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NDT Advance Access originally published online on February 27, 2007
Nephrology Dialysis Transplantation 2007 22(5):1451-1455; doi:10.1093/ndt/gfl771
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Surgical complications and renal function after kidney alone or simultaneous pancreas-kidney transplantation: a matched comparative study

Pedro Gutiérrez1, Domingo Marrero2, Domingo Hernández2, Sofia Vivancos1, Lourdes Pérez-Tamajón2, Jose Maria Rodríguez de Vera1, Antonio Alarcó3 and Jose Manuel González-Posada2

1Department of Urology, 2Department of Nephrology and 3Department of General Surgery, Hospital Universitario Canarias, Tenerife, Spain

Correspondence and offprint requests to: Dr Pedro Gutierrez, Department of Urology, Hospital Universitario de Canarias, Ofra s/n, La Laguna 38320 Santa Cruz de Tenerife, Spain. Email: pegutierrez{at}huc.canarias.org



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. In selected type 1 diabetic (T1DM) patients with end-stage renal disease (ESRD), simultaneous pancreas-kidney transplantation (SPKT) offers higher long-term graft and patient survival, but also higher initial morbidity and mortality than cadaveric kidney transplantation alone (CKTA). The development of new immunosuppressive regimens and surgical approach has improved this initial outcome, but little is known about their effect on short-term renal function and surgical complications related to the renal graft.

Methods. We analysed retrospectively the short-term follow-up of 45 T1DM patients consecutively transplanted during 42 months (20 SPKT and 25 CKTA) in order to compare short-term (6 months) renal allograft function and surgical complications related to the renal allograft in both groups.

Results. There were no differences in donor characteristics. SPKT recipients had a significantly shorter time on dialysis and cold ischaemia time, with a higher number of HLA mismatches. There was no difference in acute rejection incidence, but delayed kidney graft function was less frequent in SPKT (5% vs 32%; P < 0.05). Plasma creatinine level at discharge and 6 months was significantly lower in SPKT (1.1 ± 0.3 vs 1.6 ± 0.7; P < 0.005 and 1.1 ± 0.3 vs 1.5 ± 0.6; P < 0.05, respectively). There were no differences in surgical renal complications (haemorrhage, thrombosis or arterial stenosis, ureter leaks or stricture, lymphoceles or dehiscences). Two SPKT patients needed reintervention on the renal allograft and only one CKTA patient.

Conclusions. In the modern transplant era, SPKT in ESRD diabetic patients, offers a slightly better short-term kidney allograft function without significant increase in surgical morbidity, compared with CKTA.

Keywords: diabetes mellitus; renal transplant; renal function; simultaneous pancreas-kidney transplantation; surgical complications



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Kidney transplantation is considered the treatment of choice for medically suitable patients with end-stage renal disease (ESRD). In type 1 diabetes mellitus (T1DM) patients with ESRD, several options for renal replacement therapies exist including dialysis, kidney transplantation (living or cadaveric donor) and simultaneous pancreas-kidney transplantation (SPKT).

SPKT compared with cadaveric kidney transplant alone (CKTA) is associated with better long-term patient survival [1–4], but with a higher initial overall mortality risk [3] mainly attributed to infection [3,4] and more aggressive surgical procedure. Likewise, long-term kidney allograft survival is higher in SPKT compared with CKTA [2,4], but more favourable donor and recipient factors in SPKT patients may play a role in this fact [5]. Curiously, previous studies from single centre analyses have shown better kidney allograft function, evaluated by plasma creatinine levels or calculated glomerular filtration rate, in CKTA during follow-up [6–10]. In addition, surgical complications of the kidney transplant procedure in SKPT vs CKTA have not been analysed previously.

