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Bariatric surgery before and after kidney transplantation: a propensity score-matched analysis

Open AccessPublished:November 18, 2022DOI:https://doi.org/10.1016/j.soard.2022.11.010

      Highlights

      • Both pre- and post-transplant bariatric surgery (BS) are safe and effective.
      • The optimal timing of BS for patients with renal failure should be individualized.
      • Different conditions of each transplant candidate should be considered in detail.

      Abstract

      Background

      Obesity is becoming more prevalent in end-stage renal disease population. Bariatric surgery (BS) is increasingly considered in as an approach to become eligible for kidney transplantation (KT) or reduce obesity-related morbidities.

      Objectives

      To assess short- and long-term outcome of patients who underwent both BS and KT and to determine the optimal timing of BS.

      Setting

      Erasmus Medical Center and University Medical Center Groningen, the Netherlands.

      Methods

      Patients who underwent both KT and BS between January 2000 and December 2020 were included and stratified according to the sequence of the two operations. The primary outcomes were patient and graft survival. Secondary outcomes were postoperative complications and efficacy of weight loss.

      Results

      Twenty-two patients were included in the KT first group and 34 in the BS first group. Death-uncensored graft survival in the KT first group was significantly higher than the BS first group (90.9% vs. 71.4%, P=0.009), without significant difference in patient survival and death-censored graft survival (100% vs. 90.5%, P=0.082; and 90.9% vs. 81.0%, P=0.058). There was no significant difference in one-year total weight loss (1y TWL: median [IQR], 36.0 [28.0-42.0] vs. 29.6 [21.5-40.6] kg, P=0.424), one-year percentage of excess weight loss (1y %EWL: median [IQR], 74.9 [54.1-99.0] vs. 57.9 [47.5-79.4], P=0.155), and the incidence of postoperative complications (36.4% vs. 50.0%, P=0.316) between the KT first and BS first groups.

      Conclusions

      Both pre- and post-transplant BS are effective and safe. Different conditions of each transplant candidate should be considered in detail to determine the optimal timing of BS.

      Keywords

      Introduction

      Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2 is becoming more prevalent in patients with end-stage renal disease (ESRD).[
      • DIWAN T.S.
      • CUFFY M.C.
      • LINARES-CERVANTES I.
      • et al.
      Impact of obesity on dialysis and transplant and its management [J].
      ] Patients with obesity are predisposed to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis, which accelerates the progression of chronic kidney failure.
      • HALL J.E.
      • JONES D.W.
      • KUO J.J.
      • et al.
      Impact of the obesity epidemic on hypertension and renal disease [J].
      ,
      • GRIFFIN K.A.
      • KRAMER H.
      • BIDANI A.K.
      Adverse renal consequences of obesity [J].
      Moreover, although obesity is not an absolute contra-indication for kidney transplantation (KT), patients with obesity have reduced access to receive KT[
      • LASSALLE M.
      • FEZEU L.K.
      • COUCHOUD C.
      • et al.
      Obesity and access to kidney transplantation in patients starting dialysis: A prospective cohort study [J].
      ] since it is associated with a higher incidence of posttransplant complications, such as surgical site infection, new onset of diabetes after transplantation and delayed graft function (DGF).

      LAFRANCA J A, JN I J, BETJES M G, et al. Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis [J]. BMC Med, 2015, 13: 111.

      ,
      • AALTEN J.
      • CHRISTIAANS M.H.
      • DE FIJTER H.
      • et al.
      The influence of obesity on short- and long-term graft and patient survival after renal transplantation [J].
      Recent evidence suggests that bariatric surgery (BS) plays an effective role in achieving long-term weight loss and reducing obesity-related complications in kidney transplant patients.[
      • KIM Y.
      • BAILEY A.J.
      • MORRIS M.C.
      • et al.
      Kidney transplantation after sleeve gastrectomy in the morbidly obese candidate: results of a 2-year experience [J].
      ] To the kidney transplant recipients, BS improved renal function, graft survival and decreased obesity-related comorbidities such as diabetes mellitus and hypertension.
      • DZIODZIO T.
      • BIEBL M.
      • ÖLLINGER R.
      • et al.
      The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge? [J].
      ,
      • SCHINDEL H.
      • WINKLER J.
      • YEMINI R.
      • et al.
      Survival benefit in bariatric surgery kidney recipients may be mediated through effects on kidney graft function and improvement of co-morbidities: A case-control study [J].
      To the kidney transplant candidates, BS has been proven to be effective in weight loss and improving eligibility for KT.[
      • GAZZETTA P.G.
      • BISSOLATI M.
      • SAIBENE A.
      • et al.
      Bariatric Surgery to Target Obesity in the Renal Transplant Population: Preliminary Experience in a Single Center [J].
      • YEMINI R.
      • NESHER E.
      • CARMELI I.
      • et al.
      Bariatric Surgery Is Efficacious and Improves Access to Transplantation for Morbidly Obese Renal Transplant Candidates [J].
      • FREEMAN C.M.
      • WOODLE E.S.
      • SHI J.
      • et al.
      Addressing morbid obesity as a barrier to renal transplantation with laparoscopic sleeve gastrectomy [J].
      ] Meanwhile, the question on what is the optimal timing of BS in the kidney transplant population has not been answered unequivocally. A systematic review which enrolled 15 clinical studies with a total of 119 patients who underwent BS either before or after transplant showed that it was the safest to perform BS after transplant.[
      • DZIODZIO T.
      • BIEBL M.
      • ÖLLINGER R.
      • et al.
      The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge? [J].
      ] However, a certain group of patients also benefited from pre-transplant BS, as complication rates were acceptable and BS improved eligibility for kidney transplant.
      To our knowledge, there has been no clinical trial to directly compare the outcomes of patients who underwent both operations in different order. The aim of this study is to assess short- and long-term outcomes of ESRD patients who underwent both BS and KT, trying to determine the optimal timing of BS for ESRD patients with obesity.

