Simultaneous Pancreas-kidney Patients Research Articles

O236: The Impact of HLA Matching on Pancreas and Simultaneous Pancreas-Kidney (SPK) Transplantation Outcomes

Abstract Background This study evaluates the controversial impact of human leukocyte antigen (HLA) matching on pancreas graft survival and acute rejection. Methods Utilizing a large-scale multi-center database (UNOS/OPTN), we identified 8,005 pancreas and 7,850 simultaneous pancreas-kidney (SPK) transplant patients. Patients were classified into HLA matched (0-3 mismatches) and mismatched (4-6 mismatches) groups. Subsequently, utilizing multivariate Cox analysis, we evaluated risk-adjusted outcomes, represented through Kaplan-Meier survival curves. We also examined differences in graft survival and acute rejection based on transplant type (SPK or pancreas alone) within the same HLA mismatch group. Findings There were no significant differences in pancreas graft survival or acute rejection observed between HLA matched and mismatched groups for both pancreas and SPK transplant recipients (P > 0.05). However, among HLA mismatched patients, pancreas patients exhibited a 629-day lower pancreas graft survival than SPK patients (3774 vs. 4403 days, P < 0.001) and had a higher likelihood of experiencing acute rejection post-transplant (P < 0.001). Similarly, within the HLA matched groups, pancreas patients showed lower graft survival compared to SPK patients (3774 vs. 4403 days, P < 0.001); however, their acute rejection rates did not significantly differ (P > 0.05). Interpretation Although HLA matching was not associated with improved pancreas graft survival or a reduction in acute rejection, the results suggest a potential protective effect of the kidney in SPK transplants against the consequences of HLA mismatching. This underscores the clinical significance of considering the kidney component in donor-recipient matching for pancreas transplantation.

406.2: Utility of Donor-derived Cell-free DNA in Assessing Simultaneous Pancreas-Kidney Transplantation Rejection

Introduction: Among solid organ transplants, pancreas transplantation has one of the highest rates of acute rejection within the first 12 months. Graft biopsy, the gold standard, is risky and often not available. Hence, a non-invasive biomarker with good predictive value, such as donor-derived cell free DNA (dd-cfDNA), may be useful in predicting risk of rejection. In this study we sought to analyze the performance of a dd-cfDNA test in patients with simultaneous pancreas kidney (SPK) transplant. Methods: A retrospective study was conducted from 2017 to 2020 on patients admitted for pancreas graft biopsy at the Hospital Clínic Barcelona. Plasma samples were collected on the day of biopsy. dd-cfDNA fraction was assessed using the ProsperaTM test, a SNP-based mmPCR methodology to predict risk of rejection (including T-cell mediated rejection [TCMR] and antibody mediated rejection [ABMR]). Results: Plasma samples (n=50) were obtained from 37 SPK recipients. Pancreas biopsies were collected from 30 patients. Of the 50 plasma samples, 36 were plasma-biopsy paired and per Banff criteria were categorized as no rejection (n=21) and acute rejection (aTCMR and aABMR; n=15). Median dd-cfDNA levels were significantly elevated in samples with graft rejection diagnosis: 1.11 [0.83–1.66] vs. no rejection 0.65 [0.28–1.00]; p=0.004),especially after 45 days post transplantation (AR: 0.83[0.67–1.59], NR:0.45[0.13–0.55], p=0.004) (Figure 1). The overall performance of the test after 45 days of transplant is as follows: sensitivity 71.4%, specificity 91.6%, PPV: 83.8%, NPV:84.6%. Conclusion: dd-cfDNA assay can accurately differentiate active rejection from non rejection through a non-invasive, simple blood test in SPK patients as early as 45 days post SPK transplant.Medical writing support was provided by Nour Al Haj Baddar, Ph.D. from Natera, Inc. at San Carlos, CA.

Long-term Lower Extremity and Cardiovascular Complications after Simultaneous Pancreas-Kidney Transplant.

