Search

Efavirenz (EFV) is one of the preferred components of first-line antiretroviral treatment. EFV is characterized by a long plasma half-life (40–55 hours) with large interpatient variability, which raises the potential for individualization of therapy. Analyses of EFV levels in plasma require specialized facilities (cold storagetransport) which, in resource-limited settings, can be problematic; dried blood spots (DBS)-EFV measurements thus provide a cheap easy alternative for therapeutic drug monitoring. Our aim was to develop and validate a liquid chromatography–mass spectrometry method to quantify EFV in DBS collected as part of clinical trials in resource-limited settings.

Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review.

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.

Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-β-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients.