Increased incidence of postoperative infections associated with peritoneal dialysis in renal transplant recipients.

BACKGROUND: Infection is a frequent postoperative complication in renal transplant recipients. However, little information is available concerning the effect of pretransplantation dialysis modality on posttransplantation complications including infection. We therefore evaluated the effect of hemodialysis (HD) versus peritoneal dialysis (PD) on the incidence of postoperative infection as well as several other posttransplantation outcomes. METHODS: A retrospective analysis was performed using medical records covering the period 30 days after transplantation of 156 dialysis patients who underwent renal transplantation at a single center during a 22-month period. Of these patients, 103 received only HD, 32 received only PD, 13 received PD in the past and HD immediately before transplantation (PH/HD), and 8 received HD in the past and PD immediately before transplantation (HD/PD). The presence of culture-proven infection, types of infecting organisms, length of initial hospital stay, and incidence of rejection during the first 30 days after transplantation were determined for each patient. RESULTS: All groups were similar with regard to age, race, gender, underlying disease, donor type, incidence of delayed graft function, and perioperative antibiotic prophylaxis. There were more infectious complications within 30 days after transplantation in patients on PD just prior to transplantation (PD and HD/PD) than in HD patients (67.5% vs. 25.9%, P<0.00001). When types of infectious organisms were assessed, PD patients were found to have a greater incidence of infections with microorganisms that colonize human skin (P<0.0001). The median length of hospital stay was 3 days longer for PD patients and 6.5 days longer for HD/PD patients than for patients receiving HD (P=0.01 and 0.04), and PD and HD/PD patients were more likely to have an episode of rejection than HD patients (P=0.02). CONCLUSIONS: Renal replacement therapy with PD immediately before transplantation negatively affects outcome as compared with HD, predisposing patients to a greater incidence of postoperative infections and rejection and a longer hospital stay. Further study in a randomized controlled trial may help determine how adjustment of the dialysis method can optimize transplantation outcome.

Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation.

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.

In vitro evaluation of high-level, gentamicin-resistant enterococci isolated from bacteremic patients.

We attempted to characterize the susceptibility of high-level, gentamicin-resistant (HLGR, minimum inhibitory concentration [MIC] > 2000 micrograms/ml) enterococcal blood isolates and evaluated a small subset of these isolates for bactericidal synergy. Thirteen Enterococcus faecalis and three Enterococcus faecium isolates that were HLGR were prospectively collected. Standard broth macrodilution techniques were used to determine the MICs and minimum bactericidal concentrations to a variety of antibiotics. Two isolates were evaluated for synergy by time-kill curve methods using combinations of penicillin and streptomycin, teicoplanin and rifampin, and vancomycin and ciprofloxacin. Teicoplanin was the most active antibiotic tested, with all isolates exhibiting susceptibility to this agent. Four E. faecalis isolates and one E. faecium isolate expressed only low-level resistance to streptomycin (LLSR, MICs 32-64 micrograms/ml). Penicillin and streptomycin produced bactericidal synergy in the LLSR isolate. The other antibiotic combinations did not result in bactericidal synergy in the two isolates tested. For HLGR enterococci that are only LLSR, the combination of penicillin-streptomycin appears to provide adequate bactericidal activity. Teicoplanin may potentially be useful for streptomycin-resistant HLGR isolates.

Transplant coordinators' perceived impact of availability of multiple generic immunosuppression therapies on patients, workload, and posttransplant maintenance therapy.

Background. No studies have evaluated the impact of multiple generic immunosuppression medications on transplant coordinators (TCs) and patients. Methods. A cross-sectional, multicenter online survey of TCs managing transplant recipients' outpatient immunosuppression was undertaken to assess TCs' perceptions of the impact of multiple generic immunosuppression therapies on patients and workload. Results. Forty-six of 106 transplant centers contacted (43%) completed the survey, with usable information from 34 TCs (53% in centers performing >100 solid organ transplants annually, 82% registered nurses, and 68% with >5-year experience working with transplant patients). TCs indicated that "change in strength," "switching from branded to generics," "heavy pill burden," and "switching from one generic to another" were the four most frequent reasons for patient confusion regarding immunosuppression. TCs reported increased patient confusion over the previous year for patients on generic immunosuppression therapy: 44% answered ≥3 patient calls/day regarding confusion over immunosuppression therapy. Most TCs indicated increased workload since the introduction of generic immunosuppression therapy. TCs perceived "acute rejection rates," "rate of graft loss," and "poor patient adherence" as the three most likely consequences of multiple generic immunosuppression therapy. Conclusion. TCs associated availability of multiple generic immunosuppression therapy with increased patient confusion and time spent addressing patient concerns.

