Claudia Bösmüller

Cytomegalovirus-related complications in human hand transplantation.

Background. Up to date, 24 hands/thumbs have been transplanted in 18 patients. We herein report on cytomegalovirus (CMV) infection, disease, and the adopted treatment. Methods. Immunosuppression consisted of tacrolimus-based triple-drug therapy with antithymocyte globuline or CD25-receptor antagonist induction. Donor/recipient CMV match was negative/negative (n=8), negative/positive (n=3), positive/positive (n=3), positive/negative (n=3) and unknown in one case. Six patients (three +/−, two +/+, and one −/+) received gancyclovir i.v. followed by oral gancyclovir or valgancyclovir for prophylaxis. Results. Patient and graft survival at a mean follow-up of 42.9 months were 100% and 91%, respectively. Of all patients tested for CMV, 45.5% developed CMV infection or disease. Two patients that were given a CMV-positive graft showed very high viral loads (550 and 1200/200000 leukocytes) after transplantation. Gancyclovir treatment failed to permanently control CMV in 80% of the patients experiencing CMV infection. Those patients requiring more toxic second-line therapies (foscarnet/cidofovir) suffered from side effects such as nephrotoxicity, nausea, vomiting, and diarrhea. Conclusions. CMV infection/disease complicated the postoperative course after composite tissue allograft (CTA) transplantation in five of nine recipients challenged with the virus. The close time correlation suggests an association between virus replication and rejection in some cases. CMV represents the major infectious threat in CTA transplantation. Therefore, CMV-mismatch should be avoided and prophylaxis with valgancyclovir and anti-CMV hyperimmunoglobulin should be mandatory.

Recipient and donor body mass index as important risk factors for delayed kidney graft function.

Background. Obesity is increasingly impacting the overall health status and the global costs for health care. The increase in body mass index (BMI) is also observed in kidney allograft recipients and deceased organ donors. Methods. In a retrospective single-center study, we analyzed 1132 deceased donor kidney grafts, transplanted at our institution between 2000 and 2009 for recipient and donor BMI and its correlation with delayed graft function (DGF). Recipients/donors were classified according to their BMI (<18.5, 18.5–24.9, 25–29.9, and >30 kg/m2). DGF was defined as requirement for one dialysis within the first week after transplantation. Results. Overall DGF rate was 32.4%, mean recipient BMI was 23.64±3.75 kg/m2, and mean donor BMI was 24.69±3.44 kg/m2. DGF rate was 25.2%, 29.8%, 40.9%, and 52.6% in recipients with BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, and more than 30 kg/m2, respectively (P<0.0001). Donor BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, more than 30 kg/m2 resulted in a DGF rate of 22.5%, 31.0%, 37.3%, and 51.2% (P<0.0001). Multivariate analysis revealed recipient BMI and dialysis duration as independent risk factors for DGF. DGF results in inferior 1- and 5-year graft and patient survival. Conclusion. Recipient and donor BMI correlate with the incidence of DGF. Awareness thereof should have an impact on peri- and posttransplant measures in renal transplant recipients.

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing

Background The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. Methods We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. Results The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). Conclusions Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Lipoprotein(a) plasma concentrations after renal transplantation : A prospective evaluation after 4 years of follow-up

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.

Combined pancreas-kidney transplantation for patients with end-stage nephropathy caused by type-2 diabetes mellitus.

Background Simultaneous pancreas-kidney (SPK) transplantation is widely accepted as an optimal therapeutic option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease, but the indication for patients with type 2 diabetes mellitus (T2DM) is still controversially discussed. Methods Twenty-one T2DM recipients of a first combined pancreas-kidney graft performed at our center during a 9-year period were retrospectively analyzed with regard to demographic characteristics; cardiovascular risk factors; surgical, immunological, and infectious complications; and patient and graft survivals and compared with T1DM recipients (n=195) and 32 T2DM patients who received a kidney transplant alone (KTA) during the same period. Results Patient survival at 1 and 5 years was 96.9% and 91.6% for the T1DM group, 90.5% and 80.1% for the T2DM group, and 87.1% and 54.2% for the T2DM KTA group, respectively (P<0.001). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was calculated to be 92.6% and 80.7% for the T1DM group and 81.0% and 75.9% for the T2DM group, respectively (P=0.19). Kidney allograft survival at 5 years was 83.6% for T1DM, 80.4% for T2DM, and 52.7% for T2DM KTA (P<0.0001). Multivariate analysis adjusting for donor and recipient age, secondary complications of diabetes, body mass index, waiting time, cold ischemic time, delayed graft function, and coronary risk factors showed that differences did not remain statistically significant. Conclusion Favorable results can be achieved with SPK transplantation in type 2 diabetics with a low coronary risk profile. A high cardiac death rate impacts results of KTA and calls for stringent selection.

Evolution of pancreas transplantation: long-term results and perspectives from a high-volume center.

