Accepted Article

Received Date : 12-Aug-2014 Revised Date : 12-Nov-2014 Accepted Date : 13-Jan-2015 Article type

: Original Article

Surgical complications after kidney transplantation: Different impact of immunosuppression, graft function, patient variables and surgical performance Running head: Surgical complications in kidney transplantation

Martina Koch1 Alexandros Kantas1 Katja Ramcke2 Anna I. Drabik3 Björn Nashan1

Department of Hepatobiliary Surgery and Transplantation and Department of Medical Biometry and Epidemiology Universitätsklinikum Hamburg Eppendorf Martinistr. 52 20246 Hamburg Germany

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ctr.12513 This article is protected by copyright. All rights reserved.

Accepted Article

Corresponding author: Prof. Dr. Martina Koch Universitätsklinikum Hamburg Eppendorf Department of Hepatobiliary Surgery and Transplantation Martinistr. 52, 20246 Hamburg Phone: +49 40 7410 56136 Fax: +49 40 7410 43431 e-mail: [email protected]

Authorship MK participated in research design, wrote the paper, performed research and analyzed data AK participated in research design, performed research and analyzed data KR participated in research design, performed research and analyzed data AID analyzed data, wrote the paper BN participated in research design, wrote the paper, performed research and analyzed data

Current addresses 1

Department of Hepatobiliary Surgery and Transplantation and

Universitätsklinikum Hamburg Eppendorf Martinistr. 52 20246 Hamburg Germany

This article is protected by copyright. All rights reserved.

Accepted Article

2

St. Bernhard-Hospital gemeinnützige GmbH

Claußenstraße 3 26919 Brake Germany 3

Department of Medical Biometry and Epidemiology

Universitätsklinikum Hamburg Eppendorf Martinistr. 52 20246 Hamburg Germany

Abbreviations: ABOi

blood group incompatible transplants

AR

acute rejection

ATG

antithymocyte globulin

CNI

calcineurin inhibitors

CSA

cyclosporine A

DBD

donation after brain death

DM

diabetes mellitus

ESP

Eurotransplant senior program

EVR

Everolimus

IA

immune adsorption

IIS

intense immunosuppression

IS

immunosuppression

KTx

kidney transplantation

This article is protected by copyright. All rights reserved.

Accepted Article

LD

living donation

MOR

median odds ratio

SC

surgical complication

SIS

standard immunosuppression

Koch M, Kantas A, Ramcke K, Drabik AI, Nashan B Surgical complications after kidney transplantation: Different impact of immunosuppression, graft function and surgical skills Clin Transplant

Abstract:

The population of kidney transplant (KTx) recipients often has complex medical and immunological conditions. Surgical complications (SC) contribute to the increasing morbidity and costs in these patients. We analyzed the risk factors for SC in 405 KTx patients treated using defined immunosuppressive regimens according to their clinical and immunological risk profile: 1) standard immunosuppression (SIS) with IL-2 receptor mAb, CNI and a) mycophenolic acid (MPA) or b) mTOR inhibitor; and 2) more intense immunosuppression (IIS) with a) ATG or b) the additional use of plasma exchange and B- and T-cell- depleting agents. In a mixed effects logistic regression model, we identified the following risk factors for SC: male gender, diabetes and postoperative dialysis. No difference was found between the patients who received SIS with MPA and those who received mTOR inhibitors. The risk of suffering complications with IIS increases with age. In addition to IIS, diabetes was a risk for wound healing disorders. Therapeutic anticoagulation and a third or subsequent This article is protected by copyright. All rights reserved.

Accepted Article

retransplantation increased the rate of bleeding. We did not identify immunosuppression or patient demographics as risk factors for lymphoceles or ureter complications; however, we demonstrated that the surgeon had a significant impact on severe complications, especially those of the ureter.

Key Words: surgical complications, kidney transplantation, immunosuppression, surgical skills

Corresponding author: Prof. Dr. Martina Koch Universitätsklinikum

Hamburg

Eppendorf

Department of Hepatobiliary Surgery and Transplantation Martinistr. 52, 20246 Hamburg Phone: +49 40 7410 56136 Fax: +49 40 7410 43431 e-mail: [email protected]

Introduction: Kidney transplantation (KTx) is the favored therapy for patients with end-stage renal disease. Although the surgical procedure has been standardized for decades, several of the risk factors in transplant recipients have changed. Due to a shortage of organs, the time on dialysis increases and the patients awaiting donation after brain death (DBD) are getting older and sicker. Furthermore, the number of patients who require re-transplantation or receive blood group incompatible transplants (ABOi) and, therefore, more intense immunosuppression (IS) is increasing.

This article is protected by copyright. All rights reserved.

Accepted Article

combinations other than age and IS on complication rates and cannot exclude that our analysis is biased by further confounders. In summary, recipient related factors gender, DM or the need for therapeutic anticoagulation influences the chance for SC. Further more DGF was an independent risk factor for severe SC. While there was no difference between SIS with MPA or mTOR inhibitors IIS contributed significantly to wound healing disorders. It needs to be kept in mind, that the surgeon has an important impact on severe SC. Therefore patients with more complex medical conditions require an optimized surgical management.

1.

Azzola A, Havryk A, Chhajed P, et al. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Transplantation 2004; 77 (2): 275.

2.

Humar A, Ramcharan T, Denny R, Gillingham KJ, Payne WD, Matas AJ. Are wound complications after a kidney transplant more common with modern immunosuppression? Transplantation 2001; 72 (12): 1920.

3.