Lower extremity (LE) vascular disease and adverse cardiovascular events (ACEs) cause significant long-term morbidity after simultaneous pancreas-kidney (SPK) transplantation. This study's purpose was to describe the incidence of, and risk factors associated with, LE vascular complications and related ACEs following SPK. All SPKs performed at the authors' institution from 2000 to 2019 were retrospectively analyzed. The primary outcome was any LE vascular event, defined as LE endovascular intervention, open surgery, amputation, or invasive podiatry intervention. Secondary outcomes included post-SPK ACE. A total of 363 patients were included, of whom 54 (14.9%) required at least one LE vascular intervention following SPK. Only 3 patients received pre-SPK ankle brachial indices (ABIs). A history of peripheral artery disease (PAD) (HR 2.95, CI 1.4-6.2) was a risk factor for post-SPK LE vascular intervention even after adjustment for other factors. Fifty-nine (16.3%) patients experienced an ACE in follow-up. Requiring a LE intervention post-SPK was associated with a subsequent ACE (HR 2.3, CI 1.2-4.5). LE vascular and cardiovascular complications continue to be significant sources of morbidity for SPK patients, especially for patients with preexisting PAD. The highest risk patients may benefit from more intensive pre- and post-SPK workup with ABIs and follow-up with a vascular surgeon.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n=218). Early pancreas allograft loss occurred in 12.8% (n=28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p=0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p=0.22), surgical wound complications (p=0.12), or rejection episodes occurring in the first year (p=0.87). Despite differences in DGF, both groups had excellent renal function at 1year post-transplant (eGFR 64.1±20.8 vs. 65.8±22.9, p=0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p=0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p=0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2years (p=0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

72-OR: Clinical Burden and Impact of New-Onset Diabetic Foot Ulcers, Post-Simultaneous Pancreas Kidney Transplantation, and Kidney Only Transplantation

Background: Patients with diabetes and renal dysfunction are at risk of diabetic foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown. Aims: We evaluated the incidence of new onset DFU post SPK and KO transplant performed between 2004 and 2014 in 234 patients with diabetic kidney disease. Methods: In total 90 (51% male) SPK patients and 144 KO (66% male, 26% type 1 DM) were evaluated in a single centre retrospective study. Median (range) follow-up was 6 (3 to 13) years for both cohorts. Results: We observed that 16 (17%) of SPK and 22 (15%) KO patients respectively developed a new DFU during follow-up. Nearly 60% of new onset DFU presented within 500 days post SPK transplant. In KO cohort more than 50% of DFU presented within 1000 days post kidney transplant. In both cohorts a history of peripheral vascular disease (PVD) [37.5% vs. 4%] and pre-transplant history of DFU were associated with post transplant DFU p<0.05. In KO cohort, patients who developed a DFU were more likely to have T1DM than T2DM (29% vs. 10%), and had higher pre-transplant HbA1c, (mean ± standard deviation [7.5 ±1.2% vs. 6.8±1.4%, p<0.05]). There was no impact of DFU on SPK transplant failure. In contrast patients with DFU post KO transplant had more than five fold increased hazard ratio (HR) of transplant failure as compared to those without DFU independent of other risk factors [HR 5.19 95% CI (2.05 to 13.18) p=0.001]. Conclusion: There is a residual high burden of new onset DFU post KO or SPK transplantation. Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Disclosure A. Sharma: None. N. Fountoulakis: None. P.R. Vas: Other Relationship; Self; Sanofi-Aventis. J. Karalliedde: Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, NAPP Pharmaceuticals Limited.

Clinical features and burden of new onset diabetic foot ulcers post simultaneous pancreas kidney transplantation and kidney only transplantation

