A New Peritoneal Dialysis Solution Containing L-Carnitine and Xylitol for Patients on Continuous Ambulatory Peritoneal Dialysis: First Clinical Experience

Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of PM integrity and transport function is the key to the success of PD therapy, particularly in the long term, since the prolonged exposure to unphysiological hypertonic glucose-based PD solutions in current use is detrimental to the PM, with progressive loss of peritoneal ultrafiltration capacity causing technique failure. Moreover, absorbing too much glucose intraperitoneally from the dialysate may give rise to a number of systemic metabolic effects. Here we report the preliminary results of the first clinical experience based on the use in continuous ambulatory PD (CAPD) patients of novel PD solutions obtained through partly replacing the glucose load with other osmotically active metabolites, such as L-carnitine and xylitol. Ten CAPD patients were treated for four weeks with the new solutions. There was good tolerance to the experimental PD solutions, and no adverse safety signals were observed. Parameters of dialysis efficiency including creatinine clearance and urea Kt/V proved to be stable as well as fluid status, diuresis, and total peritoneal ultrafiltration. The promising tolerance and local/systemic advantages of using L-carnitine and xylitol in the PD solution merit further research.

The importance of the peritoneal dialysis catheter material in orderto perform optimum dialysis in veterinary medicine

This study was conducted on 44 dogs, aged between 10 months and 15 years, weighing between 0.9 and 8.5 kilograms,during 72 months. We created four batches of 11 dogs each. First batch received silicone peritoneal catheters with twoDacron cuffs, second batch received silicone peritoneal catheters without Dacron cuffs, third batch receivedpolypropylene peritoneal catheters with two Dacron cuffs and fourth batch received polypropylene peritoneal catheterswithout Dacron cuffs. All the dogs were treated with the same peritoneal dialysis solution, at the same interval, in thesame doses and at the same temperature and all the peritoneal catheters were straight Blake. In dogs from the firstbatch, we experienced minimum subcutaneous leaks of peritoneal dialysis solution and the catheters were permeablefor at least 90 days. In the second batch, we experienced constant and reduced subcutaneous leaks of peritonealdialysis solution and the catheters were permeable for at least 90 days. In the third batch, we experienced mediumsubcutaneous leaks of peritoneal dialysis solution and the catheters were permeable for at least 45 days. In the fourthbatch, we experienced important subcutaneous leaks of peritoneal dialysis solution and the catheters were permeablefor at most 15 days. The study conclusion is that the best peritoneal catheter it is represented by the silicone peritonealcatheters with two Dacron cuffs.

The importance of the peritoneal dialysis catheter material in orderto perform optimum dialysis in veterinary medicine

This study was conducted on 44 dogs, aged between 10 months and 15 years, weighing between 0.9 and 8.5 kilograms,during 72 months. We created four batches of 11 dogs each. First batch received silicone peritoneal catheters with twoDacron cuffs, second batch received silicone peritoneal catheters without Dacron cuffs, third batch receivedpolypropylene peritoneal catheters with two Dacron cuffs and fourth batch received polypropylene peritoneal catheterswithout Dacron cuffs. All the dogs were treated with the same peritoneal dialysis solution, at the same interval, in thesame doses and at the same temperature and all the peritoneal catheters were straight Blake. In dogs from the firstbatch, we experienced minimum subcutaneous leaks of peritoneal dialysis solution and the catheters were permeablefor at least 90 days. In the second batch, we experienced constant and reduced subcutaneous leaks of peritonealdialysis solution and the catheters were permeable for at least 90 days. In the third batch, we experienced mediumsubcutaneous leaks of peritoneal dialysis solution and the catheters were permeable for at least 45 days. In the fourthbatch, we experienced important subcutaneous leaks of peritoneal dialysis solution and the catheters were permeablefor at most 15 days. The study conclusion is that the best peritoneal catheter it is represented by the silicone peritonealcatheters with two Dacron cuffs.

Valsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway. Impact statement Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.

Effect of peritoneal dialysis solution with different pyruvate concentrations on intestinal injury

To investigate the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (Pyr-PDS) of different concentrations combined with intravenous resuscitation on acid–base imbalance and intestinal ischemia reperfusion injury in rats with hemorrhagic shock. Sixty rats were randomly assigned to group SHAM, group intravenous resuscitation, and four direct peritoneal resuscitation groups combined with intravenous resuscitation: group NS, LA, PY1, and PY2, that is, normal saline, lactate-PDS (Lac-PDS), lower concentration Pyr-PDS (Pyr-PDS1), and higher concentration Pyr-PDS (Pyr-PDS2), respectively. Two hours after hemorrhagic shock and resuscitation, the pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), base excess, and bicarbonate ion concentration (HCO3−) of the arterial blood were measured. The intestinal mucosal damage index and intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor-α, interleukin-6, zonula occludens-1, claudin-1, and occludin levels in intestinal issues were detected. Two hours after resuscitation, group PY2 had higher mean arterial pressure, pH, oxygen partial pressure, and base excess and lower PCO2 of arterial blood than group PY1 ( P < 0.05). Tumor necrosis factor-α and interleukin-6 levels in group PY2 were significantly lower than those in group PY1 ( P < 0.05). Zonula occludens-1, claudin-1, and occludin expression levels were significantly higher in group PY2 than in group PY1 ( P < 0.05). Direct peritoneal resuscitation with Pyr-PDS2 combined with intravenous resuscitation enhanced the hemodynamics, improved the acid–base balance, and alleviated intestinal ischemia reperfusion injury from hemorrhagic shock and resuscitation in rats. The mechanisms might include correction of acidosis, inhibition of inflammatory response, enhancement of systemic immune status, regulation of intestinal epithelial permeability, and maintenance of intestinal mucosal barrier function. Impact statement Hemorrhagic shock is a life-threatening condition after trauma or during surgery. Acid–base imbalance and intestinal ischemia reperfusion injury are two significant causes in the pathogenetic process and multiple organ dysfunction. As a result, it is urgent and necessary to find an effective method of resuscitation in order to reverse the acid–base imbalance and protect organ function. This current study confirmed the protection against hypoxic acidosis and intestinal ischemia reperfusion injury by peritoneal resuscitation with pyruvate combined with intravenous resuscitation in rats with hemorrhagic shock. And the peritoneal dialysis solution with pyruvate of high concentration plays a crucial role in the process. It provided a new idea and possible direction of fluid resuscitation for alleviating organ injuries, protecting organ functions, and improving clinical prognosis after hemorrhagic shock and resuscitation.