Sirolimus and kidney growth in autosomal dominant polycystic kidney disease

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care. All patients had an estimated creatinine clearance of at least 70 ml per minute. Serial magnetic resonance imaging was performed to measure the volume of polycystic kidneys. The primary outcome was total kidney volume at 18 months on blinded assessment. Secondary outcomes were the glomerular filtration rate and urinary albumin excretion rate at 18 months. RESULTS: At randomization, the median total kidney volume was 907 cm(3) (interquartile range, 577 to 1330) in the sirolimus group and 1003 cm(3) (interquartile range, 574 to 1422) in the control group. The median increase over the 18-month period was 99 cm(3) (interquartile range, 43 to 173) in the sirolimus group and 97 cm(3) (interquartile range, 37 to 181) in the control group. At 18 months, the median total kidney volume in the sirolimus group was 102% of that in the control group (95% confidence interval, 99 to 105; P=0.26). The glomerular filtration rate did not differ significantly between the two groups; however, the urinary albumin excretion rate was higher in the sirolimus group. CONCLUSIONS: In adults with ADPKD and early chronic kidney disease, 18 months of treatment with sirolimus did not halt polycystic kidney growth. (ClinicalTrials.gov number, NCT00346918.

Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease

Background. We initiated a randomized controlled clinical trial to assess the effect of sirolimus on disease progression in patients affected by autosomal dominant polycystic kidney disease (ADPKD). Here we report the preliminary safety results of the first 6 months of treatment. Method. A total of 25 patients were randomized to sirolimus 2 mg/day and 25 patients to no treatment except standard care. Treatment adherence was monitored electronically. At baseline and at Month 6, laboratory parameters were analysed and the urinary protein profile in 24-h urine collections was determined. Results. Both treatment groups were well balanced for age, sex and renal function. In 94.1 ± 11.4% of the study days, patients in the sirolimus group were exposed to the drug when assuming a therapeutic efficacy duration of 30 h. At Month 6, the mean sirolimus dose and trough level were 1.28 ± 0.71 mg/day and 3.8 ± 1.9 μg/l, respectively. Glomerular (albumin, transferrin, IgG) and tubular (retinol-binding protein, α1-microglobulin) protein excretion remained unchanged. Glomerular filtration rate also did not change significantly. Haematological parameters were similar in both groups, except for a mild reduction of the mean corpuscular volume of erythrocytes in patients receiving sirolimus. Lipid levels were similar in both groups. Adverse events were transient and mild, and no grade 3 or 4 events occurred. The incidence of infections was similar in the sirolimus group (80%) and the standard group (88%). The most common gastrointestinal adverse events were mucositis (72% in the sirolimus group versus 16% in the standard group, P = 0.0001) and diarrhoea (36% in the sirolimus versus 20% in the standard group, P = 0.345). Conclusion. Treatment of ADPKD patients with sirolimus with a dose of 1-2 mg/day is safe and does not cause proteinuria or impairment of GFR. Treatment adherence was excellent. (ClinicalTrials.gov number, NCT00346918.

Sailing into the wind : new disciplines in Australian higher education

Much is made of the potential of lifelong learning for individuals and organisations. In this article we tend to make much less of it, certainly with respect to its use in universities to discipline academics. Nevertheless, we argue that academics now need to re-learn the positions they occupy and the stances they take in response to the marketisation of Australian universities. In particular, we suggest that the position of (pure) critique no longer commands attention in Australian contexts of higher education, although the paper does not suggest a disregard for a critical stance purely for the sake of participation. It is in understanding the interconnections between position and stance , and how they might be strategically performed during the everyday practices of academics, that a more promising way of engaging with the venalities of the market is envisaged; a strategy that could be described as \u27sailing into the wind\u27. In discussing these matters, the paper draws on semi-structured interviews with academics located in university faculties/departments/schools of education along Australia\u27s eastern seaboard

‘Wellness’ lifts us above the Food Chaos’: a narrative exploration of the experiences and conceptualisations of Orthorexia Nervosa through online social media forums

The increasing prevalence of eating disorders has motivated a burgeoning of research from narrative methods to illuminate the cultural and social aspects of disordered eating habits. A seemingly new eating disorder, Orthorexia Nervosa, has gained visibility through the internet sphere and popular media, though scholarly attention has been scarce. This study develops qualitative understandings of the fixation with ‘clean eating’ through narrative inquiry by employing an internet ethnographic approach. Data were analysed using a thematic narrative analysis, focusing on parallels and divergences across narratives presented online. This article presents 30 male and female voices, illustrating how these individuals understand their eating habits through narratives of pursuit, resistance and recovery, which are largely motivated by the desire for physical, emotional and social change. Crucially, this study illuminates a range of cultural elements enabling eating disorders in response to the transmission of cultural values online set within the broader context and processes of reflexive-modernisation