Evaluation of Renal Transplantations Performed in the Transplantation Center at Sanko University Medical School E. Uysala,*, O.A. Gurerb, M.F. Yuzbasioglua, H. Guzela, N. Ulutasdemirc, and M. Dokurd a Transplantation Center, bDepartment of General Surgery, Sanko University School of Medicine, cZirve University, Faculty of Health Science, and dDepartment of Emergency Medicine, Sanko University School of Medicine, Gaziantep, Turkey

ABSTRACT Introduction. Renal transplantation is the optimum treatment to improve the quality and length of life in end-stage renal disease. The aim of this study is to evaluate patients who underwent renal transplantation in our transplantation center and to present our clinical experience. Methods. Living donor and cadaveric renal transplants performed in the Transplantation Center of Sanko University Medical School between 2011 and 2014 were evaluated retrospectively. In our study, important parameters, such as delayed graft function, early and late phase infections and urologic complications after the operation, results of renal transplants with marginal donors with high creatinine levels, and increase in posttransplant body mass index were evaluated regarding to the living donor and cadaveric renal transplants performed in our transplantation center. Results. We included 136 patients were (92 males [68%] and 44 females [32%]), with an average age of 38.9  9.8 years (range, 17e67). There were 63 living donor renal transplantations (43%) and 73 cadaveric renal transplantations (57%). The youngest cadaveric donor was 3 years old, and the oldest was 86. Fifteen of the cadaveric donors had blood creatinine levels around 1.5 g/dL. The highest level of creatinine from cadaveric donors was 5.1 g/dL. Conclusions. Living donor renal transplantations have higher success rate than cadaveric renal transplantations. Ureteroneocystostomy and native ureteropyelostomy seem to be safe and efficient treatment methods for ureteral complications. High creatinine levels in marginal donors do not affect graft function in early stages.

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ENAL TRANSPLANTATION is the most optimal treatment method in end-stage renal failure to improve the quantity and quality of life. Allografts are either from cadaveric or living donors. In recent years, there has been an increase in the number of living donor transplantations owing to the limitations in the number of cadaveric kidneys and longer graft functions in the kidneys received from living donors. Some strategies have been developed, such as exchanging donors and ABO-incompatible donors, to increase the number of living donor transplants. In our country, most living donors are relatives of the patients owing to some regulations. As a result of a better understanding of transplant immunology, technologic advances, and a new generation of immunosuppressives, successful renal transplantations can be performed. In our center, which was founded in 2010, renal transplants can be performed both from living and cadaveric

donors. In our study, some significant parameters have been evaluated, such as delayed graft function (DGF), early postoperative infections, transceiver relations, and complications. We sought to evaluate patients who underwent renal transplantation in our center and present our clinical experiences. MATERIAL AND METHODS We evaluated retrospectively living and cadaveric donor renal transplants performed in the Transplantation Center of Sanko

*Address correspondence to Erdal Uysal, MD, Sanko University Transplantation Center, Incilipinar Mah. Ali Fuat Cebesoy Bulv. No: 45 27090, Sehitkamil - Gaziantep, Turkey. E-mail: [email protected]

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0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.03.005

Transplantation Proceedings, 47, 1117e1121 (2015)

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UYSAL, GURER, YUZBASIOGLU ET AL Table 2. Demographics (n [ 136)*

Table 1. Cause of End-Stage Renal Disease Cause

Cadaveric (n)

Living (n)

Variable

FSGS MPGN Hypertension Diabetes IgA nephropathy Other glomerulonephritis Nephrolithiasis Other/unknown

2 2 3 2 5 7 4 48

1 1 4 3 1 6 5 42

Recipient sex Male Female Donor Living Cadaveric Dialysis history Preemptive Peritoneal Hemodialysis

Abbreviations: FSGS, focal segmental glomerulosclerosis; Ig, immunoglobulin; MPGN, membranoproliferative glomerulonephritis.

n (%)

92 (67.6) 44 (32.3) 63 (46.3) 73 (53.6) 26 (19.1) 8 (5.8) 102 (75)

*Recipients were 38.9  9.8 years old (mean  standard deviation).

