Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes.

INTRODUCTION: Peritoneal dialysis (PD) is a life maintaining treatment in patients with end-stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described. MATERIALS AND METHODS: Mesothelial (MeT-5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin-based, amino acid-based, and glucose-based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed. RESULTS: Cell proliferation and cell-mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected. CONCLUSIONS: In 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

Icodextrin-induced acute generalized exanthematous pustulosis in a patient with peritoneal dialysis.

Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young-aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead-sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/µL with neutrophile count of 17 642 cells/µL (92.3%), and c-reactive-protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper-dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high-flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin-free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin-induced AGEP should be early recognized to avoid inappropriate management.

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Complications of Peritoneal Dialysis Part II: Nonmechanical Complications.

Peritoneal dialysis (PD) is a form of KRT that offers flexibility and autonomy to patients with ESKD. It is associated with lower costs compared with hemodialysis in many countries. Unlike mechanical complications that typical arise early in the course of treatment, noninfectious, nonmechanical complications often present late in patients who are established on PD. In this review, we first discuss abnormal-appearing drained dialysate, including hemoperitoneum, chyloperitoneum, and noninfectious cloudy dialysate. The underlying cause is frequently unrelated to PD. We then discuss encapsulating peritoneal sclerosis, a rare complication of PD. Finally, we review metabolic changes associated with PD and methods to mitigate its effects.

Complications of Peritoneal Dialysis Part I: Mechanical Complications.

Peritoneal dialysis (PD) is a form of KRT that offers flexibility and autonomy to patients with ESKD. It is associated with lower costs compared with hemodialysis in many countries. However, it can be associated with unexpected interruptions to or discontinuation of therapy. Timely diagnosis and resolution are required to minimize preventable modality change to hemodialysis. This review covers mechanical complications, including leaks, PD hydrothorax, hernias, dialysate flow problems, PD-related pain, and changes in respiratory mechanics. Most mechanical complications occur early, either as a result of PD catheter insertion or the introduction of dialysate and consequent increased intra-abdominal pressure. Late mechanical complications can also occur and may require different treatment.

The influence of simvastatin in induced peritoneal fibrosis in rats by peritoneal dialysis solution with glucosis 4.25% / Influência da sinvastatina na fibrose peritoneal induzida em ratos pelo uso de solução de diálise peritoneal com glicose a 4,25%

PURPOSE: To investigate the influence of using simvastatin on the peritoneal fibrosis induced in rats using peritoneal dialysis solution with glucoses 4.25%. METHODS: Prospective controlled study in 20 non-uremic Wistar rats. The animals received a peritoneal infusion of 10 ml/100 g of peritoneal dialysis solution glucose 4.25% on a daily basis. The animals were divided in two groups: experimental and control. The experimental group received simvastatin 4 mg/kg/d, by a gastric tube. The control group did not receive any drug. The follow-up was 21 and 49 days. At the end, one surgical procedure was performed to get histological samples of visceral and parietal peritoneum. The samples were analyzed using Hematoxylin Eosin and Sirius Red, to evaluate the severity of the fibrosis. RESULTS: The analysis showed that the intensity of the fibrosis, the peritoneal thickness and the cell number in experimental and control groups were not statistically significant different in experimental and control groups. CONCLUSION: The simvastatin do not decrease the intensity of fibrosis on the peritoneal membrane that happens on rats on peritoneal dialysis.

OBJETIVO: Investigar a influência do uso da sinvastatina na fibrose peritoneal induzida em ratos pelo uso de solução de diálise peritoneal rica em glicose. MÉTODOS: Estudo prospectivo controlado, em ratos Wistar não urêmicos. Foram estudados 20 animais. Os animais foram submetidos diariamente à punção abdominal, sendo infundida solução de diálise peritoneal com glicose a 4,25% na dose de 10 ml/100 g de peso. Os animais foram divididos em dois grupos: experimental e controle. O grupo experimental recebeu sinvastatina na dose de 4 mg/kg/dia por gavagem. O grupo controle não recebeu nenhuma droga. Foram acompanhados por 21 e 49 dias. Ao final do período foram submetidos à procedimento cirúrgico para retirada de peritônio parietal e visceral. As amostras obtidas foram analisadas histologicamente, usando-se coloração Hematoxilina - Eosina e Sirius Red, para avaliação do grau de fibrose. RESULTADOS: A análise mostrou que a intensidade da fibrose, a espessura do peritônio e o número de células não atingiram diferença estatisticamente significante entre os grupos experimental e controle. CONCLUSÃO: A sinvastatina não foi capaz de alterar a intensidade da fibrose peritoneal induzida pelo uso de solução de diálise em ratos.