- Email: [email protected]
Kidney transplantation after sleeve gastrectomy in the morbidly obese candidate: results of a 2-year experience
Surgery for Obesity and Related Diseases - (2019) 1–5
Original article
Kidney transplantation after sleeve gastrectomy in the morbidly obese candidate: results of a 2-year experience Young Kim, M.D., Amanda J. Bailey, D.O., Mackenzie C. Morris, M.D., Al-Faraaz Kassam, M.D., Shimul A. Shah, M.D., M.H.C.M., Tayyab S. Diwan, M.D.* Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio Received 31 July 2019; accepted 13 September 2019
Abstract
Background: Morbid obesity serves as a barrier to kidney transplantation (KT) due to potential suboptimal posttransplant outcomes. Laparoscopic sleeve gastrectomy (LSG) has previously been shown to improve transplant eligibility through weight loss. Objectives: We aimed to examine the role LSG plays in improving patient outcomes postrenal transplantation, including possible impact on new-onset diabetes after transplant (NODAT). Setting: University Hospital. Methods: A single-center analysis was performed identifying all patients who underwent KT after LSG from 2011 to 2017 (n 5 41). Exclusion criteria included type I diabetes and previous pancreas transplantation. NODAT was defined as a new insulin requirement after KT. Delayed graft function was defined as need for dialysis within the first week after KT. Mean posttransplant follow-up period was 22 months. Results: Forty-one patients underwent KT after LSG after median time of 16 months. Median age of postLSG patients undergoing KT was 56.0 years at time of KT. Average body mass index decreased by 9 from the time of LSG to KT, and no patients regained weight at 1-year follow-up. After LSG, the number of patients with hypertension (85.4% versus 48.5%) and the number of antihypertensive medications used decreased significantly (1.6 versus .6) at time of KT (P , .001 each). At 1-year follow-up, the improvement in hypertension persisted (51.2% versus 48.5%, P 5 nonsignificant). The average insulin regimen decreased from 33.0 6 51.6 to 11.7 6 21.5 units at KT (P , .001). This improvement also persisted at 1-year follow-up (11.9 versus 11.7 units, P 5 nonsignificant). Zero patients suffered NODAT over the follow-up period (versus institutional rate of NODAT at 15.8%). One patient developed delayed graft function (2.4%, versus institutional rate of 13.3%). After 1 year postKT, there was 1 graft loss (2.4%) and no mortality. Conclusion: This is the largest reported series of KT after planned LSG in morbidly obese patients. Our results confirm excellent posttransplant outcomes among patients who otherwise would have been denied KT eligibility. (Surg Obes Relat Dis 2019;-:1–5.) Ó 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
Key words:
Kidney transplantation; Morbid obesity; Sleeve gastrectomy
Funding was provided by the University of Cincinnati Department of Surgery. This work is accepted for poster presentation at the 2019 Obesity Week in Las Vegas, NV.
* Correspondence: Tayyab S. Diwan, M.D., Associate Professor of Surgery, University of Cincinnati Department of Surgery, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558. E-mail address: [email protected] (T.S. Diwan).
https://doi.org/10.1016/j.soard.2019.09.069 1550-7289/Ó 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
2
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5
End-stage renal disease (ESRD) patients with morbid obesity have been shown to have improvement in posttransplant outcomes with laparoscopic sleeve gastrectomy (LSG) before kidney transplant (KT). Morbid obesity has traditionally served as a significant barrier to KT due to suboptimal postKT outcomes. However, through LSG, ESRD patients have been able to achieve significant weight loss and become eligible for KT. Using a matched-cohort analysis, our group has previously noted significant improvements in type 2 diabetes (T2D), hypertension (HTN), and rates of delayed graft function (DGF) and new-onset diabetes after transplantation (NODAT) with LSG compared with nonLSG kidney recipients [1]. NODAT is an important posttransplant concern due to its impact on mortality and cardiovascular disease. In 2014, a consensus group reviewed all the literature regarding NODAT and developed clinical guidelines [2]. The guidelines support a change on the name from NODAT to posttransplantation diabetes. For the purposes of the present study, however, we will continue to use NODAT. Currently, there are 4 different definitions for NODAT. These include (1) fasting blood glucose 126 mg/dL for 2 occurrences (American Diabetes Association definition); (2) hemoglobin A1C fraction .6.5% for 2 occurrences (definition by consensus guidelines); (3) use of insulin therapy after transplantation; and (4) use of insulin or oral antihyperglycemic agents after transplantation. The incidence of NODAT after KT varies widely, ranging from 2% to 50%, with the majority of studies falling somewhere in the middle [2–4]. At the University of Cincinnati, our institutional incidence of NODAT is 15.8% [1]. Risk factors for NODAT include obesity, older age, black and Hispanic race, cytomegalovirus, use of calcineurin inhibitors, steroids, and family history of T2D, and dyslipidemia [3,4]. Approximately 