Johannes van Hooff | MUMC (original) (raw)

Papers by Johannes van Hooff

Research paper thumbnail of Preservation of Renal Function and Cardiovascular Risk Factors

Transplantation Proceedings, 2006

An update is given about some factors leading to loss of renal allograft, especially in relation ... more An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

Research paper thumbnail of Increase in tacrolimus trough levels after steroid withdrawal

Transplant International, 2003

Research paper thumbnail of Lower Variability in 24-Hour Exposure During Once-Daily Compared to Twice-Daily Tacrolimus Formulation in Kidney Transplantation

Transplantation, 2013

Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), althou... more Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac QD) is also available. A reduced intrapatient variability of Tac Cmin, a surrogate marker for 24-hour drug exposure (AUC0-24), has been suggested. The variability of AUC0-24 has never been studied prospectively yet. The purpose of this study was to investigate the change in intrapatient variability of Tac AUC0-24 after converting from Tac BID to Tac QD. Forty renal transplant patients on Tac BID were converted on a 1:1 (mg/mg) basis to Tac QD in an investigator-driven comparative pharmacokinetic (PK) study. AUC0-24 was determined five times before and after conversion. Duplicate samples were collected by the patients themselves using the dried blood spot method. The main outcome measure is the change in intrapatient variability of AUC0-24 expressed as coefficient of variation (CV). Moreover, the influence of Cyp3A5 genotype polymorphism on the change in CV was studied. In total, 400 AUC0-24 profiles were available for analysis. Conversion to Tac QD resulted in a significant improvement in intra-patient CV from 14.1% to 10.9% (P=0.012). Patients with the Cyp3A5*1/*3 genotype (n=11) had a numerically larger improvement in CV than patients with the CYP3A5*3/*3 genotype. Intrapatient CV of Tac AUC0-24 improved after converting from Tac BID to Tac QD in stable renal transplant patients, especially in patients with the CYP3A5*1/3 genotype. Given the very strict protocol of this PK study, this improvement is most likely due to the different intrinsic PK properties of Tac QD and Tac BID.

Research paper thumbnail of Pretransplant pharmacokinetics: does it predict the dose of tacrolimus after renal transplantation?

Transplantation Proceedings, 2002

has been shown to be highly variable among patients. Thus, the doses administered in milligrams p... more has been shown to be highly variable among patients. Thus, the doses administered in milligrams per kilogram need to be individualized using Tac whole blood trough concentrations (C min ) to guide dosing. 2 Furthermore, the systemic exposure to Tac, area under the curve (AUC) is affected by other factors such as hematocrit and albumin concentrations and concomitant use of steroids. 3 However, a good correlation exists between trough levels and AUC, 4 and AUC correlates with efficacy of the drug. In prospective studies conducted in renal transplant patients to optimize the dose, a linear trend toward increasing rates of toxicity with increasing trough concentrations of Tac was observed. Conversely, episodes of acute rejection were associated with lower trough concentrations. The data indicate that trough levels of between 5 and 25 ng/mL should be targeted in an attempt to optimize the riskbenefit ratio. 6,7 To prevent rejection, it is well accepted that Tac whole blood trough level should be Ͼ10 ng/mL in the initial period after transplantation. The objective of this study was to characterize the oral pharmacokinetics of Tac prior to transplantation to assess possible predictors for dose adjustments after transplantation.

Research paper thumbnail of The blood rest in Kiil haemodialyzers; its dependence on type of dialyzer and blood return technique

Research paper thumbnail of The impact and evaluation of two school-based interventions on intention to register an organ donation preference

Health Education Research, 2004

The present paper describes the impact and evaluation of two intervention components-a video with... more The present paper describes the impact and evaluation of two intervention components-a video with group discussion and an interactive computer-tailored program-in order to encourage adolescents to register their organ donation preference. Studies were conducted in school during regular school hours. The video with group discussion in class had a positive impact on the intention to register an organ donation preference as well as on the intention to register as a posthumous organ donor. The computer-tailored program had no surplus value when compared to reading an extensive brochure with general information on organ donation. However, participants appreciated the tailored information more than the brochure. It may be that having provided general information before exposure to the tailored program, the tailored intervention will be more effective. This needs to be tested in a further experiment.

