Over a 23-year period, our center performed 82 renal retransplants in prior simultaneous pancreas–kidney recipients with functioning pancreatic allografts. All patients were insulin-independent at retransplantation. We aimed to quantify the risk of returning to insulin therapy and to identify factors that predispose patients to pancreatic allograft failure after renal retransplantation. Among these 82 patients, pancreatic allograft survival after renal retransplantation was 78%, 49% and 40% at 1, 5 and 10 years. When analyzing risk factors, we unexpectedly found no clear relationship between the cause of primary renal allograft failure, hemoglobin A1c (HbA1c) or fasting C-peptide level at retransplant and subsequent pancreatic allograft failure. An elevated HbA1c in the month after renal retransplant correlated with subsequent pancreatic graft loss and patients experiencing pancreatic graft loss were more likely to subsequently lose their renal retransplant. Although it is difficult to prospectively identify those patients who will return to insulin therapy after repeat renal transplantation, the relatively high frequency of this event mandates that this risk be conveyed to patients. Nonetheless, the survival benefit associated with renal retransplantation justifies pursuing retransplantation in this population.
The improved success rates in pancreas transplantation encountered after the introduction of bladder drainage, calcineurin inhibitors and University of Wisconsin solution in the mid-1980s led to a marked increase in the number of transplants performed worldwide (1). Consequently, centers have been increasingly called on to evaluate patients for retransplantation. It is not uncommon for patients to present with failure of either the pancreas or the kidney while retaining adequate function of the other allograft. A few small studies have addressed the topic of retransplantation in prior simultaneous pancreas–kidney (SPK) recipients. Thus far, such studies have investigated the outcomes of pancreas retransplantation (2–8), the technical challenges of renal retransplantation (9) or retransplantation in the event of BK virus-induced renal allograft loss (10,11). As insulin is cleared by the kidney (12), renal retransplantation may unmask a poorly functioning pancreatic allograft. It is therefore intuitive that renal retransplantation may be associated with subsequent pancreatic allograft loss, but thus far published reports describing the incidence of pancreatic allograft failure after renal retransplantation have been limited to small case series (13,14). Furthermore, factors predictive of pancreatic allograft failure after renal retransplantation have not been determined. Such information would be valuable in the preoperative counseling of patients and operative decision-making. We analyzed a large series of prior SPK recipients undergoing repeat renal transplantation in an effort to determine the effects of renal retransplantation on a functioning pancreatic allograft.
Materials and Methods
A retrospective review of all adult renal retransplantations in prior SPK recipients with functioning pancreatic allografts (n = 82) performed between January 1, 1988 and December 31, 2008 was conducted using the University of Wisconsin prospectively collected transplant database. The study was conducted under Institutional Review Board approval. Pancreatic allografts were determined to be functional at the time of renal retransplantation if patients maintained fasting normoglycemia without exogenous insulin therapy. Four patients on oral antihyperglycemic agents were included in the analysis. Survival outcomes in the 82 retransplant recipients were compared to a contemporaneous group of primary SPK recipients (n = 1000).
The primary outcomes of interest were patient, renal allograft (retransplant) and pancreatic allograft (primary transplant) survival, with secondary endpoints focused on determining which preoperative factors were predictive of subsequent pancreatic allograft loss. Pancreatic allograft loss was defined as permanent (>6 months) return to exogenous insulin use or death with a functioning graft. Renal allograft failure was defined as a return to dialysis or death with a functioning graft.
The immunosuppressive regimen used in renal retransplantation evolved over time as novel immunosuppressants were introduced. Induction therapy was used in all but four instances. A variety of agents, including basiliximab (Simulect; Novartis, Basel, Switzerland, n = 23), alemtuzumab (Campath-1H; ILEX, San Antonio, TX, USA, n = 20), antithymocyte globulin (Thymoglobulin; Genzyme, Cambridge, MA, USA n = 15), muromonab (OKT3; Ortho Biotech Products, Bridgewater, NJ, USA n = 9), antithymocyte globulin (ATGAM; Pharmacia/Upjohn, Peapack, NJ, USA n = 8), Minnesota antilymphocyte globulin (University of Minnesota, n = 2) and daclizumab (Zenapax; Roche, Basel, Switzerland n = 1) were used. The present regimen consists of basiliximab for lower risk recipients and antithymocyte globulin for highly sensitized recipients.
