Growth of a nation part II: impact of recipient obesity on whole-organ pancreas transplantation.

Obesity has reached epidemic proportions in the USA. Consequently, there is an increasing number of obese diabetic patients who would otherwise be appropriate candidates for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing recipients with body mass index (BMI) < 25, 25-29.9, and ≥30 kg/m(2) Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for SPK only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 PTx, 100 (32%) were overweight and 42 (14%) were obese. Obese recipients were older and more likely to be men. Donor demographics were similar. There was no difference in seven-d or 90-d graft loss, one-yr pancreas, kidney or patient survival, cause of graft loss or death, 30-d peak amylase or lipase, HbA1C, or C-peptide. The incidence of post-transplant technical, immunological and infectious complications was similar except for an increased incidence of cytomegalovirus infection in the obese group. Two recipients returned to insulin therapy despite normal C-peptide levels. Although technically challenging, PTx can be successful in select obese recipients with similar results compared to normal BMI recipients.

Growth of a nation part I: impact of organ donor obesity on whole-organ pancreas transplantation.

Obesity has reached epidemic proportions in the USA. Consequently, there are an increasing number of potential organ donors that are obese, but would otherwise be appropriate donors for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing donors with body mass index (BMI) <25, 25-29.9, and ≥30 kg/m(2) . Data included recipient and donor demographics, seven and 90-d graft loss, one-yr pancreas, kidney (for simultaneous pancreas and kidney transplant only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c-peptide. Of the 308 donors, 84 (27%) were overweight and 43 (14%) were obese. The overweight donors were significantly older, and the obese donors had hypertension significantly more frequently than the other two groups. There were no significant differences in recipient transplant demographics. There was no significant difference in length of stay or 90-d readmissions, seven or 90-d pancreas graft loss, one-yr graft or patient survival, peak serum amylase or lipase, HbA1C, or c-peptide. The incidence of post-transplant technical, immunological, and infectious complications were similar. Although technically challenging, PTx of allografts from obese donors can be accomplished with similar results compared to normal BMI donors.

Early steroid withdrawal in repeat kidney transplantation.

BACKGROUND AND OBJECTIVES: Kidney re-transplantation (KRT) candidates are considered at high risk for graft failure. Most of these patients are kept on a chronic steroid maintenance (CSM) regimen. The safety of early steroid withdrawal (ESW) remains unanswered in KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study was aimed at comparing the outcomes of ESW and CSM in KRT. Retrospective analysis of 113 KRT patients (ESW, n=59; CSM, n=54) was performed. All patients received rabbit anti-thymocyte globulin/steroid induction and were maintained on mycophenolate/tacrolimus (±steroids). RESULTS: One- and 5-year patient survival for the ESW and the CSM group were not significantly different (98 versus 96% and 91 versus 88%, respectively; P=0.991). No significant difference was seen in the graft survival for both groups at 1 and 5 years (98 versus 93% and 80 versus 74%, respectively; P=0.779). Mean 1- and 5-year estimated GFR was not statistically different between the groups (P=0.773 and 0.790, respectively). The incidence of acute rejection at 1 year was 17 and 22% in ESW and CSM patients, respectively (P=0.635). Compared with the ESW group, patients in the CSM group were more likely to be hyperlipidemic (P=0.044), osteoporotic (P=0.010), post-transplant diabetics (P=0.051) and required more medications to control BP (P=0.004). CONCLUSIONS: ESW seems to be a reasonable approach in KRT recipients because the short and intermediate patient survival, graft survival, and graft function is comparable to CSM immunosuppression.

Severe hypernatremia in deceased liver donors does not impact early transplant outcome.

