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ABSTRACT: The shortage of donor organs in Germany has led to the use of organs from donors with extended donor criteria (EDC). EDC have been defined on the basis of expert opinions, but their clinical relevance is controversial. This may cause loss of organs otherwise available for transplantation. We evaluated the impact of donor and recipient factors in liver transplants on patient and graft survival in a nationwide multicenter analysis, with special focus on EDC and donor risk index.
A database was created from data on livers donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organ transplantation and BQS Institute. Cox regression (significance level 5%, risk ratio [95% confidence interval]) was used for calculating the impact on patient survival (n=2095) and on graft survival (n=2175).
Patient and graft survival were significantly affected only by donor age (1.012 and 1.011/year), recipient age (1.019 and 1.014/year), creatinine (1.248 and 1.205/mg/dL), bilirubin (1.022 and 1.023/mg/dL), and high urgency status (1.783 and 1.809). Inferior organ quality resulted in lower graft survival (1.243) and donor history of smoking in lower patient survival (1.249).
Multiple Cox regression revealed no significant impact of EDC or donor risk index on patient and graft survival except for donor age after donor selection at recovery. Among recipient variables, only age, creatinine and bilirubin, and high urgency status were associated with poorer outcome.
Transplantation 11/2011; 92(12):1378-84. · 4.00 Impact Factor
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ABSTRACT: Quality assessment of renal grafts via (31)P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (Pi(O)) within the organ (PME/Pi(O)) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross-match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/Pi(O) kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80 h via (31)P MRS at 2 T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1 x 1 x 4 cm(3), it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/Pi(O) ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/Pi(O) for histidine-tryptophane-alpha-ketoglutarate (HTK)-perfused kidneys during cold ischemia was observed, and the determined value of the decay constant alpha was 0.0099 +/- 0.0012 h(-1). In University of Wisconsin solution (UW)-perfused kidneys, an alpha of 0.0183 +/- 0.0053 h(-1) was determined. Determination of the decay constant enables a usable extrapolation of PME/Pi(O) for quality assessment of UW perfusion and a reliable extrapolation for HTK-perfused human renal grafts.
NMR in Biomedicine 12/2007; 20(7):652-7. · 3.21 Impact Factor
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Günter Kirste
MMW Fortschritte der Medizin 09/2007; 149(31-32):22-3.
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Therese C Jungraithmayr,
Silke Wiesmayr,
Astrid Staskewitz, Günter Kirste,
Monika Bulla,
Henry Fehrenbach,
Jürgen Dippell,
Christel Greiner,
Martin Griebel,
Udo Helmchen,
Günter Klaus,
Heinz E Leichter,
Michael J Mihatsch,
Dietrich V Michalk,
Joachim Misselwitz,
Christian Plank,
Burkhard Tönshoff,
Lutz T Weber,
Lothar B Zimmerhackl
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ABSTRACT: Mycophenolate mofetil (MMF) based immunosuppression after renal transplantation has proven to be safe and beneficial for children and adolescents. However, long-term analysis, in particular of pediatric patients, is scarce.
Data of 140 patients receiving MMF versus azathioprine (AZA) in combination with cyclosporine A (CsA) and prednisone without induction were analyzed with a main focus on survival and renal function in long-term follow-up.
After 5 years of follow-up, 44 MMF and 20 AZA patients were still on study. Graft survival of intent to treat (ITT) groups was 90.7% for MMF and 68.5% for AZA patients (P<0.001). Cumulative rejection free survival was 51.2% in MMF versus 37.0% in AZA patients (P<0.05). In association with early acute rejections (ARE), projected half-life was 14.4/4.5 years in patients with and 18.7/14.5 years without rejection in the MMF/AZA group, respectively.
MMF based protocols improved long-term graft survival without an increase in side effects. Early ARE were associated with worse half-life of the graft, although more stressed in the AZA group. Thus, to improve quality of life in children for very long-term outcome, ARE should be further decreased and renal function should be better preserved.
