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Chapter 16
Chapter 16: Hypertension, Dyslipidemias, Tobacco
Use, and Obesity
16.1: HYPERTENSION
Observational studies and RCTs have conclusively shown 16.1.1: We recommend measuring blood pressure
that hypertension is an independent risk factor for CVD and at each clinic visit. (1C)
16.1.2: We suggest maintaining blood pressure at
<130 mm Hg systolic and <80 mm Hg
In addition, evidence from RCTs in the general population diastolic if ≥18 years of age, and <90th
has conclusively shown that reducing blood pressure re- percentile for sex, age, and height if <18
duces the risk of CVD. These trials have shown benefit to years old. (2C)
reducing blood pressure to <140/90 mm Hg even in low- 16.1.3: To treat hypertension (Not Graded):
risk adult populations. Additional benefit may extend to • use any class of antihypertensive
high-risk populations, such as those with diabetes. RCTs in CKD have generally shown that blood pressure reduc- • monitor closely for adverse effects and
tion reduces proteinuria and slows the rate of decline in drug–drug interactions; and
• when urine protein excretion ≥1 g/day
for ≥18 years old and ≥600 mg/m2/24
Life expectancy is lower in KTRs than in the general popu- h for <18 years old, consider an ACE-I
lation, and it is possible that the benefits and harm of hyper- or an ARB as first-line therapy.
tension treatment in KTRs are different than in the generalpopulation. However, the leading cause of death in KTRs isCVD, making it likely that treatments that reduce the risk of ACE-I, angiotensin-converting enzyme inhibitor; ARB,
CVD in the general population will also be cost-effective in angiotensin II receptor blocker.
KTRs. Although adverse effects of pharmacological treat-ment of hypertension in KTRs are different and likely morecommon than in the general population, small RCTs and Background
observational studies suggest that these adverse effectsare generally not severe enough to reduce quality of life or Most guidelines for the general population define hyper- tension as persistent systolic blood pressure on at least2 days ≥140 mm Hg and/or diastolic blood pressure The incidence of hypertension in KTRs is 50–90% ≥90 mm Hg if age ≥18 years, and ≥95th percentile for (435,542,543). Thus, even conservative estimates on the gender, age and height if age <18 years (Table 22). How- incidence of hypertension in KTRs suggest that hyperten- ever, these same guidelines establish treatment goals for sion is common enough to warrant close scrutiny in KTRs.
high-risk subpopulations, for example diabetes and CKD, Observational studies have shown that hypertension is an that are generally systolic <130 mm Hg and/or diastolic independent risk factor for CVD after kidney transplanta- <80 mm Hg for adults, and <90th percentile for gender, tion (Table 18) (430,544). There are also studies linking age and height for adolescents and children.
hypertension to poor graft function, although it is difficultto separate cause and effect relationships in these studies(545–547).
Rationale
There are few data to suggest how often patients shouldbe screened for hypertension after kidney transplantation.
• In the general population, there is strong evidence that However, the high incidence of hypertension, the chang- treatment of hypertension is effective in preventing ing risk for hypertension and CVD in KTRs and the ease of CVD and in retarding the progression of CKD.
obtaining blood pressure measurements are compelling ar- • In KTRs, the prevalence of hypertension is high enough guments for measuring blood pressure at every clinic visit.
Patients should be seated quietly for at least 5 min with • In KTRs, blood pressure is a risk factor for CVD and feet on the floor and arm supported at heart level. An ap- propriately sized cuff with bladder encircling at least 80% • In KTRs, there is little reason to believe that the pre- of the arm should be used. At least two measurements vention and treatment of hypertension would not also should be made. Systolic blood pressure is the point at prevent CVD and kidney allograft injury.
which the first of two or more sounds is heard (phase 1), American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
Table 22: Guideline definitions of hypertension
<90th percentilea in concurrent conditionsb <130/80 in diabetes and high riskc CKD, chronic kidney disease; ESC, European Society of Cardiology; ESH, European Society of Hypertension; ISH, International Society forHypertension; JNC, Joint National Committee; KDOQI, Kidney Disease Outcomes Quality Initiative; KTRs, kidney transplant recipients;NHBPEPWG, National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents;USPSTF, United States Preventative Services Task Force; WHO, World Health Organization.
