Accepted Article

Received Date : 27-Sep-2014 Revised Date : 13-Jan-2015 Accepted Date : 09-Feb-2015 Article type

: Original Article

INDEPENDENT RISK FACTORS FOR EARLY UROLOGIC COMPLICATIONS AFTER KIDNEY TRANSPLANTATION

Running Title: Kidney Transplant Urologic Complications

Amir A. Rahnemai-Azar M.D. 1, Brian F. Gilchrist M.D. 1, Liise K. Kayler M.D., M.S.2

1

Department of Surgery, Bronx Lebanon Hospital, Albert Einstein College of Medicine, New York City, NY

2

Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY

Corresponding Author: Liise K. Kayler

M.D., M.S.

Associate Professor of Clinical Surgery Surgical Director of Kidney Transplantation Department of Surgery, Albert Einstein College of Medicine Address: 111 East 210th Street, Bronx, NY 10467 Tel: 347-931-3931 Fax: 718-798-3857 Email: [email protected]

Authors: Rahnemai-Azar A. A. M.D., Gilchrist B. F. M.D., Kayler L. K. M.D., M.S. Title: Independent Risk Factors for Early Urologic Complications After Kidney Transplantation

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.12530 This article is protected by copyright. All rights reserved.

Accepted Article

Journal: Clin Transplant Abstract: Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). We evaluated traditional and novel potential risk factors for urologic complications following kidney transplantation. Consecutive KTX recipients between December 1, 2006 and December 31, 2010 with at least 6 months follow-up (n=635) were evaluated for overall urologic complications accounting for donor, recipient, and transplant characteristics using univariate and multivariate logistic regression. Urologic complications occurred in 29 cases (4.6%) at a median of 40 days (range 1-999) post-transplantation, and included 17 ureteral strictures (2.6%), 5 (0.8%) ureteral obstructions due to donor-derived stones or intraluminal thrombus and 7 urine leaks (1.1%). All except two complications occurred within the first year of transplantation. Risk factors for urologic complications on univariate analysis were dual kidney transplantation (p =0.04) and renal artery multiplicity (p=0.02). On multivariate analysis, only renal artery multiplicity remained significant (aHR 2.4, 95% confidence interval 1.1, 5.1, p=0.02). Donation after cardiac death, non-mandatory national share kidneys, donor peak serum creatinine > 1.5 mg/dL or creatinine phosphokinase > 1000 IU/L, and donor down time were not associated with urologic complications. Our data suggest that donor artery multiplicity is an independent risk factor for urologic complications following KTX. Key word: kidney transplant, urologic complication, risk factor, independent, graft survival

Corresponding Author: Liise K. Kayler M.D., M.S. Department of Surgery, Albert Einstein College of Medicine Address: 111 East 210th Street, Bronx, NY 10467 Tel: 347-931-3931 Fax: 718-798-3857 Email: [email protected]

INTRODUCTION Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). (1, 2) The overall incidence of urological complications ranges from 2.5% in current era, with new

This article is protected by copyright. All rights reserved.

Accepted Article

advances in surgical techniques and immunosuppression regimens, to as high as 30% in some studies; partially depending on the criteria used to define it. (2-7) These complications are associated with substantial morbidity, graft loss, excess cost and occasionally even patient death (1, 2, 5, 8). The majority of studies analyzing risk factors for urologic complications are limited in the types

of variables assessed. (2, 3, 5) On the other hand, the increasing disparity in kidney supply and demand has driven transplant centers to consider the use of kidneys with suboptimal characteristics for transplantation including previously rejected kidneys, small pediatric donor kidneys, and kidneys from donors with acute kidney injury. (9, 10) Centers have also increased the utilization of kidneys with multiple arteries and the number of double kidney transplantation. (11, 12) All these factors should be assessed to better inform patients about the risks of possible urologic complications and to improve clinical decision making about these complications. The objective of this paper is to evaluate traditional and novel risk factors for urologic

complications and assess their effects on graft survival.