Purification and kinetic characterization of the mitogen-activated protein kinase phosphatase rVH6.

The dual specificity protein-tyrosine phosphatase rVH6 belongs to a subfamily of enzymes that have in vivo and in vitro catalytic activity against mitogen-activated protein kinases. A method was developed for the expression and efficient purification of recombinant rVH6 in quantities sufficient for physical and kinetic characterization of the enzyme. Matrix-assisted laser desorption mass spectrometry verified the mass of purified rVH6 to be 43,500 +/- 150, and NH2-terminal sequence analysis confirmed the predicted amino acid sequence. Kinetic characterization of full-length rVH6 identified the critical ionizations involved in the kcat/Km parameter (apparent pKa values 5.1 and 6.6) and revealed a pH-independent kcat value of 0.014 s-1. In an attempt to define the essential catalytic core of this enzyme, amino acids 134-381 of rVH6 were expressed, purified, and characterized enzymatically. Kinetic analysis revealed that the truncated enzyme exhibited a turnover value similar to that of the full-length enzyme (kcat = 0.017 s-1), with p-nitrophenyl phosphate as substrate. Secondary structure prediction and molecular modeling of rVH6 based on the x-ray structure of the dual specificity protein tyrosine phosphatase, VHR, further supported the assignment of residues 134-381 to the core catalytic domain of rVH6. These results demonstrate that the NH2 terminus of rVH6 (residues 1-133) is not required for full enzyme activity and comprises a separate domain that may play a distinct physiological function.

Simultaneous pancreas-kidney (SPK) and pancreas living-donor kidney (SPLK) transplantation at the University of Maryland.

The evolution of enteric and portal venous drainage, better immunosuppression, and better patient care has elevated pancreas transplantation with dramatically improved results. At our center, long-term graft survival and rejection has significantly improved with portal venous drainage, which has become our gold standard. This improvement is exemplified by the excellent one-year patient and graft survival rates for SPLK transplants. SPLK has proven to be an ideal approach in uremic Type 1 diabetic patients with living donors and should become the procedure of choice for that population. Moreover, the improved monitoring of rejection has allowed a similar success of pancreas transplantation alone in non-uremic patients with brittle diabetes. The treatment of diabetes mellitus has room for great improvement, however, and there is no question that islet transplantation, xenotransplantation, and the pursuit of immunologic tolerance will play an extremely important role in that endeavor.

Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study.

OBJECTIVE: To compare portal and systemic venous drainage of pancreas transplants and demonstrate an immunologic and survival superiority of portal venous drainage. SUMMARY BACKGROUND DATA: Traditionally, solitary pancreas transplants have been performed using systemic venous and bladder drainage, but more recently, the advantages of enteric drainage have been well documented. Although physiologic benefits for portal venous drainage have been described, the impact of portal venous drainage, especially with solitary pancreas transplants, has yet to be determined. METHODS: Since August 1995, 280 pancreas transplants with enteric duct drainage were analyzed. One hundred and seventeen were simultaneous pancreas and kidney (SPK), 63 with systemic venous drainage (SV) and 54 with portal venous drainage (PV). The remainder were solitary transplants; 97 pancreas after kidney (PAK; 42 SV and 55 PV) and 66 transplants alone (PTA; 26 SV and 40 PV). Immunosuppressive therapy was equivalent for both groups. RESULTS: The groups were similar with respect to recipient characteristics and HLA matching. Thirty-six month graft survival for all transplants was 79% for PV and 65% for SV (P =.008). By category, SPK graft survival was 74% for PV and 76% for SV, PAK graft survival was 70% for PV and 56% for SV, and PTA graft survival was 84% for PV and 50% for SV. The rate of at least one rejection episode was also significantly higher in the SV group. At 36 months, for all pancreas transplants, the rejection rate was 21% for PV and 52% for SV (P <.0001). For SPK, rejection rates were 9% for PV and 45% for SV. For PAK, rejection rates were 16% for PV and 65% for SV, and for PTA 36% for PV and 51% for SV. The rejection rates for kidneys following SPK were also lower in the PV group (26% versus 43% for SV). Furthermore, the grades of rejection were milder in PV for all transplants (P =.017). By multivariate analysis, portal venous drainage was the only parameter that significantly affected rejection. CONCLUSION: Graft survival and rejection is superior for PV. These clinical findings are consistent with published reports of experimentally induced portal tolerance and strongly argue that PV drainage should be the procedure of choice for pancreas transplantation.