Overweight and obesity has reached epidemic proportion worldwide and has been described as a global pandemic. Obesity is recognized as a major and independent risk factor for cardiovascular death and its prevalence has risen dramatically over the past two decades. Similar to the general population, patients with chronic kidney disease are also increasingly obese. Contrarely, in patients with ESRD the reverse epidemiology of the obesity paradox seems to protect the hemodialysis population from cardiovascular death. Among kidney transplant recipients, overweight and obesity prevalence has risen with 60% of kidney transplant candidates being overweight or obese at the time of transplantation. Though recipient obesity negatively impacts the access to transplantation, after transplantation, short and long term outcomes are very good. The surgical procedure is not associated with major complications or death. Short term outcomes are excellent except an increased incidence of delayed graft function while long term there is a definite survival advantage compared to HD. Furthermore, prevalence of overweight and obesity rises in living kidney donors similar to the general population. Obesity related glomerulopathy, a variant of focal and segmental glomerulosclerosis, is the clinicopahtologic entity that best describes the process of kidney damage in obese individuals. Since thepathophysiologic process is similar to that of secondary FSGS due to reduced nephron mass, it may be accelerated after kidney donation. In the absence of definite guidelines, overweight donors must be informed about the increased risk of donation and obese (BMI>30 Kg/m2) donors have to be excluded from donation, at least until they lose weight. Undoubtedly the transplantation community faces a new, emerging problem: the definite advantage of survival following renal transplantation and the dramatically increased prevalence of overweight and obesity between transplant recipients and donors.
Body Mass Index, kidney recipient survival, kidney transplant survival, obese kidney donor, obese kidney transplant recipient, obesity, obesity related glomerulopathy
Assessment of nutritional status in patients and in the general population is important, as malnutrition and obesity have both been associated with decreased survival. Βody mass index (ΒΜΙ) is a more reliable indicator of nutritional status than the simple measurement of body weight. It is a useful marker, easy to calculate and it is defined as the weight in kilograms divided by the square of the height in meters (kg/m2). It may overestimate weight in muscular individuals and underestimate it in elderly persons or patients with cachexia and reduced muscle mass .
Ideal BMI has been established on the basis of cardiovascular mortality through long-term monitoring in large population studies . Increased body mass index is an independent risk factor for mortality due to ischemic heart disease, stroke, colon, endometrial and postmenopausal breast cancer.
A review of 57 prospective studies in a total of 900,000 people showed that people of both sexes had the lowest mortality at a BMI between 22.5-25 Kg/m2. Above this limit, any increase of BMI by 5 Kg/m2 resulted in an increase in all-cause mortality for all age and sex groups by 30 %.Especially cardiovascular mortality rose by 40 %, mortality due to cancer by 10 % and mortality due to respiratory and other causes by 20 %. BMI between 30-35 Kg/m2 resulted in a median survival reduction by 2-4 years while BMI between 40-45 Kg/m2 reduced median survival by 8-10 years . It should be noted that in patients with a low BMI <22.5 Kg/m2, particularly those with values <20 Kg/m2, mortality also increased mainly due to respiratory diseases and specific types of smoking associated cancer .
On the basis of cardiovascular mortality data, the National Health Institute (NIH) and the World Health Organization (WHO) developed a classification system of obesity according to BMI. In Caucasians, Hispanics and African Americans it defines as underweight people with BMI<18.5 Kg/m2, normal weight those with a BMI between 18.5 to 24.9 Kg/m2 and overweight individuals with BMI>25-29.9 Kg/m2. Obesity is defined as a BMI>30 Kg/m2 and is further classified as follows: Class I obesity: BMI 30-34.9 Kg/m2, Class II severe obesity: BMI 35-39.9 Kg/m2, Class III or morbid obesity: BMI ≥ 40 Kg/m2. This definition differs for the Asian population, as the negative impact of BMI on overall and cardiovascular mortality is observed at lower BMI levels in this population. Asians are classified as overweight at a BMI between 23 and 24.9 Kg/m2 and obese at a BMI over 25 Kg/m2 .
Waist circumference (WC) is an additional marker that has been associated with cardiovascular mortality. Men with a waist circumference>102 cm and women with a waist circumference>88cm have an increased cardiovascular risk. Patients with central or visceral obesity are at increased risk for developing diabetes mellitus, coronary heart disease, hypertension, dyslipidemia and fatty liver .
The rising prevalence of overweight and obesity in several countries has been described as a “global pandemic”. During 1980-2013 the increase in the incidence of obesity in the general population was dramatic. The proportion of adults with a body mass index (BMI) of 25 Kg/m2 or greater, increased between 1980 and 2013 from 28.8% to 36.9% in men, and from 29.8% to 38.0% in women .
The World Health Organization has already raised alarm on the adverse impact of the increasing rates of obesity on the population's health and forces all countries to systematically record and to more effectively intervene in order to at least inhibit the rate of growth by 2025.
This increase in obesity is observed in both developing and developed countries but with different sex patterns. In developed countries, the overall incidence of overweight and obesity (BMI> 25Kg/m2) is higher in men than in women though in developing countries more women than men are overweight and obese. The incidence of obesity (BMI>30 Kg/m2) is also increasing in both developed and developing countries and is higher in women than in men. Rates were increasing between 1992-2002 but the rate of increase has slowed down after 2002 .
