Risk factors of pancreatic graft loss and death of receptor after simultaneous pancreas/kidney transplantation.

Simultaneous pancreas/kidney transplants require a long graft survival and the recipient to present with more benefits than risks. We evaluated the risk factors of receptor's death and pancreatic graft loss on 2 occasions (3 and 12 months' postoperatively) in 292 transplants in whom 22 variables were evaluated. Variables were selected, 9 receivers, 8 donors, and 5 variables related to the surgical procedure. All independent variables were compared with the dependent variables of pancreatic graft losses and patient deaths. Those considered significant according to univariate analysis were analyzed by using multiple logistic regression techniques in an attempt to develop a mathematical model capable of predicting both pancreatic graft and patient losses. Lastly, based on the resulting models with all significant variables, scores were created to determine the risk of patient death and pancreatic graft loss. In the adjusted multivariate analysis, the significant variables were donor age, receiver's body mass index, initial pancreas implant, iliac venous drainage, and use of induction therapy related to pancreatic loss within 3 months after transplantation. Independent risk factors regarding the loss of patients within 12 months were body mass index and receptor induction therapy. The variables related to pancreatic graft loss within 3 months were donor age, receiver body mass index, initial use of pancreatic graft, iliac venous drainage, and induction therapy; these variables can be used for creating a risk score. The donor body mass index and the induction therapy were independently related to patient loss within 12 months after the transplant.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Delayed kidney allograft function after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is one of the treatments for insulin-dependent chronic renal failure patients. METHODS: One-year patient and kidney allograft survival rates of 150 patients undergoing SPKT were subjected to Cox regression and Kaplan-Meier analyses. Uni- and multivariate methods identified risk factors involved in allograft and patient survival. RESULTS: One-year patient and kidney allograft survival rates were 82% and 80%, respectively. Delayed graft function (DGF) (P = .001; hazard ratio [HR]5.41) and acute kidney rejection episodes (P = .016; HR 3.36) were related to 1 year patient survival as well as intra-abdominal infection (IAI) rates. (IAI). One-year kidney allograft survival was related to DGF (P = .013; odds ratio [OR] 3.39), acute rejection (P = .001; OR 4.74), and IAI (P = .003, OR 6.29). DGF was related to a time on dialysis >27 months (P = .046; OR 2.59), cold kidney ischemia time >14 hours (P = .027; OR 2.94), donor age >25 years (P = .03; OR 2.82), and donor serum sodium concentration >155 mEq/L (P < .0001; OR 1.09). Female kidney to male recipient in 17% of the cases did not increase the risk of DGF. We observed an important correlation between donor serum sodium and creatinine (P < .0001), which suggested undertreatment of diabetes insipidus secondary to brain death. CONCLUSIONS: DGF, acute rejection, and IAI were the main determinants of survival after SPKT. Improving the care of deceased donors may reduce DGF occurrence.

Intestinal obstruction due to internal hernia following pancreas transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation has evolved as the best treatment for type 1 diabetic patients at end-stage renal disease. The surgical complication rate is high, which is an important barrier to the success of this procedure. The frequent complications that require relaparotomies include fistulas, graft thromboses, and intra-abdominal abscesses. Intestinal obstructions after pancreas transplantation due to internal herniation are not common. PURPOSE: The objective of this article was to review the literature about this problem and describe our personal experience in pancreas transplantation. METHODS: We examined the cases of small bowel obstruction secondary to an internal hernia after following 292 pancreas transplantations in our center from 2000 to 2009 as well as performed a Medline literature review. RESULTS: Only 2 articles described the diagnosis and treatment of internal hernias after pancreas transplantation. However, both contribution were from the same center reporting the same 3 cases, with surgical versus radiologic perspectives. We have described our 2 cases of young pancreas-kidney transplant patients who presented with acute intestinal obstruction due to internal hernia. CONCLUSION: Although internal hernias are rare, they are potentially fatal and difficult to diagnose when they occur after pancreas transplantation. Detection with early surgery demands a high degree of clinical vigilance.

Simultaneous pancreas-kidney transplantation: which organ should be transplanted first?

Simultaneous pancreas-kidney transplantation (SPKT) has been accepted as treatment for type I diabetic patients with end-stage renal disease. Its success depends largely on the surgical technique. This study sought to compare groups of SPKT with initial pancreas implantation versus initial kidney implantation. From December 2000 to September 2006, 151 SPKT were performed by a single center. In 85 cases, the pancreas was implanted first (group 1), and in 66 cases the order was inverted (group 2). Variables were implantation sequence, pancreas and kidney ischemia time, donor age, venous drainage, previous donor peritoneal dialysis, and recipient age and gender. Outcome variables included pancreas vascular thrombosis, 3-month graft survival, 3-month patient survival, pancreas rejection episodes, intra-abdominal infection, diabetes control and reoperations. We observed a 10.6% incidence of vascular thrombosis in group 1 but none in group 2 (P = .005). In groups 1 and 2, the 3-month pancreas survivals were 74.1% and 89.4% (P = .022), and the mean hospital stays were 24.3 and 15.8 days, respectively (P = .002). Our results suggested that, when 2 different teams are involved in SPKT, with >1 exposure and the need for retractor replacement, the kidney should be transplanted first, because the pancreas may be damaged during the surgical procedure.