Research paper thumbnail of Kidney graft survival, clinical course, and HLA-A, B, and D matching in 208 patients transplanted in one center

Transplantation Proceedings

Research paper thumbnail of Blood transfusions, HLA-A and B, DR matching, graft survival, and clinical course after cadaveric kidney transplantation

Transplantation Proceedings

Research paper thumbnail of Efficacy of HL-A Matching in Eurotransplant

The Lancet, 1972

Abstract When the effect of HL-A matching on graft prognosis is analysed, the immune status of a ... more Abstract When the effect of HL-A matching on graft prognosis is analysed, the immune status of a recipient of a cadaveric kidney graft, as expressed by the presence or absence of leucocyte antibodies, should be taken into account. Over 300 kidney transplants ...

Research paper thumbnail of Priorities in Transplantation Research

Research paper thumbnail of A Comparative Study Concerning the Stability of the Anticoagulant Effect of Acenocoumarol and Phenprocoumon

Acta Medica Scandinavica, 2009

ABSTRACT

Research paper thumbnail of Recurrent postpartum renal failure in a renal allograft

Research paper thumbnail of The effect of cyclosporine A on renal graft function is dependent on donor age

Transplantation Proceedings

Research paper thumbnail of Salt-sensitivity testing in patients with borderline hypertension: Reproducibility and potential mechanisms

Journal of Human Hypertension

We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on bl... more We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on blood pressure (BP) of low sodium intake (20 mmol/day) and high sodium intake (220 mmol/day) in 10 men with borderline hypertension on two separate occasions. A difference in mean arterial pressure of 8 mm Hg between the high salt and the low salt regimen was arbitrarily chosen to define salt sensitivity. In addition, the reproducibility of changes in renal haemodynamics and in humoral factors, such as plasma renin activity, plasma aldosterone, atrial natriuretic peptide and urinary dopa and dopamine excretion, on the alteration in sodium intake were studied. As far as changes in BP are concerned, there was perfect agreement between the two tests, because in the second investigation, all subjects were classified in the same category as before. The salt-induced changes in plasma atrial natriuretic peptide and in renal excretion of dopa (dihydroxyphenylalanine) and dopamine were repeatedly and consistently different between the salt-sensitive and the salt-resistant group. The study revealed no support for a role of renal haemodynamics or the renin-angiotensin-aldosterone system in the pathophysiology of salt-induced elevations of BP in salt-sensitive subjects.

Research paper thumbnail of Detection of latent human cytomegalovirus in organ tissue and the correlation with serological status

Transplant International

The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hyb... more The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hybridization techniques in seropositive and seronegative organ donors without clinical or laboratory confirmed HCMV infection. The serum samples of these patients were screened by latex agglutination test (LA) and enzyme linked immuno sorbent assay (ELISA) for the presence of HCMV antibodies, and confirmed by immunoblotting technique (IB). For the detection of HCMV sequences in spleen tissue dot blot DNA hybridization (DBH) using probes derived from immediate-early and late regions (ES and BH fragment respectively) of the HCMV genome were used. Samples positive in DBH were further tested by in situ DNA hybridization (ISH) using the ES probe. The number of spleen tissue specimens positive for HCMV nucleic acids indicated that HCMV may be present in human beings, even without serological evidence.

Research paper thumbnail of Perfusion imaging of pancreas allografts using technetium-99m hexamethyl propylene amine oxime

Transplant international : official journal of the European Society for Organ Transplantation, 1992

The vascular integrity and major changes in perfusion can be determined by visual interpretation ... more The vascular integrity and major changes in perfusion can be determined by visual interpretation of radionuclide flow studies. We studied the potential of a new radiopharmaceutical technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) in the particular setting of pancreas transplantation. Perfusion was measured by perfusion indices (PI). Changes in graft perfusion were estimated by three independent observers. A predefined scale from 0 to 4 was used, with 0 representing no visualisation of the graft and 4 denoting sharp countour delineation and distinct demarcation from the background. In order to investigate the relation between perfusion of the pancreas graft and its exocrine function, we measured the amylase excretion rate (AER) in the urine, expressed in units per hour. It is concluded that 99mTc-HMPAO is a suitable radiopharmaceutical for pancreas allograft imaging. For the assessment of the vascular integrity in the direct postoperative period, the scintigram is very r...