Coming to the prevalence of obesity in patients with Chronic Kidney Disease, though they represent a special patient group with increased cardiovascular risk, there are no available data, only those which are extrapolated from the general population. On contrary, there are several studies in patients with end stage renal disease (ESRD).In a report from the US Renal Data System (USRDS) from 2000, Kasiske et al.  analysed the impact of BMI in hemodialysis patients. Among 30.614 patients initiating renal replacement therapy, the mean BMI was 26.0 Kg/m2. A lower incidence of obesity was observed in hemodialysis patients compared to the general population.
Since 2000, there is an increasing trend towards higher BMI levels in those patients too.
In a more recent study, Friedman et al.  analyzed data from 85,000 prospective kidney transplant recipients and reported an increase in the incidence of obesity in this patient group too. The majority (60%) of patients were overweight or obese at the time of transplantation. Between 1987 and 2001, the proportion of obese transplant recipients rose by 116%, in parallel to the general population. The highest prevalence of obesity was observed among those aged 50-70 years, those with diabetes mellitus type II and in women.
It is also worth mentioning the obesity paradox observed in hemodialysis patients. This is the phenomenon of “reverse epidemiology” of obesity in the population of patients with ESRD on hemodialysis. In contrary to the general population, in patients on hemodialysis, higher BMI not only is not associated with increased mortality, on contrary, in this patient population, mortality is reduced at higher levels of BMI.
This finding is consistent and has been reported in many ESRD cohorts. It is observed at all levels of high BMI, even in severe obesity and is independent of factors associated with recent advances in HD techniques such as better biocompatibility of dialysis membranes or developments in medication. It is also independent of regional and racial differences or co morbidities [6-11].
Johansen et al.  analyzed USRDS data of 415.000 patients on dialysis between 1995 and 2000. Increased BMI was associated with reduced all-cause mortality, even at very high BMI levels (>37 Kg/m2) for all races except Asians. These data did not change even when other nutrition assessment markers were used such as lean body mass index (LBMI) or Benn index .
There are plausible explanations for this apparently “paradox”. It is well established that hemodialysis represents a state of chronic inflammation and hypercatabolism (protein energy waisting (PEW). Chronic inflammation and malnutrition are both independent risk factors for cardiovascular mortality. Cosequently, increased body mass at least at dialysis initiation seems to act protectivelly .
An increase in the percentage of overweight and obese kidney transplant candidates was recorded in the study of Segev et al., published in 2008 . In a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006 they analysed the different categories according to BMI. From the entire cohort, a 34.3% of patients were overweight, 19.3% obese while 7.2% were classified as severely obese (class II- BMI 35-40 Kg/m2) and 2.7% as morbidly obese (Class III BMI>40 Kg/m2). The interesting point in this study is that the increasing degree of obesity was associated with a reduction in the likelihood of receiving a transplant : 2.7 % for obese candidates, which rose to 24 to 28 % in those with severe obesity and 42-44 % in candidates with morbid obesity. The authors of this article point out that although the final decision to proceed to transplantation for every given donor and recipient depends on clinical judgment, there may be a restricting policy concerning obese kidney transplant candidates. That means that high BMI is commonly used as a preface to exclude otherwise healthy individuals from transplantation.
Given the continuous increase in the prevalence of obesity in the general population as well as in hemodialysis patients and given the clear survival advantage of transplantation over hemodialysis, the transplantation community faces a new, ongoing problem: growing numbers of obese transplant candidates at the waiting lists, often without other co- morbidities.
Few data exist-if any- to suggest if there is a BMI level above which patients should be denied transplantation. The guidelines for managing obesity in this special patient group are also sparse.
The American society of Transplantation recommends supervised weight loss for obese candidates with target BMI<30 Kg/m2 with lifestyle modification and with close medical monitoring of the nutritional status. It is also stated that no patient should be excluded from transplantation according to obesity per se . Canadian guidelines (Canadian Society of Transplantation) are practically identical .
To assess the true benefit of transplantation in obese individuals, one has to answer the following questions:
- Otherwise healthy overweight patients (BMI 25-30 Kg/m2) may safely proceed to kidney donation
- Potential kidney donors with moderate obesity (BMI 30-35 Kg/m2) should be counseled carefully about the increased risk of peri- operative complications and the long term risk of chronic kidney disease
- They should be advised to lose weight prior to donation and maintain a BMI less than 30 Kg/m2.
- Limited data exist on the safety of kidney donation in the very obese (BMI>35 Kg/m2) and such patients should be discouraged from donating
Data on long term follow up of obese living donors are also limited.
In a single center study, Nogueira et al.  evaluated 36 kidney donors with a BMI> 30 Kg/m2 at a median of 6.8 ± 1.5 years post donation.
The mean estimated glomerular filtration rate (eGFR) using the MDRD equation at follow-up was 72 ± 16 ml/min which corresponds to an absolute decrease in eGFR by
27 ± 13 ml/min from the time of donation. From the 36 donors, 1.7% had eGFR between 30-60 ml/min, mainly those with a higher prevalence of albuminuria, possibly due to hyperfiltration.
Given the absence of strong guidelines the decision for the eligibility of an overweight living donor should be individualized by also taking into account the often strong will for donation. Potential donors with obesity (BMI>30 Kgr/m2) should be discouraged from donation, should be advised to lose weight prior to donation – either with nutritional surveillance or with bariatric surgery –to achieve a BMI of <30 Kg/m2. As for the obese kidney recipients, given the only slightly increased perioperative risk for minor surgical complications, the clear survival advantage over remaining on HD and the very good long term kidney and patient outcomes, one cannot medically justify their exclusion from transplantation.
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