;15(S6) (Suppl 6):
41-45.
37. Doyle SE, Matas AJ, Gillingham K, Rosenberg ME. Predicting clinical outcome in the elderly renal transplant recipient.
Kidney Int. 2000;57(5):2144-2150.
38. Shopland DR, Eyre HJ, Pechacek TF. Smoking-attributable
cancer mortality in 1991: is lung cancer now the leading
cause of death among smokers in the United States? J Natl
Cancer Inst. 1991;83(16):1142-1148.
39. Arcavi L, Benowitz N. Cigarette smoking and infection. Arch
Intern Med. 2004;164(20):2206-2216.
886
40. Zitt N, Kollerits B, Neyer U, et al. Cigarette smoking and
chronic allograft nephropathy. Nephrol Dial Transplant. 2007;
22(10):3034-3039.
41. Sung RS, Althoen M, Howell TA, Ojo AO, Merion RM. Excess
risk of renal allograft loss associated with cigarette smoking.
Transplantation. 2001;71(12):1752-1757.
42. Kheradmand A, Shahbazian H. The role of pretransplant
smoking on allograft survival in kidney recipients. Urol J.
2005;2(1):36-39.
43. Nogueira JM, Haririan A, Jacobs SC, Cooper M, Weir MR.
Cigarette smoking, kidney function, and mortality after live
donor kidney transplant. Am J Kidney Dis. 2010;55(5):907915.
44. Suneja M, Khan A, Katz DA, Kalil R, Nair R. Nodular glomerulosclerosis in a kidney transplant recipient who smokes.
Am J Kidney Dis. 2007;50(5):830-833.
45. Orth SR. Smoking: a renal risk factor. Nephron. 2000;86(1):
12-26.
46. Aker S, Ivens K, Guo Z, Grabensee B, Heering P. Cardiovascular complications after renal transplantation. Transplant
Proc. 1998;30(5):2039-2042.
47. Kasiske BL. Cigarette smoking in renal transplant recipients.
J Am Soc Nephrol. 2000;11(4):753-759.
48. Banas MC, Banas B, Wolf J, et al. Smoking behaviour of
patients before and after renal transplantation. Nephrol Dial
Transplant. 2008;23(4):1442-1446.
49. Vajdic CM, van Leeuwen MT. Cancer incidence and risk
factors after solid organ transplantation. Int J Cancer. 2009;
125(8):1747-1754.
50. European best practice guidelines for renal transplantation.
Nephrol Dial Transplant. 2002;17(Suppl 4):3-67.
51. Ojo AO, Hanson JA, Wolfe RA, Leichtman AB, Agodoa LY,
Port FK. Long-term survival in renal transplant recipients with
graft function. Kidney Int. 2000;57(1):307-313.
52. Sheil AG. Organ transplantation and malignancy: inevitable
linkage. Transplant Proc. 2002;34(6):2436-2437.
53. Penn I. Primary kidney tumors before and after renal transplantation. Transplantation. 1995;59:480-485.
54. Penn I. Malignancy after immunosuppressive therapy: how
can the risk be reduced? Clin Immunother. 1995;9:207-218.
55. Dantal J, Hourmant M, Cantarovich D, et al. Effect of long
term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin
regimens. Lancet. 28;351:623-628.
56. Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4:222-230.
57. Daneshpouy M, Socie G, Clavel C, et al. Human papillomavirus infection and anogenital condyloma in bone
marrow transplant recipients. Transplantation. 2001;71:
167-169.
58. Ponticelli C. Herpes viruses and tumours in kidney transplant
recipients: the role of immunosuppression. Nephrol Dial
Transplant. 2011;26:1769-1775.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2012; 25 ( 06 ) : 879-889
59. Friedenreich CM, Orenstein MR. Physical activity and cancer
prevention: etiologic evidence and biologic mechanisms. J
Nutr. 2002;132:3456S-3464S.
60. Williams NC, Tong A, Howard K, Chapman JR, Craig JC,
Wong G. Knowledge, beliefs and attitudes of kidney transplant recipients regarding their risk of cancer. Nephrology
(Carlton). 2012;17(3):300-306.
61. Calle EE, Thun MJ. Obesity and cancer. Oncogene. 2004;
23:6365-6378.
62. Marrett L, Theis B, Ashbury F. An Expert Panel Workshop report: physical activity and cancer prevention. Chron Dis Can.
2000;21:143-149.
63. Lindelof B, Granath F, Dal H, et al. Sun habits in kidney transplant recipients with skin cancer: a case-control study of possible causative factors. Acta Derm Venereol. 2003;83:189-193.
