The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies.

Hybrid PET/CT was compared with PET alone in the staging and restaging of patients with Ewing tumor to assess the benefit of the combined imaging technique. Methods: A total of 163 18 F-FDG PET/CT studies performed in 53 patients (age: range, 4-38 y; median, 16.5 y) with histopathologically confirmed Ewing tumor were evaluated retrospectively. All PET/CT studies included low-dose CT for attenuation correction; in 91 examinations, additional diagnostic chest CT was performed. PET and CT data were assessed independently by 2 nuclear medicine physicians and 2 radiologists, respectively. Finally, both datasets were fused by use of software and analyzed by all 4 reviewers (consensus reading). Each lesion was scored with a 5-point scale. Biopsy, imaging, or clinical follow-up served as a standard of reference. Receiver operating characteristic (ROC) analyses were performed to evaluate PET and PET/CT performance characteristics. To measure the abilities to detect and correctly localize tumor foci, localization ROC (L-ROC) curves were generated for PET. Results: A total of 609 lesions were detected by PET alone. The hybrid PET/CT technique resulted in a change of score in 160 of these lesions (26%): higher scores in 23 lesions (4%) and lower scores in 137 lesions (23%). In 49 lesions detected by PET (8%), the localization had to be changed after image fusion. Additionally, 124 (21%) more lesions were found by PET/CT than by PET alone, resulting in a total of 733 lesions. As determined by lesion-based analysis, the sensitivity, specificity, and accuracy of PET were 71%, 95%, and 88%, respectively; the corresponding values for the hybrid PET/CT technique were 87%, 97%, and 94% (P , 0.0001). The areas under the curve in the ROC analysis were 0.82 for PET and 0.92 for PET/CT (P , 0.0001), and that in the L-ROC analysis was 0.66 for PET. Conclusion: PET/CT is significantly more accurate than PET alone for the detection and localization of lesions and improves staging for patients with Ewing tumor. The hybrid technique is superior to PET alone in terms of sensitivity, specificity, and accuracy, mainly because of the detection of new lesions.

Departmental sources Background: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate-defined as the blood concentration normalized by its daily dose (the C/D ratio)-is associated with post-LTx renal impairment. Material/Methods: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone. Six months after LTx, 115 patients were categorized into 1 of 2 groups based on their Tac C/D ratio (<1.09 or ³1.09): fast (n=58) or slow (n=57) metabolizers. The renal function was determined 36 months after LTx using the estimated glomerular filtration rate (eGFR) as described by Cockcroft and Gault. Results: At the time of LTx there was no statistically significant difference between the eGFR of fast and slow metabolizers. Six months (P=0.016), 12 months (P=0.001), and 36 months (P=0.018) after LTx, fast Tac metabolizers had significantly more impaired renal function than slow metabolizers. Because of a presumption of CNI nephrotoxicity, 32.8% of fast metabolizers and 14.0% of slow metabolizers were switched from Tac to other immunosuppressants (P=0.027). Conclusions: In this study, the Tac metabolism rate appears to influence renal function after LTx, suggesting that a C/D ratio of <1.09 is associated with increased CNI nephrotoxicity in LTx recipients.

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BackgroundHigh-cut-off hemodialysis (HCO-HD) can effectively reduce high concentrations of circulating serum free light chains (sFLC) in patients with dialysis-dependent acute kidney injury (AKI) due to multiple myeloma (MM). Therefore, the aim of this study was to analyze renal recovery in a retrospective single-center cohort of dialysis-dependent MM patients treated with either conventional HD (conv. HD) or HCO-HD.Methods and ResultsThe final cohort consisted of 59 patients treated with HCO-HD (n = 42) or conv. HD (n = 17). A sustained sFLC response was detected in a significantly higher proportion of HCO-HD patients (83.3%) compared with conv. HD patients (29.4%; p = 0.007). The median duration of sFLC required to reach values <1000 mg/l was 14.5 days in the HCO-HD group and 36 days in the conv. HD group. The corresponding rates of renal recovery were 64.3% and 29.4%, respectively (chi-squared test, p = 0.014). Multivariate regression and decision tree analysis (recursive partitioning) revealed HCO-HD (adjusted odds ratio [OR] 6.1 [95% confidence interval (CI) 1.5–24.5], p = 0.011) and low initial uric acid values (adjusted OR 1.3 [95%CI 1.0–1.7], p = 0.045) as independent and paramount variables associated with a favorable renal outcome.ConclusionsIn summary, the results from this retrospective case-control study suggest in addition to novel agent-based chemotherapy a benefit of HCO-HD in sFLC removal and renal outcome in dialysis-dependent AKI secondary to MM. This finding was especially pertinent in patients with low initial uric acid values, resulting in a promising renal recovery rate of 71.9%. Further prospective studies are warranted.