      Materials and Methods

      Study design

      In this retrospective cohort study, all patients ≥18 years who have undergone both KT and BS between January 2000 and January 2020 were screened using the transplant database of Erasmus Medical Center (EMC) and University Medical Center Groningen (UMCG). All the individuals accepting BS prior to KT were to lose weight to be eligible for transplant. These patients were stratified into two groups according to the sequence of the two operations, group 1: patients who underwent KT before BS (KT first group), group 2: patients who underwent BS before KT (BS first group). A standardized immunosuppressive protocol was applied after transplantation. All patients had induction therapy with basiliximab (20mg) on postoperative day (POD) 0 and 4, tacrolimus (0.1mg per kg per day to maintain trough levels of 7-10ng/mL), mycophenolate mofetil (500mg twice daily) and prednisolone (20mg daily). ABO incompatible, cross-match positive, or high panel reactive antibody patients were treated according to local protocol. All patients were followed up until death or June 2021. All clinical data was obtained from the electronic patient dossier of EMC and UMCG. Patient demographics, co-morbidities, surgical details, postoperative complications and follow-up results were recorded. This study was approved by the Ethics Committee of the Erasmus Medical Center Rotterdam (MEC-2018-1699) and conducted in accordance with the provisions of the declaration of Helsinki.

      Kidney transplantation related outcome

      Patient and graft survival, duration of hospital stay and postoperative complications were analyzed. Patient survival was defined as the time from transplantation to death or the last follow-up. Uncensored graft survival was defined as the time from transplantation to graft failure or death or the last follow-up with a functioning graft. Death-censored graft survival was defined as the time from transplantation to graft failure or the last follow-up with a functioning graft, with censoring death with a functioning graft. Postoperative complications were recorded up to 90 days after transplantation except for the incidence of incisional hernia and rejection, which was recorded throughout the follow-up after transplantation. Allograft rejection was based on renal graft biopsy-proven diagnosis (Category 2, 3 and 4 according to Banff classification). DGF was defined as the need for dialysis in the first posttransplant week or failure of creatinine to decrease in the first 24 hours. Primary nonfunction (PNF) was defined as the absence of graft function immediately after transplantation and dialysis for 3 months post-transplant. Graft failure was defined as the need for retransplant or long-term dialysis.

      Bariatric surgery related outcome

      Efficacy of BS and postoperative complications were analyzed. Pre- and postoperative BMI, one-year total weight loss (TWL), and one-year percentage of excess weight loss (%EWL) were calculated to determine the efficacy. As a BMI of 25 was the upper limit of normal body weight, excess weight was defined as the extra weight over the BMI of 25.
      • ORIA H.E.
      • CARRASQUILLA C.
      • CUNNINGHAM P.
      • et al.
      Guidelines for weight calculations and follow-up in bariatric surgery [J].
      ,
      • DEITEL M.
      • GREENSTEIN R.J.
      Recommendations for reporting weight loss [J].
      %EWL was calculated using the formula: postoperativeweightpreoperativeweightpreoperativeexcessweight×100. Postoperative complications were registered up to 90 days and classified according to the Clavien-Dindo classification.[
      • HUSAIN F.
      • JEONG I.H.
      • SPIGHT D.
      • et al.
      Risk factors for early postoperative complications after bariatric surgery [J].
      ]

      Statistical analysis

      Baseline characteristics and both outcomes of KT and BS were compared between the two groups. Continuous variables were reported as mean ± standard deviation (SD) if normally distributed or median with interquartile range (IQR) if data was skewed using Kolmogorov-Smirnov test. Categorical variables were described as numbers and percentages. Continuous variables were compared using student’s t-test or Mann–Whitney U test. Categorical variables were compared using χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank test were used to compare patient and graft survival. Since the age at transplantation was statistically inconsistent between the two groups, the propensity score matching (PSM) was used to avoid the age-related bias when analyzing transplant related outcomes. The nearest neighbor-matching algorithm with a maximum caliper of 0.25 was used to match patients in KT first group with comparable patients in BS first group according to the age at transplantation. Statistical analyses and Kaplan-Meier curves were performed using Stata/SE 16.0. The bar graph was plotted using GraphPad Prism 9.3.1. A p-value of < 0.05 was considered statistically significant.