64. Parrish JA. Immunosuppression, skin cancer, and ultraviolet
A radiation. N Engl J Med. 2005;353:2712-2713.
65. Seukeran DC, Newstead CG, Cunliffe WJ. The compliance of
renal transplant recipients with advice about sun protection
measures. Br J Dermatol. 1998;138:301-303.
66. Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis
of melanoma induced by ultraviolet radiation. N Engl J Med.
1999;340:1341-1348.
67. Lee JE, Männistö S, Spiegelman D, et al. Intakes of fruit,
vegetables, and carotenoids and renal cell cancer risk: a
pooled analysis of 13 prospective studies. Cancer Epidemiol
Biomarkers Prev. 2009;18:1730-1739.
68. Koushik A, Hunter DJ, Spiegelman D, et al. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort
studies. J Natl Cancer Inst. 2007;99:1471-1483.
69. Stoeckli R, Keller U. Nutritional fats and the risk of type 2
diabetes and cancer. Physiol Behav. 2004;83:611-615.
70. Crous-Bou M, Rennert G, Salazar R, et al. Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer.
Mutagenesis. 2012;27:169-176.
71. Calviello G, Serini S, Piccioni E. n-3 Polyunsaturated fatty
acids and the prevention of colorectal cancer: molecular
mechanisms involved. Curr Med Chem. 2007;14:3059-3069.
72. Wang XQ, Terry PD, Yan H. Review of salt consumption and
stomach cancer risk: epidemiological and biological evidence. World J Gastroenterol. 2009;15:2204-2213.
73. Pöschl G, Seitz HK. Alcohol and cancer. Alcohol Alcohol.
2004;39:155-165.
74. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC.
Primary prevention of coronary heart disease in women
through diet and lifestyle. N Engl J Med. 2000;343:16-22.
75. Hu F, Manson J, Stampfer M, Graham C, et al. Diet, lifestyle,
and the risk of type 2 diabetes mellitus in women. N Engl J
Med. 2001;345:790-797.
76. Chambliss HO. Exercise duration and intensity in a weightloss program. Clin J Sport Med. 2005;15:113-115.
77. Nguyen TV, Smabrook PN, Eisman JA. Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study. J Bone Min Res. 1999;13:1458-1467.
78. Sarrias M, Diaz E, Escofet R. Lifestyle in patients with chronic kidney disease is associated with less arterial stiffness. J
Ren Care. 2010;36:139-144.
79. Herring MP, Puetz TW, O’Connor PJ, Dishman RK. Effect
of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and metaanalysis of randomized controlled trials. Arch Intern Med.
2012;172:101-111.
80. Heiwe S, Jacobson SH. Exercise training for adults with
chronic kidney disease. Cochrane Database Syst Rev.
2011;10:CD003236.
81. Kutner NG, Zhang R, Bowles T, Painter P. Pretransplant
physical functioning and kidney patients’ risk for posttransplantation hospitalization/death: evidence from a national
cohort. Clin J Am Soc Nephrol. 2006;1:837-843.
82. Yango AF, Gohh RY, Monaco AP, et al. Excess risk of renal
allograft loss and early mortality among elderly recipients
is associated with poor exercise capacity. Clin Nephrol.
2006;65:401-407.
83. Rosas SE, Reese PP, Huan Y, Doria C, Cochetti PT, Doyle A.
Pretransplant physical activity predicts all-cause mortality in
kidney transplant recipients. Am J Nephrol. 2012;35:17-23.
84. Hartmann EL, Kitzman D, Rocco M, et al. Physical function in
older candidates for renal transplantation: an impaired population. Clin J Am Soc Nephrol. 2009;4:588-594.
85. Painter P, Krasnoff J, Mathias R. Exercise capacity and
physical fitness in pediatric dialysis and kidney transplant
patients. Pediatr Nephrol. 2007;22:1030-1039.
86. Slakey DP, Rosner M. Disability following kidney transplantation: the link to medication coverage. Clin Transplant.
2007;21:224-228.
87. Gordon EJ, Prohaska TR, Gallant MP, et al. Prevalence and
determinants of physical activity and fluid intake in kidney
transplant recipients. Clin Transplant. 2010;24:E69-E81.
88. Macdonald JH, Kirkman D, Jibani M. Kidney transplantation: a systematic review of interventional and observational
studies of physical activity on intermediate outcomes. Adv
Chronic Kidney Dis. 2009;16:482-500.
