Reverse Epidemiology of Obesity in Hemodialysis Patients

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Reverse Epidemiology of Obesity in Hemodialysis Patients (Obesity Paradox):

Reverse Epidemiology of Obesity in Hemodialysis Patients (Obesity Paradox) Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) Alexandria

What is meant by Reverse Epidemiology ?:

What is meant by Reverse Epidemiology ?

What is meant by Reverse Epidemiology ?:

What is meant by Reverse Epidemiology ? While obesity, hypertension and hypercholesterolemia (and other parameters) are well-established indicators of poor cardiovascular health and death in general population, Reverse epidemiology holds that these states actually increase the chance of survival in many people including dialysis patients.

HD Patients vs. General Population BMI Associated Death Risk:

HD Patients vs. General Population BMI Associated Death Risk Kalantar-Zadeh : Reverse epidemiology. Journal of Renal Nutrition, Vol 15, No 1 (January), 2005: pp 142-147 Reverse epidemiology

Reverse Epidemiology of CV Risk factors It is not only OBESITY & BMI !!:

Reverse Epidemiology of CV Risk factors It is not only OBESITY & BMI !! Kamyar Kalantar-Zadeh , Denis Fouque , and Joel D. Kopple . Journal of Renal Nutrition, Vol 14, No 2 (April), 2004: pp 64-71

So Reverse Epidemiology of HD patients = Opposite to General Population :

So Reverse Epidemiology of HD patients = Opposite to General Population

Weight and body mass Is obesity protective?:

Weight and body mass Is obesity protective?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients:

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients Cohort of 1346 HD patients in Mississippi. - Followed prospectively for 1 year for hospitalization and mortality. Fleischmann et al. Kidney International (1999) 55, 1560–1567

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients:

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients Cohort of 1346 HD patients in Mississippi. - Followed prospectively for 1 year for hospitalization and mortality. Fleischmann et al. Kidney International (1999) 55, 1560–1567 Death Hazard

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients:

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients Fleischmann et al. Kidney International (1999) 55, 1560–1567

Association of body size with outcomes among patients beginning dialysis:

Association of body size with outcomes among patients beginning dialysis BMI Death Hazard Kirsten L Johansen et al. Am J Clin Nutr 2004;80:324 –32 Data on 418, 055 patients beginning dialysis between 1 April 1995 and 1 November 2000 were analyzed by using US Renal Data System data. Follow-up extended through November 30, 2001 with median follow up of 2 years.

The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS):

The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) Leavey et al, Nephrol Dial Transplant 16:2386–2394, 2001 9714 MHD patients in US & Europe from 1996 to 2000

The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS):

The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) Leavey et al, Nephrol Dial Transplant 16:2386–2394, 2001

PowerPoint Presentation:

Kalantar-Zadeh et al. Am J Epidemiol. 2012;175(8):793–803

Other Studies Supporting BMI Reverse Epidemiology:

Other Studies Supporting BMI Reverse Epidemiology The Diaphane Study. Degoulet P et al: Report of the Diaphane collaborative study. Nephron 31:103-110, 1982 Leavy et al Am J Kidney Dis 31:997-1006, 1998 Wolf et al Am J Kidney Dis 35:80-88, 2000 Kopple et al. Kidney Int 56:1136-1148, 1999 Lowrie et al . Kidney Int 62:1891-1897, 2002

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

Possible Explanations for Reverse Epidemiology of BMI:

Possible Explanations for Reverse Epidemiology of BMI 1- Hemodynamic State in Obese Individuals 2- Tumor Necrosis Factor-Receptors 3- Neurohormonal Alterations 4- Survival Bias & Time Discrepancies Between Competitive Risk Factors: Overnutrition Versus Undernutrition 5- Malnutrition–Inflammation Complex Syndrome 6- Endotoxin – Lipoprotein Hypothesis

1- Hemodynamic State in Obese Individuals:

1- Hemodynamic State in Obese Individuals * Horwich TB, Fonarow GC, Hamilton MA, et al: J Am Coll Cardiol 38:789-795, 2001 ** Fonarow GC, Chelimsky-Fallick C, Stevenson LW, et al: J Am Coll Cardiol 19:842-850, 1992

2- Tumor Necrosis Factor- Receptors:

