Simultaneous Pancreas-kidney Transplant Patients Research Articles

Impact of Donor Age on Long-Term Outcomes in Simultaneous Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for type 1 diabetes patients with end-stage renal disease. Donor characteristics are determinants of graft and patient survival. We aimed to study the impact of donor age on outcomes in SPKT. We retrospectively studied 254 patients submitted to SPKT between 2000 and 2021. Patients were classified as "younger donor" (donor age <40 years) and "older donor" (donor age ≥40 years). Fifty-three patients received grafts from older donors. Pancreas graft survival rates at 1, 5, 10, and 15 years were 89%, 83%, 77%, and 73% in the younger donor group, respectively, and 77%, 73%, 67%, and 62% in the older donor group, respectively (P=.052). Older donors and previous major adverse cardiovascular events (MACEs) were associated with pancreas graft failure at 15 years. Kidney transplant survival (1, 5, 10, and 15 years) was lower in the older donor cohort (94%, 92%, 69%, 60% vs 97%, 94%, 89%, and 84%, respectively; P=.004). Older donor, recipient age, and previous MACE predicted kidney graft failure at 15 years. Patient survival rates at 1, 5, 10, and 15 years were 98%, 95%, 91%, and 81% in the younger donor group, respectively, versus 92%, 90%, 84%, and 72% in the older donor group, respectively (P=.127). The kidney graft survival rate was lower in the older donor group, whereas pancreas graft survival and patient survival did not differ significantly. Multivariate analysis showed that a donor age of ≥40 years was an independent predictor of pancreas and kidney graft failure at 15 years in SPKT patients.

Pretransplant C-peptide Levels and Pancreas Transplant Outcomes: Risk and Reward.

We read with interest the report by Parajuli et al1, chronicling the University of Wisconsin experience in simultaneous pancreas-kidney transplantation (SPKT) according to the pretransplant fasting serum C-peptide levels. The authors demonstrated that higher pretransplant C-peptide levels predicted the risk of a composite outcome (combination of pancreas graft failure according to the United Network for Organ Sharing definition and pancreas graft dysfunction defined as initiation of any antidiabetic agent) posttransplant in patients with a type 2 diabetes phenotype.1,2 Recipients were categorized into 3 groups based on pretransplant fasting serum C-peptide levels: low (≤2 ng/mL, n = 14), medium (>2–8 ng/mL, n = 47), and high (>8 ng/mL, n = 15). The uncensored composite outcome of pancreas graft failure or dysfunction occurred in 0% in the low, 23% in the medium, and 33% of patients in the high C-peptide groups, respectively, suggesting that higher levels of pretransplant C-peptide are associated with inferior posttransplant outcomes. These findings confirm our recent report based on a case-controlled, single-center, retrospective study of 46 SPKT patients with pretransplant fasting serum C-peptide levels ≥2.0 ng/mL compared with 46 control patients (C-peptide level <0.5 ng/mL) matched for recipient age, gender, race, and transplant date.3 In our study, we likewise reported inferior mid-term outcomes in the group with higher pretransplant C-peptide levels. In our overall SPKT experience, we have 205 patients with a minimum of 5-y follow-up. Using the above C-peptide categories as per the Wisconsin study, we identified 166 patients in the low, 32 patients in the medium, and 7 patients in the high C-peptide groups. Five-y actual (uncensored) patient and graft survival rates were as follows: patient (91% low versus 93.8% medium versus 85.7% high) and kidney (80.7% versus 71.9% versus 71.4%), respectively. Using the composite end point of pancreas graft failure or dysfunction, pancreas outcomes were 25.3% low versus 34.4% medium versus 71.4% high C-peptide (P = 0.10). Similar to the Wisconsin study, we are limited by the small sample size in the high pretransplant C-peptide group but the findings indicate a trend toward a greater need for supplemental antidiabetic therapy in patients with higher pretransplant C-peptide levels. Unfortunately, what is missing from these studies is a better characterization of patients with partial pancreas allograft function (dysfunction) who continue to be free from wide glycemic excursions and do not experience hypoglycemia (despite the need for antidiabetic therapy) because of preserved counterregulatory function of the pancreas allograft.4 In our experience, we identified posttransplant weight gain, insulin resistance, and rejection as potential mitigating factors to explain these inferior outcomes. Consequently, we recommend greater emphasis on weight management strategies, behavioral modification, nutritional counseling, structured physical training programs, timely adjustments in (and use of less diabetogenic) immunosuppression, more intense long-term monitoring by the transplant center, and increased use of novel antidiabetic agents such as Glucagon-like peptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors when indicated in this unique population. We congratulate the authors on this excellent study and agree that these findings should not be an impetus to limit access to pancreas transplantation but rather help guide clinical decision-making and optimize posttransplant management.