aFor gender, age and height on three occasions.
bConcurrent conditions are CKD, diabetes and hypertensive target-organ damage (539).
cHigh risk includes patients with stroke, myocardial infarction, renal dysfunction and proteinuria.
dRecommends screening age >18 years and uses JNC 7 treatment thresholds (536).
and diastolic blood pressure is the point before the dis- within arteries immediately proximal to the allograft artery appearance of sounds (phase 5). Patients should be pro- anastomosis) (548–553), as well as factors related to vided with their specific blood pressure readings and goals the presence of the native kidneys (554–556). Treatment should include adjusting CNI dose, administering antihyper-tensive medications and managing other CVD risk factors.
Ambulatory blood pressure monitoring is warranted for the A number of small randomized trials have demonstrated evaluation of possible ‘white coat hypertension,’ episodic the efficacy and safety of lowering blood pressure with hypertension, assessing apparent drug resistance, hy- most classes of antihypertensive medications. However, potensive symptoms with blood pressure treatment and there is insufficient evidence to recommend any class of autonomic dysfunction (536). Ambulatory blood pressure antihypertensive agents as preferred for long-term therapy readings are lower than office blood pressure readings, for reducing CVD or improving long-term graft survival.
with daytime values being higher than values during sleep(Table 23) (536).
The choice of initial antihypertensive agent may be deter-mined by the presence of one or more common posttrans- Self-measured blood pressure is also useful in assessing plant complications that may be made better or worse by treatment of hypertension and improving adherence to specific antihypertensive agents (Table 24). Urine protein treatment (536). Home measurement devices should be excretion ≥1 g per 24 h if age ≥18 years (and ≥600 mg/m2 per 24 h if age <18 years) is a threshold at which bloodpressure lowering trials have shown efficacy in reducing It is unlikely that there will be RCTs in KTRs to determine the progression of kidney disease in nontransplant pa- whether blood pressure lowering reduces CVD events, tients (538). To date, there are no RCTs showing that re- or prolongs patient or graft survival. However, observa- ducing urinary protein in KTRs preserves kidney allograft tional studies have reported that hypertension is associ- ated with both CVD events and graft survival (Table 18).
Guidelines from the general population recommend tar- In general, no antihypertensive agent is contraindicated in geting <140/90 mm Hg for all patients, even low-risk KTRs. Data from nontransplant patients with CKD suggest patients. However, these same guidelines recommend tar- that ACE-Is and ARBs may be have beneficial effects on geting <130/80 mm Hg for high-risk patients, such as pa-tients with diabetes and CKD (536,538). There are indeed Table 23: Adult blood pressure thresholds for defining hyperten-
RCT data justifying this lower target in these populations.
Although many transplant patients have diabetes and manyhave reduced GFR, whether benefits outweigh risks of tar- geting <130/80 mm Hg is unclear.
Causes of posttransplant hypertension include CNI use, corticosteroids, kidney allograft dysfunction, allograft vas- cular compromise (from within the allograft itself, from within the allograft artery and its anastomosis and from American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
Table 24: Advantages and disadvantages of major antihypertensive agent classes in KTRs
High CAD riskSupraventricular tachycardia High CAD riskRecurrent stroke preventionReduce proteinuriaPolycythemia ARB, angiotensin II receptor blocker; CAD, coronary artery disease; CHF, congestive heart failure; CNI, calcineurin inhibitor; KTRs, kidneytransplant recipients; MI, myocardial infarction.
aCarvediol, bisoprolol, metoprolol succinate.
bNondihydropyridine calcium blockers.
cARBs may have similar effects as ACE-Is and may be used in patients who do not tolerate ACE-Is.
