Biomedical subjects

Bernd Döhler

Publications and source records attributed to Bernd Döhler.

11 recordsLinked to original sources

PubMed2006

No improvement of patient or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: a collaborative transplant study report.

It was reported recently that treatment of kidney transplant recipients with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) is associated with strikingly improved long-term graft and patient survival. This finding has important implications for future posttransplantation therapy recommendations. In an analysis of 17,209 kidney and 1744 heart transplant recipients, an association of treatment with ACEI/ARB with improved transplant outcome could not be confirmed. It is concluded that recommendations for a widespread use of ACEI/ARB treatment in transplant recipients are unwarranted.

Aged↗

PubMed2006

Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients.

BACKGROUND: It is widely assumed that the graft-enhancing properties of antilymphocyte induction agents and their lymphoma-inducing potential are intimately related. METHODS: The Collaborative Transplant Study (CTS) database was used to evaluate graft survival and non-Hodgkin lymphoma at 3 years according to type of induction in 112,122 patients receiving a deceased-donor renal transplant during 1985 to 2004. RESULTS: The relative risk of 3-year graft loss versus no induction was 1.07 (95% confidence interval [CI], 1.01-1.13; P=0.016) with murine anti-CD3 monoclonal antibody (OKT3), 1.03 (95% CI, 0.95-1.11; NS) with antithymocyte globulin (ATG)-Fresenius, 1.18 (95% CI, 1.02-1.35; P=0.021) with ATGAM, 0.74 (95% CI, 0.68-0.81; P<0.001) with Thymoglobulin, and 0.78 (95% CI, 0.72-0.84; P<0.001) with interleukin (IL)-2RA induction. The standardized incidence ratio of lymphoma compared with a similar nontransplant population was 21.5 (95% CI, 15.7-28.8; P<0.001) with OKT3, 4.9 (95% CI, 1.6-11.5; P=0.008) with ATG-Fresenius, 29.0 (95% CI, 12.5-57.1; P<0.001) with ATGAM, 21.6 (95% CI, 14.3-31.2; P<0.001) with Thymoglobulin, 7.8 (95% CI, 4.4-12.9; P<0.001) with IL-2RAs, and 9.4 (95% CI, 8.3-10.6 P<0.001) with no induction. CONCLUSIONS: Those agents that offered the highest rates of graft survival were not necessarily associated with the highest risk of lymphoma. Graft survival was significantly improved with Thymoglobulin and IL-2RA induction, whereas lymphoma rates were highest with ATGAM, OKT3, and Thymoglobulin. IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma.

Antilymphocyte Serum↗

PubMed2005

Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients.

A large prospective study of steroid withdrawal was performed within the framework of the Collaborative Transplant Study to analyze long-term graft and patient outcome in renal and heart transplant recipients. Steroids were withdrawn no earlier than 6 months posttransplantation. A comparison of 7-year outcomes in renal transplant recipients (94% receiving cyclosporine; 97% Caucasian) showed a benefit of steroid withdrawal versus steroid continuation in retrospectively matched controls, for graft survival (81.9% +/- 1.8% vs. 75.3% +/- 1.2%, p = 0.0001), patient survival (88.8% +/- 1.5% vs. 84.3 +/- 1.0%; p = 0.0016) and death-censored graft survival (91.8% +/- 1.3% vs. 87.9%+/- 1.0%: p = 0.0091). Steroid withdrawal was associated with improved graft survival in heart recipients also (76.2% +/- 2.4% vs. 66.9% +/- 1.7%, p = 0.0008). A total of 58.6% of renal recipients and 44.3% of heart recipients never required steroids during follow up. Rates of acute rejection and renal dysfunction did not differ between steroid-free and steroid-continuation groups. Steroid withdrawal was associated with significantly improved cardiovascular risk factors compared with steroid continuation. Rates of the development of osteoporosis and cataracts did not differ in the entire patient cohort, but were strikingly lower in patients taken off steroids during the first posttransplant year.