PATIENTS and METHODS After Institutional Review Board approval, the electronic records of adult isolated kidney

transplant recipients performed between December 1, 2006 and December 31, 2010 were reviewed. Patients who underwent simultaneous kidney and pancreas, liver, heart, or lung transplantation were excluded. Data on donor, transplant and recipient characteristics (including variables presented in Table 2) were collected from a prospectively generated internal transplant database and a retrospective review of DonorNet® and hospital medical records. Expanded criteria donor (ECD) was defined as any donor ≥ 60 years of age, or between 50 and 59 years of age with a least two of the following factors: terminal serum creatinine > 1.5 mg/dL, death from cerebrovascular accident or history of hypertension.

This article is protected by copyright. All rights reserved.

Accepted Article

Complications Urologic complications were identified by review of radiographic, laboratory, and operative

records. Urine leakage was defined as drainage or accumulation of urine around the graft or in the operative wound requiring treatment with percutaneous nephrostomy and/or operation. Ureteral obstruction was defined as impaired renal transplant function with an ultrasound finding of pelvicaliceal dilatation requiring treatment with percutaneous nephrostomy and/or ureteral operation. Antegrade nephrostogram was done to confirm the level of obstruction. Peri-nephric fluid collections causing temporary urinary obstruction were not included. Surgery Technique All ureteroneocystostomies were performed with full-thickness (1) or Lich-Gregoir techniques.

(13) Briefly, the full-thickness technique involves direct anastomosis of the spatulated ureter to the full thickness of the bladder. The Lich- Gregoir technique is a continuous suture around the spatulated circumference of the ureter and the urothelium, with closure of the bladder muscle over the anastomosis as an anti-reflux tunnel. In the case of double kidney transplantation ureters were generally anastomosed individually to the bladder. Transplants were classified as “imported” if derived from a national organ procurement organization (OPO) (the donor and recipient transplant center were in different UNOS regions) and not allocated as a 0-antigen mismatch, directed donation, or payback. Internal double-J ureteral stents were placed per surgeon preference, tended not to be placed routinely by surgeons utilizing the full-thickness technique (3.4% stented) and were routinely placed by those using the Lich- Gregoir technique (95.4% stented). Post-operative Care Foley catheters were routinely removed on post-operative day 2-3. Routine bladder ultrasounds

were obtained on all patients after the first void following removal of the Foley catheter or if considered necessary otherwise. Voiding cystourethrography was not routinely performed.

This article is protected by copyright. All rights reserved.

Accepted Article

The patients were given an immunosuppressive regimen based upon induction with basiliximab (20 mg on day 0 and 3) or polyclonal anti-thymocyte globulin (ATG, 3-4 doses of 1.5 mg/kg each) for high-risk patients (PRA > 30, re-transplants, recipient age < 18 years) as well as maintenance immunosuppression with tacrolimus, mycophenolate mofetil (or an enteric coated formulation), and steroids. Pediatric recipients (< 18 years) did not receive steroids. Tacrolimus was begun on the day after transplantation orally (0.1 mg/kg body weight divided in two dosages per day), aiming at trough levels of 10-12 ng/mL in the first month, 8–10 ng/mL for months two to three, 6-8 ng/mL for months four to six and 4-6 ng/ml thereafter. Cytomegalovirus prophylaxis with valgancylovir was provided when either the donor or recipient was seropositive. In the case of donor and recipient negative CMV titers, acyclovir prophylaxis was provided. Antibiotic prophylaxis consisted of sulfamethoxazole-trimethoprim single strength three times a week for the life of the graft as prophylaxis against Pneumocystis jiroveci. Statistical Analysis Data are provided as a mean and standard deviation (SD) for continuous variables and

proportions for binary variables. Overall kidney graft survival (defined as time to graft loss or death) plots were generated from Kaplan-Meier models. Univariate comparisons were assessed using the twosample Student’s t-test for continuous variables and the chi-squared test for categorical variables. The impact of variables on urologic complications was examined using univariate and multivariate logistic regression. In order to identify variables for inclusion in the multivariate model, variables were selected using a univariate significance of p 1.5 mg/dL, creatinine phosphokinase > 1000 IU/L, or donors with identified downtime. Also there appeared to be a trend of increased urologic complications with dual kidney transplants, donor age ≥ 60 years, re-transplants, and with ligation of the lower pole

This article is protected by copyright. All rights reserved.