the progression of diabetic and nondiabetic CKD, particu- and there are no reversible causes, bilateral native kidney larly in patients with proteinuria (538). However, RCTs in nephrectomies may be considered, especially in a KTR<40 KTRs have not had sufficient statistical power to deter- mine whether ACE-I or ARB therapy improves patient orgraft survival (557). On the other hand, ACE-Is and ARBsmay be associated with an increased risk of hyperkalemiaand anemia in KTRs (557–560). Hypertensive KTRs with is- Research Recommendations
chemic heart disease and/or CHF may benefit from ACE-Is,ARBs and/or beta-blockers (561). Diuretics may be effec- Randomized controlled trials are needed to determine: tive in treating hypertension in KTRs, since hypertensionin CNI-treated KTRs may be sodium dependent (562).
• the optimal blood pressure treatment target in KTRs; • the effect of reducing proteinuria on progression of Many patients will require combination therapy to control blood pressure. Most combinations should include a thi- • the effects of ACE-Is/ARBs on patient survival and graft azide diuretic, unless it is contraindicated. Recent stud- ies suggest that thiazides may be more effective thanpreviously thought in patients with reduced kidney func-tion (563–565). When hypertension is difficult to control, 16.2: DYSLIPIDEMIAS
especially when it is associated with otherwise unex- (These recommendations are based on KDOQI Dyslipi-
plained kidney allograft dysfunction, screening for allograft demia Guidelines and are thus Not Graded)
vascular compromise, within or proximal to the allograft 16.2.1: Measure a complete lipid profile in all
artery, should be considered. This usually requires imag- adult (≥18 years old) and adolescent (pu-
ing of the allograft vasculature using either an angiogram, berty to 18 years old) KTRs (based on
computerized tomographic angiography or magnetic reso- KDOQI Dyslipidemia Recommendation 1):
nance imaging. When hypertension is difficult to control, • 2–3 months after transplantation;
American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
• 2–3 months after a change in treatment
ney transplant recipients; LDL-C, low-density lipopro-
or other conditions known to cause
tein cholesterol.
dyslipidemias;
• at least annually, thereafter.
16.2.2: Evaluate KTRs with dyslipidemias for sec-
Background
ondary causes (based on KDOQI Dyslipi-
demia Recommendation 3)
Dyslipidemias are abnormalities in circulating lipoproteins 16.2.2.1: For KTRs with fasting triglyc-
that are associated with an increased risk of CVD. The (≥5.65
Work Group did not perform systematic reviews of the evi- mmol/L) that cannot be cor-
dence for management of dyslipidemias in KTRs since this rected by removing an underlying
was performed recently for the KDOQI Dyslipidemia Guide- cause, treat with:
lines. Rather, the recommendations of the Work Group are • Adults: therapeutic lifestyle
based on those of the KDOQI Dyslipidemia Guidelines for changes and a triglyceride-
the management of dyslipidemia in CKD (566). The Work lowering agent (based on
Group searched for, but did not find, large RCTs for dyslipi- Recommendation
demia management in KTRs published since the publica- tion of the KDOQI Dyslipidemia Guidelines. In addition, the • Adolescents:
therapeutic
Work Group searched for, but did not find, new guidelines lifestyle changes (based on
for the management of dyslipidemia in the general popula- Recommendation
tion. Therefore, the Work Group concluded that there was little new evidence to require modification of the KDOQI 16.2.2.2: For KTRs with elevated LDL-C:
Dyslipidemia Guidelines at this time. However, the Work • Adults: If LDL-C ≥100 mg/dL
Group amended the original guideline statements to apply (≥2.59 mmol/L), treat to re-
duce LDL-C to <100 mg/dL
(<2.59 mmol/L) (based on
Rationale
KDOQI Guideline 4.2);
• Adolescents: If LDL-C ≥130
(≥3.36
mmol/L),
• In the general population, there is strong evidence that reducing LDL-C decreases the risk for CVD events.