60% of ESRD patients undergoing evaluation for KT are obese and diabetic [5]. Lifestyle changes for weight loss over a 2-year period have shown that patients can maintain approximately 4-kg weight loss alone [6]. Metabolic procedures, on the other hand, improve control of T2D and HTN in addition to sustained weight loss [5,7]. Moreover, Freeman et al. [5] demonstrated a significant decline in insulin use after KT among LSG patients. Other studies have similarly analyzed modification of NODAT risk factors, and the resultant effect on overall incidence. Early corticosteroid withdrawal, for example, was found to be associated with lower insulin doses in patients with NODAT after KT [8]. In the present study, we examined the effect of LSG on postKT outcomes in morbidly obese transplant recipients with a larger study population. We hypothesized that LSG before KT would continue to show improved posttransplant outcomes with a larger population. Primary endpoints were DGF, NODAT, insulin requirements, and HTN. Secondary
endpoints were myocardial infarction, cerebrovascular accident (CVA), wound infection, surgical complications, 30day readmission rates, cytomegalovirus infection, 1-year allograft survival, and 1-year patient survival. Methods This was a single-institution study with a retrospective chart review of 41 patients. All patients met 1991 National Institutes of Health guidelines for metabolic surgery (body mass index [BMI] 40 or 35 kg/m2 with 2 obesityrelated conditions) [9]. Each patient had documented inability to achieve significant weight loss through lifestyle changes and medical regimen over a 6-month period, before LSG. All patients underwent LSG between 2011 to 2017 with close follow-up, followed by KT after meeting institutional standards for transplantation. Exclusion criteria included type I diabetes mellitus and previous pancreas transplantation. Data collected included etiology of renal failure, immunosuppression profiles, readmission, perioperative outcomes, and long-term outcomes. Perioperative outcomes included myocardial infarction, cerebrovascular accident, wound infection, and surgical complications. Long-term outcomes included cytomegalovirus infection, DGF, 1year graft loss, 1-year patient mortality, and incidence of NODAT. The patient characteristics obtained were sex, race, age, etiology of renal failure, BMI, donor type, creatinine clearance (CrCl), serum glycohemoglobin fraction, interval time from LSG to KT, postKT follow-up period, and antihypertensive medications. DGF was defined as need for dialysis within the first week after transplant [10]. For the present study, NODAT was defined by new-onset insulin requirements after KT procedure [8]. CrCl was calculated using the Cockcroft-Gault equation and used to provide an objective measure of allograft function after transplantation [11]. The formula is listed as follows: CrCl 5 ð½140 age ðyÞ ! weight ½kg = ½72 ! serum creatinine ðmg=dLÞÞ ! :85 ðif femaleÞ The LSG procedure was performed as previously described [12]. Categoric variables are described as total number (n) and percentages (%). Continuous variables are described as means and standard deviations. These data were analyzed using the Wilcoxon rank-sum test where applicable. Statistical significance was defined as P values , .05. Statistical analysis was performed using software SAS 9.4 and JMP Pro 11 (Cary, NC). This study was approved by the institutional review board (#2013-1761) and conducted per their criteria.
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5 Table 1 Demographic characteristics of the study population
Table 3 Changes in diabetes over the study period
N/mean Total patients Age at KT, y BMI at KT, kg/m2 Sex Male Female Race Caucasian Black Patients on dialysis Etiology of kidney failure T2D HTN PCKD Other
SD/%
41 56.0 32.4
69.3 63.4
22 19
53.7 46.3
22 19 39
53.7 46.3 95.1
22 11 3 5
53.7 26.8 7.3 12.2
SD 5 standard deviation; KT 5 kidney transplantation; BMI 5 body mass index; T2D 5 type 2 diabetes; HTN 5 hypertension; PCKD 5 polycystic kidney disease.
Results From December 2011 to May 2017, 41 patients with ESRD underwent LSG, followed by KT (Table 1). Mean age of postLSG patients undergoing transplantation was 56.0 6 9.3 years at time of KT. The majority of patients were male (53.7%) and Caucasian (53.7%). The number of patients receiving deceased donor kidneys (61.0%) outnumbered the living donor recipients (39.0%). Etiology of kidney failure was predominantly due to T2D (53.7%), HTN (26.8%), and polycystic kidney disease (7.3%). Average time period between LSG and KT was 480 days. Average BMI was 41.4 6 4.6 kg/m2 before LSG (Table 2). After an interval period of approximately 2 years (639.6 6 493.1 d) between LSG and KT, the mean BMI at Table 2 Changes in BMI and hypertension over the study period N/mean BMI, kg/m2 Before LSG Before KT 1-yr follow-up HTN Before LSG Before KT 1-yr follow-up Antihypertensive medications Before LSG Before KT 1yr follow-up
3
SD/%
41.4 32.4 32.1
64.6 63.4 64.7
35 19 21
85.4 46.3 51.2
1.6 .6 .7
61.1 6.8 6.8
P value* ,.001
,.001
,.001
SD 5 standard deviation; BMI 5 body mass index; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation; HTN, hypertension. * P value compares values before LSG and before KT.
