No abstract

Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P.

Long-term exposure to peritoneal dialysis fluid induces morphological alterations, including angiogenesis, leading to a loss of ultrafiltration (UF) capacity. We discuss the effect of different factors in peritoneal dialysis (PD) on angiogenesis. In addition, we describe the process of angiogenesis and the possible role of different cell types in the peritoneum upon PD contributing to new blood vessel formation. Furthermore, we review several interventions used in our rat PD exposure model to decrease angiogenesis in PD. Moreover, we show new data on the use of sunitinib to inhibit angiogenesis in this rat model. Although various interventions seem to be promising, well-randomised clinical trials showing absolute prevention of angiogenesis and UF failure are, yet, still missing. To make real progress in PD treatment, the aim should be to prevent angiogenesis as well as peritoneal fibrosis and PD-induced inflammation.

Peritoneal dialysis (PD) is associated with functional and structural changes of the peritoneal membrane, also known as peritoneal remodeling. The peritoneal membrane is affected by many endogenous and exogenous factors such as cytokines, PD fluids, and therapeutic interventions. Here, we present an overview of various studies that have investigated pharmacologic interventions aimed at regression of peritoneal damage and prolongation of PD treatment.

Peritoneal dialysis (PD) is associated with structural and functional alterations of the peritoneal membrane, consisting of fibrosis, angiogenesis, and loss of ultrafiltration capacity. Vitamin D receptor activation (VDRA) plays an important role in mineral metabolism and inflammation, but also antiangiogenic and antifibrotic properties have been reported. Therefore, the effects of active vitamin D treatment on peritoneal function and remodeling were investigated. Rats were either kept naïve to PDF exposure or daily exposed to 10 mL PDF and were treated for five or seven weeks with oral paricalcitol or vehicle control. Non-PDF-exposed rats showed no peritoneal changes upon paricalcitol treatment. Paricalcitol reduced endogenous calcitriol but did not affect mineral homeostasis. However, upon PDF exposure, loss of ultrafiltration capacity ensued which was fully rescued by paricalcitol treatment. Furthermore, PD-induced ECM thickening was significantly reduced and omental PD-induced angiogenesis was less pronounced upon paricalcitol treatment. No effect of paricalcitol treatment on total amount of peritoneal cells, peritoneal leukocyte composition, and epithelial to mesenchymal transition (EMT) was observed. Our data indicates that oral VDRA reduces tissue remodeling during chronic experimental PD and prevents loss of ultrafiltration capacity. Therefore, VDRA is potentially relevant in the prevention of treatment technique failure in PD patients.