Transplantation141ReviewIranian Jou

Transplantation
141
Review
Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011
Impact of Cigarette Smoking on Kidney Transplant Recipients
A Systematic Review
Mohammad Hossein Nourbala, Eghlim Nemati, Zohreh Rostami,
Behzad Einollahi
Introduction. Cigarette smoking has adverse effects on kidney
transplant recipients, causing cardiovascular disease, kidney
function impairment, and cancer. However, there are surprisingly
few studies on the impact of cigarette smoking among kidney
transplant recipients and its consequences after transplantation.
We performed a systematic review of the literature to identify the
effects of cigarette smoking on patient and graft survival rates
among kidney transplant recipients.
Materials and Methods. We searched the PubMed from 1968
to 2009 to identify studies on the effect of cigarette smoking
on kidney transplant recipients, using the following keywords:
kidney transplantation, cigarette, smoking, tobacco, and nicotine. The
electronic and manual searches yielded 357 articles, of which 39
were considered potentially relevant by titles and abstracts and
were selected for full text review. Twenty-seven irrelevant reports
were excluded.
Results. A total of 12 papers were selected for review, comprising
of 1801 kidney transplant recipients with a history of smoking. The
impact of cigarette smoking on kidney recipient survival was only
evaluated by 6 studies and the relative risk of smoking for death
was available in 3 reports, varying between 0.8 and 2.2. Cigarette
smoking was an independent risk factor for patient death. In
addition, on univariable and multivariable analyses, graft survival
correlated with a history of cigarette smoking and the relative risk
for graft failure ranged from 1.06 to 2.3.
Conclusions. Cigarette smoking was associated with an increased
risk of death and graft loss. Therefore, every attempt should be
made to encourage kidney transplant candidates to stop smoking.
IJKD 2011;5:141-8
www.ijkd.org
Nephrology and Urology
Research Center, Baqiyatallah
University of Medical Sciences,
Tehran, Iran
Keywords. Cigarette, smoking,
renal transplantation, graft
survival, mortality
INTRODUCTION
Cardiovascular disease (CVD) is the leading cause
of mortality among kidney transplant recipients.1,2 In
addition, smoking is a major potentially modifiable
or avoidable risk factor for CVD.3,4 Ponticelli and
colleagues5 reported that smoking was associated
with a higher risk of CVD (relative risk [RR], 1.3;
P = .02) in 864 adults kidney transplant recipients.
Furthermore, Kasiske and coworkers6,7 found that
kidney transplant smokers had a greater risk of
ischemic heart disease (RR, 1.95) compared with
nonsmoking recipients. Recipient smokers have
a significantly shorter mean survival due to
mortality from CVD, in which smoking played
an important contributing role.8,9 In addition,
established cardiovascular risk factors other than
smoking, such as hypertension, diabetes mellitus,
and dyslipidemia, are more frequent in kidney
Smoking and Kidney Transplantation—Nourbala et al
142 Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011
transplant recipients than in the general population.
These risk factors increase the risk of CVD among
kidney transplant recipients and decrease patient
and graft survivals.10
Cancer, the second cause of death in kidney
transplant recipients, is another consequence
of smoking.11 Risk factors for malignancy after
transplantation include factors common to the
general population, such as age, smoking habits,
and sun exposure.12 For example, a series of 1500
kidney transplant recipients showed that age
greater than 45 years old (P = .007) and cigarette
smoking (P = .02) were significantly associated with
an elevated risk of malignancy.13 In a series of 84
heart transplants, cigarette smoking was associated
with reduced recipient survival and increased
risk of posttransplant cancer.14 Finally, cigarette
smoking is also a known major risk factor for the
development of chronic obstructive lung disease,
with 90% of mortality from chronic obstructive
lung disease directly attributable to smoking.15
Therefore, smoking can lead to reduced patient
survival by causing lung disease.
The prevalence of smoking among kidney
transplant recipients is 25% and 35% to 40% in
American and European patients, respectively.16,17
On the other hand, cigarette smoking is the world’s
major cause of premature mortality responsible for
an estimated 5 million deaths each year.18 Although
the adverse effects of smoking in the nontransplant
setting are well known, its impact on patient
and graft survival after kidney transplantation
remains unclear. There are, however, surprisingly
few studies addressing cigarette smoking among
kidney transplant recipients. Thus, we performed
a systematic review of the literature to identify the