N/mean T2D Before LSG Before KT 1-yr follow-up NODAT Insulin requirements, m/d Before LSG Before KT 1-yr follow-up
SD/%
P value* .026
23 13 13 0
56.1 31.7 31.7 0 .017
33.0 11.7 11.9
651.6 621.5 617.2
SD 5 standard deviation; T2D 5 type 2 diabetes; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation; NODAT 5 new-onset diabetes after transplantation. * P value compares values before LSG and before KT.
time of KT was 32.4 6 3.4 kg/m2 (P , .001 versus preLSG), which reflects our previous institutional cutoff for KT at 38.0 kg/m2 (the current cutoff for KT is 40.0 kg/m2.) After a mean 1-year follow-up period, the average BMI was 32.1 6 4.7 kg/m2, (P 5 not significant versus preKT) indicating that patients did not regain weight after transplantation. None of the patients experienced a .100% excess weight loss during the study period. The majority of patients carried a diagnosis of HTN (85.4%) at initial evaluation (Table 2). After LSG, the number of patients with HTN decreased significantly to 46.3% (P , .001 versus preLSG). After 1-year follow-up, the prevalence of HTN remained similar to pretransplant rates at 51.2% (P 5 nonsignificant versus preKT). Correspondingly, the number of antihypertensive medications used among the cohort decreased from 1.6 6 1.1 medications at initial visit, to .6 6 .8 medications at time of KT (P , .001). The number of blood pressure medications did not change significantly at 1-year follow-up (P 5 nonsignificant). Table 3 details the changes in glycemic profiles over the study period. The prevalence of T2D before LSG was 56.1%. At time of KT, the number of diabetics decreased to 31.7% (P 5 .026 versus preLSG). T2D rates remained identical at 1-year follow-up visit (P 5 nonsignificant versus preKT). Insulin requirements followed a similar pattern. At initial presentation, the average insulin regimen totaled 33.0 6 51.6 units over a 24-hour period. This number decreased to 11.7 6 21.6 insulin units at time of KT (P 5 .017 versus preLSG) and did not change significantly at 1-year follow-up (P 5 nonsignificant). Five patients had complete resolution of their insulin dependence after LSG, but 2 of these patients were restarted on insulin after their KT. Zero patients developed NODAT over the follow-up period, consistent with our previous findings [1]. Posttransplant outcomes are listed in Table 4. One patient suffered an acute myocardial infarction (2.4%) and 1 patient developed a postoperative cerebrovascular accident (2.4%)
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5
4 Table 4 Outcomes after kidney transplantation
Donor type Deceased donor Living donor Perioperative complications Myocardial infarction Cerebrovascular accident Wound infection Surgical complication Readmission, 30 d Long-term outcomes CMV infection Delayed graft function Graft loss, 1-yr Patient mortality, 1-yr CrCl, mL/min Before LSG Before KT 1-yr follow-up LSG to KT interval, d PostKT follow-up period, d
N/mean
SD/%
25 16
61.0 39.0
1 1 8 3 12
2.4 2.4 19.5 7.3 29.3
3 1 1 0
7.3 2.4 2.4 0
21.9 19.3 77.5 639.6 666.4
69.5 625.2 627.6 6493.1 6619.0
P value*
,.001
SD 5 standard deviation; CMV 5 cytomegalovirus; CrCl 5 creatinine clearance; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation. * P value compares values before KT and at 1-year follow-up.
after KT. Eight patients (19.5%) developed wound infections and 3 patients developed surgical complications (7.3%). Total posttransplant 30-day readmission rates amounted to 29.3%, the majority of which were secondary to infectious concerns. Long-term outcomes are also described in Table 4. One patient suffered DGF (2.4%) after transplantation. After the 1-year postKT period, the same patient had graft loss (2.4%) and 0 patients were deceased. CrCl improved from 21.9 6 9.5 mL/min at initial visit, to 77.5 6 27.6 mL/min at 1-year follow-up (P , .001). PostKT immunosuppression medications are detailed in Supplemental Table 1. Discussion This retrospective study evaluated outcomes of 41 obese patients who underwent LSG followed by KT. These patients had an average decrease in BMI by 9 points and were able to maintain their weight loss at 1 year posttransplantation. These patients also benefitted from a significant decrease in number of antihypertensive medications and insulin requirements after LSG. The T2D rates also were also significantly reduced, and no patients developed NODAT during the study period. However, we did have 2 patients that were restarted on insulin after resolution of their insulin-dependent diabetes after SG. The low complication rate and no deaths confirm the safety of LSG before KT. The single occurrence of DGF and graft loss at 1-year of follow-up reflect excellent outcomes in this patient population.
