Conversion from Cyclosporine to Tacrolimus Improves Quality-of-Life Indices, Renal Graft Function and Cardiovascular Risk Profile

Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated.     

Detection of HLA class I and II antibodies by ELISA and complement-dependent cytotoxicity before and after transplantation

BACKGROUND: Anti-class I IgG can be detected by complement-dependent cytotoxicity (CDC) and by ELISA. We compared ELISA and CDC for both class I and class II antibodies on method agreement and relation to rejection-free and graft survival. METHODS: Peak, current, and posttransplant sera (n=429) of 143 renal allograft patients were tested by National Institutes of Health technique (NIHT), two-color fluorescence (TCF), and ELISA. Method agreement was assessed by intraclass correlation coefficient (ICC). Rejection and graft survival were analyzed by uni- and multivariate techniques. The screening results for each serum were compared, as was the change in result of current to posttransplant serum. RESULTS: The ICC of ELISA and NIHT was insufficient; it was lower for TCF than NIHT. Graft survival was not related to the result of any assay. Rejection-free survival was related to ELISA and NIHT in current and posttransplant serum. With the NIHT, the change in percent panel-reactive antibody (%PRA) correlated better with rejection than it did with ELISA. The combined antibody status of current and posttransplant serum was a risk factor for rejection in all assays, and for TCF also in multivariate analysis. The rejection rate was higher if the posttransplant serum was ELISA-negative/CDC-positive, rather than ELISA-positive/CDC-negative. For ELISA, class I specificities (and not %PRA) in peak and current sera were related to rejection, even if the antibodies were not donor-directed. In the case of the National Institutes of Health technique (NIHT), %PRA and not specificity was related to rejection. Class II antibodies were never related to rejection. CONCLUSIONS: ELISA and NEIT are complementary screening techniques in this patient population. They are of equal predictive value for rejection. The optimal strategy in combining these techniques must be determined.     

MR renography: an algorithm for calculation and correction of cortical volume averaging in medullary renographs

We evaluated a mathematical algorithm for the generation of medullary signal from raw dynamic magnetic resonance (MR) data. Five healthy volunteers were studied. MR examination consisted of a run of 100 T1-weighted coronal scans (gradient echo; TR/TE 11/3.4 msec, flip angle 60 degrees; slice thickness 6 mm; temporal resolution 2 seconds). Gadolinium-diethylene triamine pentaacetic acid (DTPA; 0. 05 mmol/kg) was injected with an injector pump (5 ml/sec). Medullary MR renographs (MRRs) were calculated for regions of interest with strong and moderate cortical volume averaging (CVA). A reference medullary MRR, devoid of CVA, was obtained. Percentual signal differences between calculated and reference medullary MRRs were estimated for each consecutive scan. Run averaged values of these differences were calculated. Mean values, after subtraction of the resting state signal, were +0.2% (SD 9.7%) and +0.7% (SD 9.0%) for areas with strong and moderate CVA, respectively. We conclude that with this algorithm reliable extraction of medullary MRRs is feasible, providing a unique tool for clinical evaluation of medullary disease. J. Magn. Reson. Imaging 2000;12:453-459.     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Prehospital endotracheal intubation in patients with severe traumatic brain injury: Guidelines versus reality

The international Brain Trauma Foundation guidelines recommend prehospital endotracheal intubation in all patients with traumatic brain injury (TBI) and a Glasgow Coma Scale (GCS) ≤ 8. Close adherence to these guidelines is associated with improved outcome, but not all severely injured TBI patients receive adequate prehospital airway support. Here we hypothesized that guideline adherence varies when skills are involved that rely on training and expertise, such as endotracheal intubation.We retrospectively studied the medical records of CT-confirmed TBI patients with a GCS ≤ 8 who were referred to a level 1 trauma centre in Amsterdam (n = 127). Records were analyzed for demographic parameters, prehospital treatment modalities, involvement of an emergency medical service (EMS) and respiratory and metabolic parameters upon arrival at the hospital.Patients were mostly male, aged 45 ± 21 years with a median injury severity score (ISS) of 26. Of all patients for whom guidelines recommend endotracheal intubation, only 56% were intubated. In 21 out of 106 severe cases an EMS was not called for, suggesting low guideline adherence. Especially those TBI patients treated by paramedics tended to develop higher levels of stress markers like glucose and lactate.We observed a low degree of adherence to intubation guidelines in a Dutch urban area. Main reasons for low adherence were the unavailability of specialized care, scoop and run strategies and absence of a specialist physician in cases where intubation was recommended. The discrepancy between guidelines and reality warrants changing practice to improve guideline compliance and optimize outcome in TBI patients.