effects of cigarette smoking on patient and graft
survival rates among kidney transplant recipients.
MATERIALS AND METHODS
We searched the PubMed database from 1968 to
2009 to identify studies that had reported the effect
of cigarette smoking on kidney transplant recipients.
Our keywords included kidney transplantation,
cigarette, smoking, tobacco, and nicotine and their
synonyms. To identify additional relevant articles,
bibliographies of qualitative topic reviews and the
identified articles were also searched. Duplicated
publications were discarded. We restricted our
search to human studies and placed no restrictions
on language. Our review aimed to address two
specific questions: (1) What is the effect of cigarette
smoking on kidney allograft survival? (2) What
is the effect of cigarette smoking on the kidney
transplant recipient survival?
There were not enough case-control and cohort
studies reporting adjusted RRs and 95% confidence
intervals (95% CI) of all-cause mortality and graft
failure among kidney transplant smokers relative
to nonsmoker patients (Table 1); therefore, we
could not assess the pooled adjusted RR and 95%
CI of these endpoints in a meta-analysis. Table 1
shows the characteristics of studies included in
this review.1,4,8,9,16,17,19-24
RESULTS
The electronic and manual searches yielded 357
papers by titles and abstracts, of which 39 were
Number of Patients
Authors Year Country Study Design All Smokers
Arend et al1 1997 Netherlands Retrospective cohort 804 394
Cosio et al8 1999 US Retrospective cohort 523 147
Kasiske and Klinger17 2000 US Retrospective cohort 1334 330
Matas et al21 2001 US Retrospective cohort 2540 …*
Sung et al19 2001 US Retrospective cohort 645 156
Woo et al9 2002 UK Retrospective cohort 515 234
Yavuz et al16 2004 Turkey Retrospective cohort 226 97
Kheradmand and Shahbazian20 2005 Iran Retrospective cohort 199 41
Zitt et al23 2007 Austria Prospective cohort 76 76
Suneja et al24 2007 US Case report 1 1
Banas et al4 2008 Germany Cross-sectional 264 156
Mohamed et al22 2009 India Retrospective cohort 303 169
Table 1. Baseline Characteristics of Studies Included in This Review
*Number of patients with a history of smoking was not provided in the article.
Smoking and Kidney Transplantation—Nourbala et al
Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011 143
considered potentially relevant and were selected
for full text review. Twenty-seven irrelevant
reports were excluded. After full text review, 9
retrospective cohort studies, 1 prospective cohort
study, 1 cross-sectional study, and 1 case report
were selected for our review (Table 1). Eighteen
hundred and one patients with a history of smoking
before kidney transplantation (ex-smoker) or after
kidney transplantation were included in this review.
The impact of cigarette smoking on kidney
recipient survival had been evaluated by 6
studies,1,8,9,16,17,19 and the RR of smoking for death
was available in 3 reports, varying from 0.8 to
2.2.1,9,17 Cigarette smoking was an independent risk
factor for patient survival, and kidney transplant
recipients with a smoking history had a significantly
shorter survival (Table 2). However, Yavuz
and colleagues, who only reported univariable
analysis, did not find a decreased patient survival
in smokers after transplantation.16 Univariable19,20
and multivariable8,9,17,19,21 analyses showed that
graft survival correlated with a history of cigarette
smoking, and the RR for graft failure ranged from
1.06 to 2.3 (Table 2). In contrast, two retrospective
cohort studies showed that cigarette smoking was
not a risk factor for graft failure on univariable
analysis.16,22 However, it should be noted that the
number of patients included in these studies was
relatively small (Table 1).
Kasiske and Klinger reported the prevalence of
cigarette smoking and its impact on patient and
graft survival in a large cohort of kidney transplant
recipients.17 The total number of pack-years smoked
reported at the time of kidney transplantation was
a stronger predictor for transplant outcomes. In
univariable analysis, smoking more than 25 packyears
at the time of kidney transplantation was
associated with increased graft loss and a higher
mortality rate (Table 2). After adjusting for multiple
predictors of kidney allograft loss, smoking more
than 25 pack-years (compared to smoking less than
25 pack-years or no smoking) was associated with a
30% higher risk of graft loss (Table 1). Having quit
smoking more than 5 year prior transplantation
reduced the relative risk of kidney allograft loss
by 34% (Table 2). This increased graft loss was
largely due to the increased mortality.17 The total
consumption of cigarette smoking was associated
with CVD; for example, the RR of smoking 11 to
25 pack-years at the time of transplantation was
1.56 (95% CI, 1.06 to 2.31; P = .02), whereas that of
smoking more than 25 pack-years was 2.14 (