<130 mg/dL (<3.36 mmol/L)
• In KTRs, there is little reason to believe that reducing (based on KDOQI Guideline
LDL-C would not be safe and effective in reducing CVD 16.2.2.3: For KTRs with normal LDL-C, el-
• In KTRs, the prevalence of dyslipidemia is high enough evated triglycerides and elevated
to warrant screening and intervention.
non-HDL-C:
In KTRs, there is moderate evidence that dyslipidemias Adults: If LDL-C <100 mg/dL
contribute to CVD and that treatment of increased LDL- (<2.59
mmol/L),
C with a statin may reduce CVD events.
triglycerides
≥200 mg/dL
(≥2.26 mmol/L), and non-
HDL-C ≥130 mg/dL (≥3.36
A large number of RCTs in the general population have mmol/L),
demonstrated that lowering LDL-C reduces CVD events non-HDL-C to <130 mg/dL
and mortality. There is less evidence that treating other (<3.36 mmol/L) (based on
lipoprotein abnormalities, such as increased triglycerides KDOQI Guideline 4.3);
or reduced HDL-C is effective. Guidelines generally recom- • Adolescents: If LDL-C <130
mend treating patients based on the level of LDL-C and the mg/dL (<3.36 mmol/L), fast-
ing triglycerides ≥200 mg/dL
(≥2.26 mmol/L), and non-
Although there are drug–drug interactions that must be HDL-C ≥160 mg/dL (≥4.14
monitored in KTRs, the use of 3-hydroxy-3-methylglutaryl mmol/L), treat to reduce non-
coenzyme A reductase inhibitors (‘statins’) is generally safe HDL-C to <160 mg/dL (<4.14
and effective in lowering LDL-C, if appropriate dose modi- mmol/L) (based on KDOQI
fication is made for patients treated with CNIs. The use of Guideline 5.3).
other lipid-lowering therapies are less certain, but poten-tially beneficial in KTRs.
HDL-C, high-density lipoprotein cholesterol; KDOQI,
The incidence and prevalence of dyslipidemia is high in Kidney Disease Outcomes Quality Initiative; KTRs, kid-
KTRs, in large part due to the fact that immunosuppressive American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
agents cause or contribute to dyslipidemias. Agents impli- If severe hypertriglyceridemia is not present, then LDL- cated in causing dyslipidemias include corticosteroids, CsA C becomes the therapeutic target. In the KDOQI Dys- and mTORi. The overall prevalence of dyslipidemia during lipidemia Guidelines, all adult KTRs are at high risk for the first year after transplantation is >50%, although the ischemic heart disease, and therefore should be treated prevalence is greatly influenced by the type of immuno- to maintain LDL-C <100 mg/dL (2.59 mmol/L) (566). The suppression used and the presence of other factors, such drug of first choice for reducing LDL-C is a statin. Doses as proteinuria, acute rejection and graft dysfunction. In any of statins usually need to be reduced by approximately case, this high prevalence of dyslipidemia justifies screen- 50% in patients treated with CsA, and probably also in patients treated with tacrolimus (although fewer data areavailable).
Observational studies suggest that hypercholesterolemiaand increased LDL-C are independently associated with The relatively small number of patients who have normal CVD events in KTRs. A RCT found that treatment of LDL- or low LDL-C, increased triglycerides and high non-HDL-C C with fluvastatin did not significantly reduce the primary likely have high levels of atherogenic lipoprotein remnants.
end point (major adverse cardiac events) (567). However, Treatment for these patients should be similar to treatment important secondary end points, including mortality, were reduced by fluvastatin, and long-term follow-up suggestedthat major adverse cardiac events were also reduced (568).
