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K Budde

Publications and source records attributed to K Budde.

At least 19 recordsLinked to original sources
PubMed2006

[Modern immunosuppression following renal transplantation. Standard or tailor made?].

Renal transplantation is by far the best therapeutic option for end-stage kidney disease with respect to quality of life, psychosocial rehabilitation, and even patient survival. Optimal immunosuppressive therapy should provide effective prophylaxis of both acute rejection and chronic allograft dysfunction. Thus immunosuppressive therapy should help to maintain good renal function and could help to prevent premature death of the recipient. With the introduction of new immunosuppressants over the last decade a dramatic reduction of acute rejection rates from approximately 50% to 15-30% could be achieved. However, the search for novel immunosuppressive drugs continues, drugs which not only lead to effective prevention of acute rejection, but also have an impact on chronic allograft dysfunction and prevent further deterioration of this multifactorial process. Based on a short presentation of the "three signal model" of immunoactivation, the most important mechanisms and characteristics of the presently available immunosuppressants are described. Because the immunosuppressive objectives change over time, a phase-dependent adaptation is necessary. At present, most centers in Germany use an immunosuppressive combination therapy, consisting of a calcineurin inhibitor (CNI; cyclosporine or tacrolimus), a glucocorticoid (prednisolone or methylprednisolone), and mycophenolic acid (MPA), which is eventually combined with an antibody (e.g., IL-2R antibody) for induction. In contrast to the clear situation 10 years ago, highly specialized knowledge is required today with respect to mechanism of action, side effects, and potential interactions. This may enable the physician to adopt patient-oriented optimal immunosuppression. In the near future more individualized treatment options will be employed, which are adapted to the characteristics and side effects of the immunosuppressant, as well as to the characteristics of the donor, the recipient, and the transplanted organ such as immunology and ischemia. Another aspect is the reduction or elimination of some immunosuppressants at the earliest possible time. With new diagnostic and genetic markers the relationship between recipient and transplanted organ will be characterized better in the future and therapy will become more individualized. Altogether, these measures as well as optimized supportive therapy will help to further improve the longevity of the transplanted organ.

Chemotherapy, Adjuvant↗
PubMed2006

[A new method for standardized diagnosis following renal transplantation. Ultrasound with contrast enhancement].

Ultrasound (US) imaging is an important diagnostic tool following renal transplantation. Unfortunately, due to the heterogeneity of the recipients and their multimorbidity, imaging procedures in the early phase after kidney transplantation are difficult and of limited use. We performed a study to evaluate the use of a contrast enhancer for US examination as a standardized method in the follow-up of kidney transplant recipients.The study included 40 recipients: 32 were examined on the 5th to 7th day following transplantation and 8 patients at the time when clinically suspicious findings occurred (acute rejection, tumor, acute tubular necrosis). Following the intravenous application of the contrast medium, pictures were taken during the arterial and parenchymatous phase and compared with conventional B-mode and power Doppler pictures of the same visual plane. Three examiners assessed different parameters of the transplant organ (max. vascularized area, suspected hematomas, tumors, rejection, acute tubular necrosis). Findings were confirmed by histological results of a biopsy if rejection, tumor, or acute tubular necrosis were suspected. Application of ultrasound contrast medium significantly increased visualization of the vascularized kidney area. Also, US findings in the follow-up after acute rejection therapy corresponded with the clinical course; 19 hematomas could be detected with contrast medium compared to only 9 without. With contrast medium a perfusion deficit was detectable in three patients compared to one patient with power Doppler US. Also, US contrast medium helped to detect tumor vascularization in two patients in whom conventional sonography suspected no abnormality. Ultrasound contrast medium enhancement is a reproducible, reliable, and easy to apply method which is superior to conventional sonography in the follow-up after kidney transplantation. This method is also helpful to detect and control acute rejections and to better visualize hematomas, deficits of perfusion, and tumors.

Adolescent↗
PubMed2006

[Ten years of laparoscopic living kidney donation. From an extravagant to a routine procedure].