Research paper thumbnail of Low systemic exposure to tacrolimus correlates with acute rejection

Transplantation proceedings

Research paper thumbnail of Relation Between Steroid Dose, Body Composition and Physical Activity in Renal Transplant Patients

Transplantation, 2000

Fat mass is increased in renal transplant (RTx) patients, which may have untoward metabolic and c... more Fat mass is increased in renal transplant (RTx) patients, which may have untoward metabolic and cardiovascular effects. The influence of steroids on body composition (BC), resting energy expenditure (REE), and substrate oxidation rates was assessed in stable RTx patients in a cross-sectional design. Also, the relation between physical activity and nutrient intake, respectively, and body composition was studied. 77 RTx patients (42 males, 35 females) were studied. Twenty-one patients were on 10 mg and 27 patients on 5 mg maintenance steroid dose; 29 patients were receiving steroid-free immunosuppression. Assessed were BC (DEXA, anthropometry), REE and substrate oxidation (indirect calorimetry), physical activity (Baecke questionnaire), and nutrient intake (dietary records). BC was not different between the 0-, 5-, and 10-mg steroid group, and no relationship existed between cumulative dose of steroids and BC. REE and substrate oxidation also did not differ between the various groups, apart from a small increase in glucose and decrease in lipid oxidation in female patients using 5-mg steroids. Especially in females, leisure time physical activity was positively related with the percentage lean body mass (r=0.571, P=0.004) and inversely related with fat mass (r= -0.588, P=0.003). Nutrient intake and BC (corrected for physical activity) were not related. No relation was observed between daily and cumulative steroid dosage and BC and between daily steroid dose and REE and substrate oxidation in RTx patients. Especially in female patients, physical activity level and the percentage of lean body mass concluded and body fat were significantly related.

Research paper thumbnail of Multicenter Randomized Trial Comparing Tacrolimus (FK506) and Cyclosporine in the Prevention of Renal Allograft REJECTION1

Transplantation, 1997

To confirm the results of a number of studies conducted in Europe, the United States, and Japan, ... more To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Research paper thumbnail of Three-Year Observational Follow-up of a Multicenter, Randomized Trial on Tacrolimus-Based Therapy with Withdrawal of Steroids or Mycophenolate Mofetil after Renal Transplant

Transplantation, 2006

The challenge in renal transplantation is to improve long-term patient and graft survival without... more The challenge in renal transplantation is to improve long-term patient and graft survival without increasing early acute rejection by minimizing immunosuppression. This multicenter, observational study investigated the effects of withdrawal of steroids or mycophenolate mofetil (MMF) from a tacrolimus-based triple regimen (tac/MMF/steroids) 3 months posttransplant at 3 years; no additional interventions or assessments were undertaken. Adult patients, included in the intent-to-treat population of the THOMAS study, participated. Patient and graft survival, adverse events, rejection episodes, and immunosuppressive and concomitant medications were assessed. Data at Year 3 was available for 718 patients (triple therapy, n=237; steroid stop, n=235; MMF stop, n=246). The original randomized regimen was maintained in 45.6% of patients in the triple, 62.6% in the steroid stop, and 53.9% in the MMF stop groups. Graft survival rates were 88.1% (triple), 86.4% (steroid stop), and 85.8% (MMF stop); patient survival was 96.1%, 95.9%, and 95.7%, respectively. The incidence of biopsy-proven acute rejection was similar in all groups between Month 7 and Year 3: 1.2% (triple), 2.0% (steroid stop) and 2.0% (MMF stop). Patients in the steroid stop group had less hypertension and significantly lower mean total cholesterol and LDL-cholesterol at Year 3 compared with Month 3 (P=0.02). Median serum creatinine levels remained stable throughout the follow-up and were comparable between groups. Immunosuppression minimization initiated at Month 3 was maintained at Year 3 in over half of the patients. Steroid withdrawal was advantageous in reducing the cardiovascular risk factors hyperlipidemia, hypertension and diabetes mellitus. Renal function was stable in all groups.