Lopau K, Syamken K, Rubenwolf P, Riedmiller H, Wanner C. Impact of mycophenolate mofetil on wound complications and lymphoceles after kidney transplantation. Kidney Blood Press Res 2010; 33 (1): 52.

4.

Albano L, Berthoux F, Moal MC, et al. Incidence of delayed graft function and wound healing complications after deceased-donor kidney transplantation is not affected by de novo everolimus. Transplantation 2009; 88 (1): 69.

5.

Holley JL, Shapiro R, Lopatin WB, Tzakis AG, Hakala TR, Starzl TE. Obesity as a risk factor following cadaveric renal transplantation. Transplantation 1990; 49 (2): 387.

6.

Flechner SM, Zhou L, Derweesh I, et al. The impact of sirolimus, mycophenolate mofetil, cyclosporine, azathioprine, and steroids on wound healing in 513 kidney-transplant recipients. Transplantation 2003; 76 (12): 1729.

7.

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240 (2): 205.

8.

Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 2007; 165 (6): 710.

This article is protected by copyright. All rights reserved.

Accepted Article

9.

Larsen K, Merlo J. Appropriate assessment of neighborhood effects on individual health: integrating random and fixed effects in multilevel logistic regression. Am J Epidemiol 2005; 161 (1): 81.

10.

Ho D, Lynch RJ, Ranney DN, Magar A, Kubus J, Englesbe MJ. Financial impact of surgical site infection after kidney transplantation: implications for quality improvement initiative design. J Am Coll Surg 2010; 211 (1): 99.

11.

Barba J, Algarra R, Romero L, et al. Recipient and donor risk factors for surgical complications following kidney transplantation. Scand J Urol 2013; 47 (1): 63.

12.

Flechner SM, Glyda M, Cockfield S, et al. The ORION study: comparison of two sirolimusbased regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients. Am J Transplant 2011; 11 (8): 1633.

13.

Kahan BD. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 2000; 356 (9225): 194.

14.

Lorber MI, Mulgaonkar S, Butt KM, et al. Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study. Transplantation 2005; 80 (2): 244.

15.

Tedesco Silva H, Jr., Cibrik D, Johnston T, et al. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients. Am J Transplant 2010; 10 (6): 1401.

16.

Vitko S, Wlodarczyk Z, Kyllonen L, et al. Tacrolimus combined with two different dosages of sirolimus in kidney transplantation: results of a multicenter study. Am J Transplant 2006; 6 (3): 531.

17.

Schneider A, Jardine AG, Schneider MP, et al. Determinants of cardiovascular risk in haemodialysis patients: post hoc analyses of the AURORA study. Am J Nephrol 2013; 37 (2): 144.

18.

Hernandez D, Rufino M, Armas S, et al. Retrospective analysis of surgical complications following cadaveric kidney transplantation in the modern transplant era. Nephrol Dial Transplant 2006; 21 (10): 2908.

19.

Cash H, Slowinski T, Buechler A, et al. Impact of surgeon experience on complication rates and functional outcomes of 484 deceased donor renal transplants: a single-centre retrospective study. BJU Int 2012; 110 (8 Pt B): E368.

20.

Eufrasio P, Parada B, Moreira P, et al. Surgical complications in 2000 renal transplants. Transplant Proc 2011; 43 (1): 142.

21.

Seow YY, Alkari B, Dyer P, Riad H. Cold ischemia time, surgeon, time of day, and surgical complications. Transplantation 2004; 77 (9): 1386.

This article is protected by copyright. All rights reserved.

Accepted Article

of discharge from the hospital, immunosuppressive groups, CIT and donor age as well as meaningful two-way interactions were considered as possible risk factors. As each predictor variable needs a minimum number of outcome events (8), prior variable selection for multivariate models of secondary outcomes was conducted by bivariate analyses of risk factors. Variables with a p-value 30, n (%)

52 (13)

33 (12)

6 (14)

7 (18)

3 (8)

3 (18)

Pat. with DM, n (%)

79 (20)

54 (20)

6 (14)

10 (25)

7 (18)

2 (12)

Pat. with therapeutic

36 (9)

24 (9)

3 (7)

5 (13)

2 (5)

2 (12)

LD, n (%)

132 (33)

74 (28)

14 (33)

6 (15)

30 (75)

8 (47)

Previous transplants,

83 (21)

30 (11)

9 (21)

19 (48)

21 (53)

4 (24)

14 (4)

3 (1)

0

7 (18)

4 (10)

0

anticoagulation

n (%) >2 KTx, n (%)

Tab. 1: Characteristics of all patients and patients in the different IS groups. Values given in italic indicate a significant difference from Group 1a (p 30

1.8 [0.9;3.8]

0.121

DM

2.6 [1.3;5.2]

0.005

LD vs. DBD

1.1 [0.5;2.5]

0.904

≥ 2 KTx

2.2 [0.6;8.3]

0.257

This article is protected by copyright. All rights reserved.

Accepted Article

DGF

3.2 [1.7;6.2]

30

1.5

0.28

0.8

0.67

2.6

0.021

2.0

0.14

1.3

0.57

DM

2.0

0.02

2.0

0.10

2.7

0.008

1.6

0.24

1.5

0.36

LD vs. DBD

0.8

0.33

1.1

0.82

0.8

0.596

1.2

0.63

1.0

0.96

> 2 KTx

1.9

0.29

5.9

0.00

1.8

0.451

3.3

0.08

Empty

DGF

5.5

Surgical complications after kidney transplantation: different impacts of immunosuppression, graft function, patient variables, and surgical performance.

The population of kidney transplant (KTx) recipients often has complex medical and immunological conditions. Surgical complications (SCs) contribute t...
218KB Sizes 0 Downloads 7 Views