University Medical School between 2011 and 2014. We evaluated DGF, early and late infections, urologic complications after the operation, results of renal transplants with marginal donors with high creatinine levels, and increase in posttransplant body mass index (BMI), grouped by living versus cadaveric renal transplants. A triple immunosuppressive protocol was used in renal transplant recipients. Antithymocyte globulin (1.5 mg/kg) induction therapy was started and continued for 5e7 days in all cadaveric graft recipients. Tacrolimus (TAC) or cyclosporine, mycophenolate mofetil, and prednisolone were started to maintain immunosuppression. A triple immunosuppressive protocol was started in living donor recipients that included mycophenolate mofetil and prednisolone with TAC or cyclosporine. In addition, basiliximab was added. The initial dosage of TAC was 0.15e0.20 mg/kg per day orally. The medicine was administered twice a day either 1 hour before meal or 2 hours after meal. As target through blood concentration for renal transplantation recipient, 12e15 ng/mL for month 1, 8e12 ng/mL for month 2, 6e10 ng/mL for month 3, and 5e10 ng/mL thereafter were set. Cyclosporine was given to 4 of our diabetic patients owing to uncontrolled hyperglycemia. Cyclosporine was begun in 3 patients owing to hyperglycemia and in 2 patients owing to TAC nephrotoxicity under TAC treatment. Initial dosage for cyclosporine was 10e14 mg/kg per day for the first 2 weeks and 5e10 mg/kg per day as a maintenance dosage. Drug dosages were adjusted according to cyclosporine A blood levels (C2) in the 2 hours after the drug intake. Cyclosporine target blood levels were maintained at C2 > 1500 ng/mL for months 0e3; C2 1200e1400 ng/mL for month 3; 800e1000 ng/ml for months 3e12; and around 600e800 ng/mL thereafter. Mycophenolate mofetil was started within the first 72 hours after renal transplantation. Mycophenolate mofetil was given as 2 daily doses for a total of 2 g/d. Basiliximab was introduced as 20 mg in 2 doses as induction therapy for living donor renal transplantations. The first dose was given 2 hours before renal transplantation and the second at 4 days posttransplantation. Basiliximab was given intravenously in 50 mL of normal saline over 20e30 minutes. Methylprednisolone was started as 15 mg/kg intravenously and reduced gradually. Oral prednisolone was administrated orally as 1 mg/kg on day 4. Patients were discharged with a prednisolone dosage of 20 mg/d; 5 mg/d prednisolone was administered as a maintenance dosage. The data obtained via analysis of the patient files were analyzed using SPSS 16.0 for windows statistical software. The data are presented as mean values  standard deviation. P < .05 was accepted as significant.

RESULTS

We performed renal transplantations on 136 patients with end-stage renal disease (Table 1), including 92 males (67.6%) and 44 females (32.3%), with an average age of 38.9  9.8 years (range, 17e67). We performed 63 living donor renal transplantations (46.3%) and 73 cadaveric renal transplantations (53.6%; Table 2). Among the transplantations, 39 (28.6%) were from first-degree relatives, and 20 (14.7%) were from patients’ wives. The duration of cold ischemia time in cadaveric donors was as 16.9 (range, 9e36 hours). The youngest cadaveric donor was 3 years old, and the oldest was 86. Acute rejection episodes occurred in 3 patients after transplantation and graft nephrectomy was performed. Acute renal vein thrombosis was observed in 1 patient. The patient unresponsive to the treatment underwent graft nephrectomy. The patient with a worsened situation died 6 hours after the renal transplantation. Eight patients (5.9%) had an infection at the early stage after transplantation, the majority being urinary tract infections (Table 3). At a late stage after transplantation 21 patients had gastroenteritis, 6 patients had sinopulmonary infection, and 5 patients had urinary infections. The patients were hospitalized and treated. None of our patients had graft loss owing to infections. Among cadaveric renal transplant recipients, the number of infections and positive cultures developed were significantly higher than living donor transplants (P < .05). The incidence of DGF in cadaveric renal transplantations was significantly higher than living donor transplants (P < .05). The ratio of mismatch was higher in living donors compared with that of cadaveric donors (P < .05). Double-J stent application and vesicoureteral reflux were significantly high in transplants from cadaveric donors (P < .05). Fifteen cadaveric donors had blood creatinine levels around 1.5 g/dL; the highest level of creatinine from cadaveric donors was 5.1 g/dL. When graft functions of the cadaveric renal transplants with normal creatinine levels and the high creatinine levels were compared, the difference was not significant in the first 6 months posttransplantation (P > .05). The BMI of the patients who underwent renal