For adolescents, the KDOQI Dyslipidemia Guidelines in- Thus, this study generally confirmed evidence from obser- creased the LDL-C target goal to reflect both the uncer- vational studies in KTRs, and RCTs in the general popu- tainty of dyslipidemia treatment in adolescents, and possi- lation, which indicate that increased LDL-C causes CVD, ble the increased risk. The US Preventive Services Task and treatment of LDL-C with a statin reduces the risk of Force (USPSTF) was unable to determine the balance between potential benefits and harm of screening chil-dren and adolescents for dyslipidemia (570). The National Although many measurements of lipoproteins can be Cholesterol Education Program Report of the Expert Panel linked to CVD events (e.g. apolipoprotein B, lipoprotein (a), on Blood Cholesterol Levels in Children and Adolescents etc.), the preponderance of evidence suggests that eleva- recommended selective screening for children and adoles- tions in LDL-C are most closely associated with CVD. As a cents with a family history of premature coronary heart result, most guidelines target the screening and treatment disease or at least one parent with a high total cholesterol of LDL-C. The measurement of LDL-C, or its estimation with the Friedewald formula, is reliable and generally available inmost major laboratories around the world. The calculationof LDL-C requires a fasting lipid panel with total cholesterol,HDL-C and triglycerides. Directly measured LDL-C changes 16.3: TOBACCO USE
little with fasting or nonfasting, but direct measurement is 16.3.1: Screen and counsel all KTRs, including
adolescents and children, for tobacco use,
and record the results in the medical
Treating an underlying cause of dyslipidemia may improve record. (Not Graded)
the lipid profile. Although there are few data in KTRs, • Screen during initial transplant hospi-
it is reasonable to expect that reducing or eliminating talization.
nephrotic-range proteinuria may improve the lipid profile.
• Screen at least annually, thereafter.
Similarly, treating poorly controlled diabetes may improve 16.3.2: Offer treatment to all patients who use to-
abnormal plasma lipids. Rarely, severe hypothyroidism may bacco. (Not Graded)
alter plasma lipoproteins. RCTs have shown that corticos-teroids, CsA and especially mTORi can cause dyslipidemiasin KTRs. In some cases, severe dyslipidemia may requiremodification of immunosuppressive medications.
KTRs, kidney transplant recipients.
The National Cholesterol Education Program Guidelines(569) and the KDOQI Guidelines on Dyslipidemia in KTRs(566) recommend first treating severe hypertriglyceridemiato avert the risk for pancreatitis. Very high levels of triglyc- Background
erides (usually in the thousands) generally indicate eleva-tions in chylomicrons. There is an association between se- Tobacco use includes the inhalation or ingestion of any to- vere hypertriglyceridemia and pancreatitis, prompting the bacco product, including: the inhalation of tobacco smoke recommendation to treat severe hypertriglyceridemia as from cigarettes, cigars, water pipes or other devices; the the first priority. How often severe hypertriglyceridemia nasal absorption of tobacco from snuff and the oral absorp- causes pancreatitis in KTRs is unknown.
tion and ingestion of tobacco from chewing.
American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
Rationale
tions between pharmacotherapies for aiding in tobacco ab-stinence and immunosuppressive agents that would pre-vent the use of either in KTRs (Table 25).
• In the general population, there is strong evidence that tobacco use causes CVD, cancer, chronic lung disease Cigarette smoking at the time of kidney transplanta- tion has been found to be an independent risk factor • In the general population, there is strong evidence that for patient survival, graft survival, ischemic heart dis- screening, prevention and treatment measures are ef- ease, cerebral vascular disease, PVD and CHF (Table 18) fective in adults. The effectiveness of clinician counsel- (438,439,442,443,586,587). Smoking has also been found ing of children and adolescents is uncertain.
to be associated with posttransplant malignancies (588).
• In KTRs, there is no reason to believe that the approach to prevention and treatment of tobacco use should be The prevalence of cigarette smoking at the time of different than in the general population.
transplantation varies between 25% and 50% (438, • In KTRs, cigarette smoking is associated with CVD and 439,586,588). The prevalence of smoking varies from country to country, likely due to differences in the preva- • In KTRs, the prevalence of tobacco use is high enough lence of smoking in the general populations of those coun- tries. However, even in countries where the prevalence isrelatively low, it is high enough to warrant interventions.
Evidence-based guidelines for the general population have Screening (and counseling) adults for tobacco use is concluded that there is strong evidence that tobacco use recommended for the general population (572–576).
causes CVD, cancer and chronic lung disease (572–578).