DGF is associated with poor outcomes, such as increased incidence of surgical complications and reversible graft function. Obesity has been shown to have significantly higher incidences of delayed graft function (26% versus 16%) [13]. Obesity has also been shown to be associated with an increased risk of graft failure compared with nonobese patients [14]. A meta-analysis previously evaluated DGF as an independent risk factor for graft failure and showed that patients with DGF had a 41% increased risk of graft loss [15]. Another complication shown to be associated with obesity is development of NODAT. This was also shown to result in an increased acute rejection rate, graft failure, and mortality [16,17]. These 2 complications cause significant morbidity and mortality, which we show can safely be mitigated with bariatric surgery. Our group previously published a novel study comparing LSG followed by KT versus a matched control group who did not undergo a weight loss procedure before transplant [1]. The patients who underwent LSG had significantly less incidence of DGF and renal dysfunction–related readmissions. In the present study, 41 patients underwent LSG before KT and showed excellent short and long-term outcomes. Both studies showed a reduction in hypertensive medications and diabetes after LSG. Morbidity rates were acceptable in both studies and excellent long-term outcomes were observed. No patients were observed to have NODAT and 1 patient was observed to have DGF. Moreover, in our experience with these 41 patients, there were no surgical complications (e.g., hemorrhage or staple line leak), no 30-day readmissions, and no patient mortality after LSG. Certainly, these outcomes are limited by small sample size, and may not truly reflect the complex medical management and co-morbidities of all morbidly obese patients with ESRD. We attribute these postLSG outcomes to increasing experience with this complex patient population, along with development of clinical care guidelines, including a multidisciplinary approach to preoperative optimization and postoperative care [12]. The previously published study was a novel comparison of LSG as a bridge to KT compared with a matched control group. In 2010, MacLaughlin et al. [18] first described the safety and efficacy of LSG in 9 patients with CKD. The weight loss after LSG allowed 4 of these patients to be added to the kidney transplant waiting list. These data were confirmed using the American College of Surgeons National Surgical Quality Improvement Program data in 2 separate studies [19,20]. However, there is a paucity of data for patients who underwent LSG followed by KT. In 2017, Kienzl-Wagner et al. [21] published a small series of 7 patients who underwent KT after their LSG. All patients had good allograft function with a serum creatinine of 1.9 6 .8 mg/dL at the time of discharge and no allograft loss. To our knowledge, the present study is the largest singlecenter experience evaluating the safety and efficacy of LSG before KT. The experience of a single center has allowed for
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5
improved granularity in retrospective chart review. The study is limited by a few factors, such as the retrospective nature of our study, small sample size, and singleinstitution experience. Conclusion In conclusion, this is the largest single-center experience of LSG before KT and our findings confirm previously published results. LSG resulted in excellent weight loss before KT and improved short- and long-term outcomes. A large prospectively controlled trial would be needed to definitively confirm our findings. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Supplementary materials Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.1016/ j.soard.2019.09.069. References [1] Kim Y, Jung AD, Dhar VK, et al. Laparoscopic sleeve gastrectomy improves renal transplant candidacy and posttransplant outcomes in morbidly obese patients. Am J Transplant 2018;18(2):410–6. [2] Sharif A, Hecking M, de Vries AP, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 2014;14(9):1992–2000. [3] Hornum M, Jorgensen KA, Hansen JM, et al. New-onset diabetes mellitus after kidney transplantation in Denmark. Clin J Am Soc Nephrol 2010;5(4):709–16. [4] Porrini E, Delgado P, Alvarez A, et al. The combined effect of pretransplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation. Nephrol Dial Transplant 2008;23(4):1436–41. [5] Freeman CM, Woodle ES, Shi J, et al. Addressing morbid obesity as a barrier to renal transplantation with laparoscopic sleeve gastrectomy. Am J Transplant 2015;15(5):1360–8.
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[6] Wadden TA, Volger S, Sarwer DB, et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med 2011;365(21):1969–79. [7] Alexander JW, Goodman HR, Gersin K, et al. Gastric bypass in morbidly obese patients with chronic renal failure and kidney transplant. Transplantation 2004;78(3):469–74. [8] Pirsch JD, Henning AK, First MR, et al. New-onset diabetes after transplantation: results from a double-blind early corticosteroid withdrawal trial. Am J Transplant 2015;15(7):1982–90. [9] Gastrointestinal Surgery for Severe Obesity. NIH Consens Statement Online 1991 Mar 25-27 [cited 2019 Oct 14];9(1):1–20. Available from: https://consensus.nih.gov/1991/1991gisurgeryobesity084html.htm. [10] Yarlagadda SG, Coca SG, Garg AX, et al. Marked variation in the definition and diagnosis of delayed graft function: a systematic review. Nephrol Dial Transplant 2008;23(9):2995–3003. [11] Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31–41. [12] Kim Y, Shi J, Freeman CM, et al. Addressing the challenges of sleeve gastrectomy in end-stage renal disease: analysis of 100 consecutive renal failure patients. Surgery 2017;162(2):358–65. [13] Furriel F, Parada B, Campos L, et al. Pretransplantation overweight and obesity: does it really affect kidney transplantation outcomes? Transplant Proc 2011;43(1):95–9. [14] Cannon RM, Jones CM, Hughes MG, Eng M, Marvin MR. The impact of recipient obesity on outcomes after renal transplantation. Ann Surg 2013;257(5):978–84. [15] Yarlagadda SG, Coca SG, Formica Jr RN, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant 2009;24(3):1039–47. [16] Bonato V, Barni R, Cataldo D, et al. Analysis of posttransplant diabetes mellitus prevalence in a population of kidney transplant recipients. Transplant Proc 2008;40(6):1888–90. [17] Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003;3(2):178–85. [18] 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(1):119–23. [19] Andalib A, Aminian A, Khorgami Z, Navaneethan SD, Schauer PR, Brethauer SA. Safety analysis of primary bariatric surgery in patients on chronic dialysis. Surg Endosc 2016;30(6):2583–91. [20] Mozer AB, Pender JRT, Chapman WH, Sippey ME, Pories WJ, Spaniolas K. Bariatric surgery in patients with dialysis-dependent renal failure. Obes Surg 2015;25(11):2088–92. [21] Kienzl-Wagner K, Weissenbacher A, Gehwolf P, Wykypiel H, Ofner D, Schneeberger S. Laparoscopic sleeve gastrectomy: gateway to kidney transplantation. Surg Obes Relat Dis 2017;13(6):909–15.