BackgroundPatients with diabetes and kidney disease are at risk of diabetes-related foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown. MethodsWe evaluated the incidence of new onset DFU post SPK and KO transplant in 235 patients with diabetic kidney disease and diabetic neuropathy. In total 90 (51% male) SPK patients and 145 KO (66% male, 26% Type 1 DM) were evaluated in a single centre retrospective study. Median (range) follow up was 6 (3 to 13) years for both cohorts. ResultsWe observed that 16 (17%) of SPK and 22 (15%) KO patients respectively developed a DFU during follow up. In both cohorts a history of peripheral arterial disease [37.5% vs. 4%] and pre-transplant history of DFU were associated with post transplant DFU (p ≪ 0.05).In KO cohort, patients who developed a DFU were more likely to have T1DM than T2DM (29% vs. 10%), p ≪ 0.05. There was no impact of DFU on SPK transplant failure. In contrast patients with DFU post KO transplant had more than five fold increased hazard ratio (HR) of transplant failure as compared to those without DFU independent of other risk factors [HR 5.19 95% CI (2.05 to 13.18) p = 0.001]. ConclusionNearly 1 in 7 patients develop a new onset DFU post KO or SPK transplantation and DFU also significantly increases risk of failure of the transplanted kidney. Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Research in contextEvidence before this studyPatients with diabetes and kidney disease are at enhanced risk of diabetic foot ulcers (DFU). Whether this risk is modified post successful kidney only (KO) or simultaneous pancreas and kidney (SPK) transplantation is unknown. Small case series and studies with short term follow up report varied rates of incidence and are from historical cohorts before the use of modern anti-transplant medications and treatments. Short term studies also suggest that post SPK the resultant normoglycaemia may reverse some features and risk markers of DFU. There are no long term studies on the incidence and impact of diabetic foot ulcers in patients with diabetic kidney disease post SPK or KO transplantation.Added value of this studyWe report the long term follow up results on DFU incidence, clinical features and related impact on transplant viability in 235 patients with diabetic kidney disease and neuropathy post successful SPK and KO transplant at a single centre. We observed that nearly 1 in 7 patients developed a DFU during follow up and that in patients who received KO transplant onset of DFU was associated with more than 5 fold increase of transplant failure.Implications of all the available evidenceOur results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Despite normoglycaemia post SPK there is a residual burden and risk of DFU. Our work establishes a clinical rationale for further research to explore putative mechanisms that could explain the association between DFU and renal transplant dysfunction.

Long-term results of protocol kidney biopsy directing steroid withdrawal in simultaneous pancreas-kidney transplant patients.

We sought to determine whether protocol biopsies could be used to guide treatment and improve outcomes in simultaneous pancreas-kidney (SPK) patients. Between 2004 and 2013, protocol biopsies were performed on SPK patients at 3-6 months and one year post-transplant. Maintenance immunosuppression consisted of a calcineurin inhibitor, anti-proliferative agent, and corticosteroid. Corticosteroid was withdrawn in negative early biopsies, maintained in subclinical/ borderline biopsies, and increased if Banff IB or greater rejection was identified. Endpoints included presence of interstitial fibrosis and tubular atrophy on biopsy at one year (IF/TA), rejection episodes, and renal and pancreas function at five years' followup. Forty-one SPK transplant patients were reviewed and a total of 75 protocol biopsies were identified. On early biopsy, 51% had negative biopsies, 44% had borderline rejection, and 5% had subclinical rejection. Renal and pancreas function were not significantly different at one, two, and five years post-transplant between negative vs. borderline early biopsy patients. No difference in the degree of IF/TA was found between these two groups. To our knowledge, this is the first study to evaluate protocol biopsies as an investigative tool prior to steroid withdrawal in SPK patients. Our study suggests that there are no detrimental functional or histological effects at five years post-transplant, despite weaning steroids in the negative biopsy group.

Randomized open-label crossover assessment of Prograf vs Advagraf on immunosuppressant pharmacokinetics and pharmacodynamics in simultaneous pancreas-kidney patients.

We assessed the pharmacokinetic and pharmacodynamic impact of converting stable simultaneous pancreas-kidney (SPK) recipients from standard tacrolimus (Prograf) to long-acting tacrolimus (Advagraf). In a randomized prospective crossover study, stable SPK recipients on Prograf were assigned to Prograf with 1:1 conversion to Advagraf or vice versa. Demographics, tacrolimus, mycophenolic acid levels, and Cylex CD4+ATP levels were taken at specified intervals in addition to standard blood work. Twenty-one patients, who were a minimum of 1year post-transplant, were entered into the study. No difference in tacrolimus or mycophenolic acid levels was noted between patients who were first assigned to Prograf or Advagraf. Additionally, Cylex levels as well as serum creatinine, lipase, and blood sugar levels were unchanged. There were no episodes of rejection during the 6-month study. It is safe to convert between Prograf and Advagraf 1:1, without major impact on pharmacokinetics or pharmacodynamics in SPK recipients.

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas-Kidney Transplantation.

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV-3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas-kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV-3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow-up tests, PIV-3 shedding was still detected 11-16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV-3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV-3 infections early after kidney or SPK transplantation were mostly mild. PIV-3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.

The Effect of Corticosteroid Withdrawal on Glucose Metabolism and Anti-GAD Antibodies in Simultaneous Pancreas-Kidney Transplant Patients.