In the present study, we performed a matched comparison of renal function and surgical complications related to the renal transplant procedure in SPKT vs CKTA, analysed in the modern transplant era.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
The study was conducted at the Hospital Universitario de Canarias, where the cadaveric kidney transplantation programme started in 1982, with around 100 procedures performed every year in the last decade. In 2002 a SPKT programme was initiated including only T1DM patients with ESRD who met the following inclusion criteria: age < 46 years, absence of coronary artery disease, no obesity [body mass index (BMI) < 28 Kg/m2], and no severe peripheral vascular disease. All T1DM patients who met the aforementioned criteria, were requested to be included on the SPKT waiting list, although the final decision was taken by the patient or the physician in charge. At the beginning of the programme, many patients without any contraindication for SPKT preferred to be included on the CKTA waiting list. Selection of SPKT recipients was made by ABO blood group match and time on the waiting list, while CKTA recipient selection was made according to HLA match.

A retrospective review of all T1DM patients with ESRD transplanted in our hospital between January 2001 and September 2004 was performed. In order to avoid donor-recipient age bias between SPKT and CKTA patients, all recipients older than 45 years or receiving a graft from a donor older than 50 years were excluded from the study. Thus, a total of 45 patients were identified: 20 received SPKT and 25 received CKTA. Demographic and clinical characteristics of the donors and recipients were obtained in each case during 6 months of follow-up. Past history of microvascular or macrovascular disease was specially considered. Ischaemic heart disease was defined as myocardial infarction (documented by elevated enzyme levels, with or without electrocardiographic changes), coronary artery revascularization or positive imaging study for ischaemia. Cerebral vascular disease was defined as transient ischaemic attacks with strokes. Peripheral vascular disease was considered with revascularization procedures or amputations [11]. Finally, retinopathy was only considered to determine whether photocoagulation treatment was needed.

All parameters were analysed with respect to the kidney graft evolution, paying special attention to renal function and surgical complications of the kidney transplant procedure. Renal function was measured by plasma creatinine level and calculated glomerular filtration rate (GFR) by the Jelliffe-2 formula that includes only age, sex and plasma creatinine level in mg/dl:


Formula

This formula has an acceptable correlation with true GFR [12].

Surgical complications were classified as (i) vascular (thrombosis and arterial stenosis), (ii) haemorrhage (considered as any haematoma related to the surgical kidney transplant procedure that required reintervention, aspiration or blood transfusion), (iii) urological (ureter stricture and leaks) and (iv) surgical wound complication (lymphocele or dehiscence) as previously defined [13].

Delayed graft function of the kidney was defined as the need for dialysis during the first week after transplantation. Vessel atherosclerosis of the donor or recipient was considered to determine whether it was referred to in the surgical procedure report.

Surgical technique
The CKTA procedure at our centre has been previously described [13]. Briefly, kidneys were placed in either the right or the left iliac fossa using an extra-peritoneal approach by a lateral incision. The renal graft vessels were anastomosed end-to-side to the recipient's external or common iliac vessels. A standard Lich–Gregoir ureteroneocystostomy was performed in all cases.

The SPKT procedure was performed through a midline incision. The pancreas-duodenal graft was placed into the right iliac fossa, with the portal vein anastomosed to the cava vein, and the common iliac artery of the ‘Y’ graft anastomosed to the recipient common right iliac artery. After reperfusion a side-to-side duodenoenterostomy was performed. Second, with the same midline incision, the kidney allograft was placed in the left iliac fossa, using an extra-peritoneal approach, with a termino-lateral anastomosis for the graft vessel and Lich–Gregoire procedure for ureteral anastomosis, similar to the CKTA procedure.

A double-J stent (Medical Engineering Corp., New York, NY) was systematically inserted and removed 1–2 weeks later, both in SPKT and CKTA. In both transplant procedures the kidney transplantation was performed by the same team of surgeons.

