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Background: The selection of patients for solitary pancreas transplantation (PTA) requires identification of individuals who will not develop acute renal dysfunction in response to immunosuppressants. A cyclosporine challenge test (CCT) was developed to predict post-PTA kidney dysfunction secondary to calcineurin inhibitor immunosuppressants. We now report on the long-term follow-up of patients who received a PTA after undergoing a CCT., Methods: Twelve potential PTA recipients were administered cyclosporine A (CsA) for 6 wk. Creatinine clearance (CrCl) was measured at 2, 4, and 6 wk. Those who did not fail the CCT received PTA. Baseline and post-transplant CrCl were retrospectively evaluated in the original cohort and in a group of matched patients who received PTA without a CCT., Results: Of the original 12 recipients evaluated with the CCT, 6 received PTA. CrCl was followed for a mean of 45.8 months. Of the 4 who remained alive, 2 went on to develop renal failure (CrCl < 30 mL/min) at 18 and 65 months post-transplant. The baseline CrCl was higher in PTA recipients who had not been selected to be studied with CCT than those that were (117 +/- 32 vs 78 +/- 13 mL/min). By 12 months post-PTA, the CrCl was no longer different between the groups selected to be screened with CCT and those that were not., Conclusions: CCT may help predict risk for short-term changes in renal function (< 18 months) in response to CsA. CCT may be most helpful in candidates for PTA with borderline renal insufficiency (60-80 mL/min).

Background: In simultaneous kidney-pancreas (SPK) transplantation, manifestations of renal allograft rejection typically become evident before those of pancreatic rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA) in prevention of renal rejection after primary SPK transplantation., Methods: In an open-label, randomized, multicenter study, patients received MMF 1.5 g twice daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The incidence of rejection was assessed at 6 months. Adverse events were tracked through 1 year. Survival data are reported through 2 years., Results: At 6 months, efficacy results for MMF vs. AZA patients, respectively, were the following: rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss, death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month efficacy trends favored MMF, and time to rejection or treatment failure was significantly longer when compared with AZA (P=0.049). One-year efficacy results for MMF vs. AZA patients, respectively, were the following: treatment of renal rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in the AZA group died. More MMF than AZA patients developed opportunistic infections (54% vs. 38%), but the pathogens did not differ., Conclusions: Trends for most efficacy parameters favored MMF over AZA, and time to renal allograft rejection or treatment failure was statistically significantly longer for MMF. The use of MMF in the treatment of SPK recipients is a useful advance.

Combined pancreas-kidney transplantation (PKT) has become generally accepted as an effective treatment option, but controversy exists regarding the early morbidity rate of the procedure. To address this issue, we retrospectively analyzed all readmissions occurring in the first 3 months after PKT. Over a 5-year period, we performed 98 PKTs with bladder drainage. The mean recipient age was 36.6 years, with a mean pretransplant duration of diabetes of 23.5 years. All patients received quadruple immunosuppression with antilymphocyte induction therapy. The mean length of initial hospital stay was 20 days. One hundred forty-five readmissions occurred in 73 patients (74.5%), with the initial readmission occurring at a mean of 8.5 days after hospital dismissal and 28 days after PKT. Twenty-five patients (25.5%) had no readmissions, 35 (36%) had one readmission, 17 (17%) had two readmissions, and the remaining 21 patients (21.5%) had three or more readmissions in the first 3 months. The mean number of readmissions was 1.5 per patient. Forty-seven patients (48%) were readmitted within 1 week, and all but one initial readmission occurred within 1 month of hospital dismissal. Causes of readmission included rejection (51), infection (32), pancreas-specific morbidity (such as dehydration, hematuria, or pancreatitis; 50), and miscellaneous causes (12). Thirteen patients (13%) underwent reoperation during readmission. The mean length of hospital stay during readmission was 7.6 days. The mean total length of hospitalization in the first 3 months after PKT was 31 days. Over the span of 5 years, no changes have occurred either in the incidence, timing, causes, or duration of readmissions. The patient survival rate is 96%, the kidney graft survival rate is 90%, and the pancreas graft survival rate is 88% after a mean follow-up of 2.6 years. Mean rehabilitation time (return to work or normal activity) after PKT was 4.0 months. In conclusion, PKT is associated with a fixed morbidity characterized by early readmission (within 1 week) in nearly half of patients and pancreas-specific morbidity as the cause in 35% of readmissions. During evaluation, prospective candidates should be counseled regarding the unique morbidity of PKT. Successful management strategies must emphasize the intensity of early follow-up and recognize the propensity toward immunologic, metabolic, exocrine, and urologic side effects.