BACKGROUND: There may be an increased risk of primary nonfunction in livers procured from donors with hypernatremia. The purported mechanism for this effect is undefined. This study analyzes early graft function for donor livers procured from patients with severe hypernatremia. METHODS: The organ procurement records for 1013 consecutive deceased liver donors between 2001 and 2008 were reviewed. Both peak and terminal serum sodium levels were categorized as (1) severe for a level 170 mEq/L or higher, (2) moderate for 160 to 169 mEq/L, and (3) normal for less than 160 mEq/L. Outcomes included 30-day posttransplant alanine aminotransferase and total bilirubin, primary nonfunction, and 30-day and 1-year graft survival. RESULTS: Within the severe hypernatremia group, there were 142 (peak) and 50 (terminal) donors, whereas the moderate group had 233 (peak) and 162 (terminal) donors. The study groups did not differ in recipient age, model for end-stage liver disease score, steatosis, and ischemia times for the peak or terminal serum sodium groups. The differing levels of hypernatremia severity did not differ importantly, for peak or terminal serum sodium, in posttransplant alanine aminotransferase or total bilirubin, or the risk of intraoperative death and primary nonfunction. Thirty-day and 1-year graft survival did not demonstrate a negative impact from donor hypernatremia. CONCLUSIONS: Posttransplant measures of early liver function and risk of failure, up to 1-year posttransplant, did not differ significantly based on peak or terminal donor serum sodium levels. These results suggest that donor serum sodium level likely has little clinical impact on posttransplant liver function.

Symptoms related to ureteral stents in renal transplants compared with stents placed for other indications.

OBJECTIVE: To use a validated questionnaire to compare indwelling ureteral stent symptoms in patients who had the ureteral stent placed during renal transplantation with patients who had retrograde insertion of the stent in a native kidney during endoscopic procedures. METHODS: Symptoms related to the presence of a ureteral stent were assessed prospectively in the two patient groups. Just before stent removal, patients completed a validated Ureteral Stent Symptom Questionnaire evaluating urinary symptoms, body pain, general health, work performance, and sexual function. Categorical scores and individual factors were qualitatively and statistically compared between the two groups. RESULTS: Twenty-eight (15 men and 13 women) patients (mean age 56, range 72-32) underwent renal transplantation with ureteral stents removed after a mean of 41 days (range 9-81). Seventeen (4 men and 13 women) patients (mean age 43, range 73-17) had ureteral stents placed in native kidneys for other indications with subsequent removal after a mean of 24 days (range 6-61). The transplant group had statistically fewer urinary symptoms (p = 0.001), pain symptoms (p < 0.001), better overall health index (p = 0.005), and improved quality of work (p = 0.008). Transplant patients complained of fewer urinary symptoms (urgency, dysuria, dribbling, and hematuria), required less additional antibiotic use, and had fewer additional clinic or hospital visits. CONCLUSIONS: Ureteral stents inserted during renal transplantation result in significantly fewer symptoms when compared with stents inserted in the native ureter. This, in part, may be because of less trigonal irritation by the stent when the ureteral implantation is in the dome of the bladder.

No difference in transplant outcomes for local and import pancreas allografts.

BACKGROUND: In the United States, pancreas allograft allocation is strictly regulated. Local centers have the first option to accept an organ, followed by regional and national allocation for those not accepted locally. For a pancreas to be imported, many centers must have previously rejected the organ for transplantation. This study reviews the outcomes of all pancreas allografts transplanted at a single center between January 2003 and November 2007. Early graft function and graft survival were stratified by geographic source of the donor pancreas. METHODS: The records of 247 pancreas recipients and the donors of 11 imported and discarded pancreas allografts were reviewed. Pancreas allograft survival is represented using a Kaplan-Meier survival curve comparing (1) locally procured and imported pancreas grafts and (2) grafts procured by a team from our own center with the grafts procured by another team. RESULTS: Of the 247 grafts, 184 (74%) were local and 63 (26%) were imported. There were no differences between the two geographic groups in 1-year graft survival (local 91%, import 90%, P=0.76). Similarly, graft survival was similar regardless of whether the organ was procured by our own team or by another center (local team 91%, another team 90%, P=0.96). CONCLUSIONS: Pancreas allografts refused by a large number of centers may still be imported and successfully transplanted without affecting survival results.