النتائج (العربية) 2:

زرع Transplantation
141 141
مراجعة Review
الإيراني مجلة أمراض الكلى | حجم 5 | عدد 3 | مايو 2011 Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011
أثر التدخين على الكلى متلقى Impact of Cigarette Smoking on Kidney Transplant Recipients
منهجية مراجعة A Systematic Review
محمد حسين Nourbala، Eghlim نعمتي، زهره رستمي، Mohammad Hossein Nourbala, Eghlim Nemati, Zohreh Rostami,
بهزاد Einollahi Behzad Einollahi
مقدمة. التدخين له آثار سلبية على الكلى Introduction. Cigarette smoking has adverse effects on kidney
متلقى، مما تسبب في أمراض القلب والشرايين والكلى transplant recipients, causing cardiovascular disease, kidney
وظيفة انخفاض القيمة، والسرطان. ومع ذلك، هناك من المستغرب function impairment, and cancer. However, there are surprisingly
قليل من الدراسات حول تأثير تدخين السجائر بين الكلى few studies on the impact of cigarette smoking among kidney
متلقى ونتائجه بعد الزرع. transplant recipients and its consequences after transplantation.
أجرينا مراجعة منهجية للأدب لتحديد We performed a systematic review of the literature to identify the
آثار التدخين على معدلات المريض وبقاء الكسب غير المشروع effects of cigarette smoking on patient and graft survival rates
بين المستفيدين زرع الكلى. among kidney transplant recipients.
المواد وطرق. بحثنا في مجلات عام 1968 من Materials and Methods. We searched the PubMed from 1968
لعام 2009 لتحديد الدراسات حول تأثير التدخين to 2009 to identify studies on the effect of cigarette smoking
على متلقي زرع الكلى، وذلك باستخدام الكلمات الأساسية التالية: on kidney transplant recipients, using the following keywords:
زرع الكلى، والسجائر، والتدخين، والتبغ، والنيكوتين. kidney transplantation, cigarette, smoking, tobacco, and nicotine. The
electronic and manual searches yielded 357 articles, of which 39
were considered potentially relevant by titles and abstracts and
were selected for full text review. Twenty-seven irrelevant reports
were excluded.
Results. A total of 12 papers were selected for review, comprising
of 1801 kidney transplant recipients with a history of smoking. The
impact of cigarette smoking on kidney recipient survival was only
evaluated by 6 studies and the relative risk of smoking for death
was available in 3 reports, varying between 0.8 and 2.2. Cigarette
smoking was an independent risk factor for patient death. In
addition, on univariable and multivariable analyses, graft survival
correlated with a history of cigarette smoking and the relative risk
for graft failure ranged from 1.06 to 2.3.
Conclusions. Cigarette smoking was associated with an increased
risk of death and graft loss. Therefore, every attempt should be
made to encourage kidney transplant candidates to stop smoking.
IJKD 2011;5:141-8
www.ijkd.org
Nephrology and Urology
Research Center, Baqiyatallah
University of Medical Sciences,
Tehran, Iran
Keywords. Cigarette, smoking,
renal transplantation, graft
survival, mortality
INTRODUCTION
Cardiovascular disease (CVD) is the leading cause
of mortality among kidney transplant recipients.1,2 In
addition, smoking is a major potentially modifiable
or avoidable risk factor for CVD.3,4 Ponticelli and
colleagues5 reported that smoking was associated
with a higher risk of CVD (relative risk [RR], 1.3;
P = .02) in 864 adults kidney transplant recipients.
Furthermore, Kasiske and coworkers6,7 found that
kidney transplant smokers had a greater risk of
ischemic heart disease (RR, 1.95) compared with
nonsmoking recipients. Recipient smokers have
a significantly shorter mean survival due to