All patients received dexamethasone or methylprednisolone at the time of renal retransplantation and maintenance therapy consisted of an antiproliferative agent, a calcineurin inhibitor and low-dose steroids. In the earlier years, azathioprine (Imuran; GlaxoSmithKline, London, UK) and cyclosporine A (Sandimmune; Sandoz, Holzkirchen, Germany) were used. Azathioprine was replaced by mycophenolate mofetil (CellCept; Roche) in 1995 and later mycophenolic acid (Myfortic, Novartis). Sandimmune was replaced by Neoral (Novartis) and then by tacrolimus (Prograf; Astellas, Tokyo, Japan). Our current maintenance immunosuppressive regimen consists of mycophenolic acid, tacrolimus and low-dose prednisone. Prednisone is tapered during the transplant hospitalization to 30 mg/day. This dose is tapered further over the first postoperative months to a baseline of 5–10 mg/day.
In the majority of cases, cytomegalovirus (CMV) prophylaxis consisted of valganciclovir for CMV-negative recipients of CMV-positive donor organs and those patients undergoing thymoglobulin induction and acyclovir for all other donor–recipient combinations for 3 months. Trimethoprim/sulfamethoxazole 160 mg/800 mg daily for 1 year was used for pneumocystis jiroveci prophylaxis. Mucosal candidiasis prophylaxis was with oral nystatin or clotrimazole tablets for 3 months.
Standard CDC cross-matching was used throughout the study period. Fasting C-peptide levels were captured from 1999 onward and determined by a quantitative chemiluminescent immunoassay by the same referral lab. The normal C-peptide reference range was 0.8–3.5 ng/mL. Clinical practice varied somewhat and not all practitioners followed C-peptide levels in patients with functioning pancreatic allografts. Hemoglobin A1c (HbA1c) levels were determined more reliably from 1991 onward and all levels were determined at our center with a normal reference range of 4.3–6.0%. The majority of patients without HbA1c values were transplanted in the earliest era.
Renal allograft biopsies were performed in patients with a creatinine elevated at least 20% above baseline and pancreas allograft biopsies were performed in patients with unexplained amylase or lipase elevations and/or hyperglycemia. All biopsies were scored using hematoxylin and eosin staining. Scoring systems evolved over time (15–17), but presently renal and pancreas biopsies are evaluated by the Banff Criteria (18,19). C4d staining to diagnose antibody-mediated rejection was introduced in 2002 for renal allograft biopsies and in 2006 for pancreas allograft biopsies. The method of recording graft loss evolved with changes in clinical practice. Chronic rejection was recorded as a clinical diagnosis in the early era and was confirmed histologically from 1990 onward. Although calcineurin-inhibitor toxicity may have contributed to graft loss, calcineurin inhibitors were generally weaned as renal function declined and calcineurin-inhibitor toxicity was not recorded as the primary cause of graft loss in any cases.
Rates of rejection, rates of infection and patient and graft survival were estimated by Kaplan–Meier analysis. Group comparisons were performed by a log-rank test. Factors potentially associated with pancreatic allograft loss after renal retransplantation were assessed using a Cox proportional hazards model. Statistical analysis was performed with SAS software. p- Values <0.05 were considered significant.
Technique of retransplantation
Retransplantation was performed by a midline incision. Fifty patients underwent nephrectomy of their prior allograft, either preoperatively (n = 5) or during the retransplant (n = 45). Preoperative nephrectomy was performed for a symptomatic, but nonfunctional allograft. In cases in which transplant nephrectomy was performed at the time of renal retransplantation, nephrectomy permitted additional space for the retransplant as well as provided the option to use the prior allograft vessels for implantation of the new renal allograft. The renal retransplant was most commonly implanted by anastomosing the vessels of the new kidney to the left external iliac vessels using standard techniques. In cases in which the failed renal allograft was left in place, any suitable portion of the iliac system was used. Typically, primary renal allografts were implanted on the left common iliac artery and vein. This typically left the external vessels available for repeat renal transplantation. In the case of patients undergoing concomitant transplant nephrectomy, the vessels of the prior renal allograft provided another potential site. Although many technical aspects of the repeat renal transplantation were not captured in the database, conserving the renal vein from the original renal transplant does expand drainage options for the repeat renal allograft. In our recent report of nine repeat SPK transplantations in prior SPK recipients, the renal vein was used for drainage of the repeat renal allograft in three cases. This technique can be helpful as dissecting a previously accessed left iliac vein can be technically challenging given its deeper location within the pelvis20.