89. Zelle DM, Corpeleijn E, Stolk RP, et al. Low physical activity and risk of cardiovascular and all-cause mortality in renal
transplant recipients. Clin J Am Soc Nephrol. 2011;6:898-905.
90. Lubrano R, Tancredi G, Bellelli E, et al. Influence of physical
activity on cardiorespiratory fitness in children after renal transplantation. Nephrol Dial Transplant. 2012;27(4):1677-1681.
91. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana
SS, Nimmo MA. The anti-inflammatory effects of exercise:
mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011;11:607-615.
92. Königsrainer I, Zieker D, Löffler M, et al. Influence of exhaustive exercise on the immune system in solid organ transplant
recipients. Exerc Immunol Rev. 2010;16:184-193.
93. Denhaerynck K, Manhaeve D, Dobbels F, Garzoni D, Nolte C,
De Geest S. Prevalence and consequences of nonadherence
to hemodialysis regimens. Am J Crit Care. 2007;16:222-235.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
887
Ponticelli and Graziani: Role of transplant recipient
94. Rahman M, Fu P, Sehgal AR, Smith MC. Interdialytic weight
gain, compliance with dialysis regimen, and age are independent predictors of blood pressure in hemodialysis patients.
Am J Kidney Dis. 2000;35:257-265.
95. Koc Y, Unsal A, Kayabasi H, et al. Impact of volume status
on blood pressure and left ventricle structure in patients undergoing chronic hemodialysis. Ren Fail. 2011;33:377-381.
96. Holmberg B, Stegmayr BG. Cardiovascular conditions in hemodialysis patients may be worsened by extensive interdialytic weight gain. Hemodial Int. 2009;13:27-31.
97. Meier-Kriesche HU, Arndorfer JA, Kaplan B. The impact of
body mass index on renal transplant outcomes: a significant
independent risk factor for graft failure and patient death.
Transplantation. 2002;73:70-74.
98. Ponticelli C, Cucchiari D, Graziani G. Hypertension in kidney
transplant recipients. Transplant Int. 2011;24:523-533.
99. Satterthwaite R, Aswad S, Sunga V, et al. Incidence of newonset hypercholesterolemia in renal transplant patients
treated with FK506 or cyclosporine. Transplantation. 1998;65:
446-449.
100. Chueh SC, Kahan BD. Dyslipidemia in renal transplant recipients treated with a sirolimus and cyclosporine-based immunosuppressive regimen: incidence, risk factors, progression,
and prognosis. Transplantation. 2003;76:375-382.
101. Van Duijnhoven EM, Cristiaans MH, Boots JM, et al. Glucose
metabolism in the first 3 years after renal transplantation in
patients receiving tacrolimus versus cyclosporine-based immunosuppression. J Am Soc Nephrol. 2002;13(1):213-220.
102. Mathew TH, Rao M, Job V, Ratnaswany S, Jacob CK. Posttransplant hyperglycemia: a study of risk factors. Nephrol
Dial Transplant. 2003;18:164-171.
103. Kasiske BL, Snyder JJ, Gilbert D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J
Transplant. 2003;3:178-185.
104. Hricik DE. Metabolic syndrome in kidney transplantation:
management of risk factors. Clin J Am Soc Nephrol. 2011;
6:1781-1785.
105. Goldsmith D, Pietrangeli CE. The metabolic syndrome following kidney transplantation. Kidney Int Suppl. 2010;118:S8-S14.
106. Johnson RK, Frary C. Choose beverages and foods to
moderate your intake of sugars: the 2000 dietary guidelines for Americans: what’s all the fuss about? J Nutr. 2001;
131:2766S-2771S.
107. Dhingra R, Sullivan L, Jacques PF, et al. Soft drink consumption and risk of developing cardiometabolic risk factors and
the metabolic syndrome in middle-aged adults in the community. Circulation. 2007;116(5):480-488.
108. Centers for Disease Control and Prevention (CDC). Vital
signs: food categories contributing the most to sodium consumption – United States, 2007-2008. MMWR Morb Mortal
Wkly Rep. 2012;61:92-98.
109. Centers for Disease Control and Prevention (CDC). CDC
grand rounds: dietary sodium reduction – time for choice.
MMWR Morb Mortal Wkly Rep. 2012;61:89-91.
888
110. Hackam DG, Khan NA, Hemmelgarn BR. The 2010 Canadian
Hypertension Education Program recommendations for the
management of hypertension: Part 2: therapy. Can J Cardiol.
2010;26(5):249-258.
111. Kokado Y, Takahara S, Ichimaru N, et al. Factors influencing
vertebral bone density after renal transplantation. Transpl Int.