2- Tumor Necrosis Factor- Receptors Dialysis patients ↑ TNF α * Poor Survival Obesity ↑ Adipose Tissue** Soluble TNF - receptors * Kalantar-Zadeh K, Kopple JD, Humphreys MH, et al: Nephrol Dial Transplant 19:1507-1519, 2004 ** Mohamed-Ali V, Goodrick S, Bulmer K, et al: Am J Physiol 277:E971-975, 1999

3- Neurohormonal Alterations:

3- Neurohormonal Alterations Sympathetic and renin –angiotensin activity are associated with a poor prognosis in states of fluid overload.* Diminished stress responses of the neurohormonal systems of obese MHD patients play a role in improving survival.* * Schrier RW, Abraham WT. N Engl J Med 341:577-585, 1999 **Weber MA, Neutel JM, Smith DH. J Am Coll Cardiol 37:169-174, 2001 Lean individuals have higher increases in plasma epinephrine and renin levels during treadmill testing despite similar baseline levels and history of hypertension in comparison to obese persons .**

4- Survival Bias & Time Discrepancies Between Competitive Risk Factors: Overnutrition Versus Undernutrition:

4- Survival Bias & Time Discrepancies Between Competitive Risk Factors: Overnutrition Versus Undernutrition *Cui Y, Blumenthal RS, Flaws JA, et al. Arch Intern Med 161:1413-1419, 2001 ** Salama P, Assefa F, Talley L, et al: JAMA 286:563-571, 2001 ***Foley RN, Parfrey PS, Sarnak MJ: Am J Kidney Dis 32:S112-119, 1998

5- Malnutrition–Inflammation Complex Syndrome:

5- Malnutrition–Inflammation Complex Syndrome Kamyar Kalantar-ZadehAmerican Journal of Kidney Diseases, Vol 38, No 6 (December), 2001: pp 1343-1350

5- Malnutrition–Inflammation Complex Syndrome:

5- Malnutrition–Inflammation Complex Syndrome Kamyar Kalantar-Zadeh , Denis Fouque , and Joel D. Kopple . Journal of Renal Nutrition, Vol 14, No 2 (April), 2004: pp 64-71

6- Endotoxin-lipoprotein hypothesis:

6- Endotoxin -lipoprotein hypothesis Nishizawa et al. Am J Kidney Dis 2001;38 S4–7. Obese patients High lipid & lipoprotein concentrations Dialysis Inflammation ↑ circulating endotoxins More inflammation & subsequent atherosclerosis Increase Mortality

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

:

Kalantar-Zadeh et al. Am J Epidemiol. 2012;175(8):793–803

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Kalantar-Zadeh et al. Am J Epidemiol. 2012;175(8):793–803

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Kalantar-Zadeh et al. Am J Epidemiol. 2012;175(8):793–803 So, it’s the muscle mass not the body fat

PowerPoint Presentation:

Kalantar-Zadeh et al. Am J Epidemiol. 2012;175(8):793–803 The protective effect conferred by high BMI is limited to those patients with normal or high muscle mass. High BMI patients with inferred high body fat have increased and not decreased mortality .

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

Should MHD Patients Gain Weight in Order to Live Longer?:

Should MHD Patients Gain Weight in Order to Live Longer? To answer the above mentioned question, 2 more fundamental questions need to be answered: (1) Is there an effective intervention that can lead to a significant gain in weight and possibly to improvement of nutritional markers in MHD patients? (2) If an effective intervention to gain weight can be found in MHD patients, will it prolong survival ? Currently, these 2 questions have remained unanswered. Indeed, virtually no major study has focused on weight gain as a primary outcome. Kamyar Kalantar-Zadeh . Journal of Renal Nutrition, Vol 15, No 1 (January), 2005: pp 142-147

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population:

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population Kamyar Kalantar-Zadeh et al. American Journal of Kidney Diseases, Vol 46, No 3 (September), 2005: pp 489-500

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population:

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population Kamyar Kalantar-Zadeh et al. American Journal of Kidney Diseases, Vol 46, No 3 (September), 2005: pp 489-500

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population:

Association of Morbid Obesity and Weight Change Over Time With Cardiovascular Survival in Hemodialysis Population Kamyar Kalantar-Zadeh et al. American Journal of Kidney Diseases, Vol 46, No 3 (September), 2005: pp 489-500 Conclusion: Weight loss was associated with increased CV and all-cause death , whereas weight gain showed a trend toward improved survival and reduced cardiovascular mortality.