Purpose: To determine the usefulness of sonographically obtained resistive indexes (RIs) in the diagnosis of pancreas allograft rejection., Materials and Methods: Findings were studied from 78 transduodenal pancreas allograft biopsies that were ultrasound-guided and cystoscopically directed. The 78 biopsies included 40 that were compared directly with baseline RI data. Biopsies were categorized by result and correlated with concurrent RIs (including 26 RIs obtained within 24 hours of biopsy) with the chi2 test for categoric variables and the Student t test for continuous variables. Sensitivity, specificity, and positive and negative predictive values were calculated with standardized formulas., Results: The mean RIs between the no rejection, mild acute rejection, and moderate acute rejection groups were not statistically significantly different; however, the mean RI associated with chronic rejection was statistically significantly higher (P < .05) than that in the other groups. The sensitivity, specificity, and positive and negative predictive values of either an elevated RI (> 0.70) or greater than 10% increase in the RI above the baseline value in the diagnosis of acute rejection were approximately 50%., Conclusion: Neither the absolute level of the RI nor the relative increase was correlated with acute rejection proved at biopsy. Changes in RIs after pancreas transplantation were a poor indicator of acute rejection, but the absolute value of the RI was elevated in cases of chronic rejection.

Mesenteric arteriovenous fistula (AVF) is an unusual complication after vascularized pancreas transplantation. We report the case of a patient who developed a mesenteric AVF in the transplanted mesenteric bundle which resulted in severe and protracted endocrine insufficiency necessitating reinstitution of insulin therapy. This was reversible with surgical correction of the AVF. This complication should be included in the differential diagnosis of pancreas allograft dysfunction.

The early detection of allograft rejection remains elusive after solitary pancreas transplantation (PTX). We have previously described a modified technique of cystoscopic transduodenal PTX biopsy using the Biopty gun under ultrasound guidance. During the last 2 years, we performed 24 solitary PTXs with prospective protocol biopsy monitoring as well as biopsies performed whenever clinically indicated. The study group included 17 pancreas transplants alone, 6 sequential pancreas after kidney transplants, and 1 sequential pancreas after liver transplant. Five patients received pancreas retransplants. A total of 92 cystoscopically directed core PTX biopsies were performed, including 50 protocol biopsies (mean 2.1 per patient). Protocol biopsies were performed at 1 month (19), 2 months (3), 3 months (20), 6 months (7), and 12 months (1) after PTX. Adequate PTX tissue for histopathologic examination was obtained in 49 cases (98%). Biopsy findings included no rejection (34), mild rejection (13), pancreatitis (1), and cytomegalovirus infection (1). Overall, 15 of the 49 evaluable biopsies (31%) had significant histopathologic findings. All but 1 of the cases of mild rejection were treated with bolus steroids. Eight of these patients subsequently developed recurrent biopsy-proven rejection within 2 months; 5 grafts were subsequently lost to rejection between 3 and 13 months after PTX. Three biopsy complications occurred: 1 hematoma, 1 pancreatitis, and 1 ileus. Patient survival is 96% and PTX graft survival (complete insulin independence) is 75% after a mean follow-up of 15 months. In the remaining 42 clinically indicated biopsies, 3 were insufficient, 8 showed no rejection, and 31 (79%) had rejection. In half of these cases, the rejection was graded as moderate to severe. In conclusion, prospective monitoring with protocol PTX biopsies may result in the earlier detection of allograft rejection and have a direct effect on improving results after solitary PTX.