Corticosteroid withdrawal may reduce insulin resistance; however, it could also influence pancreatic autoantibody profile in simultaneous pancreas-kidney (SPK) transplant patients. To evaluate the effect of corticosteroid withdrawal on glucose metabolism and anti-glutamic acid decarboxylase (GAD) antibody titers in SPK patients with type 1 diabetes after 12 months of follow-up. In this retrospective study, fasting glucose and glycated hemoglobin (A1c) were compared before and after 3, 6, and 12 months of corticosteroid withdrawal in 80 SPK patients. In addition, weight, anti-GAD, and C-peptide levels were compared before and after withdrawal. Finally, fasting and postglucose, insulin, and C-peptide levels were compared before and after withdrawal in 25 patients undergoing oral glucose tolerance test (OGTT). Fasting glucose levels did not change during corticosteroid discontinuation. After 12 months, A1c slightly increased from 4.6% (0.4%) to 4.8% (0.6%) (P < .01) and C-peptide decreased from 2.8 (1.1) ng/mL to 2.4 (1.3) ng/mL (P <. 01). In patients submitted to OGTT, glucose, insulin, and C-peptide levels did not change. There was no alteration in the proportion of anti-GAD positive tests (41% vs 45%). Anti-GAD titers remained stable or decreased in 70% of positive patients. Corticosteroid withdrawal has no significant effect on glucose metabolism and on anti-GAD profile among SPK patients.

Simultaneous pancreas-kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression.

Aims/hypothesisHigh levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage.MethodsWe assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas–kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK.ResultsWe found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner.Conclusions/interpretationTaken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.

Charcot neuroarthropathy after simultaneous pancreas–kidney transplantation: risk factors, prevalence, and outcome

We retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas-kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre-transplant values of HbA1c , received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992-1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999-2012) received lower doses of corticosteroids as part of their tacrolimus-based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre-transplant diabetic control and the use of high-dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended.

The Effect of Single Versus Dual Graft Loss On Sensitization in Simultaneous Pancreas-Kidney Transplant Recipients.

In simultaneous pancreas-kidney(SPK) transplants, failure of 1 or both grafts is a risk factor for mortality and may prompt patients to seek retransplantation. In a few small studies, graft loss with immunosuppression withdrawal has been described as a risk factor for sensitization, but no large scale verification has been reported. We hypothesize that SPK patients who lose both grafts are at higher sensitization risk than those with only one graft loss. Methods: This is a SRTR database retrospective study of 1° SPK adult patients transplanted between 1/1999-12/2011 with graft failure followed by relisting. Patients were stratified by graft loss: pancreas(Pa), kidney(Ki), or both pancreas/kidney(P/K). The 1° outcome was peak initial PRA>10 at relisting. Multivariate logistic regression was used to identify risk factors for sensitization. Results: Out of 10733 SPK patients; 1255, 749, and 879 had Pa, Ki, and P/K loss respectively. With Pa and Ki loss, 363(29%) and 320(43%) were relisted respectively. With P/K loss, 293(33%) were relisted for SPK or Ki alone. At relisting, 13%, 23%, and 58% of Pa, Ki, and P/K loss patients had a PRA>10 respectively.Figure: No Caption available.In the multivariate model, Ki and Pa loss were associated with less sensitization, while black recipients and years between graft failure and relisting were associated with more sensitizationTable: No Caption available.Conclusion: Our data suggests that SPK patients with P/K loss are at higher risk for sensitization than those with only one graft loss, and this data may have important clinical implications on how to manage immunosuppression after graft failure.

Similar Results With Solitary Pancreas Transplantation Compared With Simultaneous Pancreas–Kidney Transplantation in the New Millennium

