Lipids increase after solitary pancreas transplantation.

OBJECTIVE: The aims of this study were to determine 1) changes in lipids after solitary pancreas transplantation (SPTX) in patients with type 1 diabetes and 2) factors that influence those changes. RESEARCH DESIGN AND METHODS: Lipids were evaluated prospectively in 24 patients who underwent SPTX. Three were excluded because of early graft failure. The remaining patients (n = 21; 13 men, 8 women) were studied for changes in lipids over time (pre-SPTX, 0-2, 3-6, 7-12, and > 12 months). Glycohemoglobin, serum creatinine, BMI, and medications were also analyzed for their effects on lipid changes. RESULTS: Cholesterol, HDL, and LDL decreased in the immediate postoperative period (0-2 months), whereas triglycerides (TGs) increased (P < 0.05). At 3-6 months, cholesterol, HDL, and TG were higher than before the SPTX, whereas LDL returned to pre-SPTX levels. After 12 months, HDL and TG remained higher than their pre-SPTX levels (P < 0.05). During the study, systolic and diastolic blood pressure increased, renal function decreased, glyco-hemoglobin improved, and weight was unchanged. Changes in cholesterol/HDL ratio, HDL, and TG correlated with changes in prednisone dose (P < 0.05), and changes in TG correlated with changes in creatinine (P < 0.05). The same pattern of lipids occurred in patients prescribed or not prescribed hypolipidemic agents. CONCLUSIONS: Lipids do not improve within the 1st year after SPTX, despite improved glycemic control and blood pressure control, and renal function is worse. These results are in contrast to those reported for combined kidney-pancreas transplantation, where lipids, blood pressure, and renal function improved immediately after transplant. Further studies are needed to determine whether lipids continue to change with time after SPTX. The impact of these changes after SPTX on overall cardiovascular risk is unknown.

Analysis of hospital charges after simultaneous pancreas-kidney transplantation in the era of managed care.

BACKGROUND: The purpose of this study was to analyze and compare hospital charges in simultaneous pancreas-kidney transplant (SPKT) recipients before and after implementation of managed care principles. METHODS: Two groups were compared: 14 consecutive SPKT patients transplanted in 1991 vs. 15 consecutive SPKT patients transplanted in 1995. All patients underwent whole organ pancreas transplantation with bladder drainage and received quadruple immunosuppression with OKT3 induction. The two groups were well-matched; outliers were excluded (four in 1991 and five in 1995), and no attempt was made to convert 1991 to 1995 dollars. Patient and graft survival rates were 100%, and no major early complications occurred. All SPKTs were performed in a single hospital setting, and all inpatient charges for the initial hospitalization were analyzed retrospectively and itemized by service. RESULTS: Pharmacy, organ acquisition, and clinical laboratory services accounted for nearly 80% of charges in each group. For the initial transplant hospitalization, the 1995 group experienced significant reductions in: (1) length of stay (16.3+/-1.4-135+/-3.5 days, P=0.03); (2) total number of laboratory tests (392+/-15-224+/-60, P<10(-3)); (3) clinical laboratory charges ($23,623+/-$1,780-$11,165+/-$3,091, P<10(-6)); and (4) total inpatient charges with organ acquisition charges excluded ($87,815+/-$8,678-$75,152+/-$16,871, P=0.049). However, these potential savings were offset by a nearly 47% increase in organ acquisition charges and a 38% increase in medical/surgical supplies. Consequently, total hospital charges for SPKT were no different in 1991 and 1995. CONCLUSIONS: Despite the rising costs of medical care, we have implemented managed care principles after SPKT that were successful in stabilizing hospital charges by decreasing length of stay and clinical laboratory tests during the study period. However, escalating charges related to organ acquisition and medical/surgical supplies remain a problem.

Diet after pancreas transplantation.

OBJECTIVE: To determine whether discontinuation of insulin therapy and glucose monitoring and instructions to increase dietary salt and water intake after pancreas transplantation (PTX) resulted in changes in food choices. RESEARCH DESIGN AND METHODS: All PTX recipients who had completed a preoperative diet record, had received their PTX > 6 months before, had stable pancreas and kidney function, and were on a stable diet were invited to submit a 3-day post-PTX diet record. Of the 14 eligible, 11 agreed to participate and completed the study (2 women and 9 men). Their pre- and post-PTX diet records were analyzed by computer program. Weight, glycohemoglobin, blood pressure, medications, and fasting lipids both before and after PTX were also analyzed. RESULTS: The recipients were studied 576 +/- 60 days post-PTX, on average. Total calories and BMI were unchanged after PTX. Before PTX, 34% of calories were in fats, 49% in carbohydrate, and 17% in protein with no change in distribution of calories after PTX, although there was a trend toward greater saturated fat intake. Total salt intake was increased after PTX (P < 0.01) because of sodium bicarbonate administration, although dietary salt intake did not change. The HDL cholesterol concentration increased and cholesterol-to-HDL ratio decreased after PTX (P < 0.05), while the remaining lipids were unchanged. CONCLUSION: Weight, total calories and distribution of calories, and dietary salt were unchanged after PTX, and diet did not explain the changes in HDL cholesterol or cholesterol-to-HDL ratio. These preliminary diet results suggest that greater emphasis on dietary instruction may be needed after PTX.

Pravastatin reduces serum cholesterol and low density lipoprotein concentrations following pancreas transplantation.

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.

Anti-insulin antibodies are a cause of hypoglycemia following pancreas transplantation.

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.

Viral prophylaxis in combined pancreas-kidney transplant recipients.

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.

Pancreas transplantation: the Nebraska experience.

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.