208.4: Outcomes of Simultaneous Kidney-Pancreas Transplantation in Patients With Type-1 and Type-2 Diabetes Mellitus

Background: UNOS approved simultaneous kidney-pancreas transplantation (SKPT) for type-II diabetes mellitus (DM) in Oct 2014. In Jan 2015, we actively listed type-II DM patients with ESRD or e-GFR ≤ 20 ml/min/m2 for SKPT if they met the following criteria: age < 55 years, on insulin ≤ 1 unit/kg body weight, and a maximum allowable body mass index (BMI ≤ 30 kg/m2). The two major advantages for the type-II DM patients receiving SKPT as compared with kidney transplant alone are a much shorter waiting time and usually a better-quality kidney. There is limited data comparing outcomes of SKPT in type-I versus type-II DM. The aim of this study was to measure the change in volume of SPKT since UNOS approved it for type-II DM patients and compare death-censored 5-year graft and patient survival between type-I and type-II DM patients undergoing SKPT. Methods: We conducted a retrospective chart-review study on SKPT patients from Jan 2010 to Nov 2020 and collected data on patient demographics such as age, gender, and race. BMI, c-peptide, HbA1c, and e-GFR were noted pre-transplant and 1-year post-transplant. Outcome variables included volume of SKPT pre-and post-approval of SKPT for type-II DM patients, death-censored 5-year pancreas and kidney graft survival, and 5-year patient survival. Student’s t-test for continuous variables, Chi-square test for categorical variables, and Mantel-Cox test for survival analysis was done using SPSS. Results: As compared to type-I DM patients, type-II DM patients were older [47.4 vs 40.2 years, p-value = <0.01] and had higher BMI [32.0 vs 26.7 kg/m2, p-value = <0.01] and eGFR [76.7 vs 62.0 ml/min/1.73m2, p-value = 0.04] 1-year post-transplant (Figure 1). Among 89 SKPT, 18 (all type-I DM) were done before the approval of SKPT in type-II DM patients and 71 (41 type-I and 30 type-II DM) were done after the approval. This translated to an increase in SKPT from 3.6/year to 11.8/year (228% increase). There were no differences in death-censored 5-year kidney and pancreas graft survival and 5-year patient survival (Figure 2).Conclusion: Approval of SKPT for type-II DM by UNOS led to an increase in SKPT with no differences in kidney and pancreas graft survival or patient survival between patients with type-I and type-II DM. Obesity should be carefully screened and managed post-transplantation in type-II DM patients undergoing SKPT.

Single center results of simultaneous pancreas-kidney transplantation in patients with type 2 diabetes

Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are scarce data evaluating the association of recipient factors such as age, BMI, or pretransplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006 and 2017 with 1year of follow-up at minimum, were assessed for potential relationship of pretransplant BMI and insulin requirements with posttransplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from posttransplant diabetes (94.7% T2D vs. 92.3% T1D at 1yr, and 88.1% T2D vs. 81.1% T1D at 5yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1yr, and 89.7% T2D vs. 81.2% T1D at 5yrs). There was no significant association between BMI or pretransplant insulin requirements with posttransplant diabetes occurrence in either T1D (p=.10, .43, respectively) or T2D (p=.12, .63) patients in the cohort; or with graft failure (T1D: p=.40, .09; T2D: p=.71, .28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

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.

