Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

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© Borgis - Postępy Nauk Medycznych 2/2014, s. 90-94
*Joanna Stępniewska, Sławomir Milczarek, Piotr Skrzypek, Kazimierz Ciechanowski
Otyłość w przewlekłej chorobie nerek a transplantacja nerki – metody leczenia
The obesity in kidney transplantation candidates – methods of treatment
Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin
Head of Department: prof. Kazimierz Ciechanowski, MD, PhD
Streszczenie
Epidemia patologicznej otyłości coraz częściej dotyczy pacjentów z przewlekłą chorobą nerek, utrudniając leczenie chorób towarzyszących, zwiększając ryzyko sercowo-naczyniowe i opóźniając lub uniemożliwiając kwalifikację do przeszczepienia nerki. W większości ośrodków chirurgii transplantacyjnej warunkiem przeszczepienia nerki jest BMI pacjenta nie przekraczające 35 kg/m2. Chorzy z BMI > 35 kg/m2 są obarczeni znacznie większym ryzykiem powikłań okołooperacyjnych i pooperacyjnych, co często staje sie powodem ich dyskwalifikacji z zabiegu. Pacjenci z nadwagą i otyli poddawani hemodializie charakteryzują się niższą ogólną śmiertelnością (odwrócona epidemiologia), jednak przeszczepienie nerki powinno być u nich również postepowaniem z wyboru. Zachowawcze metody obniżania masy ciała w wielu przypadkach okazują się nieskuteczne. Leczenie farmakologiczne jest przeciwwskazane w przewlekłej chorobie nerek. Alternatywą jest leczenie bariatryczne – z akceptowalnym ryzykiem powikłań i gwarancją utrzymania efektu. Zabiegi bariatryczne powodują zaburzenia wchłaniania leków immunosupresyjnych, co wymaga indywidualizacji leczenia i systematycznej kontroli.
Summary
The epidemic of morbid obesity is becoming more likely in patients with chronic kidney disease, worsening the control of comorbid conditions and total cardiovascular risk. Furthermore, it delays or makes the kidney transplantation impossible and sometimes even bypasses obese candidate when the organ becomes available. Most surgical centers consider transplantation if BMI does not exceed 35 kg/m2. The patients with BMI > 35 kg/m2 are at great risk of perioperative and postoperative complications and are usually disqualified. Although overweight and obese, dialysed patients have lower general mortality compared to normal weight (reverse epidemiology paradox), kidney transplantation is still a treatment of choice for them. The conservative methods of weight loss fail in many cases. Pharmacological treatment is contraindicated in CKD. The alternative for these patients is bariatric surgery – with acceptable risk of complications and higher rates of successful and permanent weight loss. After the bariatric procedure the malabsorption of immunosupresive drugs occurs and the doses regimen should be individual and well controlled.
Introduction
The overweight and obesity are chronic metabolic disorders resulting from an excessive food caloric intake in relation to energy demands and lack of physical activity, which causes a positive caloric balance. As a consequence of overnutrition the extra calories are accumulated as body fat to the extent that it may have serious adverse effects on someones health. The most common and practical way of assessment the nutritional status is calculating the body mass index (BMI), also called the Quetelet’s Index. It is measured by dividing a weight in kilograms by height in square meters. If BMI exceeds 30 kg/m2, a person is considered obese. The standard World Health Organization (WHO) definition from 1997 distinguished four levels of obesity. The first one is called moderate, second – severe, third – pathological, which is a life threating condition requiring medical intervention and may be an indication for bariatric surgery and the last one fourth level named superobesity. The levels of obesity and indicating BMI values are shown in table 1.
Table 1. The levels of obesity and indicating BMI values.
LevelBMI (kg/m2)Obesity
130-34.9moderate
235-39.9severe
3> 40pathological
4> 50superobesity
The importance of pathology is also fat distribution around the body. A special type is visceral obesity, which was differentiated by WHO due to connection with certain illnesses. In this type of obesity intra-abdominal adipose tissue is stored between internal organs in the peritoneal space. Because of constant hormonal and metabolic activity it highly correlates with developing cardiovascular diseases, increased risk of diabetes and malignancy. It is usually called central obesity due to significant abdominal protrusion in opposite to weight accumulation around the hips. The prevalence is higher in males. It is recognized using waist-hip ratio (WHR) (tab. 2).
Table 2. The WHR values of viscelar obesity.