Guidelines in the general population have cited a lack of Although most studies have focused on cigarette smoking, evidence that screening adolescents and children is effec- there is evidence that any tobacco use is harmful (579).
tive, although there is likely little harm in including children Evidence-based guidelines for the general population have and adolescents (573). Screening patients includes ask- also concluded that screening patients for tobacco use ing them about their tobacco use history (including start and implementing prevention and treatment measures are and stop dates), amounts and types of tobacco used and effective, at least in the short term, in improving the likeli- prior interventions. Patients may not admit that they use hood of abstinence in adults. However, there are few stud- tobacco, and nicotine levels have been used to identify ies from the general population showing that interventions smokers among KTRs (589). However, there is insufficient are effective for more than 1 year. There is also insufficient evidence for or against the use of laboratory testing to evidence that interventions are effective in children and detect tobacco use in KTRs or in the general population.
There is no evidence to suggest when and how often to A large number of observational studies have reported screen for tobacco use in KTRs. However, there are stud- higher rates of CVD and mortality for cigarette smokers ies in the general population that indicate screening and in the general population. In addition, there have been a intervention during hospitalization is more effective than large number of RCTs showing that different smoking ces- usual care (575). Therefore, we recommend screening and sation interventions are effective in increasing the number intervention for patients during the initial hospitalization for of patients who quit smoking (580–582). Recently, RCTs kidney transplantation. There is no evidence to suggest the have also shown that smoking cessation interventions re- optimal interval after hospitalization for screening and inter- duce mortality in the general population (583,584).
vention. However, given that initial screening may not beeffective, follow-up screening would seem to be prudent.
In KTRs, there is no reason to believe that the prevention In addition, given the fact that at least some patients who and treatment of tobacco use would be different from that do not use tobacco may begin to use tobacco at some in the general population. In particular, there are no interac- time after transplantation, periodic screening is indicated.
Table 25: Pharmacological therapies for cigarette smoking cessation in KTRs
May use in combinations with other nicotine and Monitor CsA blood levels and increase CsA dose as a 4b 2 nicotinic receptor partial agonist neuropsychiatric symptoms including depressionand suicidal ideationa awww.fda.gov/Cder/Drug/infopage/varenicline/default.htm; last accessed June 21, 2008 American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
The Work Group determined that annual screening is a Table 26: Definition and classification of obesity in adults
Self-help is not adequate for smoking cessation. Both counseling and pharmacotherapy are effective, either alone or in combination. In general, the effectiveness of counseling is proportional to the amount of time spent counseling; however, even counseling for 3 min or less is effective (573). The ‘5 As’ of counseling include: (i) ask about tobacco use, (ii) advise to quit through clear and aDisease risk is higher for people with large waist circumferences personalized messages, (iii) assess willingness to quit, (iv) (men >102 cm (>40 in); women >88 cm (>35 in)); risk for type assist quitting and (v) arrange follow-up and support (573).
2 diabetes, hypertension and CVD.
Modified with permission (590).
A number of different pharmacological therapies are effec-tive in increasing the rate of smoking abstinence. Thereare five nicotine replacement aids and two other medica-tions that have been shown to be effective in RCTs in thegeneral population (Table 25) (580–582). These agents can In children, obesity is generally defined as BMI above the 95th percentile for age and sex. However, this definitionis largely based on data from the US Caucasian popula-tion, and may be less applicable to other populations. The Research Recommendations
CDC and the American Academy of Pediatrics recommendthe use of BMI to screen for overweight in children be-ginning at 2 years old (www.cdc.gov/nccdphp/dnpa/bmi/ • Randomized controlled trials are needed to determine childrens_BMI/about_childrens_BMI.htm; last accessed the optimal approach(es) for reducing tobacco use in March 30, 2009). For children, BMI is used to screen for overweight, at risk of overweight or underweight. How-ever, BMI is not a diagnostic tool in children. For example, achild may have a high BMI for age and sex, but to determine 16.4: OBESITY
if excess fat is a problem, a health-care provider would 16.4.1: Assess obesity at each visit. (Not Graded)
need to perform further assessments. These assessments • Measure height and weight at each
might include skinfold thickness measurements, evalua- visit, in adults and children.
tions of diet, physical activity, family history and other ap- • Calculate BMI at each visit.