Vascularized pancreas transplantation has assumed an increasing role in the treatment of diabetes mellitus. Through 1994, over 6000 pancreas transplants had been performed worldwide, with over 80% being combined pancreas-kidney transplants. Overall 1-year patient survival exceeds 90% and graft survival (complete insulin independence) exceeds 70%. Although successful pancreas transplantation achieves euglycemia and complete insulin independence, this occurs at the expense of hyperinsulinemia and chronic immunosuppression. The net effect of these changes on diabetic complications in the long term remains to be determined. In the short term, improvement in the quality of life and possible prevention of further morbidity associated with diabetes makes pancreas transplantation an important therapeutic option, particularly when combined with a kidney transplant, in appropriately selected diabetic patients.

A common urologic complication after pancreas transplantation with bladder drainage is hematuria. However, hematuria is usually mild and self-limiting and rarely requires open surgical intervention. We report an unusual case of refractory hematuria that began 17 days after solitary pancreas transplantation due to severe rejection. The patient developed severe duodenal segment swelling with mucosal rupture that eventually required operative therapy. This case is illustrative of the diagnosis and management of gross hematuria after pancreas transplantation and demonstrates the limitations of cystoscopic techniques. This unusual complication must be considered in the differential diagnosis of refractory hematuria with pancreas allograft dysfunction and may represent a problem unique to solitary pancreas transplantation until better immunosuppressive strategies are available.

Hyperlipidemia is a significant risk factor for atherosclerotic vascular disease. We have shown previously that pancreas transplantation (PTX) improves but does not normalize lipids in most PTX recipients. We studied whether pravastatin was effective in treating 10 patients with elevated low density lipoprotein (LDL)-cholesterol (LDL-C) following PTX. Seven men and 3 women were studied. Six received combined kidney-pancreas transplantations, while 4 received PTX alone. Age at time of PTX was 37.2 +/- 2.2 years (mean +/- SEM), and 4 had established coronary artery disease before PTX. Mean cholesterol (C), LDL-C, triglycerides (TG), and high density lipoprotein (HDL)-cholesterol (HDL-C) were 236 +/- 12, 142 +/- 6, 222 +/- 50, and 49 +/- 4 mg/dl before PTX. The LDL to HDL ratio was 3.0 +/- 0.3. After PTX, excluding the first 45 days, mean C, LDL-C, and HDL-C increased to 278 +/- 10, 178 +/- 7, and 63 +/- 6 mg/dl (all P < or = 0.05), respectively. TG, LDL to HDL ratio, and weight were unchanged. Pravastatin (11.7 +/- 0.8 mg/day, mean +/- SEM) was initiated 250 +/- 53 days after PTX. During therapy, C and LDL-C decreased on average to 231 +/- 10 and 134 +/- 8 mg/dl, respectively (both P < 0.01), while HDL did not change. The decreases in C and LDL-C were unexplained by a decrease in weight, cyclosporine dose or concentration, or increase in serum creatinine. However, prednisone dose decreased over the same interval, so a contribution from this variable cannot be excluded. No evidence of toxicity was identified during therapy. This is one of the first reports demonstrating that pravastatin is a safe and effective treatment for elevated C and LDL-C in patients following PTX. However, pravastatin did not increase HDL or decrease TG, as observed in the nontransplantation setting. Whether pravastatin or any hypolipidemia therapy can prevent cardiovascular events or mortality following PTX remains to be established.

Objective: The authors compared results and morbidity in insulin-dependent diabetes mellitus (IDDM) patients undergoing preemptive pancreas transplantation (PTx) either before dialysis or before the need for a kidney transplant with IDDM patients undergoing conventional combined pancreas-kidney transplantation (PKT) after the initiation of dialysis therapy., Summary Background Data: Combined PKT has become accepted generally as the best treatment option in carefully selected IDDM patients who either are dependent on dialysis or for whom dialysis is imminent. With improving results, the timing of PKT relative to the degree of nephropathy is evolving. However, it is not well established that the advantages of preemptive PTx can be achieved without incurring a detrimental effect on graft function or survival., Methods: Over a 4-year study period, data on the following 3 recipient groups were collected prospectively and analyzed retrospectively: 1) 38 IDDM patients undergoing combined PKT while on dialysis (PKT:D); 2) 44 IDDM patients undergoing preemptive PKT before dialysis (PKT:ND); and 3) 20 IDDM patients undergoing solitary PTx. All patients underwent whole organ PTx with bladder drainage and were treated with quadruple immunosuppression., Results: Actuarial 1-year patient survival is 100%, 98%, and 93%, respectively. One-year actuarial PTx survival (insulin-independence) is 92%, 95%, and 78%, respectively. The incidence of rejection, infection, operative complications, readmissions, and total hospital days was similar in the three groups. Long-term renal and pancreas allograft function and quality of life were similarly comparable. Rehabilitation potential favored the solitary PTx and PKT:ND groups., Conclusions: Preemptive PKT or solitary PTx performed earlier in the course of diabetes is associated with good results, facilitated rehabilitation, and may prevent further diabetic complications.

