High-dose steroid treatment increases free water transport in peritoneal dialysis patients

Arteaga, Javier de; Ledesma, Fabián; Garay, Gabriela; Chiurchiu, Carlos; Fuente, Jorge de la; Douthat, Walter; Massari, P.; Terryn, Sara; Devuyst, Olivier

doi:10.1093/ndt/gfr533

Cited by 19 publications

(18 citation statements)

References 14 publications

(20 reference statements)

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“…In contrast, the small solute transport rate, as assessed by the D/P creatinine and small pore-specific ultrafiltration, was unchanged. The potential role of the GRE-mediated effect on AQP1 was substantiated by demonstrating the expression of the glucorticoid receptor in the capillary endothelium of the human peritoneum (36). These data were the first to support the effect of corticosteroids on AQP1-mediated water transport in PD patients.…”

Section: Regulation Of Aquaporin-1 Expression To Increase Ultrafiltramentioning

confidence: 80%

“…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%

“…The identification of the ultrasmall pore offers the opportunity to modulate water transport in PD. Proof-of-principle studies in rat and mouse models (35,46) and in PD patients (36) have shown that such modulation can be achieved without modifying the osmotic gradient or the small solute transport. Whether increasing the expression of AQP1 in the peritoneal membrane or gating the already existing channels could be used to treat UF failure and overhydration in some PD patients remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…These modifications were observed in absence of any effect on the osmotic gradient or small solute transport (35). More recently, de Arteaga et al reported serial determinations of water and solute transport parameters across the peritoneal membrane (mini PET) in three PD patients that received high-dose glucocorticoids (cumulative dose of methylprednisolone: 1.0-1.2 g/m2) as standard care after a living-donor renal transplantation (36). As compared with pre-transplantation, the post-transplantation PET evidenced an ∼2-fold increase in the sodium sieving (and its surrogate marker the absolute dip of dialysate sodium concentration), paralleled by an increase in the ultrasmall pore-specific UF.…”

Section: Regulation Of Aquaporin-1 Expression To Increase Ultrafiltramentioning

confidence: 99%

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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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Section: Regulation Of Aquaporin-1 Expression To Increase Ultrafiltramentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Regulation Of Aquaporin-1 Expression To Increase Ultrafiltramentioning

confidence: 99%

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Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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“…33,54,55 We used the following antibodies: mouse monoclonal anti-human eNOS (Transduction Laboratories, Lexington, KY), purified rabbit anti-vWf (DAKO, Glostrup, Denmark), monoclonal anti-human VEGF (Santa Cruz Biotechnology, Santa Cruz, CA), and polyclonal rabbit anti-human AQP1 (Chemicon International, Temecula, CA).…”

Section: Peritoneal Sampling and Processingmentioning

confidence: 99%

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

Morelle

Sow

Hautem

et al. 2015

Journal of the American Society of Nephrology

105

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Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.

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