Immunosuppressión and other therapy
All SPKT patients received induction therapy using polyclonal antibodies (Thymoglobulin®) (1,5 mg/Kg/day for 7 days), while CKTA patients received the same polyclonal antibodies or monoclonal antibodies (Baxiliximab) (20 mg within 2 h prior to transplant surgery, followed by a second 20 mg dose 4 days after transplantation). The maintenance immunosuppressive regimen consisted of triple therapy with a calcineurin inhibitor, either ciclosporin (CsA) or tacrolimus (to maintain whole blood trough levels of 150–250 ng/ml or 8–12 ng/ml, respectively, during the first 3 months post-transplant), mycophenolate mofetil (MMF) (1 g two times per day), and prednisone (20 mg/day tapered to 10 mg/day by 3 months post-transplant).

All patients received Pneumocystis carinii and cytomegalovirus (CMV) infection prophylaxis with trimethroprim-sulfamethoxazole and ganciclovir for 3 months post-tranplant. SPKT received Vancomycin (1 dose), a cephalosporin (3 days) and fluconazole (4–6 weeks) while CKTA received only a cephalosporin (3 days).

All SPKT received anticoagulation therapy with low molecular weight heparin during in-patient hospitalization. In the CKTA there was no routine use of postoperative anticoagulation therapy unless clearly medically or surgically indicated.

Statistical analysis
All continuous variables are reported as mean ± SD, and comparisons between SPKT and CKTA were performed by non-parametric statistical test (Mann–Whitney U– test). Comparisons between categorical variables were performed with the chi-square test or Fisher-exact test as appropriate. All computations were performed using SPSS 12.0 (Chicago IL USA). Probability values of <0.05 were considered significant.

This study was approved by the Ethics Committee of the University Hospital of the Canary Islands and was conducted in accordance with the Declaration of Helsinki. Medical record review was performed according to Spanish law regulating the confidentiality and protection of clinical data.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
Donor and recipient characteristics
From January 2001 to September 2004, a total of 402 kidney transplantations were performed at our centre. T1DM was the primary disease in 51 patients, six patients being excluded because the donor or recipient was older than 45 and 50 years, respectively. Thus, we studied 45 diabetic patients, 20 SPKT and 25 CKTA recipients.

Table 1 shows the demographic and clinical characteristics of both groups. There were no differences in donor characteristics. Recipients of SPKT had shorter time on dialysis, and shorter cold ischaemia time, as well as fewer total HLA matches. Dialysis modality (haemodialysis or peritoneal dialysis) was similar in both groups, but preemptive transplantation was performed only in SPKT. Past history of micro-angiopathy or macroangiopathy was also similar in both groups. No patients presented symptomatic pre-transplant ischaemic heart disease. Previous anti-aggregation therapy was more frequently used in SPKT recipients. Induction therapy with polyclonal antibodies was more frequently used in SPKT patients, while ciclosporin therapy was more frequent in CKTA patients.


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  		Table 1. Demographic and clinical characteristics of SPKT and CKTA recipients

 
Post-transplant course
Post-transplant course characteristics are showed in Table 2. Delayed graft function was significantly lower in SPKT. The incidence of acute rejection was higher in the SPKT recipients, but the difference was not statistically significant. Interestingly, the plasma creatinine level at discharge and at 6 months was significantly lower in SPKT patients. In the same way, the calculated GFR was significanty higher in SPKT than CKTA at discharge and at 6 months. When only patients under tacrolimus therapy were analysed, similar results were found, that is, SPKT patients (n = 20) showed a lower plasma creatinine level than CKTA (n = 7), but it was only statistically signifi-cant at discharge (1.1 ± 0.3 vs 1.9 ± 0.5 mg/dl; P < 0.001 and 1.1 ± 0.3 vs 1.5 ± 0.6 mg/dl; P = NS). Hospitalization time was similar in both groups. At 6 months, one kidney had been lost in the CKTA group (acute rejection), and one in the SPKT (patient death with delayed kidney graft function and sepsis). Only one patient in the SPKT group lost the pancreas graft. One death occurred in the SPKT group (sepsis) compared with none in the CKTA group.