      Results

      Baseline characteristics

      A total of 56 patients were eligible for the study, with 22 patients (77.3% female) in the KT first and 34 patients (67.6% female) in the BS first group. Baseline characteristics of these patients are shown in Table 1. The age at transplantation in the KT first group was significantly lower than the BS first group (42.7±8.6 vs. 52.5±10.0 years, P<0.001). 14 (63.6%) and 23 (67.6%) patients were dialysis dependent before transplantation in the KT first and BS first groups respectively with a similar dialysis vintage (median [interquartile range (IQR)], 27 [19.5-44.5] vs. 27 [20-43] months; P=0.822). A significantly higher proportion of patients in the KT first group received a retransplant compared to the BS first group (36.4% vs. 2.9%, P=0.002). No significant difference was found in the causes of ESRD, smoking history, donor sources and co-morbidities between the two groups. After PSM, 21 patients were included in the matched BS first group. There was no significant difference in age at transplantation (42.7 ± 8.6 vs. 48.3 ± 9.9 years, P<0.054) and the other baseline characteristics between the two groups (Table 1).
      Table 1Clinical characteristics at the time of transplantation
      Before matchingAfter matching
      KT first (n=22)BS first (n=34)P-valueKT first (n=22)BS first (n=21)P-value
      Age at KT (years), mean ± SD42.7 ± 8.652.5 ± 10.0< 0.00142.7 ± 8.648.3 ± 9.90.054
      Male, n (%)5 (22.7)11 (32.4)0.4365 (22.7)6 (28.6)0.661
      BMI at KT (kg/m2), mean ± SD35.8 ± 4.032.1 ± 4.40.00235.8 ± 4.031.8 ± 4.50.003
      Cause of ESRD, n (%)

      Diabetes mellitus

      Primary hypertension

      Glomerulonephritis

      Congenital nephropathy

      Others
      8 (36.4)

      2 (9.1)

      4 (18.2)

      5 (22.7)

      3 (13.6)
      17 (50.0)

      5 (14.7)

      7 (20.6)

      5 (14.7)

      0 (0)
      0.2348 (36.4)

      2 (9.1)

      4 (18.2)

      5 (22.7)

      3 (13.6)
      13 (62.0)

      0 (0)

      4 (19.0)

      4 (19.0)

      0 (0)
      0.213
      Smoking history, n (%)9 (40.9)9 (26.5)0.2599 (40.9)3 (14.3)0.052
      Dialysis, n (%)

      Duration on dialysis (months), median (IQR)
      14 (63.6)

      27 (19.5-44.5)
      23 (67.6)

      27 (20-43)
      0.757

      0.988
      14 (63.6)

      27 (19.5-44.5)
      16 (76.2)

      29.5 (18.5-53.5)
      0.370

      0.822
      Donor source, n (%)

      Living-related

      Deceased
      16 (72.7)

      6 (27.3)
      20 (58.8)

      14 (41.2)
      0.28916 (72.7)

      6 (27.3)
      11 (52.4)

      10 (47.6)
      0.168
      Transplantation, n (%)

      First transplant

      Retransplant
      14 (63.6)

      8 (36.4)
      33 (97.1)

      1 (2.9)
      0.00214 (63.6)

      8 (36.4)
      20 (95.2)

      1 (4.8)
      0.021
      Co-morbidities, n (%)

      Diabetes mellitus

      Hypertension

      Cardiac disease

      Cerebrovascular disease

      Peripheral vascular disease

      Respiratory disease

      Malignancy
      8 (36.4)

      13 (59.1)

      9 (40.9)

      0 (0)

      6 (27.3)

      3 (13.6)

      0 (0)
      21 (61.8)

      23 (67.6)

      17 (50.0)

      1 (2.9)

      4 (11.8)

      6 (17.6)

      2 (5.9)
      0.063

      0.514

      0.505

      1.000

      0.167

      1.000

      0.514
      8 (36.4)

      13 (59.1)

      9 (40.9)

      0 (0)

      6 (27.3)

      3 (13.6)

      0 (0)
      13 (61.9)

      13 (61.9)

      7 (33.3)

      1 (4.8)

      2 (9.5)

      3 (14.3)

      1 (4.8)
      0.094

      0.850

      0.607

      0.488

      0.240

      1.000

      0.488
      BMI, body mass index; BS, bariatric surgery; ESRD, end-stage renal disease; IQR, interquartile range; KT, kidney transplantation.

