Obesity in kidney transplantation Dan Ridgway Consultant Surgeon

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

Audience question. What would be your main concern about a pre-dialysis patient with BMI of 35 having a live donor kidney transplant? A B C D E F Surgical complications (SSI) Risk of acute rejection Risk of delayed graft function Risk of graft loss (within 5 years) Risk of mortality compared to dialysis All of the above

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

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

What is the evidence?

Up to now…………… • 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.

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

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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• 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

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.

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

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

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. 19

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. 20

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

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

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

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P. M. Moraes-Vieira, et al. (2014). `Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th 17 cells. '. European Journal of Immunology 44(3): 794 -806.

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

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) BMI 42. 6 38. 1 P=0. 02 Surgical site infection 0 8 p=0. 004 6 month Cr (mg/dl) 1. 5 1. 6 P=0. 47 6 month graft survival 28 28 6 month pt survival 28 28

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

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): 568577.

Audience question. What would be your main concern about a pre-dialysis patient with BMI of 35 having a live donor kidney transplant? A B C D E F Surgical complications (SSI) Risk of acute rejection Risk of delayed graft function Risk of graft loss (within 5 years) Risk of mortality compared to dialysis All of the above