No difference in clinical transplant outcomes for local and imported liver allografts.

In the United States, liver allograft allocation is strictly regulated. Local centers have the first option to accept a donor liver; this is followed by regional allocation for those donor livers not used locally and then by national allocation for those donor livers not accepted regionally. This study reviews the outcomes of all liver allografts used over 6 years (2001-2007) and evaluates initial and long-term function stratified by the geographic source of the donor liver allograft. The records for 845 consecutive deceased donor liver transplants at a single center were reviewed. The geographic origin of the allograft was recorded along with donor and graft characteristics to determine the probable reason for graft refusal. Within our local organ procurement organization, there is 1 liver transplant center, and within the region, there are 8 active centers. Early graft failure included any graft loss within 7 days of transplant, and initial function was measured with liver enzymes 30 days post-transplant. Graft survival and patient survival were evaluated with Kaplan-Meier and Cox survival modeling. Median follow-up was 43 months. The geographic distribution of organs included local organs (562, 66%), regionally imported organs (126, 15%), and nationally imported organs (157, 19%). There were no differences between the 3 groups in initial graft function, intraoperative death, or early graft loss. Survival curves for the 3 study groups demonstrated no difference in survival up to 5 years post-transplant. In conclusion, liver allografts rejected for use by a large number of transplant centers can still be successfully used without early graft function or long-term survival being affected.

The case for pancreas after kidney transplantation.

Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

Bilateral sequential lung and simultaneous pancreas transplant: a new approach for the recipient with cystic fibrosis.

UNLABELLED: Cystic fibrosis (CF) is an inherited disorder that presents in childhood as a multisystem disease. Pulmonary failure and pancreatic insufficiency, including CF related diabetes (CFRD) and exocrine insufficiency, are common complications of this disease. In this report we review the first three simultaneous lung and pancreas transplantations in CF patients with diabetes. METHODS: All three CF patients presented for evaluation for lung transplantation and had pancreatic insufficiency requiring enzyme supplementation and CFRD requiring insulin. All were severely malnourished and required nutritional supplementation. SURGICAL TECHNIQUE: In each case, the allografts were procured from a single cadaveric donor. Bilateral lung transplantation was performed first using two separate thoracic incisions. The pancreas transplant was performed with systemic venous drainage and enteric exocrine drainage. RESULTS: The pancreas allografts all functioned normally with normoglycemia independent of insulin. As a result of the enteric drainage of the pancreas allograft, supplemental pancreatic enzymes were no longer required. Despite several complications detailed in the manuscript, all three remain independent of supplemental oxygen, insulin and pancreatic enzyme replacement at 4, 6 and 14 months of follow-up. CONCLUSION: Simultaneous lung and pancreas transplantation in patients with CF can be performed successfully and provides the advantages of normoglycemia and improves nutrition for patients requiring lung transplantation.

Use of extended criteria livers decreases wait time for liver transplantation without adversely impacting posttransplant survival.

INTRODUCTION: The use of extended criteria donors (ECDs) could minimize shortage of suitable donor livers for transplantation. In 3 years, the aggressive use of ECD livers has reduced the wait list at our center from 257 to 30 patients with a median wait time of 18 days without using living donors. This study compares the graft/patient survival from standard (SD) and ECD for our transplant population between 2001 and 2005. METHODS: Records of all adult liver transplant recipients over 4 years were reviewed (n = 571). ECD criteria included: age >59 years, BMI >34.9, maximum AST/ALT >500, maximum bilirubin >2.0, peak serum sodium >170, HBV/HCV/HTLV reactive, donation after cardiac death, cold ischemia time >12 hours, ICU stay >5 days, 3 or more pressors simultaneously, extensive alcohol abuse, cancer history (nonskin), active meningitis/bacteremia, or significant donor liver trauma. Outcomes included graft and patient survival at 90 days, 1 year, and 2 years. RESULTS: Sixty-eight percent of recipients (n = 388) received ECD livers. Primary factors accounting for ECD-liver status included: elevated liver function tests (20%), hypernatremia (12.6%), and extensive alcohol abuse (11.4%). Graft survival was (SD, ECD): 90-day 91%, 88%; 1-year 84%, 80%; 2-year 78%, 77%; patient survival was: 90-day 93%, 90%; 1-year 87%, 82%; 2-year 83%, 79%. Kaplan-Meier survival analysis failed to demonstrate an overall difference in graft or patient survival at any time point. Only donor age >60 years was associated with decreased graft and patient survival. CONCLUSIONS: Liver grafts from ECD can be used to dramatically reduce wait list time with outcomes comparable to those for SD without resorting to living donor liver transplantation.

