The association of early post-transplant glucose levels with long-term mortality

Aims/objective: We aimed to assess the long-term effects of post-transplant glycaemia on long-term survival after renal transplantation. Methods: Study participants were 1,410 consecutive transplant recipients without known diabetes who underwent an OGTT 10 weeks post-transplant and were observed for a median of 6.7 years (range 0.3–13.8 years). The HRs adjusted for age, sex, traditional risk factors and transplant-related risk factors were estimated. Results: Each 1 mmol/l increase in fasting plasma glucose (fPG) or 2 h plasma glucose (2hPG) was associated with 11% (95% CI −1%, 24%) and 5% (1%, 9%) increments in all-cause mortality risk and 19% (1%, 39%) and 6% (1%, 12%) increments in cardiovascular (CV) mortality risk, respectively. Including both fPG and 2hPG in the multi-adjusted model the HR for 2hPG remained unchanged, while the HR for fPG was attenuated (1.05 [1.00, 1.11] and 0.97 [0.84, 1.14]). Compared with recipients with normal glucose tolerance, patients with post-transplant diabetes mellitus had higher all-cause and CV mortality (1.54 [1.09, 2.17] and 1.80 [1.10, 2.96]), while patients with impaired glucose tolerance (IGT) had higher all-cause, but not CV mortality (1.39 [1.01, 1.91] and 1.04 [0.62, 1.74]). Conversely, impaired fasting glucose was not associated with increased all-cause or CV mortality (0.79 [0.52, 1.23] and 0.76 [0.39, 1.49]). Post-challenge hyperglycaemia predicted death from any cause and infectious disease in the multivariable analyses (1.49 [1.15, 1.95] and 1.91 [1.09, 3.33]). Conclusions/interpretation: For predicting all-cause and CV mortality, 2hPG is superior to fPG after renal transplantation. Also, early post-transplant diabetes, IGT and post-challenge hyperglycaemia were significant predictors of death. Future studies should determine whether an OGTT helps identify renal transplant recipients at increased risk of premature death. © The Author(s) 2011. This article is published with open access at Springerlink.co

Steroids in kidney transplant patients

Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment

Factors influencing general practitioner referral of patients developing end-stage renal failure: a standardised case-analysis study

<p>Abstract</p> <p>Background</p> <p>To understand why treatment referral rates for ESRF are lower in Ireland than in other European countries, an investigation of factors influencing general practitioner referral of patients developing ESRF was conducted.</p> <p>Method</p> <p>Randomly selected general practitioners (N = 51) were interviewed using 32 standardised written patient scenarios to elicit referral strategies. Main outcome measures: General practitioner referral levels and thresholds for patients developing end-stage renal disease; referral routes (nephrologist vs other physicians); influence of patient age, marital status and co-morbidity on referral.</p> <p>Results</p> <p>Referral levels varied widely with the full range of cases (0–32; median = 15) referred by different doctors after consideration of first laboratory results. Less than half (44%) of cases were referred to a nephrologist. Patient age (40 vs 70 years), marital status, co-morbidity (none vs rheumatoid arthritis) and general practitioner prior specialist renal training (yes or no) did not influence referral rates. Many patients were not referred to a specialist at creatinine levels of 129 μmol/l (47% not referred) or 250 μmol/l (45%). While all patients were referred at higher levels (350 and 480 μmol/l), referral to a nephrologist decreased in likelihood as scenarios became more complex; 28% at 129 μmol/l creatinine; 28% at 250 μmol/l; 18% at 350 μmol/l and 14% at 480 μmol/l. Referral levels and routes were not influenced by general practitioner age, sex or practice location. Most general practitioners had little current contact with chronic renal patients (mean number in practice = 0.7, s.d. = 1.3).</p> <p>Conclusion</p> <p>The very divergent management patterns identified highlight the need for guidance to general practitioners on appropriate management of this serious condition.</p

Application of Gastrointestinal Simulation for Extensions for Biowaivers of Highly Permeable Compounds

The goal of this study was to apply gastrointestinal simulation technology and integration of physiological parameters to predict biopharmaceutical drug classification. GastroPlus® was used with experimentally determined physicochemical and pharmacokinetic drug properties to simulate the absorption of several weak acid and weak base BCS class II compounds. Simulation of oral drug absorption given physicochemical drug properties and physicochemical parameters will aid justification of biowaivers for selected BCS class II compounds