Multivariate analysis of risk factors for early loss of pancreas grafts among simultaneous pancreas-kidney transplants.

UNLABELLED: To evaluate the risk factors for pancreas graft loss within 3 months postoperatively among 170 simultaneous pancreas-kidney transplantation (SPKT) we examined 38 variables. METHODS: Twenty-two variables were related to recipients; 12 to donors and 4 to the surgical procedure. In addition the latest follow-up dates as well as the transplant and/or death dates. Independent variables were examined with reference to the dependent pancreatic loss variable, excluding losses owing to deaths. Variables with statistical significance were analyzed to predict early graft loss. RESULTS: Univariate analyses determined the following significant variables: kidney cold ischemia time, older donors, non-white donors, death cause related to vascular disease, wound infection, and length of extended hospitalization. However, multivariate analysis showed that only donor age and kidney cold ischemia time were significant predictors for early pancreatic graft loss. CONCLUSION: Donor age and kidney cold ischemia time were independently related to pancreatic loss after SPKT within 3 months posttransplantation.

Analysis of reoperations and their impact on the results of pancreas transplantation.

BACKGROUND: Many factors, including the advances in surgical techniques and immunosuppression, have been brought significant improvement to graft and patient survivals of patients undergoing pancreatic transplantations. However, one third of these patients require reoperations (ReOps). PURPOSE: We sought to evaluate the distribution of ReOps in the early or late postoperative period and analyze their impact on patient and graft survivals. PATIENTS AND METHODS: This unicenter, retrospective study was performed using data from 182 patient charts after pancreas transplantation from January 2000 through December 2007. RESULTS: We performed 88 ReOps on 73 patients; 43 early and 41 late operations. The simultaneous pancreas-kidney transplantation group showed a greater incidence of premature ReOps. The group undergoing early ReOp showed a lower survival rate (87.2%) compared with the nonoperated group, but a similar survival rate (97.5%) to the late ReOp group. In relation to the survival of pancreatic grafts after 1 year, the early ReOp group showed inferior survival to the late ReOp group, both of which were significantly worse results then those of the group without ReOp. CONCLUSION: ReOps were related to the success of the procedure. When they were performed in the first 3 months they had a negative impact on patient and graft survival.

Extreme subcutaneous, intramuscular and inhaled insulin resistance treated by pancreas transplantation alone.

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.

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.

Asynchronous kidney allograft loss after simultaneous pancreas-kidney transplantation: impact on pancreas allograft outcome at a single center.

OBJECTIVE: We analyzed the clinical evolution of pancreas allografts in simultaneous pancreas-kidney transplantation (SPKT) cases after asynchronous kidney allograft loss and kidney retransplantation at a single non-United States center. PATIENTS AND METHODS: We performed a retrospective analysis of 168 SPKT from December 2000 to June 2007. RESULTS: The 5-year kidney allograft survival rate was 71%. Excluding cases of death with a functioning graft after SPKT (n = 35; 74.4%), 12 kidney allografts were lost due to acute rejection (n = 7; 15%) or chronic allograft nephropathy (n = 5; 10.6%). Delayed graft function contributed to kidney allograft loss. Five of 12 patients underwent kidney retransplantation. Sixty percent of pancreas allografts were lost after this procedure, which was attributed to either the diabetogenic effects of the immunosuppressive regimen or to the perioperative stress. Oral glucose tolerance tests performed before kidney retransplantation identified patients with good pancreas allograft function versus those with intolerance on glucose tests who received reduced glucocorticoid doses. CONCLUSIONS: In SPKT, pancreas allograft function was seriously affected by kidney retransplantation. Oral glucose tolerance tests performed before kidney retransplantation were helpful to assess beta-cell function and suggest prescription of lower steroid doses to decrease the pancreas allograft dysfunction.

FOXP3-positive regulatory cells inside the allograft and the correlation with rejection.