Original article
Kidney transplantation after sleeve gastrectomy in the morbidly obese candidate: results of a 2-year experience Young Kim, M.D., Amanda J. Bailey, D.O., Mackenzie C. Morris, M.D., Al-Faraaz Kassam, M.D., Shimul A. Shah, M.D., M.H.C.M., Tayyab S. Diwan, M.D.* Cincinnati Collaborative for Obesity Research (CCORE), Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio Received 31 July 2019; accepted 13 September 2019
Abstract
Background: Morbid obesity serves as a barrier to kidney transplantation (KT) due to potential suboptimal posttransplant outcomes. Laparoscopic sleeve gastrectomy (LSG) has previously been shown to improve transplant eligibility through weight loss. Objectives: We aimed to examine the role LSG plays in improving patient outcomes postrenal transplantation, including possible impact on new-onset diabetes after transplant (NODAT). Setting: University Hospital. Methods: A single-center analysis was performed identifying all patients who underwent KT after LSG from 2011 to 2017 (n 5 41). Exclusion criteria included type I diabetes and previous pancreas transplantation. NODAT was defined as a new insulin requirement after KT. Delayed graft function was defined as need for dialysis within the first week after KT. Mean posttransplant follow-up period was 22 months. Results: Forty-one patients underwent KT after LSG after median time of 16 months. Median age of postLSG patients undergoing KT was 56.0 years at time of KT. Average body mass index decreased by 9 from the time of LSG to KT, and no patients regained weight at 1-year follow-up. After LSG, the number of patients with hypertension (85.4% versus 48.5%) and the number of antihypertensive medications used decreased significantly (1.6 versus .6) at time of KT (P , .001 each). At 1-year follow-up, the improvement in hypertension persisted (51.2% versus 48.5%, P 5 nonsignificant). The average insulin regimen decreased from 33.0 6 51.6 to 11.7 6 21.5 units at KT (P , .001). This improvement also persisted at 1-year follow-up (11.9 versus 11.7 units, P 5 nonsignificant). Zero patients suffered NODAT over the follow-up period (versus institutional rate of NODAT at 15.8%). One patient developed delayed graft function (2.4%, versus institutional rate of 13.3%). After 1 year postKT, there was 1 graft loss (2.4%) and no mortality. Conclusion: This is the largest reported series of KT after planned LSG in morbidly obese patients. Our results confirm excellent posttransplant outcomes among patients who otherwise would have been denied KT eligibility. (Surg Obes Relat Dis 2019;-:1–5.) Ó 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
Key words:
Kidney transplantation; Morbid obesity; Sleeve gastrectomy
Funding was provided by the University of Cincinnati Department of Surgery. This work is accepted for poster presentation at the 2019 Obesity Week in Las Vegas, NV.
* Correspondence: Tayyab S. Diwan, M.D., Associate Professor of Surgery, University of Cincinnati Department of Surgery, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267-0558. E-mail address: [email protected] (T.S. Diwan).