EVALUATION OF RENAL TRANSPLANTATIONS

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Table 3. DonoreRecipient Matching and Major Clinical Events Variable

Cadaveric

Living

Donor recipient matching HLA-A, -B, -DR total mismatches 2.5  1.2* 3.1  1.6* ABO incompatible 0 0 Major clinical events Acute rejection (n, %) 2 (1.4) 1 (0.7) Infection (n, %) Early 5 (3.6) 1 (0.7) Late 14 (10.2) 7 (5.1) Recurrence original disease (n, %) 1 (0.7) 2 (1.4) PTDM (n, %) 6 (4.4) 5 (3.6) Patient died (n, %) 1 (0.7) 0

P

.032 d >.05 .05 >.05 d

Abbreviation: PTDM, posttransplant diabetes mellitus. *Data was presented as mean  SD.

transplantation were closely monitored. The average BMI before transplantation was 22.52  3.97 kg/m2, it was 24.4  4.1 kg/m2 by month 5, and 25.56  4.14 kg/m2 by month 12 (P < .05). Six patients had ureteral stenosis, and 4 patients had ureteral necrosis. Three of these transplantations were made from living donors (2 females and 1 male), and 7 were from cadaveric donors (1 female and 6 males). All patients had double-J stents and bladder capacities were between 100 and 400 mL. The mean duration between transplantation and manifesting of ureter stenosis was approximately 2 months. Extravasation was found in 4 patients owing to necrosis, all encountered in postoperative week 2. Two patients underwent native ureteropyelostomy and 2 others underwent ureteroneocystostomy for ureteral necrosis. One patient underwent ureteroureterostomy, 4 had ureteroneocystostomy, and 1 had native ureteropyelostomy for stenosis. One patient had postoperative urine leak and underwent native ureteropelvic anastomosis. He was followed conservatively by drainage. DISCUSSION

DGF is a well-known complication of transplantation, and arises frequently after renal transplantation, with a 30% incidence in cadaveric renal transplantations. It leads to increased duration of stay and dialysis requirement after the transplantation. DGF is correlated with ischemic reperfusion injury and immunologic factors [1]. In our study, the incidence of DGF observed after cadaveric renal transplantation was found to be significantly higher compared with the living donor renal transplantation. The frequency of DGF occurrence in living donor renal transplantations varied between 4% and 10%, whereas the variation was between 5% and 50% in cadaveric renal transplantations [2]. In our study, DGF was found in 40% of the cadaveric transplantations, whereas it was observed in 5% of living donor transplantations. Minimizing cold ischemia time is significantly important for DGF and graft survival, especially in cadaveric renal transplantations [3]. In cadaveric transplantations where the