mortality from CVD, in which smoking played
an important contributing role.8,9 In addition,
established cardiovascular risk factors other than
smoking, such as hypertension, diabetes mellitus,
and dyslipidemia, are more frequent in kidney
Smoking and Kidney Transplantation—Nourbala et al
142 Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011
transplant recipients than in the general population.
These risk factors increase the risk of CVD among
kidney transplant recipients and decrease patient
and graft survivals.10
Cancer, the second cause of death in kidney
transplant recipients, is another consequence
of smoking.11 Risk factors for malignancy after
transplantation include factors common to the
general population, such as age, smoking habits,
and sun exposure.12 For example, a series of 1500
kidney transplant recipients showed that age
greater than 45 years old (P = .007) and cigarette
smoking (P = .02) were significantly associated with
an elevated risk of malignancy.13 In a series of 84
heart transplants, cigarette smoking was associated
with reduced recipient survival and increased
risk of posttransplant cancer.14 Finally, cigarette
smoking is also a known major risk factor for the
development of chronic obstructive lung disease,
with 90% of mortality from chronic obstructive
lung disease directly attributable to smoking.15
Therefore, smoking can lead to reduced patient
survival by causing lung disease.
The prevalence of smoking among kidney
transplant recipients is 25% and 35% to 40% in
American and European patients, respectively.16,17
On the other hand, cigarette smoking is the world’s
major cause of premature mortality responsible for
an estimated 5 million deaths each year.18 Although
the adverse effects of smoking in the nontransplant
setting are well known, its impact on patient
and graft survival after kidney transplantation
remains unclear. There are, however, surprisingly
few studies addressing cigarette smoking among
kidney transplant recipients. Thus, we performed
a systematic review of the literature to identify the
effects of cigarette smoking on patient and graft
survival rates among kidney transplant recipients.
MATERIALS AND METHODS
We searched the PubMed database from 1968 to
2009 to identify studies that had reported the effect
of cigarette smoking on kidney transplant recipients.
Our keywords included kidney transplantation,
cigarette, smoking, tobacco, and nicotine and their
synonyms. To identify additional relevant articles,
bibliographies of qualitative topic reviews and the
identified articles were also searched. Duplicated
publications were discarded. We restricted our
search to human studies and placed no restrictions
on language. Our review aimed to address two
specific questions: (1) What is the effect of cigarette
smoking on kidney allograft survival? (2) What
is the effect of cigarette smoking on the kidney
transplant recipient survival?
There were not enough case-control and cohort
studies reporting adjusted RRs and 95% confidence
intervals (95% CI) of all-cause mortality and graft
failure among kidney transplant smokers relative
to nonsmoker patients (Table 1); therefore, we
could not assess the pooled adjusted RR and 95%
CI of these endpoints in a meta-analysis. Table 1
shows the characteristics of studies included in
this review.1,4,8,9,16,17,19-24
RESULTS
The electronic and manual searches yielded 357
papers by titles and abstracts, of which 39 were
Number of Patients
