Use of glucose disappearance rates (kG) to monitor endocrine function of pancreas allografts.

We have reported that a decline in glucose disappearance rate (kG) in pancreas transplant recipients is associated with pancreatic rejection. The purpose of this study was to determine test-retest reliability of kG monitoring and to establish the kG criteria for diagnosing abnormal graft function. Six healthy non-diabetic volunteers and 14 stable pancreas recipients underwent 2 intravenous glucose tolerance tests 7 d apart. All kG values in non-diabetic volunteers had < 15% variation between the two determinations (r = 0.96, P < or = 0.0006). Similarly, 13/14 recipients experienced < 20% variation in kG with one patients experiencing a 23% variation (r = 0.90, P < or = 0.0001). Using a 20% change from baseline as the reference value, we monitored 28 pancreas recipients for 2-36 months post-transplant. Of 253 kG values, 160 (64%) did not exceed the 20% change from baseline, 65 (26%) declined > 20% and 28 (11%) increased > 20%. Of 160 stable kG values, 154 (96%) were associated with normal graft function while 6 (4%) occurred in the context of rejection. Of 65 kG values declining by > or = 20%, 47 (72%) accurately identified acute rejections diagnosed by biopsy (70%) or response to treatment (30%), 12 (19%) were associated with identifiable causes of increased insulin resistance and only in 6 (9%) cases a cause for the decline was unidentifiable. The kG values with > 20% rise from baseline were, in 15%, associated with identifiable causes of decreased insulin resistance. The sensitivity of the kG as a marker for rejection was 88.7%, specificity 91%, positive predictive value 72.3%, negative predictive value 96.8%, and accuracy 90.5%. These data confirm that a > 20% deterioration of glucose disappearance rate is associated with pancreas allograft rejection, and confirms the utility of kG monitoring in clinical follow-up of pancreas transplant recipients.

Diagnosis, management, and outcome of late duodenal complications in portal-enteric pancreas transplantation: case reports.

BACKGROUND: Enteric drainage (ED) of pancreas allografts is an alternative to the bladder drainage (BD) technique and eliminates unique metabolic complications seen in the BD pancreas transplant recipients. Little longterm data has been reported in ED pancreas transplants. STUDY DESIGN: Of 53 patients who underwent pancreas transplantations performed with ED drainage of the exocrine secretion to a Roux-en-Y limb, who had more than 6 months graft function, four patients were identified with late duodenal segment complications (more than 6 months after transplantation) and are presented as case reports. RESULTS: The duodenal segment complications occurred between 8 and 48 months after simultaneous pancreas-kidney transplantation. Three patients were diagnosed with leakage from the duodenal segment. All were managed operatively. The fourth patient developed a distal stricture of the transplant duodenum occluding the anastomosis between the duodenum and the Roux-en-Y limb and also had a pancreatic pseudocyst. Drainage via a cyst-jejunostomy resulted in graft salvage. The mean followup after operative management of the duodenal-related complications was 15 months (range, 3-24 months). The patient, pancreas and kidney graft survival are 100%. CONCLUSIONS: Late duodenal complications occurred in 8% of pancreas transplant recipients with ED. Operative intervention in all four patients resulted in excellent graft and patient outcome and is recommended for these complications.

Use of FK506 immunosuppressive therapy in pancreas transplantation.

The purpose of this study was to evaluate the safety, efficacy, and transplant outcomes associated with FK506 rescue and maintenance therapy in pancreas transplant recipients. A chart review was conducted on 10 patients receiving FK506 after pancreas transplantation. Transplant outcomes were compared with an equivalent group of patients receiving cyclosporine. Medication dose, side effects, infections, rejection episodes, glycemic control, and graft survival were recorded from 2 to 28 weeks after transplant. Rescue therapy was successful in the patients who were converted to FK506 prior to a significant decline in glycemic control, whereas those patients who were converted after a decline in glycemic control were required to return to exogenous insulin administration. Neurological complications, nephrotoxicity, incidence of infection, hypertension, rejection, and graft survival were similar for both groups. Use of FK506 is comparable to cyclosporine in pancreas allograft recipients and successful conversion from cyclosporine to FK506 can be undertaken for rescue therapy.

Kidney-pancreas transplantation. The effect of portal versus systemic venous drainage of the pancreas on the lipoprotein composition.

We have previously shown that both kidney-alone and combined kidney-pancreas transplantation lower VLDL and IDL apoB while increasing LDL apoB, apoA-I, and HDL free cholesterol (FC). In this report, we analyze the lipoproteins of 31 patients who have undergone combined kidney-pancreas transplantation. Systemic venous drainage of the pancreas was utilized in 20 of these patients while 11 had portal venous drainage. Six lipoprotein subfractions (VLDL, IDL, LDL, HDL-L, HDL-M, HDL-D) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase HPLC) and lipid (by enzymatic assays) composition of each subfraction was determined. After three months, there were few group differences. However, the portal group had substantial reductions in VLDL apoB at both six (-50% vs. +1%) and twelve months (-57% vs. +149%, P = .042) while the systemic group had increases in VLDL apoB. Similar differences were seen in IDL apoB (six months: -38% vs. +13%; twelve months: -61% vs. +56%, P = .008). LDL apoB increased in both groups at six months (portal: +7%; systemic: +30%) but fell in the portal group at twelve months (-17% vs. +41%, P = .0007). IDL triglyceride, cholesterol ester, phospholipids, and free cholesterol also fell by 19% to 47% in the portal group while they rose by 8% to 44% in the systemic patients, six and twelve months after surgery (P < .05). In addition, the VLDL and LDL free cholesterol to phospholipid ratios (FC/PL) fell (improved) by 16% to 26% in the portal patients while they rose by 9% to 28% in the systemic subjects during this time (P < .04). Finally, there were substantial improvements in the LDL composition of the portal patients compared to the systemic patients at six (PL/apoB: +23% vs. -16%, P = .005; CE/apoB: +14% vs. -14%, P = .037) and twelve months (PL/apoB: +39% vs. -13%, P = .011; CE/apoB: +41% vs. -15%, P = .011). These data indicate that portal drainage of the transplanted pancreas reduced the number of VLDL, IDL, and LDL particles, reduced the total mass of IDL (by 35%), and normalized the VLDL and LDL particle composition. These improvements were not seen in the patients who received systemic drainage of their pancreas. HDL-M also improved in the portal patients (TG: -29% vs. +12%, P = .025) (PL: +22% vs. -5%, P = .014) (total mass: +16% vs. +0.2%, P = .044) but not in the systemic patients six months after surgery. These results suggest that portal venous drainage of the pancreas leads to greater improvements in the lipoprotein composition of IDDM patients than does systemic drainage.