Cytomegalovirus is an important cause of morbidity after solid organ transplantation. We report a case of cytomegalovirus infection involving the transplanted ureter that developed after combined pancreas-kidney transplantation. The patient presented with acute renal allograft dysfunction caused by ureteral stricture.

Objective: Hypoglycemic symptoms have been reported by more than half of pancreas transplantation (PTX) recipients. To better understand the mechanism for the hypoglycemia documented in some of these patients, we studied the glucose and pancreatic hormone response to Sustacal in patients with and without hypoglycemia following PTX., Research Design and Methods: Twelve patients with established, repeated episodes of hypoglycemia following PTX (hypo) were case-matched to PTX recipients without hypoglycemic symptoms (control; n = 7). On the day of the study, fasting glucose, free and total immunoreactive insulin (IRI), C-peptide, proinsulin, and glucagon were drawn (time 0); Sustacal was administered; and glucose, free and total IRI, and C-peptide were assayed at 15, 30, 45, 75, 120, 150, 180, and 240 min. Based on the glucose response to Sustacal, the hypo group was further divided into those whose glucose rose after Sustacal (hypo-high; n = 7) and those with no increase in glucose from baseline concentration (hypo-flat; n = 5)., Results: Before the administration of Sustacal, the hypo-high group had a lower fasting free/total IRI (0.26 +/- 0.06, mean +/- SE) than the hypo-flat (0.51 +/- 0.02) or control (0.52 +/- 0.04) groups (both P < 0.05 compared with hypo-high). The glucose response to Sustacal was greatest in the hypo-high group as defined. Area under the curve (AUC) for total IRI following Sustacal was also greatest in the hypo-high group (P < 0.05 compared with both control and hypo-flat groups), but there was no significant difference in free IRI AUC following Sustacal between the three groups. Two individuals developed hypoglycemia during the Sustacal challenge, both in the hypo-high group., Conclusions: The lower fasting free/total IRI ratio and greater increase in glucose and total IRI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of significant quantities of anti-insulin antibodies in the hypo-high group. Because anti-insulin antibodies are, in turn, an established cause of episodic hypoglycemia, this study provides the first data to support the hypothesis that significant quantities of anti-insulin antibodies are a cause of symptomatic hypoglycemia following PTX in some recipients.

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.

KPT has become the treatment of choice for many Type I diabetics with impending or actual end-stage renal disease. The techniques of organ procurement, surgical transplantation, and postoperative management are well established. The current 1- and 3-year patient and graft survival rates are at least equal to those obtained in both diabetic and nondiabetic patients receiving kidney transplants alone. Although there is significant associated morbidity unique to the pancreas transplant, this is usually manageable without influencing the outcome. With the improvement in quality of life and the potential for arresting diabetic complications, KPT is a procedure that should be seriously considered for many Type I diabetic patients with advanced nephropathy.

Between December 1991 and June 1993, the authors performed cystoscopic transduodenal biopsy of pancreas transplants in 35 consecutive patients (18 men and 17 women, aged 22-48 years [mean, 34 years]). The first 12 biopsies were performed under direct visualization and the last 23 were performed with ultrasonographic (US) guidance. Specimens were adequate for pathologic diagnosis in nine of 12 (75%) and in 22 of 23 (96%) biopsies, respectively. US-guided biopsy of pancreas transplants is safe and effective and gives increased diagnostic yield.