GenderViscelar obesity
FemaleWHR ≥ 0.8 or > 80 cm in waist circumference
MaleWHR ≥ 1 or > 94 cm in waist circumference
Epidemiology
An optimal body weight is multifactorial equation. It depends on age, gender, genetic susceptibility, comorbidities, sedentary lifestyle and dietary habits. The last two factors have the crucial meaning in obesity epidemic that affects western civilization. Obesity is the leading preventable cause of death worldwide causing 300 000 deaths each year, which can be up to twelve times higher than in communication accidents and ten times than in age-related population. In 1997 WHO recognized obesity as the global epidemic. Nowadays it affects 20% of world population and is considered a disease of affluence. During the last 20 years it’s prevalence increased by 50%. Including, it relates to over 1.1 million people. According to WHO data in 2015 there will be about 700 million people with BMI over 30 kg/m2. In Poland the occurrence of pathological obesity is also still increasing and reached 18%. It is more common in females (2.2%) than in males (0.6%). In the USA it affects 5% of adults. The women in the age between 20 and 30 who achieved BMI > 45 kg/m2 have the reduction of life- span of 8 year and men of 13 years than in general population (1, 2).
The role of obesity in CKD development
The obesity is an independent risk factor of CKD development, which in overweight patients is 40% and in obese 85% higher than in healthy controls. The initial kidney injury is caused by hyperfiltration, with time leading to proteinuria and glomerulosclerosis. The obesity involves blood pressure rise in response to compensation the decrease of renal plasma flow, increases the tubular sodium reabsorption, activates renin-angiotensin-aldosteron (RAA) system and stimulates renal sympathetic nerves. The metabolic and hormonal activity of visceral adipose tissue is considered to have an important role in pathogenesis of renal function disorder. Leptin increases tubular sodium reabsorption and influencing on tumor growth factor-β (TGF-β) and collagen type IV synthesis stimulates endothelial hyperplasia in the glomeruli. The adipose tissue secretes also proinflammatory cytokines and interleukins both aggravating fibrosis and proliferation. The glomerular disorder secondary to obesity has been termed in the literature as obesity related glomerulopathy (ORG). Its histological features are similar to that seen in focal segmental glomerular sclerosis (FSGS) with marked glomerular enlargement but lower podocytes foot-process seizure. Obesity associated conditions such as diabetes, hypertension, chronic heart failure, dyslipidemia significantly increase the risk of CKD occurrence. The more components of metabolic syndrome are present, the higher risk of CKD development is obtained (3).
The body mass and renal replacement therapy
Among the patients on renal replacement therapy, especially on haemodialysis the most common nutritional disorder is a protein-caloric malnutrition. MIA syndrome (malnutrition-inflammation-atherosclerosis) – a specific form of malnutrition in haemodialysed patients is associated with significantly increased mortality due to cardiovascular complications. The present recommendations for hemodialysed patients suggest increase in caloric intake up to 30-35 kcal/kg/day and protein up to 1.4 g/kg/day. Even if the recommendations are implemented the anthropometric features deteriorate within long term treatment. On the other hand reverse epidemiology paradox is documented on haemodialysis, which shows that patients with BMI > 27.5 kg/m2 live twice as long as patients with normal BMI values. The reason of this phenomenon is seen in the coexistence of malnutrition and chronic inflammatory state.
The obese candidat for a kidney transplant
Considering an increasing trend in prevalence of obesity in the industrialized countries, CKD as a common complication of obesity, diabetes as one of the leading causes of CKD and broad administration of steroid therapy in autoimmune diseases involving kidneys the number of obese patients started renal replacement therapy is markedly higher. This situation and reverse epidemiology paradox rise a question – do we need to treat obese patients that undergo renal replacement therapy? Is kidney transplantation an option for an obese dialysed patient? Most studies indicate that although overweight and obese dialysed patients have lower general mortality compared to normal weight, kidney transplantation is still a treatment of choice for them. It significantly improves survival rate, the comfort of life and is economically justified. Unfortunately obese patients have higher complication risk and worse long term outcome after kidney transplantation than non-obese transplanted. Most surgical centers consider transplantation if BMI does not exceed 35 kg/m2. The patients with BMI > 35 kg/m2 are at great risk of perioperative and postoperative complications and are usually disqualified. Moderately obese patients have prolonged waiting time and are sometimes bypassed if the organ becomes available. Latest studies show that the likelihood of receiving a graft decreases within increasing degree of obesity. Obese graft recipients have increased surgical and medical complication rate, worse long time outcome and higher risk of graft loss. Surgery in obese patients involves high complication rate during the first 30 days post-operation mainly because of technical difficulties during the surgery, prolonged time of the procedure, high risk of wound complication, infections, urological disorders. The delayed graft function (DGF) is more frequent among obese allograft recipients probably because of perioperative difficulties and prolonged cold ischemia time (CIT). Additionally the risk of other medical complications (pulmonary, cardiac, gastrointestinal), the mean length of hospitalization and risk of admission to intensive care units is increased among obese comparing to non-obese renal recipients. The prevalence of post-transplant diabetes and further weight gain is also higher in obese patients. For that reasons is worth to lose the weight before the operation (3-5).