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  		Table 2. Post-transplant course characteristics in SPKT and CKTA recipients

 
Surgical complications
No significant differences were observed in surgical complications according to kidney transplant procedure between the two groups during follow-up (Table 3). However, surgical wound complications (lymphocele and dehiscence) appeared only in the SPKT group. In this group, two patients had re-operations in the renal allograft (1 haemorrhage, 1 arterial stricture), while only one CKTA patient did (haemorrhage).


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  		Table 3. Surgical complications related to the kidney transplantation

 


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
The present study of T1DM patients with ESRD found that SPKT patients showed better short-term renal graft function, evaluated by plasma creatinine levels and calculated GFR, than CKTA patients. This fact is of considerable importance since short-term plasma creatinine values are associated with survival rates in this patient population. In renal transplantation, plasma creatinine is considered an independent predictor of graft loss and/or patient death [14,15]. In SPKT this has been less evaluated; however, in the largest single-centre study reported to date, Becker et al [2] observed that a high plasma creatinine value at discharge was the only factor associated with increased mortality in T1DM patients receiving SPKT as compared with CKTA.

In contrast to our study, other single-centre studies have found similar or worse graft function in diabetic ESRD patients who received SPKT as compared with those who received CKTA [6–10]. This has been related to diverse factors such as higher incidence of acute rejection [7,8], higher doses of calcineurin inhibitors [8], and greater nephrotoxicity of calcineurin inhibitors in SPKT with bladder drainage as a consequence of dehydration [10]. In our study, the acute rejection rate was similar in both groups, as was steroid-responsive rejection rate, despite the worse HLA compatibility observed in the SPKT group. It is plausible that more potent immunosuppression in SPKT patients (tacrolimus vs CsA) may help explain this. In this respect, Lee et al. [6] observed better calculated creatinine clearance in SPKT patients who received tacrolimus plus MMF, as compared with CsA plus azatioprine and tacrolimus plus azathioprine. In addition, SPKT was performed with enteric drainage in all cases in our study, and calcineurin inhibitor values were similar to those in the CKTA group (Data not shown). Finally, a shorter cold ischaemia time in SPKT recipients and a lower acute tubular necrosis rate may have contributed to a better allograft renal function at discharge and 6 months later [16].

In some large database studies the improvement in graft survival has been associated with donor- and receptor-related factors [5], while others have shown that survival is maintained even after adjusting for demographic and graft function variables [4,17]. It may be speculated that in cases with similar donor/receptor demographic data, SPKT offers advantages in patient and graft survival due to better glycaemic control. In favour of this idea is the observation of differences in survival shown by SPKT patients with loss of pancreas graft function vs those without such loss. [4].

In our study of diabetic renal transplant patients, we did not find more surgically related complications in the SPKT group as compared with CKTA, despite the fact that SPKT is a more complex procedure. Although surgical wound complications (lymphocele and dehiscence) were only detected in SPKT, the scarce number of cases made it impossible to arrive at any conclusion. Whether a better short-term renal function and decreased acute tubular necrosis rate in SPKT may play a role in these results deserves to be proven. In any case, acute tubular necrosis has been previously associated with major surgical complications, especially vascular and haemorrhagic complications [13].

The present study has certain limitations: it is a retrospective study of a small number of cases with all that it implies, but we have applied age restrictions to donors and recipients trying to minimize the possible differences. Our SPKT program was initiated relatively recently, which may imply a more careful selection of donor-recipient pairs; however, past-history of macro- or microvascular disease was similar in both groups. In addition, this also should be balanced by the inherent learning curve. SPKT patients possibly received more effective immunosuppression, but this may be counterbalanced by the worse compatibility they presented. CKTA patients had greater time on dialysis, but there is no significant correlation between time on dialysis and renal function at discharge or at 6 months (data not shown). In any case, a prospective study with a larger number of patients and longer follow-up is required to confirm these results.