      Kidney transplantation related outcome

      The KT related complications are shown in Table 2. While not reaching statistical significance, the KT first group had a shorter duration of hospital stay compared to the matched BS first group (median [IQR], 10.5 [10.0-17.5] vs. 13.0 [10.0-15.0] days; P=0.788). The incidence of urological, vascular, incisional and cardio-cerebrovascular complications was similar between the matched BS first group and KT first group (RR, 1.29; 95%CI, 0.85-1.97; P=0.232; and RR, 0.84; 95%CI, 0.26-2.70; P=1.000; and RR, 1.31; 95%CI, 0.41-4.22; P=0.721; and RR, 2.10; 95%CI, 0.21-21.42; P=0.607, respectively). Within 30 days after transplantation, DGF occurred in 3 (13.6%) and 4 (19.0%) patients in the KT first and the matched BS first groups. PNF occurred in 1 (4.8%) patient in the matched BS first group.
      Table 2Postoperative complications after transplantation
      Before matchingAfter matching
      KT first (n=22)BS first (n=34)RR (95% CI)P-valueKT first (n=22)BS first (n=21)RR (95% CI)P-value
      Duration of hospital stay (days), median (IQR)10.5 (10.0-17.5)12.5 (8.8-17.0)-0.61910.5 (10.0-17.5)13.0 (10.0-15.0)-0.788
      Urological complications, n (%)

      UTI

      Urinary leak

      Hydronephrosis

      Ureteric stricture

      Hematuria
      13 (59.1)

      7 (31.8)

      2 (9.1)

      1 (4.5)

      3 (13.6)

      0 (0)
      24 (70.6)

      13 (38.2)

      4 (11.8)

      2 (5.9)

      3 (8.8)

      2 (5.9)
      1.20 (0.79-1.80)

      1.20 (0.57-2.53)

      1.29 (0.26-6.48)

      1.29 (0.13-13.43)

      0.65 (0.14-2.92)

      -
      0.375

      0.625

      1.000

      1.000

      0.670

      0.514
      13 (59.1)

      7 (31.8)

      2 (9.1)

      1 (4.5)

      3 (13.6)

      0 (0)
      16 (76.2)

      8 (38.1)

      2 (9.5)

      2 (9.5)

      2 (9.5)

      2 (9.5)
      1.29 (0.85-1.97)

      1.20 (0.53-2.72)

      1.05 (0.16-6.77)

      2.10 (0.21-21.42)

      0.70 (0.13-3.77)

      -
      0.232

      0.666

      1.000

      0.607

      1.000

      0.233
      Vascular complications, n (%)

      Renal artery thrombosis

      Perigraft bleeding

      Lymphocele
      5 (22.7)

      3 (13.6)

      1 (4.5)

      1 (4.5)
      5 (14.7)

      1 (2.9)

      2 (5.9)

      2 (5.9)
      0.65 (0.21-1.98)

      0.22 (0.02-1.94)

      1.29 (0.13-13.43)

      1.29 (0.13-13.43)
      0.491

      0.289

      1.000

      1.000
      5 (22.7)

      3 (13.6)

      1 (4.5)

      1 (4.5)
      4 (19.0)

      0 (0)

      2 (9.5)

      2 (9.5)
      0.84 (0.26-2.70)

      -

      2.10 (0.21-21.42)

      2.10 (0.21-21.42)
      1.000

      0.233

      0.607

      0.607
      Incisional complications, n (%)

      Incisional hernia

      Surgical wound dehiscence

      Surgical site infection

      Abdominal wall infection
      4 (18.2)

      2 (9.1)

      0 (0)

      1 (4.5)

      1 (4.5)
      13 (38.2)

      6 (17.6)

      5 (14.7)

      2 (5.9)

      0 (0)
      2.10 (0.79-5.63)

      1.94 (0.43-8.77)

      -

      1.29 (0.13-13.43)

      -
      0.111

      0.460

      0.145

      1.000

      0.393
      4 (18.2)

      2 (9.1)

      0 (0)

      1 (4.5)

      1 (4.5)
      5 (23.8)

      2 (9.5)

      3 (14.3)

      0 (0)

      0 (0)
      1.31 (0.41-4.22)

      1.05 (0.16-6.77)

      -

      -

      -
      0.721

      1.000

      0.108

      1.000

      1.000
      Cardio-cerebrovascular complications, n (%)

      Angina pectoris

      Atrial fibrillation

      Transient ischemic attack
      1 (4.5)

