Репозиторий Университета

© 2018 Pirogov Russian National Research Medical University. All rights reserved. Mathematical modeling of pharmacokinetic (PK) and pharmacodynamic (PD) parameters essential for establishing correct dosing regimens is an alternative to pharmacokinetic studies (PKS) adopted in the clinical setting. The aim of this work was to compare the values of PK parameters for vancomycin obtained in an actual PKS and through MM in postoperative patients with kidney injury. Our prospective study included 61 patients (47 males and 14 females aged 60.59 ± 12.23 years). During PKS, drug concentrations at steady state Сtrough and Cpeak were measured by high-performance liquid chromatography followed by the calculation of the area under the plasma concentration-time curve AUC24. For mathematical modeling, a single-compartment model was employed; PK parameters were estimated using R 3.4.0. The values of Ctrough measured 48 h after the onset of antibiotic therapy during PKS were significantly lower than those predicted by MM (р = 0.004). In a group of patients with acute kidney injury (AKI), AUC24 measured at the end of treatment was significantly higher than its value predicted by MM (р = 0.011). The probability of achieving the target AUC24 to MIC ratio of over 400 µg•h /ml is higher in the group of patients with Ctrough = 10–15 µg /ml. Our findings confirm that the use of MM in postoperative patients with renal dysfunction is limited and therapeutic drug monitoring should be used instead.

© 2018 Media Sphera Publishing Group. All rights reserved. Obstetric atypical hemolytic uremic syndrome (aHUS) is one of the reasons for the development of acute kidney injury (AKI) and can determine the prognosis of both mother and child. Aim. Analysis of clinical manifestations, course and outcomes of obstetric aHUS. Materials and methods. 45 patients with aHUS development during pregnancy or immediately after childbirth were observed between 2011 and 2017, age from 16 to 42 years. Results and discussion. All patients had AKI (serum creatinine 521,5±388,0 μmol/l, oliguria or anuria that required initiation of hemodialysis). 93.3% pts had extrarenal manifestations of TMA with the development of multiple organ failure (MOF). The mean number of damage organs was 3,7±1,2. In all patients, the development of aHUS was preceded by obstetric complications, surgery, infection, etc. In the outcome: 53.4% women showed complete recovery of renal function, 11.1% developed CKD 4-5 stages, 35.5% had dialysis-dependent end-stage renal failure (ESDR). Maternal mortality was 23.9%. Perinatal mortality was 32.6%. The early start of eculizumab treatment (within 1-2 weeks from the onset of aHUS), compared with therapy start after 3 weeks, increased the chances of favorable outcome for mother in 5.33 times, and the chances for normalization of renal function in 48.7 times. Conclusion. Obstetric aHUS is characterized by the development of AKI in 100% of cases. In most patients, the obstetric aHUS occurs with the development of MOF. Timely diagnosis of aHUS and immediate treatment by eculizumab allows not only to save the life of patients, but also completely restore their health.