We conclude that in patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney transplantation, despite involving a more aggressive surgical procedure and worse HLA compatibility, offers a slightly better short-term renal function without significantly greater surgical complications which could favour long-term patient and graft survival.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Smets YFC, Westendrop RGJ, Van de Pijl JW, et al. (1999) Effects of simultaneous pancreas-kidney transplantation on mortality of patients with type 1 diabetes mellitus and end stage renal failure. Lancet 353:1915–1919.[CrossRef][ISI][Medline]
  2. Becker BN, Brazy PC, Becker YT, et al. (2000) Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease. Kidney Int 57:2129–2135.[CrossRef][ISI][Medline]
  3. Ojo AO, Meier-Kriesche HU, Hanson JA, et al. (2001) The impact of simultaneous pancreas-kidney transplantation on long term patient survival. Transplantation 71:82–90.[CrossRef][ISI][Medline]
  4. Reddy KS, Stablein D, Taranto S, et al. (2003) Long term survival following simultaneous kidney-pancreas transplantation alone in patients with type 1 diabetes mellitus and renal failure. Am J Kidney Dis 1:464–470.
  5. Bunnapradist S, Cho YW, Cecka M, Wilkinson A, Danovitch M. (2003) Kidney allograft and patient survival in type 1 diabetes mellitus of cadaveric kidney alone vs simultaneous pancreas/kidney transplants: a multivariate analysis of the UNOS database. J Am Soc Nephrol 14:208–213.[Abstract/Free Full Text]
  6. Lee CM, Scandling JD, Krieger NR, Dafoe DC, Alfrey EJ. (1997) Outcomes in diabetic patients after simultaneous pancreas-kidney vs kidney alone transplantation. Transplantation 64:1288–1294.[CrossRef][ISI][Medline]
  7. Douzdjian V, Bunke CM, Uber L, Rajagopalan PR. (1998) Assessment of function and survival as measures of renal graft outcomes following kidney and kidney-pancreas transplantation in type 1 diabetics. Clin Transplant 12:93–98.[ISI][Medline]
  8. Hricik DE, Phinney MS, Weigel KA, Knauss TC, Schulaki JA. (1997) Long-term renal function in type 1 diabetics after kidney or kidney-pancreas transplantation. Transplantation 64:1283–1288.[CrossRef][ISI][Medline]
  9. La Roca E, Fiorina P, Di Carlo V, et al. (2001) Cardiovascular outcomes after kidney-pancreas and kidney-alone transplantation. Kidney Int 60:1964–1971.[CrossRef][ISI][Medline]
  10. Rerolle JP, Thervet E, Anglicheau D, et al. (2002) Long-term renal allograft outcomes after simultaneous kidney and pancreas transplantation. Nephrol Dial Transplant 17:905–909.[Abstract/Free Full Text]
  11. Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. (1996) Cardiovascular disease after transplantation. J Am Soc Nephrol 7:158–165.[Abstract]
  12. Bosma RJ, Doorenbos CR, Stegeman CA, van der Heide JJ, Navis G. (2005) Predictive performance of renal function equations in renal transplant recipients: an analysis of patient factors in bias. Am J Transplant 5:2193–2203.[CrossRef][ISI][Medline]
  13. Hernandez D, Rufino M, Armas S, et al. (2006) Retrospective analysis of surgical complications following cadaveric kidney transplantation in the modern transplantera. Nephrol Dial Transplant 21:2908–2915.[Abstract/Free Full Text]
  14. Hariharan S, McBride MA, Chenskh WS, et al. (2002) Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 62:311–318.[CrossRef][ISI][Medline]
  15. Meier-Kriesche HU, Baliga R, Kaplan B. (2003) Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation 75:1291–1295.[CrossRef][ISI][Medline]
  16. Quiroga I, McShane P, Koo DD, et al. (2006) Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant 21:1689–1696.[Abstract/Free Full Text]
  17. Israni AK, Feldman HI, Propert KJ, Leonard M, Mange KC. (2005) Impact of simultaneous kidney-pancreas transplant and timing of transplant on kidney allograft survival. Am J Transplant 5:374–382.[CrossRef][ISI][Medline]
Received for publication: 25. 9.06
Accepted in revised form: 28.11.06


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This Article
Right arrow Abstract Freely available
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