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

In summary, we believe that combined PKT can be performed safely and effectively in the absence of uremia, thereby providing the potential for arresting the progression of diabetic complications prior to the development of ESRD. Furthermore, performing solitary PTx prior to the need for a kidney transplant can be accomplished with morbidity and results comparable to PKT. Rehabilitation potential tends to favor patients undergoing either solitary PTx or preemptive PKT. In selected IDDM patients without end-stage diabetic nephropathy, we believe that solitary PTx or PKT are effective treatment options and need not be considered as preemptive, especially in view of increasing waiting times and the variable progressive nature of diabetic complications. As results continue to improve, solitary PTx may offer a potential solution to the growing number of IDDM patients awaiting kidney transplantation in the United States. Ultimately, the role of solitary PTx in the treatment of IDDM will be determined by long-term studies documenting the prevention or arrest of secondary diabetic complications. In the short-term, improvement in quality of life and rehabilitation potential makes preemptive PKT or solitary PTx important therapeutic alternatives for consideration.

Despite improving results, the management of exocrine complications after pancreas transplantation remains problematic. During a 30-month period, we performed 65 pancreas transplants with bladder drainage. A total of 23 patients (35%) were managed with a long-acting somatostatin analogue (Sandostatin) for persistent hyperamylasemia or allograft pancreatitis. Sandostatin was begun at a mean of 29 days after transplant with a mean duration of therapy of 13 days. Sandostatin therapy was associated with significant reductions in the serum, urine, and peritoneal fluid amylase levels (p < 0.05). Sandostatin also caused a decrease in cyclosporine levels during oral cyclosporine use. In patients receiving Sandostatin, pancreas allograft survival was 83%. We conclude that pancreatitis remains a major cause of morbidity after pancreas transplantation. The selective use of Sandostatin can result in excellent graft salvage with low morbidity. Sandostatin appears to be safe and effective in reducing the exocrine output of the denervated pancreas allograft but also reduces cyclosporine levels.

Background: Vascularized pancreas transplantation (PTx) for type I diabetes mellitus results in euglycemia at the expense of chronic immunosuppression, hyperinsulinemia, and dyslipidemia. However, the effect of PTx on native biliary lithogenesis remains unknown., Methods: To address this issue, we retrospectively studied 72 consecutive pancreas transplant recipients and compared them with patients both with (n = 35) and without (n = 52) diabetes mellitus undergoing kidney transplantation alone (KTA). All patients underwent pretransplantation abdominal ultrasonography, which was repeated at 6- to 12-month intervals after transplantation. PTx recipients were managed with quadruple immunosuppression with OKT3 induction. Kidney transplant recipients received cyclosporine and prednisone., Results: Seventeen (30.4%) of 56 evaluable PTx recipients had gallstones at a mean interval of 13 months (range, 5 to 24) after PTx. Eleven patients underwent open cholecystectomy (with one surgical exploration of common bile duct for choledocholithiasis), three underwent laparoscopic cholecystectomy, and the other three are being managed expectantly. Gallstone analysis revealed predominantly cholesterol stones. The incidence of cholelithiasis in kidney transplant recipients with and without diabetes mellitus was 27.3% and 12.2%, respectively (p = 0.04)., Conclusions: Pancreas transplant and kidney transplant recipients with diabetes are predisposed to the development of gallstones compared with recipients without diabetes. An interaction between diabetes mellitus-induced gallbladder dysmotility and cyclosporine-induced cholestasis may be a possible mechanism. We recommend serial ultrasonographic examinations in pancreas transplant and kidney transplant recipients, and cholecystectomy in pancreas transplant recipients with cholelithiasis should be considered.

