Background: Thrombosis is a potentially life-threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS-associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS-associated hypercoagulopathy. Methods: Puromycin aminonucleoside-induced rat NS was treated with sham, Lowor High-dose MP, Pio, or combination (Pio + Low-MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively. Results: In a rat model of NS, both High-MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (p < .05). Proteinuria (p = .005) and hypoalbuminemia (p < .001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (p < .001) but not SRNS (p = .330). Conclusions: Both Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS-associated thrombotic risk. How to cite this article: Waller AP, Agrawal S, Wolfgang KJ, et al. Nephrotic syndrome-associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors.

Background Breastfeeding is the optimal nutrition for babies, and its successful initiation is one of the aims of maternity care. This paper explores the association between aspects of intrapartum care and early breastfeeding problems. Methods Analysis of routinely-collected data on all births in Victoria, Australia in 2009. Comparison of proportions and multivariate logistic regression were performed. Results Of the 69,143 women who gave birth to term, liveborn babies, 96.3% initiated breastfeeding. 77.8% of the women who initiated breastfeeding gave the last feed before discharge entirely and directly from the breast. Women who experienced a number of interventions in labour and birth were more likely than others to have a problem with this. Oxytocin infusions to induce or augment labour (Relative Risk (RR) 1.26, 95% CI 1.2, 1.3), epidural analgesia (RR 1.36, 95% CI 1.3, 1.4), and caesarean section (RR 1.58, 95% CI 1.5, 1.6) were all associated with giving some expressed breastmilk or formula at the last feed before discharge. Term, breastfed babies whose mothers experienced these interventions were more likely to be given infant formula in hospital (oxytocin infusions (RR 1.18, 95% CI 1.1, 1.2), epidural analgesia (RR 1.30, 95% CI 1.26, 1.34), and caesarean section (RR 1.70, 95% CI 1.65, 1.75)). These relationships persisted after adjustment for parity, maternal BMI, age, public/private admission status, smoking during pregnancy and socio-economic status. Conclusions Common interventions in labour and birth are associated with early breastfeeding problems. Decisions about the risks and benefits of any given intervention should take this into account.