Adrenal Cortex Hormones↗

PubMed2005

Improved long-term outcomes after renal transplantation associated with blood pressure control.

Hypertension has a negative impact on long-term outcomes after renal transplantation. We investigated the effect of a recent decline in blood pressure among renal transplant patients in the Collaborative Transplant Study (CTS) database on long-term graft and patient survival. CTS data were used to evaluate transplant outcomes in relation to recipient systolic blood pressure (SBP) for 24,404 first cadaver kidney recipients transplanted between 1987 and 2000. Patients whose SBP was > 140 mmHg at 1 year posttransplantation but controlled to < or = 140 mmHg by 3 years had significantly improved long-term graft outcome compared with patients with sustained high SBP to 3 years (RR 0.79; CI 0.73-0.86; p < 0.001). Additional examination at 5 years showed that SBP lowering after year 3 was associated with improved 10-year graft survival (RR 0.83; CI 0.72-0.96; p = 0.01), whereas even a temporary increase in SBP at 3 years was associated with worse survival (RR 1.37; CI 1.19-1.58; p < 0.001). Changes in SBP were paralleled by changes in the incidence of cardiovascular death among recipients younger than 50 but not in older recipients. Lowering SBP, even after several years of posttransplantation hypertension, is associated with improved graft and patient survival in renal allograft recipients.

Adult↗

PubMed2004

Risks of allogeneic hand transplantation.

A patient undergoing allogeneic hand transplantation needs lifelong immunosuppression with the risk of serious side effects, including life-threatening disease. The question remains: does the eventual improvement in function justify the risk? To answer this question, we try to assess the risks based on a large body of cumulative data derived from more 200,000 kidney transplants using the Collaborative Transplantation Study (CTS). Only selective data which apply to a patient population aged between 15-40 years were used (n = 58,310). Data are compared to the literature references and show superiority with respect to patient numbers, statistics, actuality, and methodology. The CTS data show that the incidence of de novo malignancies is lower than previously reported. The risk of developing any form of cancer is approximately 3%, of developing a skin cancer 1.1%, and of developing a lymphoma 0.58% within 5 years after transplantation. The risk of suffering from a cataract is 11% after 5 years, which is also lower than previously reported. Although the incidence of side effects (particularly malignant disease) is likely to be lower than previously thought, the risk-benefit question must be answered by each hand surgeon for each individual patient.

Adolescent↗

PubMed2004

Lymphomas after solid organ transplantation: a collaborative transplant study report.

We used the Collaborative Transplant Study database to analyze the incidence, risk, and impact of malignant lymphomas in approximately 200,000 organ transplant recipients. Over a 10-year period, the risk in renal transplant recipients was 11.8-fold higher than that in a matched nontransplanted population (p<0.0001). The majority of lymphomas were diagnosed after the first post-transplant year. Heart-lung transplants showed the highest relative risk (RR 239.5) among different types of organ transplants. In kidney recipients, immunosuppression with cyclosporine did not confer added risk compared with azathioprine/steroid treatment, whereas treatment with FK506 increased the risk approximately twofold. Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies, increased the risk of lymphoma during the first year. Antirejection therapy with OKT3 or ATG also increased the risk. First-year mortality in renal and heart transplant patients with lymphoma was approximately 40% and 50%, respectively, and showed no improvement in recent years. A pattern of preferential localization to the vicinity of the transplant was noted, and the prognosis of the patient was related to localization. This study highlights the continuing risk for lymphoma with time post-transplantation, the contribution of immunosuppression to increased risk, and continuing poor outcomes in patients with post-transplant lymphoma.

Adolescent↗

PubMed2004

Cytomegalovirus prophylaxis and graft outcome in solid organ transplantation: a collaborative transplant study report.

