The Performance of Equations That Estimate Glomerular Filtration Rate against Measured Urinary Creatinine Clearance in Critically Ill Patients

The performance of glomerular filtration rate- (GFR-) estimating equations was studied against creatinine clearance measured by 24-hour urine collection (CrCl24h-urine) in critically ill patients. Methods. In this substudy of the PermiT trial (https://clinicaltrials.gov/ct2/show/ISRCTN68144998), patients from King Abdulaziz Medical City-Riyadh who had CrCl24h-urine were included. We estimated GFR using Cockroft–Gault (CG), modification of diet in renal disease study (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), and Jelliffe equations. For the CG equation, we entered the actual weight in one calculation (CGactual-wt), and if BMI ≥30 kg/m2, we entered the ideal body weight (CGideal-wt) and the adjusted body weight (CGadjusted-wt) in two calculations. We calculated the MDRD equation based on 4 (MDRD-4) and 6 variables (MDRD-6). The performance of these equations was assessed by different ways including Spearman correlation, bias (difference between estimated GFR and CrCl24h-urine), precision (standard deviation of bias), and Bland–Altman plot analysis. Results. The cohort consisted of 237 patients (age 45 ± 20 years, males 75%, mechanically ventilated 99% with serum creatinine 101 ± 94 µmol/L and CrCl24h-urine 108 ± 69 ml/min/1.73 m2). The correlations between the different equations and CrCl24h-urine were modest (r: 0.62 to 0.79; p<0.0001). Bias was statistically significant for CGactual-wt (21 ml/min), CGadjusted-wt (12 ml/min), and MDRD-6 (-10 ml/min) equations. Precision ranged from 46 to 54 ml/min. The sensitivity of equations to correctly classify CrCl24h-urine 30–59.9 ml/min/1.73 m2 was 17.2% for CGactual-wt, 30.0% for CGideal-wt, 31.0% for CGadjusted-wt, 31.0% for MDRD-4, 39.1% for MDRD-6, 13.8% for CKD-EPI, and 34.5% for Jelliffe equation. Conclusions. Commonly used GFR-estimating equations had limited ability to properly estimate CrCl24h-urine and to correctly classify GFR into clinically relevant ranges that usually determine dosing of medications

Evaluation of solid-lipid nanoparticles formulation of methotrexate for anti-psoriatic activity

Background &amp; Objectives: Methotrexate (MTX) is commonly used to manage psoriasis. The drug has erratic absorption characteristics and shows several complications. The present study uses different experimental models to evaluate the solid-lipid nanoparticles of MTX (SLN-MTX) for the anti-psoriatic effect. Methods: A prepared SLN-MTX formulation was used and its permeability studies were conducted on Wistar rat abdominal skin. The organ-level distribution of the drug in the formulation was tested in mice and the in-vitro anti-psoriatic activity was determined in CL-177; XB-2 keratinocytes cell lines. The efficacy of SLN-MTX formulation was compared with standard MTX and marketed MTX preparations. The results are analyzed statistically using the student’s t-test. Results: The data suggested that MTX from the formulation was slowly released and completely (80.36%) permeated through the skin. The flux and permeation data were found to be maximum for SLN-MTX compared to marketed and standard preparations. MTX in the formulation was found to be distributed more in the liver (67.5%) and kidney (2.34%). Further, SLN-MTX formulation showed dose-dependent inhibition on the growth of keratinocytes, and the cytotoxic concentration (CTC50) was found to be the least (518 mcg/ml). Interpretation &amp; Conclusion: The findings suggested that MTX in solid-lipid nanoparticles could be a promising formulation for the management of psoriasis since the drug was slowly released, progressively inhibited the growth of keratinocytes, and distributed mostly in organs meant for elimination. More studies in this direction might establish the precise safety and efficacy of SLN-MTX formulation in psoriasis