In some cases, dense adhesive scar tissue precluded either technique and any portion of the iliac system that could be readily dissected was used. The ureter was implanted into the bladder using a standard Lich ureteroneocystostomy technique.
Mean follow-up after renal retransplantation was 5.6 ± 4.8 years. Mean follow-up from the original SPK was 13.6 ± 5.4 years.
Recipient and donor demographics
Cases were distributed throughout the study period as shown in Figure 1. As would be expected given the typical half-life of deceased donor renal transplants, the primary SPK operations in patients who subsequently underwent renal retransplantation occurred at greatest frequency in the first half of the study period and renal retransplantations tended to occur in the latter half. Characteristics of recipients and renal retransplant allograft donors are shown in Tables 1 and 2, respectively. The exocrine drainage technique used for the pancreatic allograft was bladder drainage in 72% (n = 59) of patients. Forty-one percent (n = 34) of patients were preemptively retransplanted. Of the 59% of patients who resumed dialysis before renal retransplantation, the vast majority were maintained on hemodialysis (n = 46), with only two patients undergoing peritoneal dialysis. The mean time to resumption of dialysis was 7.7 ± 4.8 years (range: 0–21.9 years) and dialysis was resumed for a mean of 1.0 ± 1.2 years (range: 0–5.3 years). Renal allografts were obtained from living-related (n = 28), living-unrelated (n = 22) or deceased (n = 32) donors, with a mean donor age of 43 years. No effort was made to either match or avoid the same HLA typing as the original SPK donor. Mean HLA mismatches to the SPK donor were 4.6 ± 1.1 and to the renal retransplant donor were 3.1 ± 1.8.
Table 1. Recipient demographics
43.8 ± 8.2
24.5 ± 4.3
Time since SPK (years)
8.1 ± 5.3
Change in BMI since SPK (kg/m2)
1.0 ± 3.3
Duration of diabetes (years)
31.4 ± 7.9
Peak PRA (%)
11.0 ± 17.7
HLA mismatches to SPK donor (n)
4.6 ± 1.1
HLA mismatches to renal donor (n)
3.1 ± 1.8
5.6 ± 1.0
7.1 ± 5.3
Exocrine drainage of pancreatic allograft
Table 2. Renal retransplant donor demographics
42.7 ± 12.5
Gender (Not recorded, n = 4)
Race (Not recorded, n = 50)
Secondary renal donor type
Donation after brain death
Donation after cardiac death
The mean time to renal retransplantation was 8 years.
Cause of primary renal allograft loss
In this group of SPK recipients who underwent renal retransplantation with functioning pancreatic allografts, the 1-, 5- and 10-year survival of the original renal allograft was 85%, 67% and 30%. Not unexpectedly, the overall renal allograft survival in all primary SPK recipients in our center is significantly higher than that seen in our cohort of SPK patients undergoing renal retransplantation with a functioning pancreatic allograft (91%, 81% and 65% at the same time points, p = 0.02; Ref. 8). The causes of original renal allograft loss were chronic rejection (n = 61), acute rejection (n = 6), renal vein thrombosis (n = 3), infection (n = 3), primary nonfunction (n = 2), renal artery thrombosis (n = 1), ureteral leak (n = 1), recurrent disease (n = 1), noncompliance (n = 1) and unknown (n = 3). Table 3 shows the primary causes of failure of the first renal allograft in the 82 subjects.