https://doi.org/10.1016/j.soard.2019.09.069 1550-7289/Ó 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
2
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5
End-stage renal disease (ESRD) patients with morbid obesity have been shown to have improvement in posttransplant outcomes with laparoscopic sleeve gastrectomy (LSG) before kidney transplant (KT). Morbid obesity has traditionally served as a significant barrier to KT due to suboptimal postKT outcomes. However, through LSG, ESRD patients have been able to achieve significant weight loss and become eligible for KT. Using a matched-cohort analysis, our group has previously noted significant improvements in type 2 diabetes (T2D), hypertension (HTN), and rates of delayed graft function (DGF) and new-onset diabetes after transplantation (NODAT) with LSG compared with nonLSG kidney recipients [1]. NODAT is an important posttransplant concern due to its impact on mortality and cardiovascular disease. In 2014, a consensus group reviewed all the literature regarding NODAT and developed clinical guidelines [2]. The guidelines support a change on the name from NODAT to posttransplantation diabetes. For the purposes of the present study, however, we will continue to use NODAT. Currently, there are 4 different definitions for NODAT. These include (1) fasting blood glucose 126 mg/dL for 2 occurrences (American Diabetes Association definition); (2) hemoglobin A1C fraction .6.5% for 2 occurrences (definition by consensus guidelines); (3) use of insulin therapy after transplantation; and (4) use of insulin or oral antihyperglycemic agents after transplantation. The incidence of NODAT after KT varies widely, ranging from 2% to 50%, with the majority of studies falling somewhere in the middle [2–4]. At the University of Cincinnati, our institutional incidence of NODAT is 15.8% [1]. Risk factors for NODAT include obesity, older age, black and Hispanic race, cytomegalovirus, use of calcineurin inhibitors, steroids, and family history of T2D, and dyslipidemia [3,4]. Approximately 60% of ESRD patients undergoing evaluation for KT are obese and diabetic [5]. Lifestyle changes for weight loss over a 2-year period have shown that patients can maintain approximately 4-kg weight loss alone [6]. Metabolic procedures, on the other hand, improve control of T2D and HTN in addition to sustained weight loss [5,7]. Moreover, Freeman et al. [5] demonstrated a significant decline in insulin use after KT among LSG patients. Other studies have similarly analyzed modification of NODAT risk factors, and the resultant effect on overall incidence. Early corticosteroid withdrawal, for example, was found to be associated with lower insulin doses in patients with NODAT after KT [8]. In the present study, we examined the effect of LSG on postKT outcomes in morbidly obese transplant recipients with a larger study population. We hypothesized that LSG before KT would continue to show improved posttransplant outcomes with a larger population. Primary endpoints were DGF, NODAT, insulin requirements, and HTN. Secondary
endpoints were myocardial infarction, cerebrovascular accident (CVA), wound infection, surgical complications, 30day readmission rates, cytomegalovirus infection, 1-year allograft survival, and 1-year patient survival. Methods This was a single-institution study with a retrospective chart review of 41 patients. All patients met 1991 National Institutes of Health guidelines for metabolic surgery (body mass index [BMI] 40 or 35 kg/m2 with 2 obesityrelated conditions) [9]. Each patient had documented inability to achieve significant weight loss through lifestyle changes and medical regimen over a 6-month period, before LSG. All patients underwent LSG between 2011 to 2017 with close follow-up, followed by KT after meeting institutional standards for transplantation. Exclusion criteria included type I diabetes mellitus and previous pancreas transplantation. Data collected included etiology of renal failure, immunosuppression profiles, readmission, perioperative outcomes, and long-term outcomes. Perioperative outcomes included myocardial infarction, cerebrovascular accident, wound infection, and surgical complications. Long-term outcomes included cytomegalovirus infection, DGF, 1year graft loss, 1-year patient mortality, and incidence of NODAT. The patient characteristics obtained were sex, race, age, etiology of renal failure, BMI, donor type, creatinine clearance (CrCl), serum glycohemoglobin fraction, interval time from LSG to KT, postKT follow-up period, and antihypertensive medications. DGF was defined as need for dialysis within the first week after transplant [10]. For the present study, NODAT was defined by new-onset insulin requirements after KT procedure [8]. CrCl was calculated using the Cockcroft-Gault equation and used to provide an objective measure of allograft function after transplantation [11]. The formula is listed as follows: CrCl 5 ð½140 age ðyÞ ! weight ½kg = ½72 ! serum creatinine ðmg=dLÞÞ ! :85 ðif femaleÞ The LSG procedure was performed as previously described [12]. Categoric variables are described as total number (n) and percentages (%). Continuous variables are described as means and standard deviations. These data were analyzed using the Wilcoxon rank-sum test where applicable. Statistical significance was defined as P values , .05. Statistical analysis was performed using software SAS 9.4 and JMP Pro 11 (Cary, NC). This study was approved by the institutional review board (#2013-1761) and conducted per their criteria.
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5 Table 1 Demographic characteristics of the study population
Table 3 Changes in diabetes over the study period
N/mean Total patients Age at KT, y BMI at KT, kg/m2 Sex Male Female Race Caucasian Black Patients on dialysis Etiology of kidney failure T2D HTN PCKD Other
SD/%
41 56.0 32.4
69.3 63.4
22 19
53.7 46.3
22 19 39
53.7 46.3 95.1
22 11 3 5
53.7 26.8 7.3 12.2
SD 5 standard deviation; KT 5 kidney transplantation; BMI 5 body mass index; T2D 5 type 2 diabetes; HTN 5 hypertension; PCKD 5 polycystic kidney disease.