2000;13(Suppl 1):S431-S435.
112. Ponticelli C, Aroldi A. Osteoporosis after organ transplantation. Lancet. 2001;357(9268):1623.
113. Adler RA, Hochberg MC. Glucocorticoid-induced osteoporosis in men. J Endocrinol Invest. 2011;34:481-484.
114. van Mierlo LA, Arends LR, Streppel MT. Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J Hum Hypertens. 2006;20:571-580.
115. Thompson WG, Holdman NR, Janzow DJ, Slezak JM, Morris
KL, Zemel MB. Effect of energy-reduced diets high in dairy
products and fibers on weight loss in obese adults. Obes
Res. 2005;13:1344-1353.
116. Zemel MB, Richards J, Mathis S, Milstead A, Gebhardt L,
Silva E. Dairy augmentation and total and central fat loss in
obese subjects. Int J Obes. 2005;29:391-397.
117. Torres MR, Francischetti EA, Genelhu V, Sajuliani AF. Effect
of a high calcium energy-reduced diet on abdominal obesity
and cardiometabolic risk factors in obese Brazilian subjects.
Int J Clin Pract. 2010;64:1076-1083.
118. Torres MR, Gioseffi C, Guimarães SS, et al. A pilot study on
the relation between dietary calcium and clinical parameters
in renal transplant recipients. J Ren Nutr. 2011;21:418-425.
119. Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de
Gaetano G. Alcohol consumption and mortality in patients
with cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2010;55:1339-1347.
120. de Gaetano G, Di Castelnuovo A, Donati MB, Iacoviello L.
The Mediterranean lecture: wine and thrombosis: from epidemiology to physiology and back. Pathophysiol Haemost
Thromb. 2003;33:466-471.
121. Elkind MS, Sciacca R, Boden-Albala B, Rundek T, Paik MC,
Sacco RL. Moderate alcohol consumption reduces risk of
ischemic stroke: the Northern Manhattan Study. Stroke.
2006;37:13-19.
122. Fierz K, Steiger J, Denhaerynck K, Dobbels F, Bock A, De
Geest S. Prevalence, severity and correlates of alcohol use
in adult renal transplant recipients. Clin Transplant. 2006;20:
171-178.
123. Gueye AS, Chelamcharla M, Baird BC, et al. The association
between recipient alcohol dependency and long-term graft and
recipient survival. Nephrol Dial Transplant. 2007;22:891-898.
124. Zelle DM, Agarwal PK, Ramirez JL, et al. Alcohol consumption, new onset of diabetes after transplantation, and allcause mortality in renal transplant recipients. Transplantation.
2011;92:203-209.
125. Giovannini L, Migliori M, Longoni BM, et al. Resveratrol, a
polyphenol found in wine, reduces ischemia reperfusion injury in rat kidneys. J Cardiovasc Pharmacol. 2001;37:262-720.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2012; 25 ( 06 ) : 879-889
126. Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de
Gaetano G. Wine, beer or spirit drinking in relation to fatal
and non-fatal cardiovascular events: a meta-analysis. Eur J
Epidemiol. 2011;26:833-850.
127. Slota M, Green M, Farley A, Janosky J, Carcillo J. The role
of gown and glove isolation and strict handwashing in the
reduction of nosocomial infection in children with solid organ
transplantation. Crit Care Med. 2001;29:405-412.
128. Kaisare S, Rao J, Dubashi N. Periodontal disease as a risk
factor for acute myocardial infarction: a case-control study
in Goans highlighting a review of the literature. Br Dent J.
2007;203:144-145.
129. Mattila KJ. Dental infections as a risk factor for acute myocardial infarction. Eur Heart J. 1993;14(Suppl K):51-53.
130. Herzberg MC, Weyer MW. Dental plaque, platelets, and cardiovascular diseases. Ann Periodontol. 1998;3:151-160.
131. Li X, Holtveit KM, Tronstad L, Olsen I. Systemic diseases
caused by oral infection. Clin Microbiol Rev. 2000;13:547-558.
132. Hurst FP, Lee JJ, Jindal RM, Agodoa LY, Abbott KC. Outcomes associated with influenza vaccination in the first
year after kidney transplantation. Clin J Am Soc Nephrol.
2011;6:1192-1197.
133. Broeders NE, Hombrouck A, Lemy A, et al. Influenza A/H1N1
vaccine in patients treated by kidney transplant or dialysis:
a cohort study. Clin J Am Soc Nephrol. 2011;6:2573-2578.
Accepted: August 29, 2012
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
889