What Is the Influence of Both Risk Donor and Risk Receiver on Simultaneous Pancreas-Kidney Transplantation?

INTRODUCTION: Some factors affect the pancreas of a marginal donor, and although their influence on graft survival has been determined, there is an increasing consensus to accept marginal organs in a controlled manner to increase the pool of organs. Certain factors related to the recipient have also been proposed as having negative influence on graft prognosis. The objective of this study was to analyze the influence of these factors on the results of our simultaneous pancreas-kidney (SPK) transplantation series. MATERIALS AND METHODS: Retrospective analysis of 126 SPK transplants. Donors and recipients were stratified in an optimal group (<2 expanded donor criteria) and a risk group (≥2 criteria). A pancreatic graft survival analysis was performed using a Kaplan-Meier test and log-rank test. Prognostic variables on graft survival were studied by Cox regression. Postoperative complications (graded by Clavien classification) were compared by χ2 test or Fisher test. RESULTS: Median survival of pancreas was 66 months, with no significant difference between groups (P > .05). Multivariate analysis showed risk factors to be donor age, cold ischemia time, donor body mass index, receipt body mass index, and receipt panel-reactive antibody. CONCLUSIONS: In our series, the use of pancreatic grafts from donors with expanded criteria is safe and has increased the pool of grafts. Different variables, both donor and recipient, influence the survival of the pancreatic graft and should be taken into account in organ distribution systems.

Intraoperative Heparinization During Simultaneous Pancreas-Kidney Transplantation: Is It Really Necessary?

INTRODUCTION: The use of intraoperative sodium heparin during simultaneous pancreas-kidney transplantation (SPKT) remains as a routine practice in some referral centers to minimize pancreatic graft thrombosis rate. One of its disadvantages is the theoretical increased risk of postoperative bleeding. In our center, we have abandoned its use since 2011. MATERIALS AND METHODS: We performed a retrospective analysis among 198 SPKTs performed in our center between the years 1989 and 2017. The variables of our study were vascular thrombosis of the pancreatic graft and hemoperitoneum and upper gastrointestinal bleeding in the mediate postoperative period (up to 2 months after the transplant). We compared these results between SPKT recipients who had undergone intraoperative heparinization (n = 157) and those who had not (n = 51). To avoid bias, a second comparison was performed using propensity score matching on the following characteristics: sex, recipient age, recipient body mass index, cold ischemia time, preoperative hemodialysis or peritoneal dialysis, time of diabetes, and Pancreas Donor Risk Index. Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas χ2 or Fisher exact test was used to compare categorical data. RESULTS: No statistically significant differences were found when comparing the use of intraoperative heparin, even after the homogenization of both groups. CONCLUSIONS: In our experience, intraoperative heparinization during SPKT surgery was not useful because it did not significantly decrease the graft thrombosis rate, and its withdrawal did not enhance hemoperitoneum or upper gastrointestinal bleeding postoperative rates.

Pancreas Donor Hypernatremia: Is it Really a Risk Factor for Simultaneous Pancreas-kidney Transplantation?

INTRODUCTION: Solid organ donor hypernatremia has been classically reported to be a risk factor for cell lysis and graft damage. National criteria for pancreatic donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be relative exclusion criteria. The aim of our study is to review the postoperative outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas graft thrombosis, early pancreatectomy, and reoperation rates regarding different ranges of donor sodium levels. MATERIAL AND METHODS: We performed a retrospective analysis among 161 SPKTs performed in our center between the years 2001 and 2017. We compared the aforementioned postoperative variables in two situations: 1) Whether the donor pancreas sodium levels were inferior to 149 mEq/L, or equal to or greater than 150 mEq/L; and 2) If they had severe hypernatremia (considering sodium levels greater than or equal to 160 mEq/L as threshold) or not. To ensure the comparability of the groups, a second comparison was performed on new samples after using propensity score matching. A Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas a χ2 test or Fisher's exact test was used to compare categorical data. RESULTS: No statistically significant differences were found between the groups that relate high donor serum sodium levels with the morbidity variables included in our study or with early pancreatic graft loss. CONCLUSIONS: In our cohort, early postoperative main morbidity and pancreas graft loss of SPKT recipients do not differ significantly regarding donor serum sodium levels.

