Protective Effects of Paricalcitol on Peritoneal Remodeling during Peritoneal Dialysis

Abstract

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.

Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

“…Peritoneal dialysis is another type of renal replacement therapy for ESRD, and peritoneal fibrosis is a significant problem associated with continuous peritoneal dialysis. Animal studies show that paricalcitol treatment can significantly reduce peritoneal dialysis-induced ECM thickening and prevent peritoneal fibrosis [ 86 , 87 ].…”

MicroRNA-21 promotes the progression of peritoneal fibrosis through the activation of the TGF-β/Smad signaling pathway: An in vitro and in vivo study

“…PD is an economic and simple dialysis method, which can remove toxic molecules and improve the survival rate (2). However, long-term exposure to a hypertonic and high glucose environment can induce inflammation, epithelial cell differentiation and angiogenesis, resulting in fibrosis (3). Peritoneal fibrosis (PF) is associated with abnormal histological changes in peritoneal tissues and parenchymal cells necrosis caused by fibrous connective tissue matrix deposition, which is also the main cause of ultrafiltration dialysis failure (4).…”

Paricalcitol attenuates TGF‐β1–induced phenotype transition of human peritoneal mesothelial cells (HPMCs)viamodulation of oxidative stress and NLRP3 inflammasome

“…In animal models of kidney disease, including obstructive nephropathy, diabetic nephropathy, and ischemia/ reperfusion injury, paricalcitol demonstrated a renoprotective effect via modulation of the TLR4-NF-kB pathway and a reduction of inflammatory cytokines (17)(18)(19)(20). There are also reports showing the beneficial effects of paricalcitol in peritoneal remodeling (21,22).…”