      0 (0)

      0 (0)

      1 (4.5)
      3 (8.8)

      1 (2.9)

      2 (5.9)

      0 (0)
      1.94 (0.22-17.50)

      -

      -

      -
      1.000

      0.393

      1.000

      0.514
      1 (4.5)

      0 (0)

      0 (0)

      1 (4.5)
      2 (9.5)

      0 (0)

      2 (9.5)

      0 (0)
      2.10 (0.21-21.42)

      -

      -

      -
      0.607

      -

      0.233

      1.000
      Others, n (%)

      Rejection

      DGF

      PNF

      NODAT

      Anemia
      10 (45.5)

      5 (22.7)

      3 (13.6)

      0 (0)

      1 (4.5)

      1 (4.5)
      18 (52.9)

      10 (29.4)

      4 (11.8)

      1 (2.9)

      2 (5.9)

      1 (2.9)
      1.17 (0.67-2.03)

      1.29 (0.51-3.28)

      0.86 (0.21-3.49)

      -

      1.29 (0.13-13.43)

      0.65 (0.04-9.82)
      0.584

      0.581

      1.000

      1.000

      1.000

      1.000
      10 (45.5)

      5 (22.7)

      3 (13.6)

      0 (0)

      1 (4.5)

      1 (4.5)
      13 (61.9)

      8 (38.1)

      4 (19.0)

      1 (4.8)

      0 (0)

      0 (0)
      1.36 (0.77-2.40)

      1.68 (0.65-4.31)

      1.40 (0.35-5.51)

      -

      -

      -
      0.280

      0.273

      0.698

      0.488

      1.000

      1.000
      BS, bariatric surgery; DGF, delayed graft function; KT, kidney transplantation; NODAT, new onset diabetes mellitus after transplantation; PNF, primary nonfunction; UTI, urinary tract infection.
      Mean follow-up after KT was 9.4 years in the KT first group, and 4.4 years in the BS first group. During follow-up, 5 (22.7%) and 8 (38.1%) patients in the KT first and matched BS first groups were diagnosed with biopsy-proven rejection (RR, 1.68; 95%CI, 0.65-4.31; P=0.273). Two (9.1%) grafts were lost in the KT first group due to chronic rejection, at 66.0 and 98.1 months after transplantation respectively. Four (19.0%) grafts were lost in the BS first group due to chronic rejection (n=2), PNF (n=1) and oxalate nephropathy (n=1), at 31.7, 68.6, 0.3 and 55.1 months after transplantation. All four were included after PSM. Four patients died in the BS first group with functioning grafts due to esophageal cancer (n=1), pneumosepsis (n=1), Covid-19 infection (n=1) and drug intoxication (n=1) respectively, and 2 cases were included in the matched BS first group. In the baseline groups, there was a significant difference in patient and graft survival (100% vs. 88.2%, P=0.041, Figure 1A; and 90.9% vs. 76.5%, P=0.009, Figure 1B), but not in death-censored graft survival (90.9% vs. 88.2%, P=0.130, Figure 1C). Whereas after PSM, graft survival was still significantly higher in the KT first group than in the matched BS first group (90.9% vs. 71.4%, P=0.009, Figure 1E), no statistical difference was found in patient survival and death-censored graft survival between the two groups (100% vs. 90.5%, P=0.082, Figure 1D; and 90.9% vs. 81.0%, P=0.058, Figure 1F).
      Figure thumbnail gr1
      Figure 1Before propensity score matching (PSM): A. Patient survival, B. Graft survival, C. Death-censored graft survival. After PSM: D. Patient survival, E. Graft survival, F. Death-censored graft survival. Kaplan-Meier method was used to assess patient and graft survival from the time of transplantation. P-values according to log-rank test. The blue curve represents the group who underwent kidney transplantation after bariatric surgery, and the red curve represents the group who underwent kidney transplantation prior to bariatric surgery.