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.

Coronary Microvascular Dysfunction Predicts Long-Term Outcome in Simultaneous Pancreas–Kidney Transplantation

BackgroundPatients with diabetes are at increased cardiovascular risk. Simultaneous pancreas–kidney transplantation (SPKT) is the treatment of choice in patients with type 1 diabetes mellitus and diabetic nephropathy. We assessed coronary flow reserve (CFR) by transthoracic echocardiography as a marker of major adverse cardiac events (MACE) in SPKT patients. MethodsWe studied 48 consecutive SPKT patients (28 male, age at SPKT 54 ± 8 years). Time from transplantation was 8.5 ± 3 years. Follow-up was 4.6 ± 1.8 years. Coronary flow velocity in the left anterior descending coronary artery was detected by Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤ 2 was considered abnormal and a sign of coronary microvascular dysfunction. MACE were cardiac death, myocardial infarction, and heart failure. ResultsCFR was 2.55 ± 0.8. CFR was ≤2 in 13 (27%) patients. CFR was lower in SPKT patients with MACE (2.1 ± 0.7 vs 2.7 ± 0.8, P = .03) and patients with MACE had a higher incidence of CFR ≤ 2 (P = .03). Time from transplantation was shorter in patients with MACE (P < .0001). Patients with CFR ≤ 2 had a lower MACE-free survival (P = .03). CFR ≤ 2 predicted the risk of MACE (P = .007) independently from coronary artery disease and metabolic control. However, this predicted role is lost when adjusted for the time from transplantation, which plays a protective role (P = .001). ConclusionsIn SPKT, CFR ≤ 2 may be a reliable marker for MACE, independent of coronary artery disease diagnosis. However, this role seems to be reduced over time. This finding suggests a gradual reduction of cardiovascular risk in SPKT patients.

Beta-Cell Replacement: Pancreas and Islet Cell Transplantation.

Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care.

Financial cost of the admissions for simultaneous pancreas-kidney transplant in a Brazilian hospital.

To perform a cost analysis of simultaneous pancreas-kidney transplantation (SPKT) in a Brazilian hospital. Between January 2008 and December 2011, 105 consecutive SPKTs at the Hospital of Kidney and Hypertension in Sao Paulo were evaluated. We evaluated the patient demographics, payment source (public health system or supplementary system), and the impact of each hospital cost component. The evaluated costs were corrected to December 2011 values and converted to US dollars. Of the 105 SPKT patients, 61.9% were men, and 38.1% were women. Eight patients died, and 97 were discharged (92.4%). Eighty-nine procedures were funded by the public health system. The cost for the patients who were discharged was $18.352.27; the cost for the deceased patients was $18.449.96 (p = 0.79). The FOR for SPKT during this period was positive at $5,620.65. The costs were distributed as follows: supplies, 36%; administrative costs, 20%; physician fees, 15%; intensive care unit, 10%; surgical center, 10%; ward, 9%. Mortality did not affect costs, and supplies were the largest cost component.

Meckel’s Diverticulum Masquerading as an Arterio-Enteric Fistula in an Adult Patient With Simultaneous Pancreas-Kidney Transplantation