Table 3. Primary cause of first renal allograft loss
Cause of primary renal graft loss
Renal vein thrombosis
Renal artery thrombosis
Pancreatic allograft survival
The pancreatic allograft survival (from the time of the original SPK) in the selected group of patients undergoing renal retransplantation with a functioning pancreatic allograft was 98%, 89% and 74% at 1, 5 and 10 years. This compares to an overall primary SPK pancreatic allograft survival rate of 88%, 77% and 64% in our center at the same time points. The artificially improved survival seen in the initial years in the group of patients selected to undergo repeat renal retransplantation with a functioning pancreatic allograft is expected. However, the survival of the pancreatic allograft from the time of renal retransplantation was only 78%, 49% and 40% at the same time intervals (Figure 2). During the first year after renal retransplantation, a steep decline in pancreatic allograft survival is noted and this relatively rapid decline then stabilizes. This survival rate does not account for the time since the original SPK transplantation. After renal retransplantation, 39 patients (48%) returned to insulin use during the study period. Primary causes of pancreatic allograft loss were chronic rejection (n = 20), death with a functioning graft (n = 11), anastomotic leak (n = 2), graft thrombosis (n = 1), insulin resistance (n = 2), pancreatitis (n = 1) and unknown (n = 2). The two cases of anastomotic leakage occurred in the period immediately after renal retransplantation.
Using a Cox proportional hazards model, we evaluated whether pancreas allograft loss after renal retransplantation correlated with age at retransplant, gender, race, BMI, duration of diabetes, time between SPK and retransplantation, change in BMI between SPK and retransplantation, preemptive renal retransplantation, enteric drainage of the pancreas allograft, donor age, donor gender, donor race, type of renal retransplant donor organ (living vs. deceased donor), induction agent, maintenance immunosuppression, panel reactive antibody (PRA) at the time of SPK, peak PRA before renal retransplantation, cause of primary renal allograft failure and complications after renal retransplantation. None of these features/characteristics were predictive of subsequent pancreatic allograft loss in this study.
Factors related to the original renal allograft did not seem to affect subsequent pancreatic allograft survival. There was no association between the length of survival (treated as a continuous variable) of the original renal allograft and subsequent pancreatic allograft failure (p = 0.98). Furthermore, although 67 primary renal allografts were lost secondary to immunologic (vs. technical or other) causes, this did not correlate with pancreatic allograft loss (p = 0.20). Although transplant nephrectomy is a plausible risk factor for sensitization, transplant nephrectomy of the primary allograft was not associated with subsequent pancreatic allograft loss in our cohort (p = 0.28).
Renal retransplant graft survival
After renal retransplantation, survival of the repeat renal allograft was 85%, 68% and 60% at 1, 5 and 10 years. Causes of graft loss were death with a functioning graft (n = 13), acute rejection (n = 6), chronic rejection (n = 6), hyperacute rejection (n = 1), renal artery stenosis (n = 1) and other (n = 3). This compares favorably to the overall adult deceased donor repeat renal allograft survival rate over the same time period in our center, which is 75%, 60% and 39% at the same time points (p = 0.03), as well as to reports from other centers (21–23).
Loss of the pancreatic allograft after renal retransplantation was associated with subsequent loss of the renal allograft (HR: 2.6, p = 0.02).
Patient survival after renal retransplantation was 92%, 77% and 71% at 1, 5 and 10 years. Causes of death were infection (n = 8), cerebrovascular infarction (n = 2), myocardial infarction (n = 2), gastrointestinal bleed (n = 2), respiratory arrest (n = 1) and unknown (n = 4). Overall SPK patient survival in our center was 97%, 89% and 80% at the same time points. Decreased patient survival after retransplantation would be expected given that an average of 8 years elapsed between the original SPK and the renal retransplant.
Patient and graft survival by era
Overall primary SPK patient, pancreatic allograft and renal allograft survival, when analyzed by 5-year era, was similar across eras (data not shown) and compares favorably to more recent SPK 1 year renal allograft survival noted in the Scientific Registry of Transplant Recipients (SRTR) from 1998 to 2004 (91–92%; Ref. 24). The 82 patients undergoing renal retransplantation with a functioning pancreatic allograft would be expected to have lower primary renal allograft survival as compared to our overall cohort as this group has been selected for those who have lost their primary renal allograft.