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

Obesity has been associated with surgical risk in ESRD patients undergoing kidney transplantation.* Many transplant centers require weight loss to achieve optimal BMI before considering a patient for kidney transplantation.** What are the disadvantage of being obese in MHD patients? Transplantation *Meier- KriescheHU , VaghelaM,Thambuganipalle R,FriedmanG , Jacobs M, Kaplan B: Transplantation 68:1294–1297, 1999 **Meier- Kriesche H-U, Arndorfer JA, Kaplan B: Transplantation 73:70–74, 2002

PowerPoint Presentation:

Studies reported that an increase in wound complications was a significant adverse effect of obesity. Johnson DW, Isbel NM, Brown AM, et al: Transplantation 74:675-681, 2002 What are the disadvantage of being obese in MHD patients? Wound Complications

What are the disadvantage of being obese in MHD patients? What if MHD patients survive longer?:

What are the disadvantage of being obese in MHD patients? What if MHD patients survive longer? It should be noted that as more effective treatments for MHD patients become available → it is possible that these patients will live longer , → so that a reversal of the reverse epidemiology and a “ back to traditional epidemiology ” may be observed if they survive long enough, → will suffer from more cardiovascular consequences . Kamyar Kalantar-Zadeh . Journal of Renal Nutrition, Vol 15, No 1 (January), 2005: pp 142-147

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

PowerPoint Presentation:

What is the evidence? What are the explanations? Can my patient eat lots of fattening and unhealthy foods to increase their weight? Should my patient gain weight to live longer? What are the disadvantages of weight gain in MHD? What are the recommendations?

Recommendations:

Recommendations It is recommended that the BMI of MD patients be maintained in the upper 50 th percentile percentile , which would be BMIs for men and women of at least approximately 23.6 and 24.0 kg/m2 , respectively.

Recommendations:

Recommendations

Recommendations:

Recommendations Meanwhile, maintaining a normal BMI and treatment of infections and undernutrition should continue to receive a high priority in the management of patients on HD. In older overweight/ obese patients, there are indications that weight loss should not be a priority, unless associated risks require weight loss. Journal of Renal Nutrition, Vol 20, No 5 (September), 2010: pp 281–292

PowerPoint Presentation:

Take Home Messages

PowerPoint Presentation:

Take Home Messages What we are only sure about is !!!! Kalantar-Zadeh : Reverse epidemiology. Journal of Renal Nutrition, Vol 15, No 1 (January), 2005: pp 142-147

Take Home Messages :

Take Home Messages Stick to recommendations:

Take Home Messages :

Take Home Messages Your patient can’t eat lots of fattening and unhealthy foods to increase their weight. Increase muscle mass decreases mortality, while increase body fat increases it.

Take Home Messages :

Take Home Messages Weight loss should not be a priority, unless associated risks require weight loss. There is no available effective approach to how increase patient BMI. There are no trials with increasing body weight as primary outcome

Take Home Messages :

Take Home Messages Treat infections and undernutrition .

Take Home Messages :

Take Home Messages It is quite possible that the dialysis population is one of several other similar subpopulations in whom a “bad-gone-good” phenomenon may indeed exist.* Hence, better examination of the reverse epidemiology is needed and may lead to improved survival. Kalantar-Zadeh K, Block G, Horwich T, et al: J Am Coll Cardiol 43:1439- 1444, 2004

Reverse Epidemiology of CV Risk factors It is not only OBESITY & BMI !!:

Reverse Epidemiology of CV Risk factors It is not only OBESITY & BMI !! Kamyar Kalantar-Zadeh , Denis Fouque , and Joel D. Kopple . Journal of Renal Nutrition, Vol 14, No 2 (April), 2004: pp 64-71 Take Home Messages

Take Home Messages Team Work :

Take Home Messages Team Work We need Nephrologists – Nutritionists Team work for: 1- Getting the most benefit for the patient. 2- More research for better evidence.

PowerPoint Presentation:

59 Thank You Gawad

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