Research paper thumbnail of Preservation of Renal Function and Cardiovascular Risk Factors

Transplantation Proceedings, 2006

An update is given about some factors leading to loss of renal allograft, especially in relation ... more An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.

Research paper thumbnail of Increase in tacrolimus trough levels after steroid withdrawal

Transplant International, 2003

Research paper thumbnail of Lower Variability in 24-Hour Exposure During Once-Daily Compared to Twice-Daily Tacrolimus Formulation in Kidney Transplantation

Transplantation, 2013

Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), althou... more Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac QD) is also available. A reduced intrapatient variability of Tac Cmin, a surrogate marker for 24-hour drug exposure (AUC0-24), has been suggested. The variability of AUC0-24 has never been studied prospectively yet. The purpose of this study was to investigate the change in intrapatient variability of Tac AUC0-24 after converting from Tac BID to Tac QD. Forty renal transplant patients on Tac BID were converted on a 1:1 (mg/mg) basis to Tac QD in an investigator-driven comparative pharmacokinetic (PK) study. AUC0-24 was determined five times before and after conversion. Duplicate samples were collected by the patients themselves using the dried blood spot method. The main outcome measure is the change in intrapatient variability of AUC0-24 expressed as coefficient of variation (CV). Moreover, the influence of Cyp3A5 genotype polymorphism on the change in CV was studied. In total, 400 AUC0-24 profiles were available for analysis. Conversion to Tac QD resulted in a significant improvement in intra-patient CV from 14.1% to 10.9% (P=0.012). Patients with the Cyp3A5*1/*3 genotype (n=11) had a numerically larger improvement in CV than patients with the CYP3A5*3/*3 genotype. Intrapatient CV of Tac AUC0-24 improved after converting from Tac BID to Tac QD in stable renal transplant patients, especially in patients with the CYP3A5*1/3 genotype. Given the very strict protocol of this PK study, this improvement is most likely due to the different intrinsic PK properties of Tac QD and Tac BID.

Research paper thumbnail of Pretransplant pharmacokinetics: does it predict the dose of tacrolimus after renal transplantation?

Transplantation Proceedings, 2002

has been shown to be highly variable among patients. Thus, the doses administered in milligrams p... more has been shown to be highly variable among patients. Thus, the doses administered in milligrams per kilogram need to be individualized using Tac whole blood trough concentrations (C min ) to guide dosing. 2 Furthermore, the systemic exposure to Tac, area under the curve (AUC) is affected by other factors such as hematocrit and albumin concentrations and concomitant use of steroids. 3 However, a good correlation exists between trough levels and AUC, 4 and AUC correlates with efficacy of the drug. In prospective studies conducted in renal transplant patients to optimize the dose, a linear trend toward increasing rates of toxicity with increasing trough concentrations of Tac was observed. Conversely, episodes of acute rejection were associated with lower trough concentrations. The data indicate that trough levels of between 5 and 25 ng/mL should be targeted in an attempt to optimize the riskbenefit ratio. 6,7 To prevent rejection, it is well accepted that Tac whole blood trough level should be Ͼ10 ng/mL in the initial period after transplantation. The objective of this study was to characterize the oral pharmacokinetics of Tac prior to transplantation to assess possible predictors for dose adjustments after transplantation.

Research paper thumbnail of The blood rest in Kiil haemodialyzers; its dependence on type of dialyzer and blood return technique

Research paper thumbnail of The impact and evaluation of two school-based interventions on intention to register an organ donation preference

Health Education Research, 2004

The present paper describes the impact and evaluation of two intervention components-a video with... more The present paper describes the impact and evaluation of two intervention components-a video with group discussion and an interactive computer-tailored program-in order to encourage adolescents to register their organ donation preference. Studies were conducted in school during regular school hours. The video with group discussion in class had a positive impact on the intention to register an organ donation preference as well as on the intention to register as a posthumous organ donor. The computer-tailored program had no surplus value when compared to reading an extensive brochure with general information on organ donation. However, participants appreciated the tailored information more than the brochure. It may be that having provided general information before exposure to the tailored program, the tailored intervention will be more effective. This needs to be tested in a further experiment.

