Surgical complications are the main cause of pancreatic allograft loss in pancreas-kidney transplant recipients.

We examined surgical complications among a group of diabetic type 1 patients (IDDM) with end-stage renal disease (ESRD) who had undergone pancreas-kidney transplantations (PK). Between October 1993 and August 2004, 70 SPK were performed using bladder (n = 14) or enteric (n = 56) drainage. Donors were selected according to standard criteria (mean age, 27.6 years; range, 17-49). All patients received cyclosporine-based immunosuppression. All pancreata functioned immediately, whereas 2 patients needed postoperative dialysis. Four patients (5.7%) lost their pancreatic graft due to vascular thrombosis; both patients underwent urgent allograft pancreaectomy and pancreas retransplantation (re-PT). One of them (1.4%) experienced a venous thrombosis and died due to a pulmonary embolism at 12 hours after re-PT. The other 3 patients had uneventful postoperative courses and were discharged with good pancreatic and renal function. Three patients in the bladder group (21.4%) had an anastomotic leak, which resolved with a bladder catheter. Four patients in the enteric group (7.1%) who experienced an anastomotic leak needed a second surgical procedure but in 3 of them allograft pancreatectomy was necessary. Relaparotomy was required in the other 3 patients due to hemorrhage (1 patient) or occlusion (2 patients). Acute rejection episodes, which occurred in 16 patients (22.8%), were treated with steroid boluses. With a mean follow-up of 72 months (range, 3-129), 2 patients have died at 8 and at 36 months, respectively, after SPK due to acute myocardial infarction (2.9%). Chronic rejection was the leading cause of pancreatic failure in 5 patients (7.1%) and of renal failure in 2 patients (2.8%). Patient, kidney, and pancreas survival rates were 95.8%, 92.9%, and 81.5%, respectively. Surgical complications were the leading cause of pancreatic allograft loss in IDDM and ESRD patients submitted to SPK.

Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo-controlled study.

Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), affecting the lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA) pharmacokinetics. This prospective, randomized and placebo-controlled, double-blind study involved 42 kidney graft recipients. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Esapent, Pharmacia) and 21 pts (P) received placebo (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were investigated 1, 3, 6, 9 and 12 months after graft. The two groups were comparable for age, weight, M/F ratio, hypertension prevalence and baseline lipids. Active treatment did not affect total and HDL-cholesterol, but significantly lowered triglycerides (E:120 +/- 12 vs P:166 +/- 21 mg/dl, p < 0.0001). At one year, E pts had lower creatinine than P (1.26 +/- 0.06 vs. 1.88 +/- 0.2 mg/dl, p < 0.05), comparable CyA dosage, and a larger CyA area under the curve (AUC) (n.s.), with a higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak (n.s.). The larger AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of better CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.

Is the dialysate fluid source of complement activating factors?

To distinguish between membrane-induced and dialysate-induced mechanism of complement activation attending hemodialysis (HD), the C3a plasma level and blood neutrophil count profiles have been determined during procedures performed with noncellulosic membranes, as PAN and PMMA (with minimal complement-activating potential) and, by comparison, with new cuprophane (that displays the greatest complement-activating potential). Furthermore, PAN and PMMA membranes have been used in 2 other blood purification methods: high efficiency hemofiltration (HEHF), in which there is no dialysate on the other side of the membrane, and hemofiltration without substitution fluid and with reinfusion of dialysis-regenerated hemofiltrate (HWSF), in which the dialysate is separated from the blood circuit by the hemofiltrate circuit. In addition, sequential dialysis-ultrafiltration (UFD) experiments with PAN membranes have been performed, where dialysate was present only in the second part of the procedure. In all the HD and UFD procedures LAL test assays were performed on dialysate at the same times as C3a and neutrophil determinations. Our findings seem to suggest that the dialysate can be a source of complement activating factors; complement activation detectable by C3a plasma levels can ensue when LAL test-positive material is present in the dialysate.

Influence of technical factors and different immunosuppressive regimens on kidney graft survival. Retrospective analysis on 300 kidney transplants.

300 patients underwent kidney transplantation. Uretero-neocystostomy was performed by means of the Politano-Leadbetter technique in the first 185 patients and direct ureterovesical anastomosis in the other 115 patients. Immunosuppression included conventional therapy (steroids, antilymphocyte globulins, azathioprine) and the association cyclosporine A and steroids. Retrospective analysis on these 300 patients indicates that the improved 1 year graft survival rate (85% vs 64%) we observed in the latest years has depended to the same extent, on improved surgical technique and on advent of cyclosporine A in our therapeutic protocols. Cyclosporine A at low starting doses immediately adjusted on whole blood trough levels (200-400 ng/ml) proved to be superior to other therapeutic schedules reported in this study (1-year graft survival rate: 94% vs 84%-73%). Direct ureterovesical anastomosis was characterized by a net reduction of urologic complications (2.5% vs 9.7%).

Immunological monitoring of viral infections in renal transplant recipients.

Twelve viral episodes occurred in 54 antilymphocyte globulin-treated renal transplant recipients (two primary cytomegalovirus, seven cytomegalovirus reactivations, one chickenpox, two influenza). In 11 of 12 cases the ratio between peripheral T4 and T8 subsets fell (from 1.698 to 0.986, p less than 0.01) due both to a reduction of T4+ and to an increase of T8+ cells. T10+ and 5/9 subsets also increased. Suppressor T-cell function, as measured by two simultaneous assays, was enhanced. In antibody-negative CMV patients the reversal of T4/T8 ratio preceded the appearance of specific IgM. T4/T8 ratios rapidly returned to normal in mild episodes, but remained reverted in symptomatic CMV patients for several months, despite a reduction in the immunosuppressive regimen. Symptomatic viral episodes displayed marked imbalances in T cell subset numbers and function, while in asymptomatic cases the changes were less evident.