Accepted Article

Received Date : 27-Sep-2014 Revised Date : 13-Jan-2015 Accepted Date : 09-Feb-2015 Article type

: Original Article

INDEPENDENT RISK FACTORS FOR EARLY UROLOGIC COMPLICATIONS AFTER KIDNEY TRANSPLANTATION

Running Title: Kidney Transplant Urologic Complications

Amir A. Rahnemai-Azar M.D. 1, Brian F. Gilchrist M.D. 1, Liise K. Kayler M.D., M.S.2

1

Department of Surgery, Bronx Lebanon Hospital, Albert Einstein College of Medicine, New York City, NY

2

Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY

Corresponding Author: Liise K. Kayler

M.D., M.S.

Associate Professor of Clinical Surgery Surgical Director of Kidney Transplantation Department of Surgery, Albert Einstein College of Medicine Address: 111 East 210th Street, Bronx, NY 10467 Tel: 347-931-3931 Fax: 718-798-3857 Email: [email protected]

Authors: Rahnemai-Azar A. A. M.D., Gilchrist B. F. M.D., Kayler L. K. M.D., M.S. Title: Independent Risk Factors for Early Urologic Complications After Kidney Transplantation

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.12530 This article is protected by copyright. All rights reserved.

Accepted Article

Conflict of Interest None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript

Table 1. Incidence of Urologic complications Complication

N

Percent of Transplants

Days to diagnosis th

th

th

50 (25 , 75 percentile)

Urologic Complication Leak Stricture Stone or Intraluminal thrombus

29 7 17 5

4.6 1.1 2.6 0.8

4 (3, 20) 72 (38, 192) 41 (11, 46)

Table 2. Univariate analysis of risk factors for the development of urologic complications.

Characteristics (reference group)

Donor Age-years ≤3 4-35 36-59 ≥60 Donor race, African-American Donor gender, female (male) Deceased donor (living donor) Donor, death by CVA (not CVA) Donor, hypertension (no hypertension) Donor, history of diabetes (no diabetes) Donation after cardiac death (DBD) Expanded criteria donor (SCD) Non-Mandatory National Share Donor, peak serum creatinine > 1.5 (mg/dL) Double kidney transplant performed Pulsatile perfusion performed Resistive index at 4 hours > 0.4 mm Hg Creatine phosphokinase > 1000 IU/L Downtime > 0 minutes Recipient Age (years) ≤3 4-35 36-59 60-69 ≥ 70

N (%) or th th th 50 , 25 , 75 percentile

Urologic Complication % vs. reference

Odds Ratio

95% Confidence Interval

P value

57 (9) 231 (36) 275 (43) 72 (12) 122 (19.2) 266 (42) 532 (84) 140 (26) 140 (26) 45 (9) 88 (17) 114 (18) 120 (19) 140 (22) 59 (9) 399 (75) 35/389 (9) 111/274 (41) 113/456 (25)

5.3 3.5 4.4 8.3 0.8 3.8 vs. 5.2 4.7 vs. 3.9 5.7 vs. 4.3 5.0 vs. 4.6 6.7 vs. 4.2 3.4 vs. 5.0 7.0 vs. 4.1 5.0 vs. 4.5 1.4 vs. 5.5 10.2 vs. 4.0 5.3 vs. 3.0 2.9 vs. 5.9 4.5 vs. 4.3 3.5 vs. 5.5

1.55 ref 1.27 2.53 0.14 0.72 1.22 1.34 1.09 1.51 0.68 1.79 1.12 0.25 2.72 1.79 0.47 1.05 0.63

0.40, 6.03 ref 0.51, 3.17 0.85, 7.57 0.12, 1.06 0.33, 1.57 0.85, 3.58 0.56, 3.17 0.45, 2.68 0.43, 5.25 0.20, 1.31 0.77, 4.14 0.45, 2.83 0.06, 1.07 1.06, 6.98 0.60, 5.32 0.06, 3.28 0.33, 3.4 0.21, 1.88