Ten years ago the first laparoscopic living donor nephrectomy (LDN) was performed. Today, LDN is a routine operation in many US-American transplantation centers and an increasing number of centers in Europe are practicing LDN. In this article the different aspects of LDN for donor, kidney, recipient and operating surgeon are evaluated. We performed a literature research concerning LDN and the different aspects. Our own experience, as the largest LDN center in Germany, is part of the evaluation. Laparoscopic extraction of a kidney from a living donor is as safe for the donor as the open approach. At the same time, LDN offers multiple advantages like reduced pain and shorter convalescence. For the donated kidney and the recipient no disadvantages occur from the laparoscopic technique, as long as special intra- and perioperative demands are met. For the operating surgeon multiple developments have expanded the technical armentarium. LDN is safe for donor, recipient and kidney. Central issue of an optimal LDN is sufficient experience with laparoscopic urological techniques.

Directed Tissue Donation↗
PubMed2006

Effect of mycophenolate mofetil monotherapy on T-cell functions and inosine monophosphate dehydrogenase activity in patients undergoing a kidney transplantation.

The aim of this study was to assess the effects of 1 g of mycophenolate mofetil (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity among patients undergoing kidney transplantation. Five patients undergoing renal transplantation from a living donor were enrolled in this study. Compared to baseline (before MMF intake), CD25 and CD71 expression were significantly decreased during the first hour following MMF intake. T-cell proliferation and IMPDH activity also decreased dramatically. Thereafter, all biomarker levels increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity, returned to almost baseline values, whereas T-cell proliferation remained below baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF ingestions. In conclusion, administration of 1 g of MMF was associated with a transient decrease in CD25 expression in addition to a temporary dramatic decrease in both T-cell proliferation and IMPDH activity.

Antigens, CD↗
PubMed2006

Conversion to enteric-coated mycophenolate sodium from various doses of mycophenolate mofetil: results of a prospective international multicenter trial in maintenance renal transplant patients receiving cyclosporine.

Conversion from mycophenolate mofetil (MMF, CellCept) to enteric-coated mycophenolate sodium (EC-MPS, myfortic) is safe and effective in renal transplant patients treated with the standard dose of 2 g MMF. In this 6-month, international, multicenter, open-label, single-arm trial, a large cohort of maintenance renal transplant patients receiving different doses of MMF were converted under normal clinical conditions to equimolar doses of EC-MPS. Mean calculated creatinine clearance remained stable from the time of study entry (59.6 +/- 19.7 mL/min) to the end of the study (58.3 +/- 19.8 mL/min). Adverse events were reported by 152 patients (67%), with gastrointestinal complications being observed in 45 patients (20%). Thirty-three patients (15%) experienced adverse events or infections with a suspected relation to EC-MPS, including one case of anemia and two cases of leukopenia. Eleven patients (4.9%) required a reduction in EC-MPS dose and seven patients (3.1%) permanently discontinued EC-MPS owing to adverse events. At month 6 after conversion, five patients (2.2%) experienced biopsy-proven acute rejection. There were no graft losses or deaths. These data support earlier findings that stable maintenance renal transplant patients receiving MMF with cyclosporine with or without corticosteroids can be converted to EC-MPS with no compromise in efficacy and tolerability, and no adverse effect on renal function.

Adult↗
PubMed2006

FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.0 mg plus reduced-dose cyclosporine (RDC), with mycophenolate mofetil (MMF) plus FDC. The primary efficacy endpoint was the composite incidence of first treated biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation at month 12. Primary efficacy with FTY720 2.5 mg and MMF (32.4% and 30.2%; p = NS), plus mortality and BPAR incidence, were comparable. Patients receiving FTY720 5.0 mg plus RDC were discontinued from treatment due to increased risk of acute rejection (primary endpoint incidence 47.3%). FTY720 was associated with lower creatinine clearance (month 12: 53.1, 56.0 vs. 65.1 mL/min; p < 0.001) and more macular edema cases (2.2% and 1.3% vs. 0%), whereas cytomegalovirus infections were higher with MMF (6.2% and 10.6% vs. 18.1% p < 0.0001 and p = 0.0139, respectively). FTY720 2.5 mg provided comparable rejection prophylaxis over 12 months versus MMF; however, FTY720 5.0 mg did not support a 50% reduction in cyclosporine exposure. The cause of macular edema cases and lower creatinine clearance with FTY720 in de novo transplantation needs further investigation.