Internal hernia after pancreas transplantation with enteric drainage: an unusual cause of small bowel obstruction.

BACKGROUND: Although complications involving leaking at the enteric anastomosis site, graft thrombosis, and intraabdominal abscess formation have been well documented after pancreas transplantation, the occurrence of small bowel obstruction in this setting has received scant attention. Although uncommon, intestinal obstruction after pancreas transplantation may have atypical etiologies. In this article, we will review three unusual cases of intestinal obstruction in pancreas transplant recipients. The value of computed tomographic (CT) enteroclysis in equivocal situations in the diagnosis of the obstruction is emphasized. METHODS: In this study, we reviewed the posttransplant course of all pancreas transplants performed between July 1, 2002 and June 1, 2004. We specifically focused on all patients that required reexploration for suspected small bowel obstruction at any time after transplantation. RESULTS: A total of 65 pancreas transplants were performed between July 1, 2002 and June 1, 2004. Pancreas graft survival was 97%, and patient survival was 98.5%. Five (7.7%) patients presented with mechanical small bowel obstruction, three of which were secondary to internal herniation of small intestine through a defect posterior to the pancreas allograft. All patients recovered well postsurgically. DISCUSSION: Small bowel obstruction is an uncommon complication after pancreas transplantation. CT enteroclysis in the evaluation of small bowel obstruction may assist the patient care decision-making process by providing information on the location and severity of the obstruction in the clinical situation where conventional abdominal CT and radiography are equivocal. Prompt detection of small bowel obstruction with early surgical intervention can minimize complications and preserve allograft function.

Ipsilateral placement of simultaneous pancreas and kidney allografts.

The current standard technique for simultaneous kidney pancreas transplantation usually involves transplanting the pancreas to the right and the kidney to the left iliac system. Here we describe a previously unreported technique where both organs are transplanted to the right iliac system through a single midline incision. Forty-nine patients underwent simultaneous ipsilateral pancreas and kidney transplantation. All pancreas grafts were drained enterically. Overall patient, pancreas, and kidney survival were 96% (47/49), 92% (45/49), and 94% (46/49) respectively. The 45 patients with functioning grafts are insulin free and off of dialysis. Mean serum creatinine at 1, 3, 6, and 12 months was 1.7+/-1.3, 1.2+/-0.3, 1.3+/-0.3, and 1.3+/-0.4 mg/dL, respectively. The placement of the pancreas and kidney transplants on the same side is safe and does not compromise patient or graft survival. This approach preserves the left iliac system for future retransplantation if necessary.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution for organ preservation in clinical pancreas transplantation.

BACKGROUND: University of Wisconsin (UW) solution is currently the standard preservation solution used for abdominal organ transplantation. This study assesses the efficacy of histidine-tryptophan-ketoglutarate (HTK) compared with UW in pancreas transplantation. METHODS: Between October 2002 and August 2003, 20 pancreas transplants were performed. Patients were divided into two groups: UW (n=10) and HTK (n=10). Donor and recipient demographics were similar in both groups. The mean cold ischemia time for both groups was 11 +/-3 hr. RESULTS: There was an anticipated difference between total preservative volumes used (HTK: 4.5 +/- 1.2 L vs. UW: 3.4 +/-0.8 L; P =0.03). Patient and graft survivals to date were 100% in both groups. Serum fasting blood glucose, peak amylase, and serial amylase levels remained comparable at all intervals posttransplantation. CONCLUSIONS: Within this range of cold ischemia time, UW and HTK demonstrate similar efficacy in pancreas preservation.