IntroductionThe purpose of this study was to analyze our single-center outcomes according to pancreas transplant (PT) category in the new millennium by using standardized management protocols. Patients and MethodsWe retrospectively studied 202 consecutive PTs (179 with portal-enteric drainage) in 192 patients; all received either rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and tapered corticosteroids or early steroid withdrawal. Unlike simultaneous pancreas/kidney (SPK) transplant, solitary PT (SPT) recipients were managed with routine perioperative anticoagulation and surveillance pancreas biopsies. ResultsFrom November 2001 to March 2013, we performed 162 SPK transplants, 35 pancreas after kidney transplants, and 5 pancreas-alone transplants (40 SPTs). Demographic characteristics were mostly comparable; however, the SPT group had younger donors, shorter waiting time, fewer HLA mismatches, and fewer African-American recipients but more retransplants (all, P < .05). With a mean follow-up of 5.5 versus 7.5 years, overall patient (86.4% SPK vs 86.8% SPT), kidney graft (74% SPK vs 80% SPT), and pancreas graft (both 65%) survival rates were comparable. Although mortality rates were similar, mortality patterns differed because no SPT recipients died early, whereas the 1-, 3-, and 5-year mortality rates after SPK transplant were 4%, 9% and 12%, respectively (P < .05). The most common causes of pancreas graft loss were death with functioning grafts in SPK recipients and acute/chronic rejection in SPT recipients. Rates of early thrombosis were 8.6% in SPK patients and 5% in SPT patients. Cumulative clinical acute rejection rates were similar between groups (SPK 29% vs SPT 27.5%; P = NS). ConclusionsIn the setting of depleting antibody induction and tacrolimus-based therapy, HLA matching, careful donor and recipient selection, portal-enteric drainage, selective perioperative anticoagulation, and surveillance SPT biopsy monitoring, similar medium-term outcomes can be achieved in SPK transplants and SPTs in the new millennium.

Conversion From Twice-Daily to Once-Daily Tacrolimus in Simultaneous Pancreas-Kidney Transplant Patients

BackgroundData on the effectiveness of once-daily tacrolimus (Tac-QD) in simultaneous pancreas-kidney (SPK) transplant patients are limited, which is of particular concern because diabetic gastroparesis may affect absorption. The aim of this study was to evaluate the clinical impact of converting SPK patients from twice-daily (Tac-BD) to Tac-QD. MethodsFrom November 2008 to August 2011, 27 SPK recipients (out of 130) were converted from Tac-BD to Tac-QD. Demographics, prescribed doses, trough levels, and creatinine, glucose, and HbA1c values were collected prospectively at the time of conversion and at 1, 2, 3, 6, and 12 months after conversion. ResultsThe mean time from transplantation to conversion was 35.81 ± 27.31 months, with 20 patients (74.07%) converted to Tac-QD >12 months after transplantation. There were no significant differences in the tacrolimus dose and trough levels before and after conversion and at all points during the follow-up. Creatinine, glucos,e and HbA1c levels remained stable throughout. Eight patients (29.63%) with gastroparesis had clinical outcomes, drug doses, and trough levels similar to all other patients. ConclusionsStable SPK recipients can safely be converted from Tac-BD to Tac-QD, with no clinical impact on the transplant function. Gastroparesis does not appear to influence tacrolimus dose requirements or trough levels.

2317 THE EFFECT OF SIMULTANEOUS PANCREAS KIDNEY TRANSPLANTATION ON THE 10-YEAR CARDIOVASCULAR DISEASE RISK OF TYPE 1 DIABETIC PATIENTS