Adult↗
PubMed2006

Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPA, myfortic).

AIM: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population. METHODS: All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented. RESULTS: Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups. CONCLUSIONS: These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.

Adult↗
PubMed2005

Pharmacokinetics of the immunosuppressant everolimus in maintenance renal transplant patients.

The novel macrocyclic immunosuppressant everolimus has been approved for use in renal and heart transplantation. The objective of this randomized, double-blind, placebo-controlled, dose-escalating Phase 1 study was to evaluate the pharmacokinetic profile of different dosing regimens of everolimus. Fifty-four subjects were randomized for 4-weeks treatment with everolimus (n = 44) or placebo (n = 10). Steady state was reached by day 4 of multiple dosing with evidence for dose-proportionality over the dose range tested. Systemic accumulation was 1.6- to 2.2-fold with multiple dosing. Steady-state predose trough concentrations were well correlated with AUC (r = 0.87, p < 0.001). Within-subject coefficients of variation for the tablet formulation ranged from 10-19% and between-subject coefficients from 34-60% for Cmax and AUC. There was no effect of common demographic parameters (age, sex, weight) on variability in steady-state exposure. These results support the clinical use of everolimus in renal transplantation.

Area Under Curve↗
PubMed2005

Problems of cyclosporine absorption profiling using C2-monitoring.

UNLABELLED: The present study sought to validate the concept of C2 monitoring in 41 de-novo transplant patients treated with microemulsion of cyclosporine, mycophenolatesodium, steroids and basiliximab. RESULTS: After 6 months patient and graft survival was 98%, rejection rate was 19%. In the first week only a few patients achieved the suggested C2 levels (19% > 1500, 50% > 1200 ng/ml) despite an increased cyclosporine (CsA) dose. After 14 days 63% of patients reached C2 > 1500 ng/ml (83% C2 > 1200) despite decreased CsA dose. 35% of patients had intermittent high C0 (> 300) and low C2 (< 800), suggesting poor and/or slow absorption. Most of them suffered from CsA toxicity. There was a significant (p < 0.05) change of absorption as measured by C2/C0 leading to an increase of C2/dose. CONCLUSIONS: C2 monitoring may be useful to better estimate the CsA exposure in individual patients; however our results indicate some limitations of the current concept of C2 monitoring. Despite increase of dosage many patients do not reach the proposed levels. A significant proportion of patients are poor and/or slow absorbers. CsA toxicity may not be detected by C2 monitoring alone. With the use of basiliximab and mycophenolatesodium lower target levels seem to be sufficient.

Antibiotics, Antineoplastic↗
PubMed2005

Graft function, cardiovascular risk factors, and sex hormones in renal transplant recipients on an immunosuppressive regimen of everolimus, reduced dose of cyclosporine, and basiliximab.

A prospective, randomized trial evaluated the combination of everolimus of 1.5 or 3 mg/d with steroids, basiliximab, and low-dose cyclosporine (CsA) adjusted by C2 monitoring in 256 renal transplant recipients. CsA C2 target levels, initially set at 600 ng/mL, were tapered over time posttransplant. The median serum creatinine concentrations were 130 mumol/L in both sirolimus groups (1.5 and 3 mg/d) at 6 months. Biopsy-proven acute rejection (BPAR) occurred in 13.7% and 15.1% of patients in the 1.5 and 3 mg/d groups, respectively. The incidence of BPAR was significantly higher among patients with everolimus trough levels < 3 ng/mL. Posttransplant diabetes mellitus occurred rarely, and blood pressure control appeared favorable; however, serum cholesterol levels were increased by approximately 50%, and serum triglycerides by approximately 100%. Serum testosterone concentrations increased after renal transplantation in both everolimus groups. Concentration-controlled everolimus therapy combined with low-dose CsA provides effective protection against rejection with good renal function and safety profiles.

Antibodies, Monoclonal↗
PubMed2005

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study.