BACKGROUND: Foxp3 is a transcription factor associated with regulatory T cells. Little is known about the role of Foxp3+ regulatory T cells in relation to graft rejection in humans. METHODS: By using a quantitative polymerase chain reaction assay, we measured the levels of messenger RNA (mRNA) for Foxp3 in 27 samples obtained at allograft nephrectomy for acute nonvascular rejection (ANVR; n = 7), or acute vascular rejection (AVR; n = 15), or loss due to a nonimmune cause (LNIC; n = 5, as control). Granzyme B was also analyzed as a positive control for the host-driven immune response. RESULTS: Median Foxp3 mRNA levels correlated with the severity of rejection: LNIC 1.000, ANVR 1.429, and AVR 3.904 (P = .022 for LNIC and AVR by the Kruskal-Wallis test). The receiver operating characteristic curve for AVR demonstrated an area under the curve of 0.733 (P = .04; 95% CI, 0.528-0.939). The levels of granzyme B mRNA also showed the same profile but did not reach statistical significance. CONCLUSIONS: The presence of mRNA for Foxp3 inside the graft suggested specific homing during severe episodes of acute rejection. Its presence may indicate the development of host immunoregulatory responses during the ongoing cytolytic activity. In addition, assessment of Foxp3 mRNA inside the graft may distinguish vascular from nonvascular rejection.

Severe hyperkalemic type 4 renal tubular acidosis after kidney transplantation: a case report.

BACKGROUND: Hyperkalemia after transplantation is a common event, occurring in up to 70% of patients. It is usually asymptomatic but sometimes manifests as muscle weakness or cardiac arrhythmias. METHODS: Case report. RESULTS: At 102 days after a second cadaveric kidney transplantation, a 15-year-old boy, was admitted to the emergency room with severe muscle weakness. His examinations showed a serum potassium of 9.8 mEq/L; blood pH 7.1; serum bicarbonate 7.6 mmol/L; and creatinine 2.5 mg/dL. He was initially treated with sodium bicarbonate, calcium gluconate, and furosemide. Subsequent investigation showed hyperchloremic metabolic acidosis, urinary pH <5.5, positive urinary anion gap, reduced transtubular potassium gradient (TTKG, 1.5) and low levels of aldosterone (0.7 ng/mL), suggesting the presence of type 4 renal tubular acidosis (RTA). Other causes of hyperkalemia were excluded in the present case. Serum levels of potassium returned to normal when fludrocortisone was added to the bicarbonate supplementation. This case of severe hyperkalemic secondary to type 4 RTA after kidney transplantation only responded to the combination of alkali and mineralocorticoid therapies.

Pancreas retransplantation: outcomes of 20 cases.

The objective of this paper was to evaluate our initial experience with pancreas retransplantation. From January 26, 1996 to February 2005, 285 pancreas transplantations were performed, including 20 (7%) retransplants. The causes of primary graft loss were graft thrombosis in 11 (55%, 7 venous and 4 arterial); 4 (20%) chronic rejections; 2 (10%) ischemia/reperfusion injury; 1 severe graft pancreatitis; 1 primary nonfunction; and 1 sepsis. Venous drainage was placed in the iliac vessels in 14 (70%), vena cava in 5 (25%), and portal drainage in 1. The exocrine drainage was vesical in 16 (80%) and enteric in 4 (20%). In 14 cases (70%), the primary graft was removed before and in 6 (30%) at the time of retransplantation. Immunosuppression was based on antilymphocyte induction, tacrolimus, mycophenolate mofetil, and steroids in all patients. One-year patient and graft survivals were 95% and 85%. In conclusion, pancreas retransplants were feasible with results comparable to a primary pancreas transplantation.

Influence of pancreas transplantation alone on native renal function.

Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) > or = 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl < or = 70 mL/min (n = 20) and group 2, CrCl > 70 mL/min (n = 25). The data were analyzed using Student's t-test (P < or = .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n = 5) or graft loss (n = 8) during the first year or follow-up shorter than 1 year (n = 8). The mean value of CrCl decreased 28.8% (85.0 +/- 31 versus 60.5 +/- 36 mL/min; P < .001). There was also a 39.3% reduction among group 1 subjects (P = .003), including 10 who displayed CrCl < or = 30 mL/min. There was also a 24.4% reduction among group 2 (P = .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl > 70 mL/min. Patients with CrCl < 70 mL/min show a significant risk of worsened renal function.

Expression of cyclooxygenases during renal allograft rejection.

The aim of this work was to determine the expression of cyclooxygenases (COX-1 and COX-2) during acute human renal allograft rejection. RT-PCR and immunohistochemistry were performed. The COX-2 mRNA was more abundant than COX-1 mRNA in the group with acute rejection (P <.001). The locations of COX-1 and COX-2 protein were consistent with the literature. Expression of COX-2 immunoreactive protein was higher in interstitial cells in the group with acute rejection than in the control group (P =.04). COX-2 protein was more abundant than COX-1 protein in the group with acute rejection, including podocytes (P <.001), proximal tubular cells (P <.001), collecting duct cells (P =.003), and interstitial cells (P <.001). In conclusion, COX-2 which is up-regulated during acute human renal allograft rejection, may play a role in renal inflammation.