Validation of the Pancreatic Donor Risk Index in Simultaneous Pancreas-Kidney Transplantation Performed in Córdoba Hospital From 2000 to 2015.

BACKGROUND: The Pancreatic Donor Risk Index (PDRI) was developed in 2010 in the United States to predict graft survival after pancreas transplantation, based on donor characteristics and logistical and technical conditions. The aim of the study was to validate the utility of PDRI as a pancreas allograft survival predictor in simultaneous pancreas-kidney transplantation (SPK) transplants performed in our hospital between 2000 and 2015. METHODS: This retrospective analysis of 126 SPK transplants was performed by the same surgical team from the years 2000 to 2015. Donor variables that are integrated in the PDRI were calculated (age, sex, race, creatinine serum levels, body mass index, height, cold ischemia time, cause of death, type of pancreas transplant). Pancreatic graft survival at 1 and 5 years was calculated by use of the Kaplan-Meier test. Comparison of survival curves between PDRI risk quartiles was calculated by use of the log-rank test. Association between graft survival and variables integrating the PDRI was calculated by use of univariate Cox regression analysis. RESULTS: Log-rank analysis found no statistically significant association between global graft survival and PDRI quartiles. Univariate Cox regression analysis showed a statistically significant association between graft survival and cold ischemia time (P < .05). CONCLUSIONS: PDRI was not a useful tool to predict pancreatic graft outcomes in a Spanish reference population.

Influence of surgical complications on kidney graft survival in recipients of simultaneous pancreas kidney transplantation.

PURPOSE: Simultaneous pancreas-kidney transplantation is the gold standard treatment for patients with end-stage renal failure secondary to insulin-dependent diabetes mellitus. This kind of transplantation is a complex operation associated with a high incidence of surgical complications and mortality risk which could influence graft survival. The aim of this study was to establish the influence of different grades of postoperative complications, classified according to Clavien-Dindo, on the rate of kidney graft loss. METHODS: We performed an observational retrospective review of all simultaneous transplantations performed between February 1989 and May 2012. Factors examined were related to recipient and donor characteristics, surgical procedures, and postoperative outcomes. For this purpose, Kaplan-Meier analyses and Cox-Regression tests are used. RESULTS: One hundred thirty-nine transplantations were performed. Complications grades I, II, and IIIa were experienced in 81 (58.3%) patients, and grades IIIb and IVa-b in 55 (39.6%). Multivariate analysis showed an influence of panel reactive antibody (hazard ratio [HR]: 10.79; P = .003), incidence of acute rejection (HR: 2.55; P = .03), and complications grouped into grades IIIb and IVa-b (HR: 3.63; P = .02). Kaplan Meier analysis showed worse kidney graft survival rate in groups grades IIIb and IVa-b compared to grades I, II, and IIIa (86.6% vs 98.7% at 1 year and 81.8% vs 97.3% at 5 years; P = .001). CONCLUSIONS: Despite being the gold standard treatment for these patients, pancreas and kidney transplantations have numerous complications which could influence the prognosis of graft kidney survival.

Index high insulin resistance in pancreas-kidney transplantation contributes to poor long-term survival of the pancreas graft.

BACKGROUND: Pancreas-kidney transplantation (PKT) is the best therapeutic option for diabetic patients with end-stage renal failure. Peripheral insulin resistance and the percentage of remaining ß-cells in the PKT have been little studied in medical literature. METHODS: We analyzed PKT performed in our hospital from January 1992 to January 2014, with follow-up for 5 years. Metabolic values related to glycemic were studied, namely, proteinuria, peptide C, glucose, insulin, and glycosylated hemoglobin. We analyzed insulin resistance (homeostatic model assessment [HOMA]-IR), the percentage of remaining ß-cells (HOMA-ß), and the influence of these variables on the glycemic profile and graft survival. RESULTS: In the study period, 156 simultaneous PKT were performed in our center. At 2 years posttransplantation, the median value of HOMA-IR kidney-pancreas was 4. We compared transplantation with lower HOMA-IR (<4) and higher HOMA-IR (>4). HOMA-ß (36 [26-67] vs 29 [14-42]; P = .04), glucose (86 [80-90] vs 81 [74-89]; P = .018), and body mass index (BMI; 24 [21-27] vs 21 [19-24]; P = .013) were greater in the group HOMA-IR>4 versus HOMA-IR<4 group, respectively, after 3 months. These differences in glycemic profile were maintained until the first year after transplantation. At 2 and 5 years of follow-up, the HOMA-IR>4 group showed higher glucose levels and greater BMI, but not differences in HOMA-ß. At 1 and 5 years posttransplantation, pancreatic graft survival in the HOMA-IR>4 group (82.9% vs 92.5%) was lower compared with the HOMA-IR<4 group (67% vs 87.5%; P = .016). CONCLUSIONS: PKT exhibit an altered glycemic profile in the posttransplantation follow-up associated with the percentage of remaining ß-cells and peripheral insulin resistance. PKT patients with peripheral insulin resistance showed decreased pancreatic graft survival.