Objective:To describe the evolution of pancreas transplantation from 1979 to 2011. The aim was to examine factors influencing long-term patient and graft survival, surgical methods, and risk factors influencing organ performance after transplantation. Background:Pancreas transplantation has become the therapy of choice for patients suffering insulin-dependent diabetes and end stage renal failure. Methods:Retrospective analysis of 509 consecutive pancreas transplants (442 simultaneous pancreas and kidney [SPK], 20 pancreas transplanted alone [PTA], and 47 pancreas transplanted after kidney [PAK]), performed at the University Hospital Innsbruck. The data were statistically analyzed using the Kaplan-Meier method and log-rank test. Results:After overcoming initial immunological and technical problems between 1979 and 1988 (5-year pancreas graft survival rate, 29.7%), pancreas transplantation evolved during the second decade (1989–1996; 5-year pancreas graft survival rate, 42.2%). Technical changes, optimized immunosuppression, careful pretransplant evaluation, and improved graft monitoring have become standard in the last decade and result in excellent 5-year patient (94.3%), kidney (89.4%), and pancreas (81.5%) graft survival. Five-year graft survival was superior in SPK (68.8%) compared with PAK (62.5%) and PTA (16.4%). SPK retransplantation can be carried out safely with 5-year patient (87.5%) and pancreas graft (75.0%) survival. Overall 5-year patient survival after loss of the first pancreas graft is significantly better in patients who underwent retransplantation (89.4% vs. 67.9%, P = 0.001). Long-term pancreas graft survival is independent of donor body mass index, sex, and cause of death, anastomosis time and the number of human leukocyte antigen (HLA) mismatches, recipient age, body mass index, sex, current panel reactive antibodies, and waiting time. Significant risk factors for reduced graft survival are cold ischemia time and donor age. Conclusions:During the last 32 years, many problems in pancreas transplantation have been overcome and it may currently represent the therapeutic gold standard for some patients with diabetes and end stage renal failure.

Protein levels of heme oxygenase-1 during reperfusion in human kidney transplants with delayed graft function

Abstract: Introduction:  Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long‐term allograft survival. Heme oxygenase‐1 (HO‐1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO‐1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF.

Rejection of kidney and pancreas after pancreas-kidney transplantation.

On the basis of 26 combined pancreas-kidney transplants we questioned whether both organs undergo rejection simultaneously. Reliable diagnosis of pancreas-graft rejection was made possible by monitoring exocrine graft function, including quantitative measurements of pancreatic juice, its amylase content, and pancreatic juice cytology. In addition, diagnosis of pancreas rejection was based on regular flow studies, daily urinary neopterin excretion, and a retrospective analysis of the clinical course. Clinical symptoms, blood chemistry, and, primarily, histology were used to assess rejection of the kidney allograft. In 18 cases the kidney and pancreas were rejected together; in 8 cases the kidney or the pancreas was rejected. Although both organs were rejected at the same time in most cases, either organ can be rejected alone. Thus, the kidney cannot be used to monitor the pancreas allograft in every case.

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long‐term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan–Meier and log‐rank analyses were carried out for 1‐ and 5‐year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five‐year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006–1.037; P = 0.006). As longer AT closely correlates with inferior long‐term patient survival, it has to be considered as a major risk factor for inferior long‐term results after deceased donor kidney transplantation.

Tacrolimus monotherapy following alemtuzumab induction in combined kidney-pancreas transplantation: results of a prospective randomized trial.

BACKGROUND We investigated the safety and efficacy of Campath induction and tacrolimus (TAC) maintenance therapy compared to ATG induction with TAC +MMF + steroids in de novo kidney-pancreas transplanted patients. MATERIAL/METHODS 14 patients (Group A) received Campath 30 mg + methylprednisolone 500 mg before revascularization followed by TAC monotherapy, and 16 patients (Group B) ATG 8 mg/kg with TAC + MMF+ steroids (withdrawn at month 3). TAC trough levels (ng/mL) of 12-15 were aimed for in both groups until month 6 and thereafter 6-12. RESULTS 1-year patient survival was 100% in both groups; kidney and pancreas survival in Group A was 93% each. In Group B 1-year kidney and pancreas survival was 100% and 87%, respectively. A total of three pancreas grafts were lost due to thrombosis of the graft vein within the first month. The only kidney loss was due to initial non-function. All biopsy-proven acute rejections of renal transplants (n=3 in Group A, n=0 in Group B) were reversible. No acute pancreas graft rejection was demonstrated. Infectious complications, lipid metabolism and blood pressure were comparable in both groups, as were other adverse events. No tumor occurred. At 12 months 13 patients in each group were steroid-free; the mean serum creatinine level was 1.44 mg/dL in Group A and 1.33 mg/dL in Group B. All patients were exogenous insulin-free. CONCLUSIONS At one year efficacy and safety of Campath +TAC monotherapy were comparable to those of ATG + TAC + MMF + steroids in a limited number of combined kidney-pancreas transplant recipients.