Authors Year Country Study Design All Smokers
Arend et al1 1997 Netherlands Retrospective cohort 804 394
Cosio et al8 1999 US Retrospective cohort 523 147
Kasiske and Klinger17 2000 US Retrospective cohort 1334 330
Matas et al21 2001 US Retrospective cohort 2540 …*
Sung et al19 2001 US Retrospective cohort 645 156
Woo et al9 2002 UK Retrospective cohort 515 234
Yavuz et al16 2004 Turkey Retrospective cohort 226 97
Kheradmand and Shahbazian20 2005 Iran Retrospective cohort 199 41
Zitt et al23 2007 Austria Prospective cohort 76 76
Suneja et al24 2007 US Case report 1 1
Banas et al4 2008 Germany Cross-sectional 264 156
Mohamed et al22 2009 India Retrospective cohort 303 169
Table 1. Baseline Characteristics of Studies Included in This Review
*Number of patients with a history of smoking was not provided in the article.
Smoking and Kidney Transplantation—Nourbala et al
Iranian Journal of Kidney Diseases | Volume 5 | Number 3 | May 2011 143
considered potentially relevant and were selected
for full text review. Twenty-seven irrelevant
reports were excluded. After full text review, 9
retrospective cohort studies, 1 prospective cohort
study, 1 cross-sectional study, and 1 case report
were selected for our review (Table 1). Eighteen
hundred and one patients with a history of smoking
before kidney transplantation (ex-smoker) or after
kidney transplantation were included in this review.
The impact of cigarette smoking on kidney
recipient survival had been evaluated by 6
studies,1,8,9,16,17,19 and the RR of smoking for death
was available in 3 reports, varying from 0.8 to
2.2.1,9,17 Cigarette smoking was an independent risk
factor for patient survival, and kidney transplant
recipients with a smoking history had a significantly
shorter survival (Table 2). However, Yavuz
and colleagues, who only reported univariable
analysis, did not find a decreased patient survival
in smokers after transplantation.16 Univariable19,20
and multivariable8,9,17,19,21 analyses showed that
graft survival correlated with a history of cigarette
smoking, and the RR for graft failure ranged from
1.06 to 2.3 (Table 2). In contrast, two retrospective
cohort studies showed that cigarette smoking was
not a risk factor for graft failure on univariable
analysis.16,22 However, it should be noted that the
number of patients included in these studies was
relatively small (Table 1).
Kasiske and Klinger reported the prevalence of
cigarette smoking and its impact on patient and
graft survival in a large cohort of kidney transplant
recipients.17 The total number of pack-years smoked
reported at the time of kidney transplantation was
a stronger predictor for transplant outcomes. In
univariable analysis, smoking more than 25 packyears
at the time of kidney transplantation was
associated with increased graft loss and a higher
mortality rate (Table 2). After adjusting for multiple
predictors of kidney allograft loss, smoking more
than 25 pack-years (compared to smoking less than
25 pack-years or no smoking) was associated with a
30% higher risk of graft loss (Table 1). Having quit
smoking more than 5 year prior transplantation
reduced the relative risk of kidney allograft loss
by 34% (Table 2). This increased graft loss was
largely due to the increased mortality.17 The total
consumption of cigarette smoking was associated
with CVD; for example, the RR of smoking 11 to
25 pack-years at the time of transplantation was
1.56 (95% CI, 1.06 to 2.31; P = .02), whereas that of
smoking more than 25 pack-years was 2.14 (