duration of cold ischemia time was 1.5 g/dL are recognized as marginal remains controversial. Our donor with the highest creatinine level had a blood creatinine level of 5.1 g/dL. The recipient of this kidney had his urine volume and creatinine levels back to normal in 12 and 23 days after transplantation, respectively. Thirty cadaveric renal transplantations were performed using both of the cadaveric donor’s kidneys. Graft functions in the kidney recipients at month 6 were normal. When the graft functions in the recipients of each of the kidney pairs were compared at months 1 and 6, no difference was observed (P > .05). The recipients of cadaveric donors who were 3 and 86 years of age had normal graft functions. In our study, urinary infection were observed frequently during the early stages after cadaveric transplantations. Takai et al [5] have also shown that urinary tract infections occur in 28% after cadaveric renal transplantations, and in 23% after living donor transplantations. In our study, development of urinary tract infections was 21% after cadaveric and 11% after living donor transplantations. The high frequency of urinary infections might be owing to long cold ischemia times, donor age, and presence of ureteric stent. Among the complications observed in the later stages, gastroenteritis was most common and respiratory tract infection was the next most common. Cytomegalovirus infections are the most cause of secondary graft loss and mortality after renal transplantation [6]. None of our patients had cytomegalovirus infection. The ratio of mismatch was higher in living donors compared with cadaveric donors in our study. HLA- and ABO-incompatible renal transplantations can be performed successfully with living donors in experienced transplantation centers [7,8]. Therefore, absolute HLA compatibility is not sought for living donors, resulting in an increasing ratio of mismatches. However, in cadaveric donor transplantations, compatibility of any 2 antigens from HLA-B and -DR together with a negative crossmatch, is considered as a sufficient compliance [9]. Six patients had ureteral stricture and 4 patients had ureteral necrosis. Ureteroneocystostomy or native ureteropyelostomy was performed depending on the patient and the cause of the complication. The patient who underwent or native ureteropyelostomy had vesicoureteral reflux and was followed conservatively. Three patients with ureteral complications received allografts from a living donor. Ureteral complications are especially seen after cadaveric renal transplantation (average rate of 2%e20%) [10e12]. However, there are studies showing that urologic complications are seen in lesser ratios (eg, 3%e5%

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[13,14]). In our study, the total urologic complication ratio was 7%. Cadaveric renal transplantations showed higher urologic complication ratios than living renal transplantations. Our total urologic complication rate was consistent with the published literature, but it was a little high. Failure of ureter vascularization and insufficient blood supply are assumed to be responsible for these urologic complications. Excessive dissections near the renal artery and vein may cause vascular damage and subsequent ureteral necrosis. Recipients who develop urologic complications generally receive allografts from older donors, and this may be a reason for high complication rates. Keeping cold ischemia time short, not excessively dissecting the renal pelvis and periureteral tissue in particular, paying attention to anastomosis technique, and controlling rejection by applying suitable immunosuppressive therapy are significant factors in the reduction of urologic complications [14]. Placing a doubleJ stent also provides reducing urologic complications [15]. We routinely used the ureter in cadaveric renal transplantations. It is still a widely controversial issue whether or not a double-J stent is required in renal transplantations. We think that the use of a Double-j stent can decrease complications in cadaveric renal transplantations, kidneys with long cold ischemia times, cases of abnormal bladder (such as neurogenic, small, ureteral injury), and comorbidity in the recipient. We identified renal arterial thrombosis in 1 of our patients by Doppler graft analysis performed in 24 hours after transplantation. Renal function did not improve and the patient underwent surgery. We observed that the transplanted kidney infarcted and applied graft nephrectomy. Acute renal arterial thrombosis is an important complication that can lead to graft loss if not identified and treated immediately [16]. Acute rejection was detected in 3 patients. One had undergone living donor transplantation and the other 2, cadaveric renal transplantation. The patient who underwent living donor transplantation had total HLA compatibility with a negative cross-match. The patient did not respond to rejection treatments and therefore underwent graft nephrectomy. One patient with a cadaveric renal allograft died 6 hours after the operation. Hemodialysis could not be performed owing to problems in intravenous access. The BMI of the patients who underwent renal transplantation were closely monitored. The average BMI before transplantation was 22.52  3.97 kg/m2, 24.4  4.1 kg/m2 by month 6, and 25.56  4.14 kg/m2 month 12 (P < .05). Of the patients with malnutrition problems during the pretransplant period, 68% recovered within the first year. There is a significant increase in patients’ BMI in the first posttransplant year. BMI is relevant to diabetes, hypertension, and allograft nephropathy. BMI should be carefully considered in the follow-up of patients who undergo renal transplantation, and early nutritional changes with dietary and exercise programs should be performed for overweight recipients.