Results From December 2011 to May 2017, 41 patients with ESRD underwent LSG, followed by KT (Table 1). Mean age of postLSG patients undergoing transplantation was 56.0 6 9.3 years at time of KT. The majority of patients were male (53.7%) and Caucasian (53.7%). The number of patients receiving deceased donor kidneys (61.0%) outnumbered the living donor recipients (39.0%). Etiology of kidney failure was predominantly due to T2D (53.7%), HTN (26.8%), and polycystic kidney disease (7.3%). Average time period between LSG and KT was 480 days. Average BMI was 41.4 6 4.6 kg/m2 before LSG (Table 2). After an interval period of approximately 2 years (639.6 6 493.1 d) between LSG and KT, the mean BMI at Table 2 Changes in BMI and hypertension over the study period N/mean BMI, kg/m2 Before LSG Before KT 1-yr follow-up HTN Before LSG Before KT 1-yr follow-up Antihypertensive medications Before LSG Before KT 1yr follow-up
3
SD/%
41.4 32.4 32.1
64.6 63.4 64.7
35 19 21
85.4 46.3 51.2
1.6 .6 .7
61.1 6.8 6.8
P value* ,.001
,.001
,.001
SD 5 standard deviation; BMI 5 body mass index; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation; HTN, hypertension. * P value compares values before LSG and before KT.
N/mean T2D Before LSG Before KT 1-yr follow-up NODAT Insulin requirements, m/d Before LSG Before KT 1-yr follow-up
SD/%
P value* .026
23 13 13 0
56.1 31.7 31.7 0 .017
33.0 11.7 11.9
651.6 621.5 617.2
SD 5 standard deviation; T2D 5 type 2 diabetes; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation; NODAT 5 new-onset diabetes after transplantation. * P value compares values before LSG and before KT.
time of KT was 32.4 6 3.4 kg/m2 (P , .001 versus preLSG), which reflects our previous institutional cutoff for KT at 38.0 kg/m2 (the current cutoff for KT is 40.0 kg/m2.) After a mean 1-year follow-up period, the average BMI was 32.1 6 4.7 kg/m2, (P 5 not significant versus preKT) indicating that patients did not regain weight after transplantation. None of the patients experienced a .100% excess weight loss during the study period. The majority of patients carried a diagnosis of HTN (85.4%) at initial evaluation (Table 2). After LSG, the number of patients with HTN decreased significantly to 46.3% (P , .001 versus preLSG). After 1-year follow-up, the prevalence of HTN remained similar to pretransplant rates at 51.2% (P 5 nonsignificant versus preKT). Correspondingly, the number of antihypertensive medications used among the cohort decreased from 1.6 6 1.1 medications at initial visit, to .6 6 .8 medications at time of KT (P , .001). The number of blood pressure medications did not change significantly at 1-year follow-up (P 5 nonsignificant). Table 3 details the changes in glycemic profiles over the study period. The prevalence of T2D before LSG was 56.1%. At time of KT, the number of diabetics decreased to 31.7% (P 5 .026 versus preLSG). T2D rates remained identical at 1-year follow-up visit (P 5 nonsignificant versus preKT). Insulin requirements followed a similar pattern. At initial presentation, the average insulin regimen totaled 33.0 6 51.6 units over a 24-hour period. This number decreased to 11.7 6 21.6 insulin units at time of KT (P 5 .017 versus preLSG) and did not change significantly at 1-year follow-up (P 5 nonsignificant). Five patients had complete resolution of their insulin dependence after LSG, but 2 of these patients were restarted on insulin after their KT. Zero patients developed NODAT over the follow-up period, consistent with our previous findings [1]. Posttransplant outcomes are listed in Table 4. One patient suffered an acute myocardial infarction (2.4%) and 1 patient developed a postoperative cerebrovascular accident (2.4%)
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4 Table 4 Outcomes after kidney transplantation
Donor type Deceased donor Living donor Perioperative complications Myocardial infarction Cerebrovascular accident Wound infection Surgical complication Readmission, 30 d Long-term outcomes CMV infection Delayed graft function Graft loss, 1-yr Patient mortality, 1-yr CrCl, mL/min Before LSG Before KT 1-yr follow-up LSG to KT interval, d PostKT follow-up period, d
N/mean
SD/%
25 16
61.0 39.0
1 1 8 3 12
2.4 2.4 19.5 7.3 29.3
3 1 1 0
7.3 2.4 2.4 0
21.9 19.3 77.5 639.6 666.4
69.5 625.2 627.6 6493.1 6619.0
P value*
,.001
SD 5 standard deviation; CMV 5 cytomegalovirus; CrCl 5 creatinine clearance; LSG 5 laparoscopic sleeve gastrectomy; KT 5 kidney transplantation. * P value compares values before KT and at 1-year follow-up.