C-peptide and HbA1c
The fasting C-peptide level before renal retransplantation was available in 42 patients. A subset analysis in these patients was unable to correlate a C-peptide level less than 3.5 ng/mL before retransplantation with subsequent pancreas allograft loss (p = 0.14). In addition, no correlation with pancreas allograft loss was demonstrated when fasting C-peptide values were analyzed as continuous variables (p = 0.21). Twenty-five patients had C-peptide levels determined upon resumption of insulin therapy. All of these patients had detectable C-peptide and only two patients had levels less than <1 ng/mL.
HbA1c values were available before renal retransplantation in 56 patients. In a subset analysis of these patients, a HbA1c value greater than 5.9% (normal < 6.0%) at the time of renal retransplant was not predictive of subsequent pancreatic allograft failure (p = 0.45). A similar analysis using HbA1c as a continuous variable likewise was unable to correlate preoperative HbA1c levels with subsequent pancreas allograft survival (p = 0.52). On the other hand, an elevated HbA1c level (treated as a continuous variable) at 1 month after renal retransplantation was predictive of subsequent pancreatic allograft failure (HR: 2.42, p = 0.002). C-peptide levels at this point were not predictive.
Table 4 shows both fasting C-peptide and HbA1c levels before renal retransplantation for patients with and without pancreatic allograft function at 1 year. Patients that did not survive for at least 1 year after renal retransplantation or who did not have 1 year of follow-up data at the time of analysis, were excluded.
Table 4. Fasting C-peptide and HbA1c levels before renal retransplantation for patients with and without pancreatic allograft function at 1 year (patients with survival and follow-up ≥1 year after renal retransplantation)
Pancreatic function <1 year
Pancreatic function ≥1 year
7.3 ± 6.5, n = 9
7.1 ± 5.7, n = 25
5.4 ± 0.87, n = 10
5.3 ± 0.73, n = 37
No difference was noted in either pancreas, renal or repeat renal allograft survival between eras in which C-peptide and HbA1c testing were reliably performed.
Twenty-nine patients experienced at least one episode of pancreatic allograft rejection before subsequent renal retransplantation. We observed a possible correlation between the number of pancreatic allograft rejection episodes occurring before renal retransplantation and subsequent pancreatic allograft loss, but this did not reach statistical significance (p = 0.18; Figure 3). Overall, 17 of 39 patients who lost their pancreatic allograft had at least one episode of rejection before renal retransplantation. Of these patients, 4 (24%) expired with a functioning graft and 10 (59%) lost their graft from immunologic causes (other causes: thrombosis n = 1, pancreatitis n = 1, unknown n = 1). Twenty-two of 53 patients without any episodes of pancreatic allograft rejection before retransplantation subsequently experienced loss of their pancreatic allograft. Of these, 7 (32%) expired with a functioning graft and 10 (45%) lost their graft from immunologic causes (other causes: pancreatic leak n = 2, insulin resistance n = 2, unknown n = 1).
Although there may be a slight trend towards worse pancreatic allograft survival after renal retransplantation if the patient had experienced a prior episode of pancreatic allograft rejection, we did not observe a correlation between pancreatic allograft survival and prior episodes of renal allograft rejection. That is, pancreatic allograft survival after renal retransplantation was not dependent on whether the patient had experienced a defined prior rejection episode involving the first renal allograft (p = 0.99). Furthermore, immunologic causes of failure of the first renal allograft, including acute, chronic and hyperacute rejection were not predictive of pancreatic allograft function after renal retransplantation (p = 0.41).
Perioperative and postoperative complications after both primary SPK and repeat renal transplantation
Complications associated with the original operation, including reoperative complications (p = 0.90) and length of stay (p = 0.67) were not predictive of pancreatic allograft loss after renal retransplantation. Furthermore, there was no association between postoperative intra-abdominal infectious complications and subsequent pancreatic allograft loss after retransplantation (p = 0.99). In addition, we were unable to detect a correlation between episodes of clinically diagnosed transplant pancreatitis after the original SPK and pancreatic allograft loss after renal retransplantation (p = 0.24).