النتائج (العربية) 3:

زرع
141

استعراض Iranian journal of أمراض الكلى | حجم 5 | | رقم 3 مايو 2011
تأثير تدخين السجائر على زرع الكلى المستفيدين

مراجعة منهجية محمد حسين nourbala إغليم نعمتی, زهره
بهزاد رستمي، einollahi
مقدمة.تدخين السجائر له آثار سلبية على الكلى
المتلقين زرع، مما تسبب في أمراض القلب والشرايين والكلى
وظيفة البصر،و السرطان.ومع ذلك، هناك عدد قليل من غرابة
دراسات عن آثار تدخين السجائر بين الكليتين
المتلقين زرع ونتائجه بعد زرع
نفذنا مراجعة منهجية الدراسات لتحديد
آثار التدخين على المريض و الطعم معدلات البقاء على قيد الحياة

المواد بين المتلقين زرع الكلى. و الأساليب.بحثنا في مجلات من 1968
في عام 2009، بغية تحديد دراسات على تأثير تدخين السجائر
على المتلقين زرع الكلى، وذلك باستخدام الكلمات التالية:
زراعة الكلى, السجائر, تدخين التبغ و النيكوتين.
ويميلون في البحث اليدوي الإلكتروني 357 مقالة، منها 39
تعتبر ذات الصلة المحتملة من خلال عناوين وملخصات و تم اختيار
كاملا مراجعة النص.سبعة وعشرون أهمية التقارير
استبعدت نتائج
.ما مجموعه 12 ورقة تم اختيارها لإجراء الاستعراض، التي تشمل
1801 المتلقين زرع الكلى مع تاريخ من التدخين.
تأثير تدخين السجائر على الكلية المتلقي البقاء ليس إلا
تقيمه 6 دراسات و الخطر النسبي عن التدخين الموت
كان متاح في 3 تقارير يتراوح بين 0.8 و 2-2.سيجارة
التدخين هو عامل خطر مستقل وفاة المريض.في
أيضا على univariable وتحليلات multivariable والابتزاز البقاء
ترتبط مع تاريخ من تدخين السجائر و الخطر النسبي
للحصول على طعم الفشل يتراوح بين 1.6 إلى 2-3
الاستنتاجات.تدخين السجائر كان مرتبطا مع زيادة خطر الموت
و طعم الخسارة.ولذلك، ينبغي
كل محاولةلتشجيع زراعة الكلى المرشحين بالتوقف عن التدخين.. 5:141-8

ijkd 2011 www.ijkd. org

مركز أبحاث الكلى و المسالك البولية baqiyatallah

علوم پزشكي تهران، ايران
الكلمات الرئيسية.السجائر, التدخين,

زراعة الكلى، طعم البقاء

مقدمة الوفيات بأمراض القلب والأوعية الدموية التعويضية) هو السبب الرئيسي في الوفيات
بين المتلقين زرع الكلى - 1.2 في
بالإضافة إلىالتدخين هو احتمال كبير للتعديل
أو عوامل الخطر التي يمكن تفاديها CVD. ر بونتيتشلي وما يرتبط بها من

colleagues5 أفادت أن التدخين مع ارتفاع اختطار CVD (الخطر النسبي [ر]، 1-3؛
ع 02) في 864 الكبار المتلقين زرع الكلى
وعلاوة على ذلك، kasiske ووجدت أن coworkers6,7

زرع الكلى المدخنين قد تعاظم خطر مرض القلب الإقفاري (ص ص 1.95) مقارنة
غير المدخنين من المتلقين.المتلقي مدخنين
أقصر بكثير يعني البقاء بسبب
الوفيات الناجمة عن للبخار فيه التدخين لعب
بدور هام في المساهمة - 8.9 في بالإضافة إلى ذلك،
المنشأ عوامل الخطر القلبية الوعائية عدا
التدخين، مثل ارتفاع ضغط الدم، السكري،
الدهون والسمن، هي أكثر شيوعا في الكلية التدخين و زرع الكلى nourbala وآخرون

142 Iranian journal of أمراض الكلى | حجم 5 | | رقم 3 مايو 2011
المتلقين زرع أكثر من عامة السكان.
من عوامل الخطر هذه زيادة اختطار CVD بين المتلقين زرع الكلى انخفاض المريض

و طعم البقاء 10
السرطان السبب الثاني للوفيات في الكلى
المتلقين زرع هو نتيجة أخرى smoking.11 عوامل خطر الخباثة بعد