after KT. Eight patients (19.5%) developed wound infections and 3 patients developed surgical complications (7.3%). Total posttransplant 30-day readmission rates amounted to 29.3%, the majority of which were secondary to infectious concerns. Long-term outcomes are also described in Table 4. One patient suffered DGF (2.4%) after transplantation. After the 1-year postKT period, the same patient had graft loss (2.4%) and 0 patients were deceased. CrCl improved from 21.9 6 9.5 mL/min at initial visit, to 77.5 6 27.6 mL/min at 1-year follow-up (P , .001). PostKT immunosuppression medications are detailed in Supplemental Table 1. Discussion This retrospective study evaluated outcomes of 41 obese patients who underwent LSG followed by KT. These patients had an average decrease in BMI by 9 points and were able to maintain their weight loss at 1 year posttransplantation. These patients also benefitted from a significant decrease in number of antihypertensive medications and insulin requirements after LSG. The T2D rates also were also significantly reduced, and no patients developed NODAT during the study period. However, we did have 2 patients that were restarted on insulin after resolution of their insulin-dependent diabetes after SG. The low complication rate and no deaths confirm the safety of LSG before KT. The single occurrence of DGF and graft loss at 1-year of follow-up reflect excellent outcomes in this patient population.
DGF is associated with poor outcomes, such as increased incidence of surgical complications and reversible graft function. Obesity has been shown to have significantly higher incidences of delayed graft function (26% versus 16%) [13]. Obesity has also been shown to be associated with an increased risk of graft failure compared with nonobese patients [14]. A meta-analysis previously evaluated DGF as an independent risk factor for graft failure and showed that patients with DGF had a 41% increased risk of graft loss [15]. Another complication shown to be associated with obesity is development of NODAT. This was also shown to result in an increased acute rejection rate, graft failure, and mortality [16,17]. These 2 complications cause significant morbidity and mortality, which we show can safely be mitigated with bariatric surgery. Our group previously published a novel study comparing LSG followed by KT versus a matched control group who did not undergo a weight loss procedure before transplant [1]. The patients who underwent LSG had significantly less incidence of DGF and renal dysfunction–related readmissions. In the present study, 41 patients underwent LSG before KT and showed excellent short and long-term outcomes. Both studies showed a reduction in hypertensive medications and diabetes after LSG. Morbidity rates were acceptable in both studies and excellent long-term outcomes were observed. No patients were observed to have NODAT and 1 patient was observed to have DGF. Moreover, in our experience with these 41 patients, there were no surgical complications (e.g., hemorrhage or staple line leak), no 30-day readmissions, and no patient mortality after LSG. Certainly, these outcomes are limited by small sample size, and may not truly reflect the complex medical management and co-morbidities of all morbidly obese patients with ESRD. We attribute these postLSG outcomes to increasing experience with this complex patient population, along with development of clinical care guidelines, including a multidisciplinary approach to preoperative optimization and postoperative care [12]. The previously published study was a novel comparison of LSG as a bridge to KT compared with a matched control group. In 2010, MacLaughlin et al. [18] first described the safety and efficacy of LSG in 9 patients with CKD. The weight loss after LSG allowed 4 of these patients to be added to the kidney transplant waiting list. These data were confirmed using the American College of Surgeons National Surgical Quality Improvement Program data in 2 separate studies [19,20]. However, there is a paucity of data for patients who underwent LSG followed by KT. In 2017, Kienzl-Wagner et al. [21] published a small series of 7 patients who underwent KT after their LSG. All patients had good allograft function with a serum creatinine of 1.9 6 .8 mg/dL at the time of discharge and no allograft loss. To our knowledge, the present study is the largest singlecenter experience evaluating the safety and efficacy of LSG before KT. The experience of a single center has allowed for
Young Kim et al. / Surgery for Obesity and Related Diseases - (2019) 1–5
improved granularity in retrospective chart review. The study is limited by a few factors, such as the retrospective nature of our study, small sample size, and singleinstitution experience. Conclusion In conclusion, this is the largest single-center experience of LSG before KT and our findings confirm previously published results. LSG resulted in excellent weight loss before KT and improved short- and long-term outcomes. A large prospectively controlled trial would be needed to definitively confirm our findings. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. Supplementary materials Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.1016/ j.soard.2019.09.069. References [1] Kim Y, Jung AD, Dhar VK, et al. Laparoscopic sleeve gastrectomy improves renal transplant candidacy and posttransplant outcomes in morbidly obese patients. Am J Transplant 2018;18(2):410–6. [2] Sharif A, Hecking M, de Vries AP, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 2014;14(9):1992–2000. [3] Hornum M, Jorgensen KA, Hansen JM, et al. New-onset diabetes mellitus after kidney transplantation in Denmark. Clin J Am Soc Nephrol 2010;5(4):709–16. [4] Porrini E, Delgado P, Alvarez A, et al. The combined effect of pretransplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation. Nephrol Dial Transplant 2008;23(4):1436–41. [5] Freeman CM, Woodle ES, Shi J, et al. Addressing morbid obesity as a barrier to renal transplantation with laparoscopic sleeve gastrectomy. Am J Transplant 2015;15(5):1360–8.
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