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

Adult↗
PubMed2005

Accurate prediction of kidney allograft outcome based on creatinine course in the first 6 months posttransplant.

Most attempts to predict early kidney allograft loss are based on the patient and donor characteristics at baseline. We investigated how the early posttransplant creatinine course compares to baseline information in the prediction of kidney graft failure within the first 4 years after transplantation. Two approaches to create a prediction rule for early graft failure were evaluated. First, the whole data set was analysed using a decision-tree building software. The software, rpart, builds classification or regression models; the resulting models can be represented as binary trees. In the second approach, a Hill-Climbing algorithm was applied to define cut-off values for the median creatinine level and creatinine slope in the period between day 60 and 180 after transplantation. Of the 497 patients available for analysis, 52 (10.5%) experienced an early graft loss (graft loss within the first 4 years after transplantation). From the rpart algorithm, a single decision criterion emerged: Median creatinine value on days 60 to 180 higher than 3.1 mg/dL predicts early graft failure (accuracy 95.2% but sensitivity = 42.3%). In contrast, the Hill-Climbing algorithm delivered a cut-off of 1.8 mg/dL for the median creatinine level and a cut-off of 0.3 mg/dL per month for the creatinine slope (sensitivity = 69.5% and specificity 79.0%). Prediction rules based on median and slope of creatinine levels in the first half year after transplantation allow early identification of patients who are at risk of loosing their graft early after transplantation. These patients may benefit from therapeutic measures tailored for this high-risk setting.

Creatinine↗
PubMed2005

Laparoscopic versus open donor nephrectomy in Germany: impact on donor health-related quality of life and willingness to donate.

INTRODUCTION: Laparoscopic living donor nephrectomy (LDN) offers multiple advantages to the donor. Since 1999 LDN has become the only surgical approach for living kidney donation in our department. To our knowledge a donor health-related quality of life (QoL) has not yet been performed with standardized and validated questionnaires to compare laparoscopic with open nephrectomy. We therefore performed a study with two questionnaires (SF-36/GBB-24) and one set of open questions for all donors in our department. METHODS: Questionnaires were sent out to all donors between 1983 and 2001 with at least a 1-year follow-up. To exclude a bias a maximum response rate was sought; donors who did not answer were recontacted as well as their recipients or their physicians to motivate them for participation. RESULTS: The response rate was (89.8%). Except for less limb pain in the laparoscopy group, no difference could be detected for donors QoL with respect to the surgical method. Willingness to donate again was not affected by the surgical method. Nevertheless if asked again today, most donors want laparoscopic kidney retrieval. CONCLUSIONS: Donors health-related QoL is not affected by the surgical method when queried retrospectively. Nevertheless, most donors today would favor laparoscopy, if they could chose again. How laparoscopy affects a reluctant donor to step forward must be determined in a prospective study.

Attitude↗
PubMed2005

Differences in reporting of acute rejections between American and European publications of large immunosuppressive trials impair comparability of study results.

This study examined the use of different definitions for acute rejection in recent large multicenter trials performed in America and Europe in order to assess whether systematic differences exist between both scientific cultures. We systematically selected recent publications on multicenter randomized controlled trials, investigating immunosuppressive regimens in de novo kidney transplant recipients. Publications included were classified according to the type of acute rejection reported: group 1 reported no or only one type of rejection rate (biopsy-proven or treated); group 2 reported information on both treated and biopsy-proven rates. Other potential factors (journal's impact-factor, study size) were compared within the subgroups. To determine the rates of treated but not biopsy-proven acute rejections, additional analyses were performed within subgroup 2. The reviewed publications were 24/44 (54.5%) European (E) and 20/44 (45.5%) American (A) origin. Eighteen of 44 publications reported no or only one type of rejection rate (group 1); 26 publications reported treated as well as biopsy-proven rates (group 2). Significantly more European publications reported both treated and biopsy-proven rates (E: 18/24 [75.0%] vs A: 8/20 [40.0%]; P = .019). Group 1 American papers were published in higher-ranked journals than European ones. The rate of blindly treated rejections did not differ significantly (A: 6.13% [range 0% to 12.8%] vs E: 8.43% [range 0% to 16.9%]) and the proportion of blindly treated rejections was slightly lower in American studies (A: 18.5% vs E: 26.5%). Our systematic review showed large discrepancies with a trend to report biopsy-proven rejection rates only in recent years.