Several additional posttransplant factors which might arise after renal retransplantation and which could impact pancreatic allograft function or survival were also examined. There was no noted correlation between BK virus infection (diagnosed on biopsy, urine cytology and/or blood or urine PCR), CMV viremia or episodes of pancreas rejection after repeat renal transplantation and subsequent pancreatic allograft loss. The relatively small numbers of patients experiencing these events, as well as the time-varying covariant nature of the analysis, complicates meaningful interpretation of these factors.
Oral antihyperglycemic agents
There was no association between the use of oral antihyperglycemics before renal retransplantation and subsequent pancreatic allograft loss (p = 0.14), although the number of patients on oral antihyperglycemic agents was small in our study (n = 4). Two of these patients were initiated on insulin immediately after renal retransplantation and the other two did not require insulin therapy during the study period. These four patients had partial pancreatic allograft function before renal retransplantation, with demonstrable fasting C-peptide. Patients were monitored for hypoglycemia upon institution of oral antihyperglycemics and short-acting insulinotropic agents were used when possible. These patients were included in the study, as they did not require exogenous insulin at the time of renal retransplantation.
Immunosuppression after repeat renal transplantation
The majority of patients were maintained on tacrolimus after renal retransplantation (n = 52), with fewer (n = 24) patients on cyclosporine and six on a calcineurin-inhibitor avoidance regimen. There was no difference in pancreatic graft loss when analyzed by type of calcineurin inhibitor used for maintenance immunosuppression (p = 0.47).
We have accumulated more than 25 years of experience with simultaneous pancreas and kidney transplantation, having now performed more than 1000 primary SPK transplants. Despite this large series, retransplantation in this patient population remains a relatively uncommon occurrence. Asymmetric rejection leading to graft loss of one organ, while retaining function of the other, occurs even less commonly.
As clinicians evaluate patients for retransplantation, the decision to offer renal retransplantation alone as compared to a repeat SPK is difficult if the patient remains insulin free, as there are no major studies tracking the effect of renal retransplantation on a functioning pancreatic allograft. Pancreatic function is rather granular and the degree of “normal” graft function that is required to maintain euglycemia in the unstressed state is variable among different patients and depends both on graft quality and on numerous metabolic factors in the recipient. Presumably, a marginal graft may be able to maintain normoglycemia, particularly in patients with renal failure and poor insulin clearance. Despite adequate glycemic control pretransplant, renal retransplantation introduces a number of stressors to recipients which may challenge euglycemia and lead to recurrence of insulin dependency. Higher doses of glucocorticoids after renal retransplantation, changes to calcineurin-inhibitor therapy and increased clearance of insulin by a well-functioning renal allograft may unmask marginal pancreatic allograft function and/or worsen insulin resistance, even in the absence of technical complications from the retransplant procedure. The presence of detectable C-peptide at the resumption of insulin therapy suggests that the failure of the pancreatic allograft may, in fact, be partly because of relative insulin deficiency and insulin resistance.
In our overall center experience with primary SPK transplantation, there is an initial, relatively steep decline in pancreas graft survival presumably because of the technical and immunological hurdles associated with the transplant operation. After this period, the rate of graft loss stabilizes to a relatively steady, predictable rate. Interestingly, a similar effect occurs after renal retransplantation. Renal retransplantation transiently increases this steady graft loss during the first year after retransplantation.
The relatively rapid rate of early pancreas graft loss after renal retransplantation seems to stabilize and slow over time and subsequently parallels the rate of pancreatic allograft failure in patients that do not undergo renal retransplantation. The decreased pancreatic allograft survival noted after renal retransplantation must be interpreted in the context that the renal retransplantation was performed, on average, 8 years after the original SPK. In our series, two pancreatic allograft failures were related to technical complications from the renal retransplantation, stressing the need for operative meticulousness in these challenging reoperations.