Transplantation 04/2007; 83(7):900-5. · 4.00 Impact Factor
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ABSTRACT: The objective of this study was to determine outcome after living-donor kidney transplantation in a single-center institution in Germany.
From 1976 to May 2005, a total of 298 living-donor kidney transplants were performed at the University of Freiburg. Most recipients (78.8%) were placed on cyclosporine, mycophenolate mofetil, and corticosteroids maintenance immunosuppression. Cox proportional hazard model was applied to analyze predictors for patient and graft survival. Mean follow-up was 5.3 years.
According to Kaplan-Meier calculation, 1-, 5-, and 10-year patient survival was 98.6, 92.7, and 86.8%, respectively. Kidney function rate was 95.5, 82.8, and 67.9%, respectively. A 5-year graft function rate continued to increase from 79.5% in patients transplanted before 1996 to 83.6% in patients transplanted thereafter. In a Cox regression model recipient age above 50 years, duration of dialysis above 2 years and preexisting type 1 diabetes mellitus were associated with a decreased patient survival. Graft survival was mostly influenced by the type of immunosuppression and preexisting hypertension of the recipient.
Our results demonstrate that living-donor kidney transplantation is a highly effective therapy for patients with end stage renal failure. Updates in immunosuppression, recipient selection, and operative technique may have contributed to the improved graft survival over the past three decades.
Langenbeck s Archives of Surgery 02/2007; 392(1):23-33. · 1.81 Impact Factor
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ABSTRACT: For years ABO-incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long-term results regarding patient and organ survival rates, increased morbidity during the early post-transplant period prevented a broad application of this method. Recently, a new protocol including the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short-term results.
From April 2004 to September 2005, 11 patients were prepared for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 : 1024. Immunoadsorption treatment was started in parallel with immunosuppressive medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM) were lowered to the aimed pre-transplant threshold of <1 : 8. During the early postoperative period, additional immunoadsorption treatments were performed, if the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14), respectively.
Transplantation could be conducted in eight of 11 patients (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was 7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case, respectively. On average, each patient received seven immunoadsorption treatments. All transplants showed primary function and no humoral rejections occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers after each immunoadsorption treatment and thus could not be transplanted. One patient died 4 months after transplantation with a functioning graft due to sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of the remaining seven patients now is 1.6 mg/dl.
The use of antigen-specific immunoadsorption and an immunosuppressive regimen consisting of a conventional triple immunosuppressive therapy has shown excellent short-term results. The immunoadsorption treatment using antigen-specific columns is highly effective and even patients with high isoagglutinin titers can be transplanted. This protocol is an option for end-stage renal disease patients who have no blood group-compatible donor.
Xenotransplantation 04/2006; 13(2):108-10. · 2.33 Impact Factor
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ABSTRACT: We sought to determine the impact of kidney transplantation with simultaneous unilateral nephrectomy on perioperative morbidity and patient and graft survival.
From January 1990 to May 2004, 75 kidney transplantations with simultaneous unilateral nephrectomy (group NE+) were performed at the University of Freiburg. Of these, 49 had polycystic kidney disease. Patients of group NE+ were matched with 75 kidney transplants without nephrectomy (group NE-). Immunosuppressive maintenance therapy in both groups was based on cyclosporine A, mycophenolate mofetil or azathioprine, and prednisone. Mean follow up was 4.1 yrs (range 0.3-11.7 yrs).
Patient survival rate at 1 and 5 yrs was 95% and 84% versus 95% and 93% in group NE+ and NE-, resp. (P=0.56). Accordingly, kidney function rate was 85% and 74% in group NE+ versus 89% and 79% in group NE- (P=0.89). Perioperative (90 days) mortality rate in group NE+ was 1.3% and 2.7% in group NE- (P=0.56). Perioperative surgical complications were similar in both groups.