Introduction: Simultaneous pancreas-kidney (SPK) transplantation is a treatment for patients with type1 diabetes (DM) and end-stage renal disease (ESRD). Complications of SPK transplantation include peripancreatic abscess, enterocutaneous fistula, and rarely, gastrointestinal bleeding (GIB). We report a case of an adult patient with SPK transplantation who presented with massive GIB caused by Meckel’s diverticulum. Case Report: A 40-year-old male presented 3 years after SPK transplantation to an outside hospital with maroon-colored stool and dizziness. His co-morbidities included DM, ESRD, coronary artery disease, hepatitis C, nonalcoholic steatohepatitis, and cirrhosis. He was hypotensive (94/43), but otherwise, vitals were within reference range. His exam was significant for a soft abdomen with normoactive bowel sounds and mild confusion without any focal deficits or asterixis. Labs were notable for a hemoglobin of 5.9 g/dL, creatinine 1.73 mg/dL (baseline 1.1 mg/dL), BUN 64 mg/dL, and liver function tests within reference range. An esophagogastroduodenoscopy (EGD) revealed presumed Dieulafoy’s lesion, which was cauterized and clipped. Colonoscopy showed mild inflammation, but no obvious source of bleeding. Biopsies were negative for infection or inflammatory bowel disease. The patient was transferred to our center for management of persistent GIB (requiring 26 units of blood total) and worsening renal function. At our center, EGD, colonoscopy, push enteroscopy, tagged RBC scan, and provocative angiography were negative for the source of bleeding. Video capsule endoscopy showed a large amount of red blood in the small bowel without adequate identification of the source lesion. Exploratory laparotomy with intraoperative small bowel endoscopy was performed, which demonstrated a healthy appearing anastomosis with a more distal Meckel’s diverticulum full of clotted blood. The diverticulum was excised without recurrent bleeding. Discussion: The differential for lower GIB is vast, but in adult patients, Meckel’s diverticulum is a rare cause. Patients status-post SPK transplantation have additional considerations for GIB, including anastomotic site ulcer, pseudoaneurysm, arterioenteric fistula, severe graft rejection, and cytomegalovirus infection. This is a rare case of GIB secondary to Meckel’s diverticulum in patients with SPK transplantation. Clinicians should be aware of Meckel’s diverticulum as a cause of massive GIB in SPK transplant patients. A high index of suspicion and timely evaluation can improve morbidity and mortality.

Pancreas transplantation: The Wake Forest experience in the new millennium.

To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels. In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

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 ...

Role of Early Systemic Inflammatory Response in Simultaneous Pancreas-Kidney Transplantation

Pancreas grafts are susceptible to surgical complications mostly related to exocrine secretions and the low microcirculatory blood flow through the gland. During simultaneous kidney-pancreas transplantation, the systemic response depends on reperfusion of two organs acute graft pancreatitis, immunotherapy, coagulopathy, bleeding, and other factors. We performed a retrospective review of 10 adult simultaneous pancreas-kidney transplant patients to evaluate progression of early postoperative inflammation in the absence of infection. All patients were treated with four-drug therapy. We performed analyses of procalcitonin (PCT), C-reactive protein, serum creatinine, amylase, and lipase levels over the first 5 postoperative days.Relatively high peak PCT levels (maximum 130 ng/mL) were reached within 24 to 48 hours postoperatively followed by a moderate decrease. Consistent with this observation, the serum creatinine, amylase, and lipase levels decreased continuously to normal concentrations within the first week. The increased PCT levels seemed depend upon the surgical procedure and intraoperative events. PCT was superior to C-reactive protein to discriminate infection from inflammation in this setting. The dynamics of PCT levels, rather than absolute values, seemed to be important. Lack of a decrease in PCT levels after the peak, suggested an infectious complication or the development of sepsis. Monitoring and assessment of PCT levels may help in early recognition of infection and institution of therapy.

Simultaneous pancreas-kidney transplantation: Pro et Contra

The review addresses the questions of history, clinical features and outcomes of simultaneous pancreas-kidney transplantation in patients with diabetesmellitus type 1. This approach was shown to have positive aspects, such as improvement of glycemic control, rapid normalization and long-termmaintenance of glycated hemoglobin levels, disappearance of hypoglycemic events, and deceleration of coronary artery disease progression resultedin reduced incidence of cardiovascular mortality. Operative risk and post-transplantation complications are also described in details.