Lymphedema associated with sirolimus in renal transplant recipients.

Lymphoceles are common in renal transplant recipients who receive sirolimus (SRL). However, a recent MEDLINE search revealed no reports of lymphedema related to SRL. We describe three cases of lymphedema that resolved or improved on discontinuation of SRL. No other likely causes of lymphedema were discovered. Recognizing the association may lead to early discontinuation of SRL, which may prevent permanent disfigurement. It may also prevent unnecessary investigations. The mechanisms of this phenomenon are not clear. We hypothesize that increased lymph flow along with disrupted lymphatics in the affected extremities may explain this complication of SRL. Further studies are necessary to confirm our findings.

The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin.

Polyclonal antibodies, such as equine antithymocyte globulin (ATGAM), are known to induce antibody formation. This study evaluated the in vivo effect of sirolimus on antibody formation associated with the use of equine antithymocyte globulin in renal transplant recipients. Recipients of either a living-related donor or cadaveric renal allograft received azathioprine (AZA) (n = 15), mycophenolate mofetil (MMF) (n = 12), or sirolimus (n = 15) in addition to baseline immunosuppression with corticosteroids, cyclosporine, and equine antithymocyte globulin. Immediately before transplantation and weekly for at least 1 month, sequential serum specimens were tested for the presence of human anti-equine antibody using an enzyme-linked immunosorbent assay (ELISA). Anti-equine antibody formation was significantly different among the three treatment groups. Fewer patients receiving MMF (17%, p = 0.007 vs. AZA) and sirolimus (13%, p = 0.003 vs. AZA) developed anti-equine antibody compared with AZA (66%). There was no significant difference (p = 0.81) in the sensitization to equine antithymocyte globulin when comparing the patients receiving MMF or sirolimus. In the sensitized patients, high anti-equine antibody titers (>1 : 500) were more common in those receiving AZA (n = 3) than MMF (n = 0) or sirolimus (n = 1). Compared to AZA, sirolimus, when given in combination with cyclosporine A, significantly reduced anti-equine antibody formation to a degree similar to MMF.

Creatinine reduction ratio and 24-hour creatinine excretion on posttransplant day two: simple and objective tools to define graft function.

To devise objective criteria for early diagnosis of delayed graft function (DGF), 59 adult living donor kidney transplants with immediate graft function (IGF) and 51 cadaveric kidney transplants were investigated for creatinine reduction ratio (CRR2) from posttransplant day 1 to day 2 and 24-h urine creatinine excretion (UC2) on day 2. The mean CRR2 in living donor transplants was 53% (SD +/- 11); the distribution of CRR2 was gaussian, and all of them had UC2 >1000 mg. Criteria for DGF were developed on the basis of living donor transplant: CRR2 < or =30% (2SD below 53%) +/- UC2 < or =1000 mg. Overall, 24 cadaver transplant recipients (47%) developed DGF (CRR2 < or =30%); 13 patients (25%) had mild DGF (UC2 >1000 mg), and the remaining 11 (22%) had severe DGF (UC2 < or =1000 mg). All the patients with severe DGF had a measured creatinine clearance <25 ml/min on day 7, and 8 of 11 were dialyzed within the first week of transplantation. Patients with IGF and mild DGF had a creatinine clearance of > or =25 ml/min on or before day 7, and none of them were dialyzed. Calcineurin inhibitors were avoided or delayed in five patients with mild DGF and all patients with severe DGF. In conclusion, diagnosing DGF within 48-h after transplantation is simple and may be valuable in the management of these patients.