Kidney transplantation with concomitant unilateral nephrectomy has no negative impact on patient or graft survival and is associated with a reasonable morbidity rate.
Transplantation 04/2006; 81(6):874-80. · 4.00 Impact Factor
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ABSTRACT: The human cytomegalovirus (CMV) is a major cause of morbidity and mortality in transplant patients. In this study, we compared the diagnostic value of pp65 antigen test, qualitative nested polymerase chain reaction (PCR), and quantitative Taqman PCR in predicting the clinical outcome of CMV infection.
A total of 169 samples derived from 59 organ-transplant recipients (kidney n= 46, liver n= 11, kidney and pancreas n= 2) were analyzed. Peripheral blood leukocytes (PBL) were isolated using dextran gradient centrifugation, and 2 x 10 cells were analyzed for pp65 antigen by immunofluorescence. A crude DNA extract obtained from the same number of cells was used for qualitative nested PCR and quantitative Taqman PCR analysis. RESULTS.: The correlation coefficient of pp65 antigen test and Taqman PCR was R= 0.699 (P = 0.001). With cut-off values for pp65 antigen test set at greater than 10 positive nuclei per 2 x 10 PBL, sensitivity was 91%, and positive predictive value (PPV) was 70%. When the corresponding cut-off value for Taqman PCR was applied (>125000 genome copies per 2 x 10 PBL), a sensitivity of 83% and a PPV of 68% were found. Both assays allowed for the monitoring of successful antiviral therapy. Although qualitative nested PCR was highly sensitive (95%), it was less useful in predicting CMV disease (PPV 47%) and in therapy control.
Our data show that pp65 antigen test and Taqman PCR are almost equivalent in the monitoring of CMV infection and disease when identical cell numbers are used for both assays.
Transplantation 06/2004; 77(11):1692-8. · 4.00 Impact Factor
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Therese Jungraithmayr,
Astrid Staskewitz, Günter Kirste,
Michael Böswald,
Monika Bulla,
Rainer Burghard,
Jürgen Dippell,
Christel Greiner,
Udo Helmchen,
Bernd Klare, [......],
Heinz E Leichter,
Michael J Mihatsch,
Dietrich V Michalk,
Joachim Misselwitz,
Christian Plank,
Uwe Querfeld,
Lutz T Weber,
Manfred Wiesel,
Burkhard Tönshoff,
Lothar B Zimmerhackl
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ABSTRACT: Mycophenolate mofetil (MMF)-based immunosuppression has reduced the acute rejection rate in adults and in children in the early posttransplantation period. Three-year posttransplantation results have been reported for adults but not for children thus far. In the present open-labeled study, patients 18 years old and younger were evaluated prospectively for up to 3 years after renal transplantation (RTX).
Eighty-six patients receiving MMF in combination with cyclosporine and prednisone without induction were evaluated for patient survival, transplant survival, renal function, arterial blood pressure, adverse events, and opportunistic infections. These patients were compared with a historic control group (n=54) receiving azathioprine (AZA) instead of MMF.
Patient survival after 3 years was 98.8% in the MMF group and 94.4% in the AZA group (NS). Intent-to-treat analysis of graft survival demonstrated superiority for MMF (98% vs. 80%; P<0.001). Cumulative acute rejection episodes occurred in 47% of patients in the MMF group versus 61% in the AZA group (P<0.05). Renal function was not significantly different, neither after 3 years nor in the long-term calculation. Antihypertensive medication was administered to 73% to 84% of patients, similar in both groups. Opportunistic infections were recorded only for MMF. Infection rates were comparable to those reported in adults.
These results suggest that MMF is safe and beneficial as a longer term maintenance immunosuppressive drug in children and adolescents.
Transplantation 02/2003; 75(4):454-61. · 4.00 Impact Factor
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ABSTRACT: Background. Acute rejection episodes (ARE) of kidney transplants are considered as risk factor in the development of chronic rejection. In adult renal transplantation (RTx), ARE have been significantly reduced by mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) and steroids (Pred). Reports of pediatric RTx on a maintenance immuno-suppression with MMF are restricted to patients (P) after antibody induction therapy.