Urological complications are common following pancreas transplantation with bladder drainage. Some investigators have excluded patients from pancreas transplantation because of abnormal preoperative urodynamics. To determine the risk of an abnormal bladder in bladder-drained pancreas transplantation, we prospectively evaluated 23 type I diabetic patients undergoing pancreas transplantation with preoperative urodynamics. For study purposes, criteria for an abnormal urodynamic evaluation were a bladder capacity of greater than 1,000 cc, absence of normal detrusor contractility and an abnormal voiding pattern. In addition, an abnormal study was defined by the presence of 2 or more of the following: 1) suppressed proprioception at 250 cc or at a volume of greater than 50% of bladder capacity, 2) peak flow of less than 10 cc per second, 3) interval to peak flow of greater than 30 seconds or 4) post-void residual of greater than 150 cc. Of the 23 patients 10 (43%) had abnormal preoperative urodynamic studies. All 23 patients underwent pancreas transplantation with bladder drainage, alone or in combination with a kidney transplant. The incidence of urological complications was 3.1 and 3.4 per patient, respectively, in the normal and abnormal groups (p = 0.126). Patient and graft survival rates were similar between the 2 groups (p > 0.5). We were unable to show that abnormal preoperative urodynamic studies preclude successful pancreas transplantation with bladder drainage or predict an increase in postoperative complications.

Despite improved results in vascularized pancreatic transplantation, the incidence of technical complications continues to be high. Vascular complications are an important source of morbidity. Previously undescribed is the occurrence of an arteriovenous fistula (AVF) in the transplanted mesenteric bundle. We have identified this unusual complication in three of 90 consecutive recipients of pancreatic transplant. The first patient presented with severe and protracted endocrine insufficiency, which was effectively reversed by direct surgical ligation of the AVF. The second patient presented with hematuria, which likewise, resolved with correction of the AVF. The third instance was diagnosed immediately after transplant and was successfully corrected by direct surgical ligation. The operative approach with establishment of proximal vascular control differed in each instance. Clinical presentation was variable and diagnosis was suggested by physical examination, duplex ultrasonography and radionuclide perfusion scanning. Arteriography was confirmatory. Mesenteric AVF can be easily identified and corrected at the time of reoperation without compromising allograft function.

Currently, diabetes mellitus is the most common cause of renal failure in adults. However, combined pancreatic and renal transplantation (PRT) remains controversial when compared with renal transplantation alone (RTA) in diabetic recipients. We analyzed the results and morbidity in four age-matched groups--31 patients with Type I diabetes undergoing PRT before dialysis, 30 patients with diabetes who are dependent of dialysis undergoing PRT, 31 concurrent and historic patients with Type I diabetes undergoing RTA and 31 concurrent patients without diabetes undergoing RTA. All patients received cadaver donor organs and were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. The four groups were comparable with respect to age, weight, gender, duration and severity of diabetes, dialysis type, number of retransplants, degree of sensitization, preservation time and matching. The groups differed with regard to duration of dialysis and period of follow-up evaluation, pretransplant blood transfusions, racial distribution and OKT3 induction therapy. PRT was associated with a greater morbidity rate as evidenced by a slightly higher incidence of rejection, infections and reoperations. The number of readmissions and hospitalization period during the first 12 months was also greater after PRT versus RTA. However, none of these differences were significant. No detrimental effect was noted on renal allograft function at one year; patient and graft survival was actually higher in the PRT groups. Quality of life was improved in nearly 90 percent of PRT recipients. Although the improved results after PRT may be attributed to selection bias, only lesser differences were noted among the four study groups. The aforementioned data suggest that appropriate patient selection can overcome the morbidity associated with PRT, resulting in excellent patient and graft survival with the potential for complete rehabilitation.

Although combined pancreas-kidney transplantation (PKT) has become a valid treatment option for selected type I diabetics, the timing of PKT relative to the degree of nephropathy remains controversial. We analyzed results and morbidity in 30 type I diabetics undergoing PKT after starting dialysis (PKT:D) versus 31 type I diabetics undergoing PKT prior to dialysis (PKT:ND). The two groups were similar with the respect to age, duration and severity of diabetes, gender, race, preservation time, retransplants, sensitization, HLA-matching, and CMV status. The mean preoperative serum creatinine was higher in the PKT:D group (9.9 +/- 3.4 vs. 3.9 +/- 1.9 mg/dl PKT:ND, P < 0.01). All patients were managed with quadruple immunosuppression with OKT3 induction. Actuarial patient survival is 100% (PKT:D) and 96.8% (PKT:ND). Renal and pancreas allograft survival are 97% and 93%, respectively, in both groups. The incidence of rejection, infection, operative complications, reflux pancreatitis, and total hospital days was similar in both groups. Long-term renal and pancreas allograft function and quality of life were like-wise comparable. No adverse coagulation or immunologic effects were noted in the PKT:ND group. Rehabilitation potential favored the PKT:ND group. PKT can be performed safely and effectively in the absence of uremia. In selected type I diabetics with significant nephropathy, we believe that PKT is the best treatment option and need not be considered as preemptive, especially in view of increasing waiting times and the variable progressive nature of diabetic complications.

