[Invasive treatment of hypertension : Update 2016]. / Interventionelle Hypertonietherapie : Update 2016.

Invasive treatment methods-more specifically renal denervation and baroreceptor activator therapy-have been used for the treatment of therapy-resistant hypertension for several years now. In particular, renal denervation has aroused great interest because it was easy to perform and the first studies provided very promising results. Meanwhile, however, three randomized, blinded studies have been published, and none showed a significant benefit of renal denervation compared to a sham procedure. In addition, in several studies it was demonstrated that intensification of drug therapy, particularly with spironolactone, is at least comparable. Carotid sinus node baroreceptor activator therapy tends to be superior to renal denervation, but the probe currently used is not optimal. The first results by inserting an arteriovenous shunt between the iliac artery and vein are promising, but lack long-term safety data. Currently, all invasive treatment procedures should be performed within the framework of studies or accurate register surveys.

Targeting the protein kinase C family in the diabetic kidney: lessons from analysis of mutant mice.

The protein kinase C (PKC) superfamily comprises proteins that are activated in response to various pathogenic stimuli in the diabetic state. Hyperglycaemia is the predominant stimulus that induces the activation of distinct PKC isoforms within a cell, each mediating specific functions, probably through differential subcellular localisation. The contribution of individual PKC isoforms can be directly addressed in vivo using innovative PKC-isoform-specific knockout (KO) mouse models, which are providing key insights into the physiological function of PKC isoform diversity in the development of diabetic nephropathy. Such studies can be a valuable complementary approach to more commonly used pharmacological analyses using agents such as ruboxistaurin mesylate (Arxxant, LY333531), which is claimed to specifically inhibit the PKC-beta-isoform. As expected given the multiple and specific properties of the isoforms in vitro, deletion of different PKC isoform signalling pathways leads to distinct phenotypes in mice. Notably, KOs of the individual PKCs assigned specific non-redundant biological functions to each isoform, which were not compensated for by the others. Thus, PKC isoform specificity and cellular diversity seem to be responsible for the divergent outcomes leading to albuminuria and/or renal fibrosis according to studies on the streptozotocin-induced mouse model of diabetes. This review discusses the role of individual PKC isoforms in diabetic nephropathy and their potential therapeutic implications. Defining and targeting mediators of increased intracellular activation in the diabetic microvasculature will have important clinical and therapeutic benefits and help in the design of novel effective therapies in the near future.