Although the HbA1c at 1 month after renal retransplantation correlates with subsequent graft loss, the group of patients who will lose their pancreas after renal retransplantation remains difficult to identify before renal retransplantation. This is particularly important, as pancreatic allograft failure is associated with subsequent loss of the renal retransplant. This may be, in part, because of the fact that the most common cause of renal retransplant allograft loss in our series was death with a functioning graft. In our review of 82 patients, there were no preoperative variables that were definitively predictive of subsequent pancreatic allograft loss after renal retransplantation. Nonetheless, the analysis did seem to uncover a possible correlation between the number of episodes of pancreatic allograft rejection before renal retransplantation and subsequent pancreas graft loss. This trend did not reach significance, which may be because of the relatively small number of patients in the study. This is intuitive and the predictive value seems to increase with the number of episodes of rejection.
Anecdotally, intraoperative evaluation of a prior pancreatic allograft is predictive of subsequent graft loss. Experienced pancreatic surgeons finding a small, shrunken pancreatic allograft may correlate this appearance with ultimate graft loss despite the detection of secreted C-peptide in the fasting state before renal retransplantation. However, such intraoperative assessment is of little value for preoperative patient counseling or for understanding the natural history of pancreatic allograft function after repeat renal transplantation in SPK recipients. This anecdotal finding raises the intriguing possibility of using preoperative CT imaging to evaluate the size of the pancreatic allograft and correlating CT appearance with subsequent graft loss. Furthermore, as renal retransplantation and additional immunosuppression clearly adds stressors to the pancreatic allograft and may unmask a poorly functioning graft, glucose tolerance testing may prove to be of value in determining the quality of pancreatic allograft function before renal retransplantation.
Although the length of follow-up in this study is an asset, it adds complexity to the analysis as available laboratory studies and immunosuppressive agents have changed over time. We did not observe a correlation between preoperative HbA1c or fasting C-peptide levels and subsequent pancreatic allograft loss. However, this may be secondary either to an incomplete data set from the earlier years of our program or to the low overall number of patients undergoing renal retransplantation with functioning pancreatic allografts. As more experience in retransplantation accrues, these values may prove more helpful in the preoperative evaluation of the SPK recipient with renal allograft failure.
The duration of the study period also introduces significant time bias, particularly as standards of care and techniques have evolved over time. This is clearly evident in regards to our understanding of the immunologic challenges of retransplantation. Recognition of acute and chronic rejection and the contributions of humoral immunity, has vastly improved over the duration of the study. Donor-specific antibody testing was available beginning in 2005 and we were unable to draw any meaningful conclusions from the patient group (only 2 of the 82 patients in the cohort underwent primary SPK during this period and only 27 of the renal retransplants were performed after 2005). As our understanding of the role of sensitization improves and novel immunosuppressants are integrated into practice, further experience may improve future results.
The duration of the study also introduces another significant time bias in terms of technique: bladder versus enteric drainage. Not unexpectedly, more patients with bladder drainage, which was performed earlier in our experience, have undergone renal retransplantation. This is likely a result of the length of time that has passed since the original SPK operation and the expected half-life of a renal allograft, rather than a predilection for bladder-drained pancreas recipients to experience renal allograft failure.
Despite technical and immunologic challenges, it is apparent that repeat renal transplantation in prior SPK recipients can be performed safely, with excellent renal and reasonable pancreatic allograft survival. Furthermore, the vast majority of renal allograft losses occurred not from technical complications associated with the retransplant, but from immunologic causes or death with a functioning graft. After renal retransplantation, patients tended to expire not from causes related to the reoperation, but primarily from cardiopulmonary and infectious causes.
Renal retransplantation is remarkably successful in prior SPK recipients and should be offered without hesitation to patients fit to undergo the procedure. Nonetheless, 20–25% of patients will experience loss of the pancreatic allograft within the first year after retransplantation. The strong survival benefits associated with renal transplantation in diabetic patients (7,25–27) and the survival benefits of renal retransplantation versus return to dialysis (21,22) suggest that renal retransplantation should be aggressively pursued in this patient population, despite a potential risk to the pancreatic allograft. The benefits of the renal allograft clearly outweigh potential benefits from the pancreatic allograft, justifying acceptance of possible subsequent pancreatic allograft failure. The group of patients that will experience pancreatic allograft loss remains difficult to identify preoperatively.
The authors wish to thank Barbara Voss, Delores Robillard and Glen Leverson for assistance in the analysis of data and the preparation of this manuscript.
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.