An analysis of renal function in pancreas-kidney and diabetic kidney-alone recipients at two years following transplantation.

Pancreas-kidney recipients (SPK) are at higher risk for rejection than diabetic kidney-alone recipients (KA), and thus generally receive higher doses of maintenance immunosuppression. This has lead to concern that the potential benefits to renal function, brought about by posttransplant euglycemia, may be negated by the nephrotoxicity of immunosuppression. We therefore sought to compare patterns of renal function in diabetic patients following SPK and KA transplantation. Serum creatinine levels, corrected glomerular filtration rates (cGFR), and whole blood TDX cyclosporine levels were recorded on 25 SPK and 17 KA at 3, 6, 12, and 24 months posttransplant when patients were free of acute renal dysfunction. The SPK recipients had significantly higher cyclosporine levels at each of the measurement points as compared with the KA recipients (P < or = .01). In spite of these higher cyclosporine levels, the SPK recipients showed stable creatinine and cGFR levels throughout the study, as did the KA group until 24 months. At 24 months, the KA group experienced a rise in creatinine from 1.3 +/- .09 ng/dl at 3 months to 1.6 +/- .07 ng/dl at 24 months (P < or = 0.006). Urine albumin excretion was examined at 24 months, and 6 of 8 KA patients found to have abnormally elevated levels compared with only 3 of 9 SPK patients. These findings indicate that SPK recipients experience stable renal function despite significantly higher cyclosporine levels, while KA recipients demonstrate early signs of deteriorating function at the 2-year follow-up.

Early improvement in cardiac function occurs for pancreas-kidney but not diabetic kidney-alone transplant recipients.

Noninvasive M mode echocardiography with Doppler recording was prospectively performed on type I diabetic recipients of pancreas-kidney (n = 20), pancreas-after-kidney (n = 2), and kidney-alone (n = 11) allografts to determine whether the return of euglycemia by pancreas transplantation in the uremic diabetic person was associated with improved cardiac function. Each patient was studied preoperatively and at 6 and 12 months posttransplant. Echocardiographic parameters which were compared included measures of systolic function (shortening fraction), diastolic function (early/active peak velocity ratio, early/active integral ratio), and left ventricular geometric parameters (interventricular septal thickness, posterior wall thickness, left ventricular mass). The only statistically significant improvement observed for kidney-alone recipients was an increased shortening fraction from baseline (24.91%) to 6 months (32.13%, P < or = 0.0188). In contrast, the pancreas group demonstrated sustained improvement in all outcomes with measures at 12 months consistently showing a significant improvement from baseline which was also significantly better than that reported for the kidney-alone group. This study showed stabilization of cardiac function by echocardiography for diabetic kidney-alone recipients, whereas significant improvement in function occurred for pancreas-kidney recipients. The improvement in cardiac function for pancreas recipients was seen at 6 months with continued improvement evident at 12 months.

Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: effect of kidney and pancreas transplantation.

Chronic renal failure (CRF) in nondiabetics is associated with a number of lipoprotein abnormalities that place these patients at high risk for atherosclerosis. This study compared the lipoprotein composition of nondiabetic controls (n = 68) with that of patients with insulin-dependent diabetes mellitus ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], high-density lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC]) and lipid (by enzymatic assays) composition of each subfraction was determined. The only abnormalities found in IDDM patients were increases in IDL and HDL-L triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC) level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG, apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2) elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid (PL) levels (with an increased CE/TG ratio in VLDL only); (3) decreased HDL-M apo A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4) decreased lecithin:cholesterol acyltransferase (LCAT) activity. Twenty-five of the IDDM + CRF patients underwent combined pancreas and kidney (P + K) transplantation, and 12 patients received only a kidney transplant. Lipoprotein composition was determined at 3, 6, and 12 months posttransplant. Both types of transplantation resulted in similar alterations in lipoprotein composition, even though there was essential normalization of blood glucose levels in most of the patients who received a pancreas transplant (hemoglobin A1C [HbA1C], 9.1% +/- 1.1% v 5.7% +/- 0.3% at 12 months, P < .01). These posttransplant changes included (1) no improvement in the elevated TG level in any lipid subfraction even though there was some reduction in apo C-III levels in VLDL; (2) reductions in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL apo C-III and FC concentrations despite an increase in LCAT activity; and (4) increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)