0.5284 ref 0.6054 0.0955 0.0574 0.4099 0.7171 0.5095 0.8447 0.5173 0.5337 0.1763 0.8009 0.0616 0.0371 0.2934 0.4630 0.9335 0.4035

6 112 299 176 42

0 5.4 5.0 4.0 2.4

n/a ref 0.93 0.73 0.43

n/a ref 0.35, 2.5 0.24, 2.2 0.05, 3.7

n/a ref 0.8890 0.5837 0.4423

This article is protected by copyright. All rights reserved.

Accepted Article

Recipient race, AA (non-AA) 211 (33) 6.6 vs. 3.4 1.94 0.92, 4.09 0.0830 Recipient gender, female (male) 240 (38) 5.4 vs. 4.1 1.36 0.64, 2.87 0.4254 2 Recipient body mass index (kg/m ) 27.2, 22.8, 31.3 NA 1.00 0.94, 1.06 0.9486 Recipient, Panel reactive antibodies > 0 (0) 97 (15) 7.2 vs. 4.1 1.82 0.76, 4.40 0.1803 Recipient, history of diabetes (without) 167 (27) 4.2 vs. 4.7 0.89 0.37, 2.12 0.7868 Recipient, not on dialysis (requiring dialysis) 105 (17) 1.9 vs. 5.1 0.36 0.09, 1.55 0.1700 Recipient, re-transplantation (first transplant) 87 (14) 8.1 vs. 4.0 2.09 0.87, 5.06 0.1011 Recipient Thymoglobulin induction (other) 136 (21) 7.4 vs. 3.8 2.02 0.92, 4.46 0.0811 >1 renal arteries (1 renal artery) 146 (23) 8.2 vs. 3.5 2.48 1.16, 3.34 0.0194 Lower pole artery ligated (all other cases) 8 (1.3) 12.5 vs. 4.5 3.05 0.36, 25.4 0.3052 Ureteral stent placement (no stent) 305 (48) 4.9 vs. 4.2 1.17 0.55, 2.46 0.6840 Days to ureteral stent removal 43, 34, 52 NA 0.99 0.98, 1.01 0.2195 Cold ischemia time > 24 hours (≤ 24 hours) 268/527(51) 4.9 vs. 4.6 0.95 0.43, 2.13 0.9065 AA, African-American; CVA, cerebrovascular accident; DBD, donation after brain death; SCD, standard criteria donor. *Denominator included when full sample size not available for analysis. Additionally, data on donor cause of death, donation after cardiac death, donor history of diabetes and hypertension, peak serum creatinine, double kidney transplant, machine perfusion, and resistive index greater than 4 at 4 hours, are based on the deceased-donor sample size.

Figure 1.

Figure 1 Legend. Graft survival of the patients with urologic complications after kidney transplant versus the ones without urologic complications.

This article is protected by copyright. All rights reserved.

Accepted Article

Authors Contribution Amir A. Rahnemai-Azar: Concept and Design, Data Analysis, Drafting article. Brian F. Gilchrist: Drafting article, Critical revision, Approval. Liise K. Kayler: Concept and Design, Data Analysis, Drafting article, Critical revision, Approval.