Methods. The efficacy and safety of MMF combined with CyA and Pred in pediatric RTx without induction therapy were evaluated in an open-labeled multicenter study.
Results. From 10/1996 to 6/1999, 65 pediatric P (MMF group) were followed for at least 6 months, 58 of 65 for 12 months. These P were compared with 54 retrospectively analyzed pediatric P who were transplanted between 1990 and 1996 and had received CyA, Pred, and azathioprine for immunosuppression (historic AZA group). Within the first 6 months after RTx, 18 of 65 (MMF group) and 32 of 54 (historic AZA group) P showed clinical signs of acute rejection (P <0.01). Thereafter only one further P in the MMF group developed a first ARE. Graft loss due to rejection occurred in one MMF- and seven AZA-treated P (P <0.05). The creatinine-clearance 3 and 6 months after RTx was higher in the MMF group. Major adverse events (MMF group) included infections of the urinary and the upper respiratory tract, diarrhea, and leukopenia. Cytomegalovirus-infection occurred in 13 P and 2 P developed cytomegalovirus disease. One P developed PTLD 10 months after RTx and recovered after the reduction of immunosuppression.
Conclusions. The combination of MMF, CyA, and Pred reduced ARE in pediatric RTx without incurring major side effects.
Transplantation 03/2001; 71(5):638-644. · 4.00 Impact Factor
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ABSTRACT: Objective: To investigate whether calcium antagonists are nephroprotective in hypertensive cyclosporine-treated renal allograft recipients.
Methods: We studied 50 hypertensive and 17 normotensive renal transplants (eight females, nine males; 14-54 years, mean age 38.8 ± 3.5 years). Hypertensive patients were randomized to be treated with (+Ca; 11 females, 13 males; 20-65 years, mean age 43.1 ± 3 years) or without (-Ca; 15 females, 11 males; 25-60 years, mean age 41.3 ± 2.5 years) a calcium antagonist (nitrendipine or nifedipine). Additional antihypertensives were given stepwise according to a standardized protocol: β1-adrenoceptor blocker, diuretic α1-adrenoceptor blocker or vasodilator. Data were analysed at 0, 1, 2 and 3 years on an intention-to-treat basis.
Results: Hypertensive patients had a higher body mass index at 0/3 years (23.7 ± 0.6/25.1 ± 0.6 kg/m2) than normotensive patients (22.2 ± 0.6/22.1 ± 0.7 kg/m2). During the study, blood pressure in normotensive transplants was always slightly, but not significantly, lower than that of transplants with treated hypertension. There was no difference between the groups (+Ca) and (-Ca). Cr51-ethylenediaminetetracetic acid (EDTA) clearance (0/2 years) was 58 ± 4/57 ± 6 ml/min in normotensives, 52 ± 4/47 ± 4 ml/min in hypertensives (+Ca) and 47 ± 4/49 ± 6 ml/min in hypertensives (-Ca). Proteinuria (0/3 years) was 0.16 ± 0.04/0.15 ± 0.02 g/24 h in normotensive, 0.26 ± 0.08/0.23 ± 0.05 g/24 h in hypertensives (+Ca) and 0.26 ± 0.07/0.22 ± 0.05 g/24 h in hypertensives (-Ca).
Conclusions: Post-transplant hypertension is associated with higher body mass index and poor renal function. No difference in the course of Cr51-EDTA clearance, serum creatinine, proteinuria or blood pressure was observed between groups treated with or without calcium antagonists. Calcium antagonists and conventional antihypertensive treatment have the same nephroprotectice effect in hypertensive renal transplants, when treatment is started 3 months after transplantation.
Journal of Hypertension 07/2000; 18(8):1115-1119. · 4.02 Impact Factor