Simultaneous pancreas-kidney transplantation: infectious complications and microbiological aspects.

OBJECTIVE: The purpose of this study was to describe the clinical and microbiological characteristics of the infectious complications among simultaneous pancreas-kidney transplantations (SPKT). MATERIALS AND METHODS: Among the first 45 SPKT the mean age was 34 years (range, 21 to 49) and the mean duration of follow-up 13 months (range, 2 to 27 months). RESULTS: Twenty-three patients (51%) presented at least one to three episodes (1.7 mean) of infectious complications that needed hospitalization. The etiology of the infections included 71% bacterial (44% gram-negative rods and 27% gram-positive cocci), 16% viral (12% from CMV and 4% from Herpes sp) and 13% fungal (8% by Candida sp and 4% by others fungus). Wound and urinary infections were most frequent, occurring in 22% and 28% of the patients, respectively. All patients who were submitted to vesical drainage developed infections in contrast a rate of only 44% among patients undergoing enteric drainage. CONCLUSION: Infectious complications are the main cause of morbidity and mortality following simultaneous pancreas-kidney transplantation, especially with vesical drainage. The use of enteric drainage combined with administration of broad spectrum prophylactic antibiotics is recommended.

Risk factors for the development of posttransplantation diabetes mellitus in simultaneous pancreas and kidney recipients.

We sought to determine the risk factors involved in the development of posttransplantation diabetes mellitus (PTDM) following simultaneous pancreas and kidney transplantation. Correlations were sought between tacrolimus (FK-506) levels/dose 2-hour capillary glucose (CG) and glycosylated hemoglobin (HbA(1c)), cyclosporine (CSA) levels/dose with HbA1c, 2-hour CG with prednisone dose and body mass index (BMI) and PTDM. Four patients (9.3%) developed PTDM. Three treated with FK-506 had altered 2-hour CG at 3 months after transplantation; 1 prescribed CSA displayed diabetes diagnosed after 1 year. There was no statistically significant difference among HbA(1c) values and FK-506 (P =.18) or CSA (P =.81) doses or FK-506 (P =.53) and CSA (P =.54) levels. In contrast, there was a statistically significant relationship between elevated 2-hour CG (> or =200 mg/dL) and daily prednisone dose (9.7 mg vs. 16.2 mg; P =.003). There was no correlation between 2-hour CG and FK-506 dose (P =.084) or FK-506 levels (P =.075). The greater BMI correlated with an increased risk of PTDM (21.25 +/- 3.13 kg/m(2) vs 24.67 +/- 2.38 kg/m(2); P =.034). Two-hour CG may be a useful tool to screen the diabetogenic effects of corticosteroids. A BMI increase should be discouraged due to the risk of PTDM.

Risk of bacterial infection in patients under intravenous iron therapy: dose versus length of treatment.

Some studies have suggested that intravenous iron therapy may be associated with an increased risk of infection. We analyzed the incidence of bacterial infection in 111 hemodialysis patients. Group 1 (n = 39, transferrin saturation <20%) received 10 doses of 100 mg of intravenous iron saccharate, 3 doses per week (28 treatment days); Group 2 (n = 13, transferrin saturation <20%) received 20 doses, 3 doses per week (70 treatment days); and Group 3 (n = 59, transferrin saturation 20-50%) received 10 doses, 1 dose per week (70 treatment days). The follow-up was 150 days for all groups, and all infectious episodes were recorded. Pulmonary infection was the most frequent event observed in all of the groups. In an incidence-density analysis, Group 2, which received a total of 20 doses, presented a significantly higher incidence of infection than Group 3, which received only 10 doses over the same period (0.13 versus 0.06 infections per patient per month, p = 0.04). No difference was observed between Groups 1 and 2 suggesting that the risk of infection during iron therapy is dose dependent rather than time length dependent.

Musculoskeletal manifestations of bacterial endocarditis.

CONTEXT: The incidence of staphylococcal infection has been increasing during the last 20 years. OBJECTIVE: Report a case of staphylococcal endocarditis preceded by musculoskeletal manifestations, which is a rare form of clinical presentation. DESIGN: Case report. CASE REPORT: A 45-year-old-man, without addictions and without known previous cardiopathy, was diagnosed as having definitive acute bacterial endocarditis due to Staphylococcus aureus. Its etiology was community-acquired, arising from a non-apparent primary focus. In addition, the musculoskeletal symptoms preceded the infective endocarditis (IE) by about 1 month, which occurred together with other symptoms, e.g. mycotic aneurysms and petechiae. Later, the patient showed perforation of the mitral valve and moderate mitral insufficiency with clinical control.