Research paper thumbnail of Kidney graft survival, clinical course, and HLA-A, B, and D matching in 208 patients transplanted in one center

Transplantation Proceedings

Research paper thumbnail of Blood transfusions, HLA-A and B, DR matching, graft survival, and clinical course after cadaveric kidney transplantation

Transplantation Proceedings

Research paper thumbnail of Efficacy of HL-A Matching in Eurotransplant

The Lancet, 1972

Abstract When the effect of HL-A matching on graft prognosis is analysed, the immune status of a ... more Abstract When the effect of HL-A matching on graft prognosis is analysed, the immune status of a recipient of a cadaveric kidney graft, as expressed by the presence or absence of leucocyte antibodies, should be taken into account. Over 300 kidney transplants ...

Research paper thumbnail of Priorities in Transplantation Research

Research paper thumbnail of A Comparative Study Concerning the Stability of the Anticoagulant Effect of Acenocoumarol and Phenprocoumon

Acta Medica Scandinavica, 2009

ABSTRACT

Research paper thumbnail of Recurrent postpartum renal failure in a renal allograft

Research paper thumbnail of The effect of cyclosporine A on renal graft function is dependent on donor age

Transplantation Proceedings

Research paper thumbnail of Salt-sensitivity testing in patients with borderline hypertension: Reproducibility and potential mechanisms

Journal of Human Hypertension

We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on bl... more We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on blood pressure (BP) of low sodium intake (20 mmol/day) and high sodium intake (220 mmol/day) in 10 men with borderline hypertension on two separate occasions. A difference in mean arterial pressure of 8 mm Hg between the high salt and the low salt regimen was arbitrarily chosen to define salt sensitivity. In addition, the reproducibility of changes in renal haemodynamics and in humoral factors, such as plasma renin activity, plasma aldosterone, atrial natriuretic peptide and urinary dopa and dopamine excretion, on the alteration in sodium intake were studied. As far as changes in BP are concerned, there was perfect agreement between the two tests, because in the second investigation, all subjects were classified in the same category as before. The salt-induced changes in plasma atrial natriuretic peptide and in renal excretion of dopa (dihydroxyphenylalanine) and dopamine were repeatedly and consistently different between the salt-sensitive and the salt-resistant group. The study revealed no support for a role of renal haemodynamics or the renin-angiotensin-aldosterone system in the pathophysiology of salt-induced elevations of BP in salt-sensitive subjects.

Research paper thumbnail of Detection of latent human cytomegalovirus in organ tissue and the correlation with serological status

Transplant International

The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hyb... more The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hybridization techniques in seropositive and seronegative organ donors without clinical or laboratory confirmed HCMV infection. The serum samples of these patients were screened by latex agglutination test (LA) and enzyme linked immuno sorbent assay (ELISA) for the presence of HCMV antibodies, and confirmed by immunoblotting technique (IB). For the detection of HCMV sequences in spleen tissue dot blot DNA hybridization (DBH) using probes derived from immediate-early and late regions (ES and BH fragment respectively) of the HCMV genome were used. Samples positive in DBH were further tested by in situ DNA hybridization (ISH) using the ES probe. The number of spleen tissue specimens positive for HCMV nucleic acids indicated that HCMV may be present in human beings, even without serological evidence.

Research paper thumbnail of Perfusion imaging of pancreas allografts using technetium-99m hexamethyl propylene amine oxime

Transplant international : official journal of the European Society for Organ Transplantation, 1992

The vascular integrity and major changes in perfusion can be determined by visual interpretation ... more The vascular integrity and major changes in perfusion can be determined by visual interpretation of radionuclide flow studies. We studied the potential of a new radiopharmaceutical technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) in the particular setting of pancreas transplantation. Perfusion was measured by perfusion indices (PI). Changes in graft perfusion were estimated by three independent observers. A predefined scale from 0 to 4 was used, with 0 representing no visualisation of the graft and 4 denoting sharp countour delineation and distinct demarcation from the background. In order to investigate the relation between perfusion of the pancreas graft and its exocrine function, we measured the amylase excretion rate (AER) in the urine, expressed in units per hour. It is concluded that 99mTc-HMPAO is a suitable radiopharmaceutical for pancreas allograft imaging. For the assessment of the vascular integrity in the direct postoperative period, the scintigram is very r...