A major problem in pancreas transplantation is the lack of a reliable method for the early detection of rejection. Over a 32-month period, we performed 61 combined pancreas-kidney transplants with pancreaticoduodenocystostomy. All patients received quadruple immunosuppression with OKT3 induction. Urine cytologic monitoring was performed on Papanicolaou-stained membrane filters for cell counts and cytocentrifuge preparations for HLA-DR antigen staining. The final diagnosis of rejection was based on clinical criteria, a rise in serum creatinine, histopathology, and hypoamylasuria. Cytologic features of acute rejection included hypercellularity with lymphocyturia, increased numbers of epithelial cells and positive antibody staining for HLA-DR antigen. A total of 36 definite acute rejection episodes occurred in 28 patients, with 19 confirmed by histopathology. Satisfactory urine cytologic specimens were available in 28 rejection episodes and corroborated the diagnosis in 21 cases, for a sensitivity of 75% compared with 75% and 50% with serum creatinine and urine amylase, respectively. When the urine cytologic score was combined with HLA-DR antigen staining, sensitivity improved to 93%. Thirteen false-positive diagnoses occurred in the remaining 1444 urine cytologic specimens available for evaluation, for a specificity for rejection of 99%. The positive predictive value of cell counts was 62% and negative predictive value was 99%. Patient survival is 98.4%, kidney allograft survival is 96.7%, and pancreas allograft survival is 93.4% after a mean follow-up of 15 months. Only 2 immunologic graft losses occurred (1 kidney, 1 pancreas). In conclusion, urine cytologic monitoring shows promise as a simple, reliable, and noninvasive method to detect rejection after combined pancreas-kidney transplantation with bladder drainage. Prospective studies are needed to assess the role of urine cytologic monitoring after solitary pancreas transplantation.

This study was designed to compare changes in lipid status following organ transplantation between type I diabetes mellitus (DM-I) patients receiving combined pancreas-kidney transplantation (PKT) with those receiving kidney transplantation alone (KTA). A retrospective chart review was used to identify pre- and posttransplantation fasting total cholesterol (TC) and triglycerides (TG) in three groups: DM-I patients receiving KTA (DM:KTA; n = 14), DM-I patients receiving PKT (DM:PKT; n = 20), and kidney transplant recipients without DM (NDM; n = 16). The groups were matched for age, gender, weight, duration of dialysis, smoking history, and duration of diabetes mellitus. Linear regression was used to analyze differences in lipid trends over time (up to 24 months posttransplantation) and the effects of prednisone dose, cyclosporine dose, and serum creatinine. Preoperative TC was significantly lower in the DM:KTA group (P < 0.05) compared with DM:PKT or NDM. There were no significant differences in preoperative TG between the three groups. TC and TG decreased over time only in DM:PKT (P = 0.0112, P = 0.0278, respectively). TC increased and TG was unchanged over time in DM:KTA (P = 0.0003, P = 0.1103, respectively). Neither TC nor TG changed over time in NDM. Trends of TC and TG for DM:PKT were significantly different from DM:KTA (P < 0.01 for both). Trend of TC for NDM was also significantly different from DM:PKT (P = 0.0061). Prednisone dose was significantly related to TC in DM:KTA and NDM (P < 0.01) while cyclosporine dose was significantly related to TC for DM:KTA only (P = 0.0013) in the presence of time. None of the variables tested (prednisone dose, cyclosporine dose, and serum creatinine) significantly affected TG in the presence of time. In summary, TC and TG decreased over time only in DM:PKT. In contrast, TC increased while TG was unchanged in DM:KTA over the same interval (0-24 months). If these trends continue, the beneficial change in lipids in the DM:PKT group may translate into a net improvement in atherosclerosis-mediated events for diabetic patients with chronic renal failure who receive PKT compared with those who do not.