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Renal Vascular Surgery (II)1 Apr 20132317 THE EFFECT OF SIMULTANEOUS PANCREAS KIDNEY TRANSPLANTATION ON THE 10-YEAR CARDIOVASCULAR DISEASE RISK OF TYPE 1 DIABETIC PATIENTS Alex Jiang, Tom McGregor, Neal Rowe, Vivian McAlister, Paul Martin, Alp Sener, and Patrick Luke Alex JiangAlex Jiang London, Canada More articles by this author , Tom McGregorTom McGregor London, Canada More articles by this author , Neal RoweNeal Rowe London, Canada More articles by this author , Vivian McAlisterVivian McAlister London, Canada More articles by this author , Paul MartinPaul Martin London, Canada More articles by this author , Alp SenerAlp Sener London, Canada More articles by this author , and Patrick LukePatrick Luke London, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2258AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is uncertain whether pancreas transplantation in type 1 diabetics with renal impairment improves overall patient health and survival. The aim of this study was to look at the impact of pancreas transplant on simultaneous pancreas kidney (SPK) recipients using the Framingham Risk Score (FRS) for 10-year cardiovascular disease (CVD) risk. METHODS A retrospective review was performed on 55 SPK transplant patients. 20 solitary kidney (SK) recipients were analyzed as controls. The two groups were matched in terms of type 1 diabetes status and age. The FRS for 10-year CVD risk was calculated and compared between the two groups pre-operatively and one-year post-operatively. Individual risk factors were also compared separately to determine which factors conferred the most significant influence on cardiac risk reduction. This included systolic blood pressure (SBP), cholesterol levels and anti-hypertensive medications. RESULTS Using the FRS calculator, we determined that pre-operative risk score for SPK transplant group was 12.5±8.4% compared with 8.8±7.0% one-year post-operatively (p = 0.0002). There was no statistically significant difference in SK transplant group when comparing the pre and post-operative CVD risks. One year post-operatively, SPK patients had decreased their total number of antihypertensive medications by a mean of at least one agent (p = 0.0000003) and had reduced their dependences on statins (p = 0.001). SPK transplantation also lowered ‘patients' triglyceride levels from 1.42±0.82 mmol/L to 1.08±0.51 mmol/L (p = 0.007). Additionally, SPK recipients had significantly lower HbA1c level compared to SK recipients one-year post-operatively (5.7±1.0 vs 7.3±1.6 %, p = 0.01). However, there was no significant statistical difference between pre and post-operative SBP, LDL or HDL values. CONCLUSIONS SPK transplantation has a positive impact on patient health based on the analysis of FRS for 10-year CVD risk one-year post-operatively. It reduced the CVD risk from intermediate (10-20%) to low (<10%) risk range. Resulting impact of pancreas transplantation on cardiovascular complications including myocardial infarction, stroke and death continue to be studied. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e950 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Jiang London, Canada More articles by this author Tom McGregor London, Canada More articles by this author Neal Rowe London, Canada More articles by this author Vivian McAlister London, Canada More articles by this author Paul Martin London, Canada More articles by this author Alp Sener London, Canada More articles by this author Patrick Luke London, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical Impact of Conversion from Prograf to Advagraf in Simultaneous Kidney-Pancreas Transplant Recipients

Introduction: Advagraf is a modified release preparation of Tacrolimus absorbed throughout the intestinal tract. Due to the GI tract disturbances in simultaneous pancreas-kidney (SPK) recipients, there are concerns about the efficacy of Advagraf in these patients. Given the lack of data in this area, we set to investigate what is the clinical impact of conversion from twice-daily to once-daily Tacrolimus in SPK recipients. Methods: Between November 2008 and December 2011, 27 SPK recipients have been converted from Prograf to Advagraf. Demographic data, drug doses and levels, serum creatinine, serum glucose and HbA1C, the incidence of rejection episodes as well as patient and graft outcome data were prospectively collected at the time of conversion and at 1, 2, 3, 6, 18 and 24 months following conversion. Results: The mean time to conversion following transplantation was 35.8 ± 5.26 months. 11 SPK recipients (40.7%) were converted on a 1:1 mg basis, whilst another 11 patients required conversion on a +/- 1 mg basis compared to the Prograf dose. Only 4 patients were switched with a dose change > 1 mg. During follow-up, 13 (48%) patients had no dose change following conversion, whilst 11 (40.7%) patients required only 1 or 2 dose adjustments. The mean Advagraf dose at conversion (0.10±0.01 mg/kg) was comparable with the Prograf dose immediately pre-conversion (0.096±0.01 mg/kg) (p=0.98, paired T-test). There were no significant variations in subsequent Advagraf doses at all timepoints during the follow-up (p=0.99, Kruskal-Wallis test). The C0 tacrolimus level pre-switch (8.85±0.87 μg/L) was comparable with the levels postconversion at all time points during the study (p=0.72, Kruskal-Wallis) (fig. 1) with no need for increased monitoring frequency. Serum creatinine levels, the glucose and HbA1c levels remained stable over time with no clinical change following conversion. Only one patient experienced one episode of acute rejection following conversion. 5 patients were converted back to Prograf (1 - acute rejection, 1 - diarrhoea and 1 -CNI toxicity, 2 unspecified). One patient was switched to Sirolimus due to high CNI levels. There was no allograft loss and no patient deaths in this series.Figure: [Tacrolimus C0 levels in SPK patients on Advagraf]Conclusion: Stable SPK recipients can safely be converted from Prograf to Advagraf, with no clinical impact on the transplant function and survival and no changes in drug dosing or levels. Further studies are needed to determine the optimum time for conversion in these patients.