Prediction model to discard a priori liver allografts.

BACKGROUND: The use of expanded criteria for donors to expand the donor pool has increased the number of discarded liver grafts in situ. The aim of our study was to elaborate a prediction model to reduce the percentage of liver grafts discarded before the procuring team is sent out. METHODS: We analyzed the donor factors of 244 evaluated candidates for liver donation. We performed a multiple logistic regression to evaluate the probability of liver grafts discarded (PD). RESULTS: The PD was determined by use of 3 variables: age, pathological ultrasonography, and body mass index >30. The area under curve was 82.7%, and, for a PD of 70%, the false-positive probability was 1.2%. CONCLUSIONS: We have created a useful clinical prediction model that could avoid up to 20% of discarded liver grafts.

Human fibrinogen patches application reduces intra-abdominal infectious complications in pancreas transplant with enteric drainage.

PURPOSE: The purpose of the study was to analyze the incidence of intra-abdominal infectious complications after the application of a fibrinogen sealant to the duodenojejunal anastomosis in simultaneous pancreas-kidney transplants (SPK) with enteric drainage. METHODS: Results of 68 SPKs with enteric drainage were prospectively assessed. A fibrinogen and thrombin sheet was applied to the duodenojejunal anastomosis in 34 patients, who were compared to a control group of 34 patients. The incidence and severity of intra-abdominal infectious complications and the 1-year patient and grafts survival were analyzed. RESULTS: Eighteen patients experienced intra-abdominal infectious complications. Grade 1a complications occurred in the study group, whereas surgery was required only in patients from the control group: complications grade 3a (15%) and complications grade 3b (18%) (p = 0.003 vs. study group, respectively). The overall rate of anastomotic leakage (complications grade 2b and 3b) was 10%, all of which occurred in the control group. The length of hospital stay was higher in the control group was 34.6 ± 11.3 days vs. 22.8 ± 11.1 days (p = 0.03). There were no significant differences in 1-year patient and graft survival between groups. CONCLUSIONS: In our study, the application of fibrinogen and thrombin sheets was associated to a decrease in the number and severity of intra-abdominal infectious complications.

Consolidation of enteric drainage for exocrine secretions in simultaneous pancreas-kidney transplant.

INTRODUCTION: Management of the exocrine drainage of the pancreatic graft in simultaneous pancreas kidney (SPK) transplantation has been a matter of debate for years. There is currently a trend toward a more physiological enteric drainage (ED). This study compared short- and long-term complications and graft survival in patients with enteric versus bladder exocrine secretion drainage. PATIENTS AND METHODS: Between January 1995 and November 2005, we performed 75 SPK transplants: 55 with ED and 20 with bladder drainage (BD). The rates of complications and graft survival were monitored over at least 36 months after transplantation. RESULTS: Mean posttransplant follow-up was 119.5 +/- 6.6 months. Urinary infection, hematuria, reflux pancreatitis, and repeat surgery rates were all significantly higher among the BD area. There was no intergroup difference in rejection rates or in the incidence of graft thrombosis, transplantectomy, anastomotic dehiscence, or intra-abdominal abscesses. Pancreas and kidney graft survival rates were similar in the two groups. CONCLUSIONS: In our experience, ED was more physiological than BD, and was associated with fewer complications.

One hundred one simultaneous pancreas-kidney transplantations: long-term outcomes at a single center.