The latest recommendations indicate initial non-pharmacological, conservative management of obesity. It should involve clues used for general population, beginning with setting an achievable aim, for example loss of 5-10% body mass during 3-6 months. The obtaining of negative net caloric balance is crucial – mostly by decrease in total caloric uptake with simultaneous increase in energy expenditure. It involves lifestyle and behavioral modifications and increase in physical activity (30-60 minutes of varied intensity exercises every day most days of the week). The pharmacological intervention should be considered after failure of conservative treatment. The drug options including orlistat, sibutramine and rimonabant used widely in obesity treatment have many limitations in CKD patients. Orilstat may lead to increase in oxalate urine concentration leading to oxalate nephropathy. Additionally it interacts with cyclosporin a decreasing its plasma concentration. Sibutramine causes blood pressure elevation, tachycardia, hypokalemia and QT interval increase. It is contraindicated in diabetic patients. One of the main contraindications for rimonabant is kidney disease (6-9).
Case 1

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Piśmiennictwo
1. Hsu C, McCulloch CE, Iribarren C et al.: Body mass index and risk for end-stage renal disease. Ann Intern Med 2006; 144: 21-28.
2. Alexander JW, Goodman HR, Gersin K et al.: Gastric bypass in morbidly obese patients with chronic renal failure and kidney transplant; Transplantation 2004 Aug 15; 78(3): 469-474.
3. Marszałek R, Ziemiański P, Lisik w et al.: Bariatric surgery as a bridge for kidney transplantation in obese subjects. Case report. Ann Transplant 2012; 17(1): 108-112.
4. Segev DL, Simpkins CE, Thompson RE et al.: Obesity impacts access to kidney transplantation. J Am Soc Nephrol 2008; 19: 349-355.
5. Cacciola RAS, Pujar K, Ilham MA et al.: Effect of degree of obesity on renal transplant outcome. Transplant Proc 2008; 40: 3408-3412.
6. Friedman AN, Miskulin DC, Rosenberg IH et al.: Demographics and trends in overweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis 2003; 41: 480-487.
7. Modanlou KA, Muthyala U, Xiao H et al.: Bariatric surgery among kidney transplant candidates and recipients: analysis of the United States Renal Data System and literature review. Transplantation 2009 Apr 27; 87(8): 1167-1173.
8. Gore JL, Pham PT, Danovitch GM et al.: Obesity and outcome following renal transplantation. Am J Transplant 2006; 6: 357-363.
9. 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.
10. MacLaughlin HL, Hall WL, Patel AG, Macdougall IC: Laparoscopic sleeve gastrectomy is a novel and effective treatment for obesity in patients with chronic kidney disease. Obes Surg 2012; 22: 119-123.
11. Szomstein S, Rojas R, Rosenthal RJ: Outcomes of laparoscopic bariatric surgery after renal transplant. Obes Surg 2010; 20: 383-385.
12. Buch KE, El-Sabrout R, Butt KM: Complications of laparoscopic gastric banding in renal transplant recipients: a case study. Transplant Proc 2006; 38: 3109-3111.
13. Koshy AN, Coombes JS, Wilkinson S et al.: Laparoscopic gastric banding surgery performed in obese dialysis patients prior to kidney transplantation. Am J Kidney Dis 2008; 52: (4): e15-e17.
14. Rogers CC, Alloway RR, Alexander JW et al.: Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study. Clin Transplant 2008: 22: 281-291.
15. Himpens J, Dapri G, Cadiere GB: a prospective randomized study between laparoscopic gastric banding and laparoscopic isolated sleeve gastrectomy: results after 1 and 3 years. Obes Surg 2006; 16: 1450-1456.
otrzymano: 2013-11-20
zaakceptowano do druku: 2014-01-08

Adres do korespondencji:
*Joanna Stępniewska
Department of Nephrology, Transplantology and Internal Medicine Pomeranian Medical University
ul. Powstańców Wielkopolskich 72,
70-111 Szczecin
tel./fax +48 (91) 466-11-96
asia_stepniewska@wp.pl

Postępy Nauk Medycznych 2/2014
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