Metabolic Long-Term Follow-Up of Functioning Simultaneous Pancreas-Kidney Transplantation Versus Pancreas Transplantation Alone: Insights and Limitations

Pancreas transplantation involves a set of procedures that, in some cases, lead to different complications and outcomes. The aim of this study was to analyze the long-term effects of pancreas transplantation regarding carbohydrate and lipid metabolism parameters to determine differences between simultaneous pancreas-kidney (SPK) transplantation and pancreas transplantation alone (PTA). Sixty-four patients (46 SPK and 18 PTA), with an immunosuppression protocol based on tacrolimus plus mycophenolate mofetil and prednisone, were evaluated for at least 1 year after transplantation. No patient made use of any hypoglycemic or hypolipidemic drugs. Comparisons were performed between SPK and PTA patients using the chi-square test, Fischer's exact test, and unpaired Student's t test, as appropriate. Patients were 39.8+/-9.3 years old, predominantly male (60.9%), with a mean follow-up of 25.4+/-10.4 months after transplantation. The PTA group exhibited worse renal function and higher tacrolimus levels than the SPK group. Fasting glucose, 2 hr plasma glucose after overload, C-peptide, and HbA1C were within the normal range, with no statistically significant differences between the PTA and SPK groups. Insulin (INS) and the homeostasis model assessment of INS resistance index were above the normal range in both the groups. Lipids were also similar between groups. The majority of patients with long-term functioning pancreas transplant achieved good glucose control without use of exogenous INS or oral antidiabetic drugs, although they were hyperinsulinemic. There were no significant differences concerning glucose and lipid parameters between the SPK and PTA groups, even though the PTA patients exhibited higher tacrolimus levels and worse renal function.

Reported Isolated Pancreas Rejection Is Associated With Poor Kidney Outcomes in Recipients of a Simultaneous Pancreas Kidney Transplant

We hypothesized that many reported and presumed isolated pancreas acute rejection episodes in simultaneous pancreas kidney patients may in fact be missed concordant kidney acute rejection episodes. To test this hypothesis, we undertook an analysis of the Organ Procurement and Transplant Network database from 1995 to 2006 to assess the impact of reported isolated pancreas rejection on kidney allograft outcomes. The primary outcome of interest was kidney graft status beyond the first posttransplant year. For overall graft survival, we found that when pancreas alone rejection was compared with no rejection there was a significant difference between the curves (log-rank P<0.0001). In addition, this endpoint was also significant for death censored graft survival (log-rank P=0.0036). For both overall and death censored graft survival the multivariate analyses demonstrated an increased risk (adjusted hazards ratio: 2.46, 3.22, respectively) for patients reported to have pancreas alone rejection. These results indicate that patients with isolated pancreas rejection have worse renal allograft survival than patients reported as having no acute rejection and fare at least as poorly as those with reported kidney graft rejection supporting the concept of concordance of acute rejection in the majority of patients.

Nasogastric Decompression Is Not Necessary After Simultaneous Pancreas-Kidney Transplantation

To determine whether eliminating routine nasogastric (NG) decompression after simultaneous pancreas-kidney (SPK) transplantation would reduce hospital length of stay without any increase in complications. University of Wisconsin performs all pancreas transplantations with enteric drainage of exocrine secretions. Traditionally, NG tube decompression has been used for 5 postoperative days. This strategy was supported by the fact that most patients with diabetes have a history of gastroparesis. However, to date, no study has evaluated whether NG decompression is necessary post pancreas transplantation. We have conducted a retrospective review of 182 primary SPK transplant recipients from 2002 to 2005. Before August 2004 we used NG decompression for 5 days postoperatively and resumed diet 24 hours after tube removal. After this period, diets were initiated with return of bowel function. We eliminated routine NG decompression in 2004. One hundred and thirty-two patients had NG decompression and 50 patients did not. Induction therapy changed during the study timeframe from basiliximab in the NG group to alemtuzumab in the no NG group. Maintenance therapy was similar between the 2 groups consisting of prednisone, mycophenolate mofetil, and tacrolimus. Patients managed without NG tubes had significantly shorter length of stay (9.1 +/- 3.93 days) compared with patients managed with NG tube decompression (13.8 +/- 8.99 days) (P < 0.0001). Only 6 patients initially managed without NG tubes required NG placement during their hospital stay, including 2 patients returned to the operating room for nongastrointestinal complications. No differences existed between groups in complications, graft or patient survival. Historically, NG tube decompression has been recommended postoperatively in SPK patients. These data refute this traditional clinical practice. SPK patients managed without NG decompression have shorter hospital length of stay, equivalent graft survival, and no increased morbidity.