      Bariatric surgery related outcome

      The BS related outcomes are shown in Table 3. In the KT first group, BS included sleeve gastrectomy (n=17) and Roux-en-Y gastric bypass (n=5). In the BS first group, they were sleeve gastrectomy (n=16), Roux-en-Y gastric bypass (n=16) and gastric banding (n=2). The age at BS was similar between the two groups (48.3±9.4 vs. 48.3±10.9 years, P=0.998). The preoperative BMI was not different between the KT first and BS first group (median [IQR], 39.7 [37.9-44.0] vs. 42.0 [40.0-45.8] kg/m2, P=0.090). The median interval between KT and BS was 5.5 years (IQR 2.4-6.4) in the KT first group and 2.7 years (IQR 1.5-6.7) in the BS first group. Mean follow-up after BS was 3.8 years in the KT first group, and 8.7 years in the BS first group. After one year’s follow-up the BMI of both groups was within the range of obesity but showed comparable reduction (30.1±6.5 vs. 32.0±4.1, P=0.215). There was no significant difference in one-year TWL and %EWL between the KT first and BS first groups (1y TWL: median [IQR], 36.0 [28.0-42.0] vs. 29.6 [21.5-40.6] kg, P=0.424; 1y %EWL: median [IQR], 74.9 [54.1-99.0] vs. 57.9 [47.5-79.4], P=0.155). Figure 2 illustrates the different types of BS performed between 2000 and 2020. Operations that were done in the early 2000s mainly included gastric bypass and adjustable gastric banding, while sleeve gastrectomy was not commonly used until 2009-2012. Obviously, over the last decade the sleeve has become the most common procedure. Postoperative complications were classified according to the Clavien-Dindo classification (Table 4). Only grade Ⅰ to Ⅲ complications were found in both groups and there was no significant difference in the incidence of each grade and total complications (KT first vs. BS first, grade Ⅰ: 18.2% vs. 8.8%, P=0.415; grade Ⅱ: 13.6% vs. 14.7%, P=1.000; grade Ⅲa: 0% vs. 2.9%, P=1.000; grade Ⅲb: 4.5% vs. 23.5%, P=0.074; total: 36.4% vs. 50.0%, P=0.316).
      Table 3Clinical outcomes at and after bariatric surgery
      KT first (n=22)BS first (n=34)P-value
      Age at BS (years), mean ± SD48.3 ± 9.448.3 ± 10.90.998
      Pre-BS BMI (kg/m2), median (IQR)39.7 (37.9-44.0)42.0 (40.0-45.8)0.090
      Type of BS, n (%)

      SG

      RYGB

      GB
      17 (77.3)

      5 (22.7)

      0 (0)
      16 (47.1)

      16 (47.1)

      2 (5.8)
      0.063
      Time between KT and BS (years), median (IQR)5.5 (2.4-6.4)2.7 (1.5-6.7)0.123
      BMI at one year after BS (kg/m2), mean (SD)30.1 ± 6.532.0 ± 4.10.215
      One-year TWL (kg), median (IQR)36.0 (28.0-42.0)29.6 (21.5-40.6)0.424
      One-year %EWL, median (IQR)

      SG

      RYGB

      GB
      74.9 (54.1-99.0)

      74.9 (54.1-107.4)

      67.1 (32.5-93.5)

      -
      57.9 (47.5-79.4)

      52.5 (40.0-73.4)

      63.7 (54.0-89.1)

      46.0 (37.2-54.8)
      0.155
      BS, bariatric surgery; BMI, body mass index; GB, gastric banding; IQR, interquartile range; KT, kidney transplantation; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy; TWL, total weight loss; %EWL, the percentage of excess weight loss.
      Figure thumbnail gr2
      Figure 2Number of bariatric surgeries undertaken in different periods.GB, gastric banding; RYGB, Roux-en-Y gastric bypass; SG, sleeve gastrectomy.
      Table 4Postoperative complications after bariatric surgery according to the Clavien-Dindo classification
      ComplicationsKT first (n=22)BS first (n=34)p-value
      Grade Ⅰ, n (%)

      Persistent vomiting requiring antiemetics

      Transient elevation of serum creatinine

      Dyspnea requiring oxygen therapy

      Dumpling syndrome

      Postoperative atrial fibrillation
      4 (18.2)

      1

      3

      0

      0

      0
      3 (8.8)

      0

      0

      1

      1

      1
      0.415
      Grade Ⅱ, n (%)

      Anastomotic bleeding requiring hemostatics

      Urinary tract infection requiring antibiotics

      Splenic lesion requiring blood transfusions

      Infected abdominal hematoma requiring antibiotics

      Postoperative anemia requiring blood transfusions
      3 (13.6)

      0

      1

      0

      2

      0
      5 (14.7)

      1

      1

      1

      1

      1
      1.000
      Grade Ⅲa, n (%)

      Abscess caused by port infection requiring drainage
      0 (0)

      0
      1 (2.9)

      1
      1.000
      Grade Ⅲb, n (%)

      Anastomotic stenosis requiring surgical reconstruction

      Anastomotic bleeding requiring surgical hemostasis

      Anastomotic leak requiring surgical repair

      Gastric perforation requiring surgical repair

      Internal herniation treated by surgery

      Small intestine damage repairing surgical repair
      1 (4.5)

      0

      0

      0

      0

      1

      0
      8 (23.5)

      2

      2

      1

      1

      1

      1
      0.074
      Grade Ⅳa, n (%)0 (0)0 (0)-
      Grade Ⅳb, n (%)0 (0)0 (0)-
      Grade Ⅴ, n (%)0 (0)0 (0)-
      Total, n (%)8 (36.4)17 (50.0)0.316