Nonmarginal-Donor Duodenal Ulcers Caused by Rejection After Simultaneous Pancreas and Kidney Transplantation: A Case Report

Objective Pancreas transplantation has been associated with the highest surgical complication rate among routinely performed organ transplant procedures. Complications can be caused not only from the pancreas itself but also from the simultaneously transplanted duodenum: gastrointestinal bleeding, duodenal ulcer, pseudoaneurysm, arterioenteric fistula, and severe rejection. Herein we report a patient who underwent simultaneous pancreas-kidney transplantation (SPKT) and experienced a duodenal perforation because of rejection. Methods The 60-year-old man with insulin-dependent diabetes underwent SPKT with enteric drainage. At 15 days there after he displayed melena. Results We suspected it to be caused by rejection and ischemic changes. We slightly increased the doses, of tacrolimus and methylprednisolone. But 17 days after SPKT, the ulcer perforated, requiring a repair operation and increased dose of mycophenolate mofetil. However, the ulcers perforated repeatedly, requiring 4 repair operations. Unfortunately the patient developed pneumonia that mitigated continues repairs or rejection therapies, so we expated the duodenum and pancreas but saved the kidney. The pathologic findings showed the ulcer to have been caused by severe rejection. Despite those episodes, the patient was weaned from hemodialysis. Conclusions Perforation of the transplanted duodenum is one of the most difficult complications among SPKT patients. This potentially lethal complication may be caused by mucosal rejection, ischemic changes, and the exocrine output from the pancreatic graft.

Long-Term Survival of Simultaneous Pancreas-Kidney Transplantation: Influence of Early Posttransplantation Complications

BackgroundComplications that develop in the early posttransplantation period after simultaneous pancreas-kidney transplantation (SPKT) can contribute to poor long-term survival of grafts and patients. Patients and MethodsWe studied 86 SPKTs that were performed between 2000 and 2010 in our hospital, analyzing all complications in the early posttransplantation period and their impact on long-term survival in patients and grafts. ResultsThe mean age of the patients was 38.77 ± 7.13 years (79.1% male). Of the 86 SPKT patients, 22.1% were on peritoneal dialysis (PD) before transplantation, 68.6% were on hemodialysis (HD), and 9.3% had not received any substitutive renal therapy. The immunosuppressive regimens consisted of induction with basiliximab followed by tacrolimus, mycophenolate mofetil, and steroid therapy. More than 75% of patients experienced an infection in the early posttransplantation period: bacteremia (37.2%), central catheter infection (7%), wound infection (4.7%), urinary tract (14%) and positive abdominal drain culture (45.3%). Approximately one third (31.4%) of patients underwent a reoperation, primarily due to bleeding (21.95%) or infection (19.51%). One fifth of patients (19.8%) experienced an acute rejection episode. The 3-year survival of the pancreas was lower among PD patients (82%) compared with patients who did not undergo dialysis before SPKT (100%). The 5-year survival rate of both grafts was lower among patients who underwent a reoperation than those who did not: pancreas survival rates, were 70% versus 93%, respectively (P = .015) and kidney graft survival rates were 75% versus 96%, respectively (P = .0017). Five-year patient survival rates were also lower among reoperated patients than those who were not (85% vs 97%, respectively), although the difference was not significant (P = .27). ConclusionsComplications in the early posttransplantation period after SPKT were frequent, increasing morbidity and inpatient stay. One third of our patients underwent a reoperation, which had a negative impact on graft survival.