INTRODUCTION: Among patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney (SPK) transplantation is associated with increased survival compared with solitary kidney transplants or dialysis. METHODS: A retrospective, descriptive study was performed on 101 consecutive SPK transplantation performed in our center over the last 20 years. We excluded six pancreas alone, eight pancreas after kidney, and four retransplantations. We analyzed demographic characteristics and patient and graft survivals. We also compared patient and pancreatic graft survivals between three periods: 1989 to 1999, 2000 to 2003, and 2004 to 2007. In the first period, bladder drainage was performed in all patients. In the second and third periods, it was replaced by enteric drainage. RESULTS: Overall patient survival was 83.2%. Kidney graft loss occurred in 12 (11.8%) patients and pancreas graft loss in 21 (20.7%) patients. Overall pancreatic graft survival was 79.2% with a 1-year value of 87.1%. By periods, pancreatic graft survival was 75% during the bladder drainage era; 76.9% in the second period; and 85.7% in the third period (P = .88). CONCLUSION: SPK transplantations in diabetic patients with end-stage renal disease were associated with improving pancreas graft survival throughout the study period.

Contribution of marginal donors to liver transplantation for hepatitis C virus infection.

The use of marginal liver donors can affect the outcomes of liver transplantation in patients with hepatitis C virus (HCV) infection. There are no firm conclusions about which donor criteria are important for allocation of high-risk grafts to recipients with HCV cirrhosis. We performed 120 consecutive liver transplantations for HCV infection between 1995 and 2005. Marginal donor criteria were considered to be: age >70 years, macrovesicular steatosis >30%, moderate-to-severe liver preservation injury, high inotropic drug dose (dopamine >15 microg/kg/min; epinephrine, norepinephrine, or dobutamine at any doses), peak serum sodium >155 mEq/L, any hypotensive episode <60 mm Hg and >1 hour, cold ischemia time >12 hours, ICU hospitalization >4 days, bilirubin >2 mg/dL, AST and/or ALT >200 UI/dL. Graft survival with donors showing these marginal criteria was compared with optimal donors using Kaplan-Meier analysis and the log-rank test. Independent predictors of survival were computed with the Cox proportional hazards model. Fifty-six grafts (46%) were lost during follow-up irrespective of the Model for End-Stage Liver Disease (MELD) scores of the recipients in each category. Upon univariate analysis, grafts with moderate-to-severe steatosis (P = .012), those with severe liver preservation injury (P = .007) and prolonged cold ischemia time (P = .0001) showed a dismal prognosis at 1, 3, and 5 years. Upon multivariate analysis, fat content (P = .0076; OR = 4.2) and cold ischemia time >12 hours (P = .034; OR = 7.001) were independent predictors of graft survival. Among HCV recipients, marginal liver donors worked similar to those from "good" donors, except for those with fatty livers >30%, especially when combined with a prolonged cold ischemia time.

Anti-TNF-alpha treatment and bile duct drainage restore cellular immunity and prevent tissue injury in experimental obstructive jaundice.

Several experimental studies of obstructive jaundice (OJ) have shown the presence of immunosuppressive state associated with the rise of tumor necrosis factor-alpha (TNF-alpha) concentration in plasma. The present study evaluates the impact of anti-TNF- alpha administration or bile duct drainage on the inflammatory response, liver injury and renal insufficiency in obstructed rats. OJ was induced by the ligation of bile duct in Wistar rats. The parameters were determined at 14 and 21 days after OJ. Two additional groups of animals were treated with anti-TNF-alpha antibodies or submitted to bile duct drainage at 14 days, and sacrificed 21 days after OJ. Cholestasis decreased glucose, and enhanced urea, creatinin, bilirubin and transaminases. Cholestasis increased the number of different inflammatory cells (T and B lymphocytes, and monocytes-macrophages) but reduced the expression of the corresponding cellular activation markers. This low responsiveness of the inflammatory cells was related to a decreased free radical production and phagocytic activity of cells. Anti-TNF-alpha and bile duct drainage reduced tissue injury, and prevented the reduction of the number and activity of T lymphocytes and phagocytic cells observed at the advanced stages of cholestasis. In conclusion, anti-TNF- alpha and bile duct drainage improved cell immunodeficiency, and reduced liver injury, cholestasis and renal insufficiency in experimental OJ.