      Discussion

      In this retrospective cohort study, we compared baseline characteristics, postoperative complications, and outcomes between patients with either a KT first or BS first approach. Our analysis showed that death-uncensored graft survival in the KT first group was significantly higher than the BS first group, but there was no significant difference in patient survival, death-censored graft survival or post-transplant complications. Both pre- and post-transplant BS achieved remarkable weight loss and the incidence of postoperative complications is acceptable.
      Ideally, BS should be initiated as early as possible. A randomized clinical trial by Cohen et al. showed that BS is associated with remission of albuminuria and improvement of renal function in patients with early-stage chronic kidney disease, which may help patients eventually avoid KT.[
      • COHEN R.V.
      • PEREIRA T.V.
      • ABOUD C.M.
      • et al.
      Effect of Gastric Bypass vs Best Medical Treatment on Early-Stage Chronic Kidney Disease in Patients With Type 2 Diabetes and Obesity: A Randomized Clinical Trial [J].
      ] However, when it comes to patients with ESRD, another study showed that BS only improved transplant candidacy and stable weight loss, but not renal function[
      • KASSAM A.F.
      • MIRZA A.
      • KIM Y.
      • et al.
      Long-term outcomes in patients with obesity and renal disease after sleeve gastrectomy [J].
      ]. Moreover, pre-transplant BS may have prolonged time on dialysis to establish sufficient weight loss and recover from long-term complications, which remains an independent predictor of mortality after KT.[
      • HELANTERA I.
      • SALMELA K.
      • KYLLONEN L.
      • et al.
      Pretransplant dialysis duration and risk of death after kidney transplantation in the current era [J].
      ] When transplant is technically feasible despite being overweight, patients with an expected long waiting time because of blood type O or B, might decide to have BS first. However, because kidney donors are so scarce, the opportunity to receive a donor kidney may often postpone the consideration of BS. In our study, patients with severe obesity (BMI ≥ 40 kg/m2) were more likely to have BS before transplant, which caused higher baseline BMI in the BS first group.
      During the long-term follow-up, four patients in the BS first group died. On this basis, we directly compared the outcomes of patients who underwent BS before and after KT. Our results demonstrated that the difference in mortality was not statistically significant, but death-uncensored graft survival was significantly higher in the cohort with post-transplant BS. In the recently published study comparing pre- and post-transplant BS with matched controls respectively, Cohen et al. found that mortality was significantly lower in the patients with post-transplant BS, but not the pre-transplant BS.[
      • COHEN J.B.
      • LIM M.A.
      • TEWKSBURY C.M.
      • et al.
      Bariatric surgery before and after kidney transplantation: long-term weight loss and allograft outcomes [J].
      ] Although the findings of the two studies are different, both show that patients undergoing BS after KT benefit more.
      Roux-en-Y gastric bypass, as one of the bariatric surgeries, aims to induce decreased absorption of nutrients in the small intestine. This raises the concern of malabsorption of immunosuppressive agents in transplant recipients. A pilot study by Rogers et al. showed that transplant recipients with gastric bypass surgery required higher dosage of immunosuppressive agents to maintain similar concentrations compared to non-bypass patients.[
      • ROGERS C.C.
      • ALLOWAY R.R.
      • ALEXANDER J.W.
      • et al.
      Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study [J].
      ] The study by Yemini et al. observed that tacrolimus blood concentrations declined slightly but remained within therapeutic range without serious rejection among transplanted patients who underwent laparoscopic Roux-en-Y gastric bypass.[
      • YEMINI R.
      • NESHER E.
      • WINKLER J.
      • et al.
      Bariatric surgery in solid organ transplant patients: Long-term follow-up results of outcome, safety, and effect on immunosuppression [J].
      ] However, it is not advisable to increase the tacrolimus dose solely based on bodyweight. Our previous experience found that such practices resulted in overexposure in more than half of overweight patients.[
      • ANDREWS L.M.
      • DE WINTER B.C.M.
      • TANG J.T.
      • et al.
      Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.
      ] In this data, graft rejection occurred in 7 (33.3%) patients receiving Roux-en-Y gastric bypass and 8 (32.0%) patients receiving other types of BS (RR 1.04, 95% CI 0.45-2.39, P=0.923). Although not significantly different, more research into the pharmacokinetics of immunosuppressive agents among transplant recipients with obesity is needed.
      Another potential complication of BS is the formation of calcium oxalate stones in the kidneys. Obesity itself can increase the risk of kidney stone formation.[
      • TAYLOR E.N.
      • STAMPFER M.J.
      • CURHAN G.C.
      Obesity, weight gain, and the risk of kidney stones [J].
      ] Furthermore, Roux-en-Y gastric bypass is associated with oxalate nephropathy and graft loss.