• Measure waist circumference when
weight and physical appearance sug-
The USPSTF found ‘fair evidence’ that BMI is a reason- gest obesity, but BMI is <35 kg/m2.
able measure for identifying children and adolescents who 16.4.2: Offer a weight-reduction program to all
are overweight, or at risk for becoming overweight, and obese KTRs. (Not Graded)
that overweight children and adolescents are at increasedrisk for becoming obese adults. Therefore, BMI thresh- BMI, body mass index; KTRs, kidney transplant recipi-
olds should be used to define overweight based on per- centiles of the general population for age and sex (Table 27)(591).
Background
Obesity in adults is defined, as it is in major guidelines Table 27: Definition and classification of obesity for children and
for the general population, as body mass index (BMI) ≥30 kg/m2 (Table 26). Because some individuals may have BMI ≥30 kg/m2 that is not due to excess body fat, it is recommended that the definition of obesity in adults in- clude waist circumference ≥102 cm (≥40 in.) in men and Body mass index can be calculated either as weight in aBMI calculated either as weight in kilograms divided by height in kilograms divided by height in meters squared, or as weight meters squared, or weight in pounds divided by height in inches in pounds divided by height in inches squared multiplied by squared multiplied by 703. Percentile for age and sex.
703 (both methods yielding units kg/m2).
American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
Rationale
kcal/day for men can be effective. Increased physical activ-ity may help to sustain weight reduction and reduce CVDrisk independent of weight reduction. Exercise may also • In the general population, there is strong evidence that be beneficial, although a small RCT in KTRs failed to show obesity is a risk factor for CVD events and mortality in that counseling to encourage exercise reduced weight or CVD risk factors at 1 year (603). Nevertheless, exercise • In the general population, there are few studies exam- capacity increased in this study, and there was no harm ining the effects of obesity treatment on CVD events or mortality, but there is evidence that the benefitsof treating obesity on intermediate outcomes for CVD A large number of RCTs have examined pharmacologic in- terventions for weight loss in the general population. These • In KTRs, obesity is associated with CVD events and trials have shown modest weight reduction from medica- tions vs. placebo at 12 months (604). There are few long- • In KTRs, there is little reason to believe that weight term studies, and even fewer studies that have examined reduction measures are not equally effective as in the health outcomes. In a 4-year RCT, 52% completed treat- general population; however, there is some reason to ment with orlistat while 34% completed treatment with believe that pharmacological and surgical management placebo. Mean weight loss was greater with orlistat (–5.8 of obesity may be more likely to cause harm than in kg) vs. placebo (–3.0 kg, p < 0.001). The cumulative inci- dence of diabetes was 6.2% with orlistat vs. 9.0% withplacebo (p = 0.0032). In a RCT, comparing the cannabinoidreceptor antagonist rimonabant with placebo in 839 pa- Observational studies in the general population have tients, rimonabant failed to reduce the primary end point, shown that obesity is an independent risk factor for CVD change in atheroma volume on coronary intravascular ultra- (592). Obesity is also associated with a number of risk sound (605). Of concern are reports of psychiatric adverse factors for CVD, including hypertension, dyslipidemias and effects from rimonabant (606). Altogether, it remains un- clear whether the benefits outweigh harm of pharmaco-logical management of obesity in the general population.