References 1. Kayler L, Kang D, Molmenti E, Howard R. Kidney transplant ureteroneocystostomy techniques and complications: review of the literature. Transplantation proceedings. 2010;42(5):1413-20. Epub 2010/07/14. 2. Englesbe MJ, Dubay DA, Gillespie BW, Moyer AS, Pelletier SJ, Sung RS, et al. Risk factors for urinary complications after renal transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2007;7(6):1536-41. Epub 2007/04/14. 3. Streeter EH, Little DM, Cranston DW, Morris PJ. The urological complications of renal transplantation: a series of 1535 patients. BJU international. 2002;90(7):627-34. Epub 2002/11/02. 4. Routh JC, Yu RN, Kozinn SI, Nguyen HT, Borer JG. Urological complications and vesicoureteral reflux following pediatric kidney transplantation. The Journal of urology. 2013;189(3):1071-6. Epub 2012/10/02. 5. Zavos G, Pappas P, Karatzas T, Karidis NP, Bokos J, Stravodimos K, et al. Urological complications: analysis and management of 1525 consecutive renal transplantations. Transplantation proceedings. 2008;40(5):1386-90. Epub 2008/07/01. 6. Shoskes DA, Hanbury D, Cranston D, Morris PJ. Urological complications in 1,000 consecutive renal transplant recipients. The Journal of urology. 1995;153(1):18-21. Epub 1995/01/01. 7. Politano VA, Leadbetter WF. An operative technique for the correction of vesicoureteral reflux. The Journal of urology. 1958;79(6):932-41. Epub 1958/06/01. 8. Tavakoli A, Surange RS, Pearson RC, Parrott NR, Augustine T, Riad HN. Impact of stents on urological complications and health care expenditure in renal transplant recipients: results of a prospective, randomized clinical trial. The Journal of urology. 2007;177(6):2260-4; discussion 4. Epub 2007/05/19. 9. Pascual J, Zamora J, Pirsch JD. A systematic review of kidney transplantation from expanded criteria donors. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2008;52(3):553-86. Epub 2008/08/30. 10. Merion RM, Ashby VB, Wolfe RA, Distant DA, Hulbert-Shearon TE, Metzger RA, et al. Deceaseddonor characteristics and the survival benefit of kidney transplantation. JAMA : the journal of the American Medical Association. 2005;294(21):2726-33. Epub 2005/12/08. 11. Saidi R, Kawai T, Kennealey P, Tsouflas G, Elias N, Hertl M, et al. Living donor kidney transplantation with multiple arteries: recent increase in modern era of laparoscopic donor nephrectomy. Arch Surg. 2009;144(5):472-5. Epub 2009/05/20. 12. Troppmann C, Wiesmann K, McVicar JP, Wolfe BM, Perez RV. Increased transplantation of kidneys with multiple renal arteries in the laparoscopic live donor nephrectomy era: surgical technique and surgical and nonsurgical donor and recipient outcomes. Arch Surg. 2001;136(8):897-907. Epub 2001/08/17.

This article is protected by copyright. All rights reserved.

