l-Carnitine is an osmotic agent suitable for peritoneal dialysis

Bonomini, Mario; Pandolfi, Assunta; Liberato, Lorenzo Di; Silvestre, Sara Di; Cnops, Yvette; Tomo, Pamela Di; D'Arezzo, Mario; Monaco, M.P.; Giardinelli, Annalisa; Pietro, Natalia Di; Devuyst, Olivier; Arduini, Arduino

doi:10.1038/ki.2011.117

Cited by 35 publications

(37 citation statements)

References 44 publications

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“…In undertaking these studies, it was essential to include an osmotic control as the osmotic pressure generated by 10 mg/ml protein could be responsible for the induction of numerous systems via activation of cell stress pathways. Mannitol applied at an equimolar concentration was selected for this purpose as it is often used as an osmotic control in both protein and glucose studies [14,15,16]. However, there was no difference between the mannitol control and no BSA control in any experiment indicating that osmotic pressure is not important in albumin-driven EMT.…”

Section: Discussionmentioning

confidence: 99%

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Albumin-Induced Epithelial Mesenchymal Transformation

Ibrini

Fadel²,

Chana³

et al. 2012

Nephron Exp Nephrol

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Background: Progressive chronic kidney disease is often associated with albuminuria and renal fibrosis linked to the accumulation of myofibroblasts producing extracellular matrix. Renal myofibroblasts are derived from a number of cells including tubular epithelial cells (TECs) through epithelial mesenchymal transformation (EMT). This study explores the hypothesis that exposure of TECs to albumin induces EMT. Methods: Normal rat TECs (NRK52E) were exposed in culture to de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days. Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation into myofibroblasts was assessed by light and electron microscopy, immunofluorescence and Western blotting for α-smooth muscle actin (α-SMA), E-cadherin and transforming growth factor-β1 (TGF-β1). We also investigated the expression of fibroblast-specific protein-1 (FSP-1) and collagens I, III and IV. TGF-β1 biological activity, mRNA and protein were measured. A neutralising anti-TGF-β1 antibody was used to analyse the role of TGF-β1 in albumin-induced EMT. Results: Exposure of TECs to dBSA led to binding/uptake of albumin as well as fibroblastic morphological changes. Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p = 0.0002) and de novo expression of fibroblast markers α-SMA and FSP-1 (ANOVA p = 0.0001) in a time-dependent manner. It also increased expression and activity of TGF-β1. Neutralisation of TGF-β1 significantly reduced EMT (p < 0.01). Conclusion: This study demonstrates that in vitro, albumin induces the transformation of TECs into cells with myofibroblast characteristics; a process that may be TGF-β1 dependent.

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Section: Discussionmentioning

confidence: 99%

“…Serum free DMEM with no dBSA added was used as the primary control. Mannitol at an equimolar concentration to dBSA was also used as an osmotic control due to its wide application for this purpose [14,15,16]. …”

Section: Methodsmentioning

confidence: 99%

Albumin-Induced Epithelial Mesenchymal Transformation

Ibrini

Fadel²,

Chana³

et al. 2012

Nephron Exp Nephrol

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“…The studies outlined above support the validity of the TPM, which can now be tested against a simple and validated mouse model (48) allowing direct measurement of free-water transport in conditions of modified expression and, potentially, gating of AQP1. Assessing water transport across the peritoneum has already been shown to be useful for in vivo investigations of drugs or molecular pathways regulating AQP1 (35,36,47). Whether biochemical modifications of AQP1 (e.g.…”

Section: Discussionmentioning

confidence: 99%

Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated. ABSTRACTPeritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a threepore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haplo-insufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.The development of peritoneal dialysis (PD) as a successful therapy for patients with end stage renal disease has been paralleled by the need to understand the transport mechanisms operating in the peritoneal membrane. Functional alterations in the dialysis capacity of the...

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“…Recently, l-carnitine [molecular weight (M w ): 161] was proposed as a novel osmotic agent and tested for a short time in both rodent and human studies (15). The physical properties of l-carnitine are similar to those of G, and the molecule is chemically stable and has been shown to have a good safety profile.…”

mentioning

confidence: 99%

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

Rippe

2013

Perit Dial Int

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l-Carnitine is an osmotic agent suitable for peritoneal dialysis

Cited by 35 publications

References 44 publications

Albumin-Induced Epithelial Mesenchymal Transformation

Albumin-Induced Epithelial Mesenchymal Transformation

Water transport across the peritoneal membrane

Article Commentary: Hyperbranched Polyglycerol: A Future Alternative to Polyglucose in Peritoneal Dialysis Fluids?

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