Mycophenolic acid (MPA) is an effective treatment for active lupus nephritis despite its variable efficacy in different ethnic groups. Here we tested whether pharmacokinetic monitoring may help to optimize dosing of MPA in an Asian population. Patients with biopsy-proven class III or IV lupus nephritis (ISN/RPS category) were treated with mycophenolate mofetil or enteric-coated mycophenolate sodium. One month after initiating treatment we measured plasma MPA levels in eight samples taken over a 12-h period after drug administration. The mean area under the time-dependent curve for MPA of responding patients was significantly higher than those not responding. Successful treatment was seen in patients with areas >45 mg h/l. The dosage of the drug was not related to MPA pharmacokinetics. In the mycophenolate mofetil group, however, MPA-area under the curve was positively, and significantly, correlated with trough or 1 h after dose concentrations and associated with a therapeutic response. Thus, our study shows that MPA pharmacokinetics were positively correlated with therapeutic responses of mycophenolate, suggesting that controlling the concentrations may improve its therapeutic efficacy in lupus nephritis. As the absorption and pharmacokinetic peak of enteric-coated tablets is slower, it is important to take different formulations into account when determining optimal MPA concentrations.

Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.

The first population pharmacokinetic model of tacrolimus in Thai adult kidney transplant patients was developed and validated. Haemoglobin and duration of tacrolimus therapy could partly explain the interindividual variability in the apparent clearance of tacrolimus. This manuscript also provides a summary review of previously reported population pharmacokinetic models of twice daily tacrolimus in adult kidney transplant recipients.

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p < 0.0001); BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.

The accuracy of the estimated glomerular filtration rate (eGFR) in cancer patients is very important for dose adjustments of anti-malignancy drugs to reduce toxicities and enhance therapeutic outcomes. Therefore, the performance of eGFR equations, including their bias, precision, and accuracy, was explored in patients with varying stages of chronic kidney disease (CKD) who needed anti-cancer drugs. The reference glomerular filtration rate (GFR) was assessed by the 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method in 320 patients and compared with the GFRs estimated by i) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, ii) the unadjusted for body surface area (BSA) CKD-EPI equation, iii) the re-expressed Modification of Diet in Renal Disease (MDRD) study equation with the Thai racial factor, iv) the Thai eGFR equation, developed in CKD patients, v) the 2012 CKD-EPI creatinine-cystatin C, vi) the Cockcroft-Gault formula, and vii) the Janowitz and Williams equations for cancer patients. The mean reference GFR was 60.5 ± 33.4 mL/min/1.73 m2. The bias (mean error) values for the estimated GFR from the CKD-EPI equation, BSA-unadjusted CKD-EPI equation, re-expressed MDRD study equation with the Thai racial factor, and Thai eGFR, 2012 CKD-EPI creatinine-cystatin-C, Cockcroft-Gault, and Janowitz and Williams equations were −2.68, 1.06, −7.70, −8.73, 13.37, 1.43, and 2.03 mL/min, respectively, the precision (standard deviation of bias) values were 6.89, 6.07, 14.02, 11.54, 20.85, 10.58, and 8.74 mL/min, respectively, and the accuracy (root-mean square error) values were 7.38, 6.15, 15.97, 14.16, 24.74, 10.66, and 8.96 mL/min, respectively. In conclusion, the estimated GFR from the BSA-unadjusted CKD-EPI equation demonstrated the least bias along with the highest precision and accuracy. Further studies on the outcomes of anti-cancer drug dose adjustments using this equation versus the current standard equation will be valuable.

Background: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. Methods: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. Results: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. Conclusions: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. Clinical trial registration: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.

Based upon currently available evidences in KTRs, the impact on kidney allograft function appears to be comparable between ER-Tac and IR-Tac.

No abstract