UYSAL, GURER, YUZBASIOGLU ET AL

One patient suffered a major hemorrhage during laparoscopic left donor nephrectomy. Using the same side gonadal vein, the short graft renal artery was lengthened successfully, despite chaos during the emergency. The gonadal vein was reported previously as being used to lengthen the renal vein, but there are not enough data on its use in renal artery lengthening. Graft function was normal in the follow-up of this patient. The findings of this study are consistent with previous studies. We did not have any unique findings during our experience; however, we did not find any negative effects of renal transplantation from marginal cadaver donors with a high creatinine level on graft function in the early posttransplant period. In conclusion, as a result, living donor renal transplantation has a higher success rate than cadaveric renal transplantations. Cold ischemic time should be kept as minimal as possible for better graft survival. High creatinine levels in marginal donors do not affect graft function in early stages. Posttransplant BMI increases were notable. Balanced and appropriate meal plans should be prepared for the patients. Ureteral complications are more observed frequently in cadaveric transplants compared with living donor transplants. Ureteroneocystostomy and native ureteropyelostomy are safe and efficient treatment methods for ureteral complications and can be considered as treatment methods depending on the patient and the cause of the ureteral complication. Multidisciplinary studies should be performed to increase the number of cadaveric and living donor renal transplants. REFERENCES [1] Perico N, Cattaneo D, Sayegh MH, et al. Delayed graft function in kidney transplantation. Lancet 2004;364:1814e27. [2] Sellers MT, Gallichio MH, Hudson SL, et al. Improved outcomes in cadaveric renal allografts with pulsatile preservation. Clin Transplant 2000;14:543e9. [3] Shao MJ, Ye QF, Ming YZ, et al. Risk factors for delayed graft function in cardiac death donor renal transplants. Chin Med J (Engl) 2012;125:3782e5. [4] Warlé MC, Cheung CL, Teerenstra S, et al. Cold ischaemia time and outcome of renal transplantation. Ned Tijdschr Geneeskd 2010;154:B539. [5] Takai K, Tollemar J, Wilczek HE, et al. G Urinary tract infections following renal transplantation. Clin Transplant 1998;12: 19e23. [6] Akalin H. Infectious complications of kidney transplantation. J Surg Med Sci 2006;2:70e8. [7] Dharnidharka VR, Agodoa LY, Abbott KC. Risk factors for hospitalization for bacterial or viral infection in renal transplant recipientsean analysis of USRDS data. Am J Transplant 2007;7: 653e61. [8] Cremaschi E, Maggiore U. Living donor kidney transplantation: new modalities and future directions. G Ital Nefrol 2014;31(4). pii: gin/31.4.12. [9] Becker LE, Süsal C, Morath C. Kidney transplantation across HLA and ABO antibody barriers. Curr Opin Organ Transplant 2013;18:445e54. [10] Praz V, Leisinger HJ, Pascual M, et al. Urological complications in renal transplantation from cadaveric donor grafts: a retrospective analysis of 20 years. Urol Int 2005;75:144e9.

EVALUATION OF RENAL TRANSPLANTATIONS [11] Raman A, Lam S, Vasilaras A, et al. Influence of ureteric anastomosis technique on urological complications after kidney transplantation. Transplant Proc 2013;45:1622e4. [12] Almeida F, Branco F, Cavadas V, et al. Urological complications after 134 pediatric kidney transplants: a single-center study. Transplant Proc 2013;45:1096e8. [13] Davari HR, Yarmohammadi H, Malekhosseini SA, et al. Urological complications in 980 consecutive patients with renal transplantation. Int J Urol 2006;13:1271e5.

1121 [14] Nane I, Kadioglu TC, Tefekli A, et al. Urologic complications of extravesical ureteroneocystostomy in renal transplantation from living related donors. Urol Int 2000;64:27e30. [15] Haberal M, Karakayali H, Sevmis S, et al. Urologic complication rates in kidney transplantation after a novel ureteral reimplantation technique. Exp Clin Transplant 2006;4:503e5. [16] Fallahzadeh MK, Yatavelli RK, Kumar A, et al. Acute transplant renal artery thrombosis due to distal renal artery stenosis: a case report and review of the literature. J Nephropathol 2014;3:105e8.

Evaluation of renal transplantations performed in the Transplantation Center at Sanko University Medical School.

Renal transplantation is the optimum treatment to improve the quality and length of life in end-stage renal disease. The aim of this study is to evalu...
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