Acute Disease↗
PubMed2004

Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study.

BACKGROUND: Studies have provided conflicting results as to the protective role of calcium channel blockers (CCB) in cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function. Lacidipine is a dihydropyridine CCB that possesses antioxidative, anti-atherosclerotic, and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model. METHODS: We conducted a multicenter prospective, randomized, placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy. The aim of this 2-year study was to assess the effects of lacidipine on graft function (plasma iohexol clearance), renal plasma flow, anastomotic arterial blood flow, deterioration of renal function, blood pressure, acute rejection, and hospitalization rate. RESULTS: A total of 118 recipients were available for intention-to-treat analysis on efficacy (lacidipine: n=59; placebo: n=59). Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance, was persistently better in lacidipine-treated patients from 1 year onwards (respectively, P<0.01 and P<0.05). Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients. Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60% (log-rank test: P=0.57). Study groups did not differ in acute rejection rate, trough blood cyclosporine concentrations, blood pressure, number of antihypertensive drugs, hospitalization rate, and adverse event rate. CONCLUSIONS: The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering.

Acute Disease↗
PubMed2004

Quality of life of living kidney donors in Germany: a survey with the Validated Short Form-36 and Giessen Subjective Complaints List-24 questionnaires.

BACKGROUND: Most studies evaluating the impact of kidney donation on donors' quality of life (QOL) have limitations such as small cohort size, unmatched references, use of nonstandardized and nonvalidated questionnaires, or low response rates. METHODS: We performed a study on donors' QOL that was designed to avoid these limitations. All available living renal donors in our department in the last 18 years were included in the study. QOL was assessed with two validated, standardized questionnaires (Short Form-36, Giessen Subjective Complaints List [Giessener Beschwerdebogen]-24) and compared with gender- and age-matched references. In addition, specific questions relating to kidney donation were asked. RESULTS: The response rate (89.8%) is one of the highest reported for studies on QOL of living kidney donors. Most donors had an equal or better QOL than the healthy population. Donors' willingness to donate again (93.4%) or recommend living-donor kidney transplantation (92.4%) was high, irrespective of complications. A small number of donors experienced financial drawbacks or occupational disadvantages. Donors aged 31 to 40 years were found to be at risk of QOL deterioration after organ donation. Donor and recipient complications had a significant impact on donors' QOL. One third of the donors found that the psychologic care preceding and after kidney donation was insufficient. CONCLUSIONS: Our findings support the practice of living-donor kidney transplantation as a good means to meet the persisting organ shortage. Further effort must be put into minimizing donor and recipient complications. The specific demands of younger donors should be further elucidated. In addition to medical follow-up, living kidney donors should also be offered lifelong psychologic counseling.

Adolescent↗
PubMed2004

[Evaluation and follow-up of living kidney donors].

An increase in waiting time for a cadaveric organs and a better graft-function, graft- and patient-survival with kidneys from a living donors have lead to an increase in living-donor renal transplantation in the therapy of end-stage renal disease. In Germany, with the implementation of a transplantation law in 1997 and due to improved surgical techniques (laparoscopy) the proportion of living renal donors has almost tripled during the last five years. The transplantation law also names the potential donors, including not only genetically related but also emotionally related donors. Inclusion criteria for living donation are age > 18 years, mental ability to give consent and an altruistic motivation (exclusion of financial benefits for the donor). If ABO blood group compatibility between donor and recipient is given and a cross match does not reveal immunologic obstacles a thorough medical and psychological examination must be performed with the potential donor. All risk factors for the donor beyond the actual operation must be excluded. Therefore all organ-systems have to be evaluated and risks for the donor as well as transferable pathologies and infections must be ruled out. International guidelines help to perform an efficient evaluation. Following organ donation the donor should be medically controlled as requested by law. Also, psychological counselling should be offered. The aim is to minimize risks for the single kidney and to recognize early potentially kidney damaging affections.

Contraindications↗