      • CHOUDHURY R.A.
      • HOELTZEL G.
      • PRINS K.
      • et al.
      Sleeve Gastrectomy Compared with Gastric Bypass for Morbidly Obese Patients with End Stage Renal Disease: a Decision Analysis [J].
      ,
      • KHORGAMI Z.
      • SHOAR S.
      • ANDALIB A.
      • et al.
      Trends in utilization of bariatric surgery, 2010-2014: sleeve gastrectomy dominates [J].
      In a systematic review evaluating the risk of hyperoxaluria in patient who underwent BS, it was concluded that Roux-en-Y gastric bypass was associated with increased urine oxalate and these patients had a significantly higher risk of stone formation.[
      • UPALA S.
      • JARUVONGVANICH V.
      • SANGUANKEO A.
      Risk of nephrolithiasis, hyperoxaluria, and calcium oxalate supersaturation increased after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis [J].
      ] In our study, oxalate deposits were found in four patients, all of whom had undergone Roux-en-Y gastric bypass. One of them lost the graft due to oxalate nephropathy. For this reason, sleeve gastrectomy may be a preferred choice compared to Roux-en-Y gastric bypass. Dietary interventions such as a low oxalate and salt diet show promising results in decreasing oxaluria and calcium oxalate relative supersaturation indexes.[
      • ESCRIBANO J.
      • BALAGUER A.
      • ROQUÉ I FIGULS M.
      • et al.
      Dietary interventions for preventing complications in idiopathic hypercalciuria [J].
      ] Our colleagues first proposed that a systematic low-oxalic acid diet with supplementation of calcium, cholestyramine and sodium bicarbonate and intensifying dialysis effectively prevented oxalate nephropathy in a cohort of patients with enteric hyperoxaluria.[
      • ROODNAT J.I.
      • DE MIK-VAN EGMOND A.M.E.
      • VISSER W.J.
      • et al.
      A Successful Approach to Kidney Transplantation in Patients With Enteric (Secondary) Hyperoxaluria [J].
      ] It may be beneficial for the transplant candidates and recipients who have undergone Roux-en-Y gastric bypass to adhere to such a low-oxalic acid diet.
      Due to the introduction of minimally invasive and robotic surgery, it is currently possible to perform robot-assisted kidney transplantation (RAKT). By RAKT, the graft is placed in the abdominal cavity through a Pfannenstiel incision, and vascular and ureteral anastomoses are then performed robotically. Although the Pfannenstiel incision seems the same length as the open surgery, RAKT has its own advantages in specific populations. For patients with centripetal obesity, it provides more flexible operation space in the pelvic region while the operative area of iliac fossa is difficult to expose due to abdominal fat accumulation using open surgical approach. With the help of RAKT, patients who were previously declined may have the opportunity of transplant. Spaggiari et al. were the first to publish their randomized trial in which 11 patients underwent simultaneous robotic-assisted kidney transplantation and sleeve gastrectomy.[
      • SPAGGIARI M.
      • DI COCCO P.
      • TULLA K.
      • et al.
      Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure [J].
      ] Compared to patients with class Ⅱ (BMI 35-39.9 kg/m2) and class Ⅲ obesity (BMI ≥ 40 kg/m2) who received RAKT alone, estimated blood loss, readmission rates, incidence of surgical complications and graft survival at one-year follow-up were comparable. Also, renal graft function was similar, indicating that performing kidney transplantation and sleeve gastrectomy simultaneously does not have a negative effect on graft function. As long-term data is not yet available, it is premature to conclude that simultaneous KT and BS should become the gold standard in ESRD patients.
      Our study is limited by several factors. Firstly, the present study is a retrospective cohort analysis, of which a potential selection bias is unavoidable. To minimize this bias, we combined the data of two high volume transplant centers, which resulted in one of the largest cohorts of ESRD patients who underwent both BS and KT. However, the baseline BMI of patients in the BS first group was still higher and they may have a potentially higher risk of postoperative complications. Secondly, in this population of ESRD patients with obesity, some died after BS while awaiting KT. Unfortunately, these data were not collected prospectively. Thirdly, as the study involves patients over a 21-year period, the safety and public acceptance of BS have been tremendously improved. This dynamic change should be also taken into consideration when evaluating the robustness of the results.

      Conclusions

      In conclusion, both pre- and post-transplant BS are effective and safe approaches to lose weight among ESRD patients. The optimal timing of BS should be individualized, the severity of obesity, expected waiting time and willingness of patients should all be considered. With the major advances in robotic surgery, simultaneous KT and BS may become an additional option in the future. Nonetheless, careful attention should be warranted in both preoperative evaluation and postoperative management and more studies are needed to elucidate the optimal treatment for this group of patients.

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