In comparison with the MDRD(4) formula, the CKD-EPI equation leads to higher estimates of GFR in young people and lower estimates in the elderly. On a population level, this may lead to higher estimates of kidney function. However, in routine clinical practice where the population is predominantly elderly, the opposite may be true. The introduction of eGFR(CKD-EPI) necessitates reconsidering the definition of CKD. We suggest introducing age-dependent threshold values and/or the use of urinary albumin excretion to improve risk stratification.
PurposeThe aim of this study was to develop a clinically applicable limited sampling strategy for ambulatory Caucasian kidney transplant patients to estimate area under the curve in a 24-h period (AUC0–24) of prolonged-release tacrolimus.MethodsTwenty six kidney recipients, at least 6 months after transplantation, receiving prolonged-release tacrolimus, were enrolled. In each patient, seven blood samples were collected during a period of 24 h by use of the validated dried blood spot method. Best subset selection multiple linear regression was performed to derive limited sampling strategy (LSS). The equations were constrained to include a maximum of three samples collected within 4 h after the intake to maintain clinical applicability. To assess the predictive performance of LSS, residuals for each patient were calculated based on models fitted to a dataset where that patient was omitted.ResultsThe prediction formula for the AUC0–24 using the time points 0, 2, and 4 h after ingestion (C0h-C2h-C4h) provided the highest correlation with the AUC0–24 (r2 = 0.95): AUC0–24 = 44.9 + 8.9 × C0h + 2.1 × C2h + 7.6 × C4h. Measures for bias and precision, i.e., median percentage prediction error (MPPE) and median absolute prediction error (MAPE), were 0.4 and 4.8 %, respectively. For the same patients, the correlation between C24h and AUC0–24 was worse (r2 = 0.77) while MPPE and MAPE were 6.2 and 7.2 %, respectively.ConclusionIn the outpatient department, a LSS using C0h-C2h-C4h can be used for reliable estimation of the AUC0–24 of prolonged-release tacrolimus.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1863-6) contains supplementary material, which is available to authorized users.
High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.
Our data demonstrate that HNF1β is a novel repressor of human PTH gene transcription, which could contribute to the development of hyperparathyroidism in patients with HNF1β mutations or deletions.
Summary
Trough concentrations of prolonged‐release tacrolimus are usually measured at 24 h after taking the drug in the morning. It is impractical to measure these trough concentrations in patients who visit the outpatient clinic in the afternoon. Trough concentrations obtained in the afternoon may also be suitable for estimating the 24‐h exposure. We therefore aimed to assess the usefulness of tacrolimus concentrations measured at 32 h postdose for therapeutic drug monitoring in renal transplant patients who take prolonged‐release tacrolimus. We measured tacrolimus pharmacokinetics in 26 patients using prolonged‐release tacrolimus. Eleven blood samples were taken during a period of 32 h after ingestion by use of a validated dried blood spot method. Tacrolimus concentrations were measured with HPLC‐tandem mass spectrometry. The mean concentrations at 24 and 32 h postdose were 8.3 μg/l (7.5–9.1) and 6.7 μg/l (6.1–7.4), respectively (P < 0.0001). The Spearman correlation coefficients between these concentrations and 24‐h exposure were 0.83 and 0.82, respectively (both P < 0.01). In conclusion, delayed trough level measurement provides lower values and therefore requires adjustment of the target range. However, levels measured until 32 h after ingestion remain strongly correlated with 24‐h exposure. This warrants the use of delayed trough level measurement to improve patient convenience.
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