273 BK Nephropathy (BKVN) in Simultaneous Kidney-Pancreas Transplant (SKPT): Potentially Preventable Cause of Renal Allograft Loss

BK NEPHROPATHY (BKVN) IN SIMULTANEOUS KIDNEYPANCREAS TRANSPLANT (SKPT): POTENTIALLY PREVENTABLE CAUSE OF RENAL ALLOGRAFT LOSS Asjad Sardar , Muhammad Mujtaba , Jonathan Fridell , Muhammad Yaqub, Dennis Mishler, Asif Sharfuddin, Tim Taber Department of Medicine 1 Department of Surgery 2 Indiana University School of Medicine/Clarian Transplant Institute Immunosuppression (IS) reduction is the main stay of BKVN management; this approach can put SKPT patients (pts) at a high risk of pancreatic allograft rejection. This fear of pancreatic rejection leads to inadequate BKVN management in SKPT pts. More than 50% of SKPT pts afflicted with BKVN lose their kidneys. Single center, retrospective case study reviewed the data of 138 SKPT patients from 1/06 to 6/10. BKVN definition was qPCR > 10000 copies/ml of serum and > 30% rise in seurm creatinine from baseline. Induction was with rATG and maintenance steroid free IS with Tacrolimus ± Sirolimus or Mycophenolate. Quarterly urine screening for BK virus was done for first two years and once a year thereafter. 6 pts were diagnosed with BKVN. Mean time to diagnosis was 13 months. Median serum creatinine was 2.1 mg/dl at diagnosis. The geometric mean BK serum viral load was 1,758,000 DNA copies/ml. Pts were managed with IS reduction alone with biweekly monitoring of BK viral loads and blood chemistries. Median time to BKVN clearance was 5.6 months. No renal allograft was lost to BKVN. From BKVN diagnosis to clearance there was a 96% reduction of MM dose. 100% reduction in Sirolimus and 40% reduction in 12hr Tac trough level. At a Median 19 month pt follow up post BK clearance, pts had excellent renal function without evidence of pancreatic allograft loss. Early detection and intervention in BKVN by Immunosuppression reduction alone with close monitoring of renal and pancreatic allograft function can potentially prevent renal allograft loss in SKPT without compromising pancreatic allograft

Mycophenolate Mofetil Versus Enteric-Coated Mycophenolate Sodium After Simultaneous Pancreas-Kidney Transplantation

Introduction Adverse gastrointestinal events are frequent after mycophenolate use. The objectives of the present study were to report the incidence of acute noninfectious diarrhea, to determine the risk factors, and to compare the severity of reactions between mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) after simultaneous pancreas kidney transplantation (SPKT). Methods We included 165 SPKT patients from December 2000 to May 2007. Uni- and multivariate analyses were performed, using acute noninfectious diarrhea as the dependent variable. P < .05 was considered significant. Results Mean age and duration of dialysis and of diabetes were 34.9 ± 8.2 years, 27.3 ± 18.3 months, and 21.9 ± 16.2 years, respectively. Sixty-three percent used MMF, 36.4% used EC-MPS, and 0.6% used azathioprine. Multivariate analysis showed that the duration of diabetes ( P = .049, confidence interval [CI] 1.0– 1.13) and MMF use ( P = .013, 95% CI 0.2–0.82) were the main determinants of acute diarrhea after SPKT. MMF dose reduction (79.2% vs 62.3%, P = .024) and severity of diarrhea associated with orthostatic hypotension were more pronounced among MMF than EC-MPS patients (42.4% vs 15.1%, P = .001). There was no difference between MMF and EC-MPS after dose reduction in relation to the occurrence of acute kidney rejection (30.8% vs 26.7%, P = .53). Conclusions Acute noninfectious diarrhea after SPKT was related to the duration of diabetes and to prescription of MMF. Preferential use of EC-MPS was associated with a lower necessity of dose reduction and less severe episodes of acute diarrhea compared with MMF, although dose reduction was equally associated with acute episodes of kidney rejection.

Orthotopic Kidney Retransplantation in Simultaneous Pancreas Kidney Transplant Patients With Renal Failure

Traditionally transplant nephrectomy was required as a separate procedure prior to retransplantation in simultaneous pancreas kidney transplant patients. An alternative approach combining both procedures is described, during which the rejected kidney is removed and replaced orthotopically by the new allograft.