Accepted Article

13. Lich R, Jr., Howerton LW, Davis LA. Childhood urosepsis. The Journal of the Kentucky Medical Association. 1961;59:1177-9. Epub 1961/12/01. 14. Butterworth PC, Horsburgh T, Veitch PS, Bell PR, Nicholson ML. Urological complications in renal transplantation: impact of a change of technique. British journal of urology. 1997;79(4):499-502. Epub 1997/04/01. 15. Salvatierra O, Jr., Kountz SL, Belzer FO. Prevention of ureteral fistula after renal transplantation. The Journal of urology. 1974;112(4):445-8. Epub 1974/10/01. 16. Nane I, Kadioglu TC, Tefekli A, Kocak T, Ander H, Koksal T. Urologic complications of extravesical ureteroneocystostomy in renal transplantation from living related donors. Urologia internationalis. 2000;64(1):27-30. Epub 2000/04/27. 17. Krol R, Ziaja J, Chudek J, Heitzman M, Pawlicki J, Wiecek A, et al. Surgical treatment of urological complications after kidney transplantation. Transplantation proceedings. 2006;38(1):127-30. Epub 2006/03/01. 18. Neri F, Tsivian M, Coccolini F, Bertelli R, Cavallari G, Nardo B, et al. Urological complications after kidney transplantation: experience of more than 1,000 transplantations. Transplantation proceedings. 2009;41(4):1224-6. Epub 2009/05/23. 19. Guerra EE, Didone EC, Zanotelli ML, Vitola SP, Cantisani GP, Goldani JC, et al. Renal transplants with multiple arteries. Transplantation proceedings. 1992;24(5):1868. Epub 1992/10/01. 20. Roza AM, Perloff LJ, Naji A, Grossman RA, Barker CF. Living-related donors with bilateral multiple renal arteries. A twenty-year experience. Transplantation. 1989;47(2):397-9. Epub 1989/02/01. 21. Hsu TH, Su L, Ratner LE, Trock BJ, Kavoussi LR. Impact of renal artery multiplicity on outcomes of renal donors and recipients in laparoscopic donor nephrectomy. Urology. 2003;61(2):323-7. Epub 2003/02/25. 22. Aydin C, Berber I, Altaca G, Yigit B, Titiz I. The outcome of kidney transplants with multiple renal arteries. BMC surgery. 2004;4:4. Epub 2004/03/17. 23. Slagt IK, Ijzermans JN, Visser LJ, Weimar W, Roodnat JI, Terkivatan T. Independent risk factors for urological complications after deceased donor kidney transplantation. PloS one. 2014;9(3):e91211. Epub 2014/03/13. 24. Carter JT, Freise CE, McTaggart RA, Mahanty HD, Kang SM, Chan SH, et al. Laparoscopic procurement of kidneys with multiple renal arteries is associated with increased ureteral complications in the recipient. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2005;5(6):1312-8. Epub 2005/05/13. 25. Dunkin BJ, Johnson LB, Kuo PC. A technical modification eliminates early ureteral complications after laparoscopic donor nephrectomy. Journal of the American College of Surgeons. 2000;190(1):96-7. Epub 2000/01/07. 26. Kuo PC, Cho ES, Flowers JL, Jacobs S, Bartlett ST, Johnson LB. Laparoscopic living donor nephrectomy and multiple renal arteries. American journal of surgery. 1998;176(6):559-63. Epub 1999/02/02. 27. Dinckan A, Tekin A, Turkyilmaz S, Kocak H, Gurkan A, Erdogan O, et al. Early and late urological complications corrected surgically following renal transplantation. Transplant international : official journal of the European Society for Organ Transplantation. 2007;20(8):702-7. Epub 2007/05/22. 28. Duty BD, Conlin MJ, Fuchs EF, Barry JM. The current role of endourologic management of renal transplantation complications. Advances in urology. 2013;2013:246520. Epub 2013/09/12. 29. Alberts VP, Minnee RC, Bemelman FJ, van Donselaar-van der Pant KA, Laguna Pes P, Idu MM. Ureteral reconstruction after renal transplantation: clinical outcome and risk factors. Urologia internationalis. 2012;88(3):333-7. Epub 2012/01/31.

This article is protected by copyright. All rights reserved.

Accepted Article

30. van Roijen JH, Kirkels WJ, Zietse R, Roodnat JI, Weimar W, Ijzermans JN. Long-term graft survival after urological complications of 695 kidney transplantations. The Journal of urology. 2001;165(6 Pt 1):1884-7. Epub 2001/05/24. 31. Gurkan A, Yakupoglu YK, Dinckan A, Erdogdu T, Tuncer M, Erdogan O, et al. Comparing two ureter reimplantation techniques in kidney transplant recipients. Transplant international : official journal of the European Society for Organ Transplantation. 2006;19(10):802-6. Epub 2006/09/12. 32. Nie Z, Zhang K, Huo W, Li Q, Zhu F, Jin F. Comparison of urological complications with primary ureteroureterostomy versus conventional ureteroneocystostomy. Clinical transplantation. 2010;24(5):615-9. Epub 2009/11/21. 33. Riediger C, Muller MW, Bachmann J, Novotny A, Thorban S, Matevossian E, et al. Native ureteropyelostomy: an effective therapy for urinary tract complications following kidney transplantation. ANZ journal of surgery. 2014;84(9):643-8. Epub 2014/01/25. 34. Trilla E, Lorente D, Salvador C, Planas J, Placer J, Celma A, et al. Native ureteropyelostomy in the treatment of obstructive uropathy in adult renal transplant. Experience and technical alternatives. Actas urologicas espanolas. 2014;38(8):552-6. Epub 2014/03/19.

This article is protected by copyright. All rights reserved.

Independent risk factors for early urologic complications after kidney transplantation.

Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). We evaluated traditional and novel poten...
211KB Sizes 0 Downloads 7 Views