Research paper thumbnail of Low systemic exposure to tacrolimus correlates with acute rejection

Transplantation proceedings

Research paper thumbnail of Relation Between Steroid Dose, Body Composition and Physical Activity in Renal Transplant Patients

Transplantation, 2000

Fat mass is increased in renal transplant (RTx) patients, which may have untoward metabolic and c... more Fat mass is increased in renal transplant (RTx) patients, which may have untoward metabolic and cardiovascular effects. The influence of steroids on body composition (BC), resting energy expenditure (REE), and substrate oxidation rates was assessed in stable RTx patients in a cross-sectional design. Also, the relation between physical activity and nutrient intake, respectively, and body composition was studied. 77 RTx patients (42 males, 35 females) were studied. Twenty-one patients were on 10 mg and 27 patients on 5 mg maintenance steroid dose; 29 patients were receiving steroid-free immunosuppression. Assessed were BC (DEXA, anthropometry), REE and substrate oxidation (indirect calorimetry), physical activity (Baecke questionnaire), and nutrient intake (dietary records). BC was not different between the 0-, 5-, and 10-mg steroid group, and no relationship existed between cumulative dose of steroids and BC. REE and substrate oxidation also did not differ between the various groups, apart from a small increase in glucose and decrease in lipid oxidation in female patients using 5-mg steroids. Especially in females, leisure time physical activity was positively related with the percentage lean body mass (r=0.571, P=0.004) and inversely related with fat mass (r= -0.588, P=0.003). Nutrient intake and BC (corrected for physical activity) were not related. No relation was observed between daily and cumulative steroid dosage and BC and between daily steroid dose and REE and substrate oxidation in RTx patients. Especially in female patients, physical activity level and the percentage of lean body mass concluded and body fat were significantly related.

Research paper thumbnail of Multicenter Randomized Trial Comparing Tacrolimus (FK506) and Cyclosporine in the Prevention of Renal Allograft REJECTION1

Transplantation, 1997

To confirm the results of a number of studies conducted in Europe, the United States, and Japan, ... more To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Research paper thumbnail of Three-Year Observational Follow-up of a Multicenter, Randomized Trial on Tacrolimus-Based Therapy with Withdrawal of Steroids or Mycophenolate Mofetil after Renal Transplant

Transplantation, 2006

The challenge in renal transplantation is to improve long-term patient and graft survival without... more The challenge in renal transplantation is to improve long-term patient and graft survival without increasing early acute rejection by minimizing immunosuppression. This multicenter, observational study investigated the effects of withdrawal of steroids or mycophenolate mofetil (MMF) from a tacrolimus-based triple regimen (tac/MMF/steroids) 3 months posttransplant at 3 years; no additional interventions or assessments were undertaken. Adult patients, included in the intent-to-treat population of the THOMAS study, participated. Patient and graft survival, adverse events, rejection episodes, and immunosuppressive and concomitant medications were assessed. Data at Year 3 was available for 718 patients (triple therapy, n=237; steroid stop, n=235; MMF stop, n=246). The original randomized regimen was maintained in 45.6% of patients in the triple, 62.6% in the steroid stop, and 53.9% in the MMF stop groups. Graft survival rates were 88.1% (triple), 86.4% (steroid stop), and 85.8% (MMF stop); patient survival was 96.1%, 95.9%, and 95.7%, respectively. The incidence of biopsy-proven acute rejection was similar in all groups between Month 7 and Year 3: 1.2% (triple), 2.0% (steroid stop) and 2.0% (MMF stop). Patients in the steroid stop group had less hypertension and significantly lower mean total cholesterol and LDL-cholesterol at Year 3 compared with Month 3 (P=0.02). Median serum creatinine levels remained stable throughout the follow-up and were comparable between groups. Immunosuppression minimization initiated at Month 3 was maintained at Year 3 in over half of the patients. Steroid withdrawal was advantageous in reducing the cardiovascular risk factors hyperlipidemia, hypertension and diabetes mellitus. Renal function was stable in all groups.