We investigated relationships between cytomegalovirus (CMV) seropairing and CMV prophylaxis on graft outcome in recipients of solid organ transplants. Transplants carried out from 1985 to 2002 and reported to the Collaborative Transplant Study were analyzed. In cadaver kidney recipients, CMV prophylaxis was significantly associated with improved graft survival only in the seronegative-recipient/seropositive-donor combination (at 3 years: 79.4% with prophylaxis vs. 73.5% without prophylaxis; RR 0.80, p < 0.0001). Among patients who had a functioning graft at 1 year, significantly fewer patients who received CMV prophylaxis received rejection treatment in the preceding year (26.3%), compared with patients who did not receive prophylaxis (32.4%) (p = 0.0001), suggesting an inhibitory effect of CMV prophylaxis on acute rejection. Significant improvements in graft survival after CMV prophylaxis were found also in CMV-negative recipients of CMV-positive heart, and lung or heart-lung transplants, but not liver transplants. The age of the recipient had a differential effect on graft and patient survival after CMV prophylaxis. Use of antilymphocyte antibodies or mycophenolate mofetil was not associated with an enhanced CMV effect on graft outcome. These results may contribute to a better understanding of the influence of pretransplant CMV serology on the effect of CMV prophylaxis.

Adolescent↗

PubMed2002

Prolongation of long-term kidney graft survival by a simultaneous liver transplant: the liver does it, and the heart does it too.

BACKGROUND: Whereas some authors reported that kidney transplants were protected from rejection by simultaneous liver grafts, other authors failed to obtain evidence for a kidney graft-protective role for the liver. METHODS: The survival rate of 383 kidney grafts in recipients of combined kidney-liver transplants performed between 1985 and 2000 and reported to the international Collaborative Transplant Study (CTS) was analyzed and compared retrospectively with that of a matched group of control patients who were transplanted with kidneys only. In addition, 105 combined kidney-heart transplants performed during the same time period were analyzed. RESULTS: At 1 year, the survival rate of kidney grafts in recipients of kidney-liver transplants was significantly lower than that in kidney only recipients (P<0.0001). Subsequently, however, kidneys in kidney-liver recipients fared much better so that the success rates were virtually identical after 8 years of follow-up (62.1+/-3.5% vs. 61.9+/-2.3%, P=ns). Half-life times after the first posttransplant year were 27.6 and 14.5 years for combined or single kidney grafts, respectively, and the projected 20-year graft survival rates were 46% and 35%, respectively. The 8-year survival rate of kidney grafts in recipients of combined kidney-heart recipients was 63.5+/-6.2%, the associated half-life time 31.6 years, and the projected 20-year graft survival rate 49%. CONCLUSIONS: The long-term kidney graft survival rate is higher in recipients of combined kidney-liver transplants than in recipients of kidney grafts only. Because the success rate is equally high in recipients of combined kidney-heart transplants, it is necessary to reexamine the hypothesis that the liver possesses a unique capacity of protecting a simultaneous kidney graft from rejection.

Adult↗

PubMed2002

Soluble CD30 as a predictor of kidney graft outcome.

BACKGROUND: In the present study, we investigated whether the soluble form of CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is increased in sera of potential kidney graft recipients. We also investigated whether the pretransplantation serum sCD30 content is related to kidney graft survival. METHODS: Pretransplantation sera of 844 cadaver kidney recipients from three transplant centers in Germany were tested for serum sCD30 content using a commercially available ELISA kit. RESULTS: Kidney graft recipients showed a significantly higher serum sCD30 content than healthy controls (P<0.0001). High sCD30 serum content was associated with graft rejection. The 2-year graft survival rate in recipients with a high pretransplantation serum sCD30 was 68+/-6%, significantly lower than the 86+/-1% rate in recipients with a low sCD30 (P<0.0001). Importantly, high sCD30 was indicative of an increased risk of graft loss even in recipients without lymphocytotoxic alloantibodies. CONCLUSION: These data show that an elevated pretransplantation serum sCD30 reflects an immune state that is detrimental for kidney graft survival.

Adult↗

PubMed2002

Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30.

The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (> or =100 U/ml) was 64 +/- 2%, significantly lower than the 75 +/- 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.

Adult↗

PubMed2002

The effect of donor gender on graft survival.

Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.

Actuarial Analysis↗