1. Obesity in kidney transplantation…. Dan Ridgway, Consultant Surgeon, Royal Liverpool University Hospital

2. Audience question. What would be your main concern about a pre-dialysis patient with BMI of 35 having a live donor kidney transplant? ASurgical complications (SSI) BRisk of acute rejection CRisk of delayed graft function DRisk of graft loss (within 5 years) ERisk of mortality compared to dialysis FAll of the above

3. Why worry? Success of transplantation Epidemiology of obesity Individual patient outcomes Regulatory scrutiny Stewardship

5. D. L. Segev, et al. (2008). `Obesity impacts access to kidney transplantation.'. Journal of the American Society of Nephrology : JASN 19(2):349-355.

6. What is the evidence?

7. Low quality evidence. Registry data. Outcomes – perioperative complications -short term complications (3-6 months) -medium term graft and pt survival (upto 5 years) BMI centric. Wrong comparator. Pre vs post transplant obesity. No interventional RCTs for pre-Tx obesity. Up to now……………

8. H. U. Meier-Kriesche, et al. (1999). `The effect of body mass index on long-term renal allograft survival.'. Transplantation 68(9):1294-1297.

9. Not simply ‘obesity’…. More likely to be elderly More likely to be diabetic More likely to be from ethnic minority background

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14. Obesity (BMI) at listing has no consistent effect on DGF, AR and graft or pt survival in individual observational studies. Meta-analysis implies 40% increased risk of DGF. Slightly increased risk of AR. No increased risk of mortality upto 5 years under ‘new’ immunosuppression. 14

15. S. P. Curran, et al. (2014). `Increased recipient body mass index is associated with acute rejection and other adverse outcomes after kidney transplantation.'. Transplantation 97(1):64-70.

17. J. D. Schold, et al. (2007). `A "weight-listing" paradox for candidates of renal transplantation?'. American Journal of Transplantation 7(3):550-559.

18. M. Z. Molnar, et al. (2011). `Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients.'. American Journal of Transplantation 11(4):725-736.

19. 19 C. P. Kovesdy, et al. (2010). `Body mass index, waist circumference and mortality in kidney transplant recipients.'. American Journal of Transplantation 10(12):2644-2651.

20. 20 K. Kalantar-Zadeh, et al. (2012). `Mortality prediction by surrogates of body composition: an examination of the obesity paradox in hemodialysis patients using composite ranking score analysis.'. American Journal of Epidemiology 175(8):793-803.

23. J. H. Kuo, et al. (2012). `Renal transplant wound complications in the modern era of obesity.'. The Journal of Surgical Research 173(2):216-223

24. BMI is a poor measure of ‘fatness’ and CV risk in CKD More discerning anthropometrics needed Avoid sarcopenic obesity 23

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27. Abdominal obesity Visceral obesity Surgical injury Donor factors Immune injury activation Fat is immunologically active tissue

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29. P. M. Moraes-Vieira, et al. (2014). `Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells.'. European Journal of Immunology 44(3):794-806.

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32. J. S. Gill, et al. (2013). `The survival benefit of kidney transplantation in obese patients.'. American Journal of Transplantation 13(8):2083-2090.

33. J. Oberholzer, et al. (2013). `Minimally invasive robotic kidney transplantation for obese patients previously denied access to transplantation.'. American Journal of Transplantation 13(3):721-728. Robotic (n=28)Conventional (n= 28) BMI42.638.1P=0.02 Surgical site infection08p=0.004 6 month Cr (mg/dl)1.51.6P=0.47 6 month graft survival 28 6 month pt survival28

34. 32 Viseral obesity and sarcopenia is a pro- inflammatory milieu. Graft factors can adjust Tx risks. SCD, ECD and LD transplants reduce mortality at 1 year compared to equivalent wait-listed patients.

36. P.-T. T. Pham, et al. (2013). `Kidney transplantation in the obese transplant candidates: to transplant or not to transplant?'. Seminars in Dialysis 26(5):568- 577.

37. Audience question. What would be your main concern about a pre-dialysis patient with BMI of 35 having a live donor kidney transplant? ASurgical complications (SSI) BRisk of acute rejection CRisk of delayed graft function DRisk of graft loss (within 5 years) ERisk of mortality compared to dialysis FAll of the above