Pharmacokinetics of enteric coated mycophenolate sodium in lupus nephritis (POEMSLUN)

Mycophenolate mofetil (MMF) or enteric coated mycophenolate sodium (EC-MPS) and steroids are used for induction and maintenance therapy in severe lupus nephritis (LN). Blood concentrations of mycophenolic acid (MPA), the active metabolite of these drugs varies among LN patients. The objective of this study was to examine whether concentration controlled (CC) dosing (via therapeutic drug monitoring) of EC-MPS result in a higher proportion of participants achieving target exposure of MPA compared to fixed dosing (FD). An additional aim of the study was to evaluate the influence of CC dosing on clinical outcomes.Nineteen participants were randomly assigned either to FD or CC group. All the participants were eligible to have free and total measurements of MPA over a period of 8-12 hours on three different occasions. Area under the concentration-time curve between 0 and 12 hours (AUC0-12) was calculated using non-compartmental method. Dose of EC-MPS was titrated according to AUC0-12 in the CC group.Thirty-two AUC0-12 measurements were obtained from 9 FD and 9 CC participants. Large interpatient variability was observed in both groups but was more pronounced in FD group. There were no significant differences between FD and CC participants in any pharmacokinetic parameters across the study visits except for total C0 (FD 2.0 ± 0.3 mg/L vs. CC 1.1 ± 0.3; p = 0.01) and dose-normalised C0 (FD 2.9 ± 0.2 mg/L/g vs. CC 2.1 ± 0.7 mg/L/g; p = 0.04) at the second visit and total AUC0-12 (FD 66.6 ± 6.0 mg[BULLET OPERATOR]h/L vs. CC 35.2 ± 11.4 mg[BULLET OPERATOR]h/L; p = 0.03) at the third visit. At the first study visit, 33.3% of the FD and 11.1% of the CC participants achieved the target AUC (p = 0.58). From the second visit, none of the FD participants, compared to all the CC participants, achieved target AUC0-12 (p = 0.01). More CC participants achieved remission compared to FD participants (absolute difference of -22.2, 95% confidence interval -0.19-0.55; p = 0.62). The mean free MPA AUC0-12 was significantly lower in those who had complete remission.CC participants reached target AUC0-12 quicker. Larger studies are required to test clinical efficacy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Epidemiology of biopsy-proven glomerulonephritis in Queensland adults

Aim There is a paucity of data pertaining to the incidence of biopsy-proven glomerulonephritis (GN) in Australia. This retrospective study aims to review the data from all adult native renal biopsies performed in the state of Queensland from 2002 to 2011 - comparing results with centres from across the world. Methods Pathology reports of 3697 adult native kidney biopsies were reviewed, of which 2048 had GN diagnoses. Age, gender, clinical indication and histopathology findings were compared. Results The average age at biopsy was 48 ± 17 years. Male preponderance was noted overall (∼60%), with lupus nephritis being the only individual GN with female predilection. The average rate of biopsy was 12.04 per hundred thousand people per year (php/yr). Nephrotic and nephritic syndromes comprised approximately 75% of all clinical indications that lead to GN diagnoses. IgA nephropathy (1.41 php/yr) was the most common primary GN followed by focal segmental glomerulosclerosis (1.02 php/yr) and crescentic GN (0.73 php/yr). Diabetic nephropathy (0.84 php/yr), lupus nephritis (0.69 php/yr) and amyloidosis (0.19 php/yr) were the most commonly identified secondary GN. Conclusion IgA nephropathy is the predominant primary GN in Queensland, and nephrotic syndrome the most common indication for a renal biopsy. While crescentic GN incidence has significantly increased with time, focal segmental glomerulosclerosis incidence has not shown any trend. Incidence of GN overall appears to increase with age. The annual rate of biopsy in this study appears lower than previously published in an Australian population

Assessment of cardiac structure and function in kidney failure: understanding echocardiography and magnetic resonance imaging for the nephrologist

Cardiovascular disease is the leading cause of death in patients with kidney failure or on chronic dialysis. Patients on chronic dialysis have a 10- to 50-fold increased risk of sudden cardiac death compared to patients with normal kidney function. Adverse changes in cardiac structure and function may not manifest with clinical symptoms in patients with kidney failure and, therefore, pose a challenge in identifying cardiac dysfunction early. Fortunately, there are multi-modality cardiac imaging techniques available, including echocardiography and cardiac magnetic resonance imaging, that can help our understanding of the pathophysiology of cardiac dysfunction in kidney failure. This review describes the benefits and limitations of these two commonly available cardiac imaging modalities to assess cardiac structure and function, thereby aiding nephrologists in choosing the most appropriate investigative tool based on individual clinical circumstances. For the purposes of this review, cardiac imaging for detection of coronary artery disease has been omitted

A protocol for the pharmacokinetics of enteric coated mycophenolate sodium in lupus nephritis (POEMSLUN): An open-label, randomised controlled trial

Introduction: Mycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN) and have fewer side effects than pulsed intravenous cyclophosphamide. Blood concentrations of mycophenolic acid (MPA), the active metabolite of EC-MPS, vary between participants despite fixed dosing. Interpatient variability has been studied in transplantation, but not well documented in LN. The relationship between MPA concentration and its clinical effect on LN has not been described