A number of RCTs in the general population have shownthat diet may cause modest weight reduction, at least Pharmacological treatment of obesity has not been ade- over a period of 12 months. Pharmacological interventions quately studied in KTRs. Adverse effects of available agents are more effective in weight loss than diet alone, but are limit their usefulness in the general population, and are associated with more adverse effects. Bariatric surgery is likely to have an even greater potential for adverse effects effective, and may improve health outcomes. Guidelines in KTRs. Orlistat may interfere with the absorption of fat- in the general population generally recommend screening soluble vitamins, and there have been case reports of an and treatment of obesity (www.cdc.gov/healthyweight/ interaction between orlistat and CsA, resulting in lower assessing/bmi/childrens_BMI/about_childrens_BMI.html; CsA levels (607–609). Studies in the general population last accessed July 27, 2009) (591,593–597).
have shown that sibutamine can cause weight loss, butadverse effects are common and include increased blood Observational studies in adult KTRs have reported an asso- pressure and heart rate (604). There have been no studies ciation between obesity and mortality, CVD mortality and There have been no RCTs examining the long-term effects Counseling standard weight reduction diets, as recom- of bariatric surgery on health outcomes in the general pop- mended in guidelines in the general population, is unlikely ulation. Nevertheless, bariatric surgery appears to be more to cause harm in KTRs. The effects of pharmacological effective than diet in causing weight reduction (610,611). In management of obesity in KTRs are largely unexplored.
the largest case-control study to date, gastric bypass, verti- Anecdotal evidence suggests that bariatric surgery can cal banded gastroplasty or gastric banding caused, respec- be performed safely in KTRs and results in weight loss, tively, −25%, −16% and −14% weight losses from base- at least over a relatively short duration of follow-up (598– line to 10 years (612). Importantly, there were 129 deaths in the control group and 101 deaths in the surgery group(p = 0.04). The most common cause of death in this study Small, uncontrolled trials in KTRs suggest that diet and was myocardial infarction (612). In another large observa- other behavior modifications are safe and help reduce tional study, all-cause mortality (p < 0.0001), deaths from weight over the short term (601,602). There is no evidence diabetes (p = 0.0005) and deaths from coronary artery that any one diet is more effective than any other. A reason- disease (CAD) (p = 0.006) were lower among 7925 pa- able goal is to create a caloric deficit of 500–1000 kcal/day.
tients who had undergone bariatric surgery compared to Diets of 1000–1200 kcal/day for women and 1200–1500 7925 matched controls (613). Thus, it appears that bariatric American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79 Chapter 16
Table 28: National Heart Lung Blood Institute weight-loss treatment guidelinesa
BMI, body mass index.
a. Modified with permission (590).
b. Comorbidities considered important enough to warrant pharmacotherapy are: established coronary heart disease, other atheroscleroticdiseases, type 2 diabetes, sleep apnea, hypertension, cigarette smoking, high LDL-C, low HDL-C, impaired fasting glucose, family historyof early CVD, and age (male ≥45 years, female ≥55 years).
c. Comorbidities considered important enough to warrant surgery are: established coronary heart disease, other atheroscleroticdiseases, type 2 diabetes, and sleep apnea.
surgery can produce sustained weight reduction and im- dyslipidemias, hypertension and diabetes. However, CVD events may take decades to develop. Few studies haveexamined the safety and efficacy of weight reduction in Guidelines in the general population recommend weight children or adolescents. The USPSTF concluded that evi- loss surgery in patients with severe obesity, that is dence was insufficient to recommend for or against rou- BMI ≥40 kg/m2 or ≥35 kg/m2 with comorbid conditions.
tine screening for obesity in children and adolescents Bariatric surgery may include gastric banding or gastric as a means to prevent adverse health outcomes. There bypass (Roux-en-Y). Uncontrolled studies suggest that are likewise few studies on the treatment of obesity in bariatric surgery may be performed safely in selected KTRs children and adolescent KTRs; therefore, there is no ba- (598–600). However, the incidence of complications may sis for a different recommendation than for the general Guidelines in the general population recommend tailoringtreatment to the severity of obesity and its comorbidities Research Recommendations
Childhood obesity in the general population is associated • Additional research is needed to determine the effect with a higher prevalence of CVD risk factors, such as of bariatric surgery on outcomes in KTRs.
American Journal of Transplantation 2009; 9 (Suppl 3): S71–S79

Source: http://www.tts.org/kdigo/downloads/kdigo/S3-C16_HypertensionDyslipidemiasTobaccoUseObesity.pdf