Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment. We assessed blood pressure and markers of CKD, including proteinuria, albuminuria, and renal pathology. Furthermore, we determined if HS feeding resulted in an impaired myogenic response, subsequent to ER stress. 4-PBA treatment reduced salt-induced hypertension, proteinuria, and albuminuria and preserved myogenic constriction. Furthermore, renal pathology was reduced with 4-PBA treatment, as indicated by lowered expression of profibrotic markers and fewer intratubular protein casts. In addition, ER stress in the glomerulus was reduced, and the integrity of the glomerular filtration barrier was preserved. These results suggest that 4-PBA treatment protects against proteinuria in the SS rat by preserving the myogenic response and by preventing ER stress, which led to a breakdown in the glomerular filtration barrier. As such, alleviating ER stress serves as a viable therapeutic strategy to preserve kidney function and to delay the progression of CKD in the animal model under study.

Our findings suggest that the adverse effects of opioids, especially nausea and vomiting, may reduce or eliminate any net benefit of opioid therapy unless pain relief is significant (>2 points on a 10-point scale). Further research should investigate patient values and preferences regarding opioid overdose, diversion, and death.

Borderline personality disorder (BPD) is associated with high rates of self-harm, suicide attempts, and death by suicide in adults and adolescents. Screening and assessment of BPD in self-harming adolescents could be an important clinical intervention. The aim of this article was to identify whether existing clinical practice guidelines (CPGs) for the care of self-harm in adolescents considered the screening, diagnosis, and/or treatment of BPD. Previous work by Courtney, Duda, Szatmari, Henderson, and Bennett (2018) used Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods to identify 10 CPGs relevant to self-harm in children and adolescents. In this study, the 10 CPGs were reviewed for content about screening, assessment, and/or treatment recommendations for adolescents with BPD. Out of the 10 CPGs, 4 acknowledged the association between BPD and self-harm in adolescents. There was minimal to no guidance provided in the CPGs regarding specific screening, assessment, or treatment strategies for BPD. This may be due to the lack of evidence for efficacy and effectiveness of screening for BPD, thereby limiting the development of guideline recommendations. Studies that examine the impact of screening for BPD in clinical settings are needed. In the interim, CPGs should cite the prevalence of BPD in adolescents who self-harm and reference research showing the benefit of treatment with dialectical behavioral therapy for self-harm and suicide attempts in youth with BPD.

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