| 1. |
- Albinsson, Sebastian, et al.
(författare)
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Arterial remodeling and plasma volume expansion in caveolin-1 deficient mice.
- 2007
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Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293, s. 1222-1231
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Tidskriftsartikel (refereegranskat)abstract
- Caveolin- 1 ( Cav- 1) is essential for the morphology of membrane caveolae and exerts a negative influence on a number of signaling systems, including nitric oxide ( NO) production and activity of the MAP kinase cascade. In the vascular system, ablation of caveolin- 1 may thus be expected to cause arterial dilatation and increased vessel wall mass ( remodeling). This was tested in Cav- 1 knockout ( KO) mice by a detailed morphometric and functional analysis of mesenteric resistance arteries, shown to lack caveolae. Quantitative morphometry revealed increased media thickness and media- to- lumen ratio in KO. Pressure- induced myogenic tone and flow- induced dilatation were decreased in KO arteries, but both were increased toward wild- type ( WT) levels following NO synthase ( NOS) inhibition. Isometric force recordings following NOS inhibition showed rightward shifts of passive and active length- force relationships in KO, and the force response to alpha 1- adrenergic stimulation was increased. In contrast, media thickness and force response of the aorta were unaltered in KO vs. WT, whereas lumen diameter was increased. Mean arterial blood pressure during isoflurane anesthesia was not different in KO vs. WT, but greater fluctuation in blood pressure over time was noted. Following NOS inhibition, fluctuations disappeared and pressure increased twice as much in KO ( 38 +/- 6%) compared with WT ( 17 +/- 3%). Tracer- dilution experiments showed increased plasma volume in KO. We conclude that NO affects blood pressure more in Cav- 1 KO than in WT mice and that restructuring of resistance vessels and an increased responsiveness to adrenergic stimulation compensate for a decreased tone in Cav- 1 KO mice.
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| 2. |
- Grände, Gustaf, et al.
(författare)
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Unaltered Size-selectivity of the Glomerular Filtration Barrier in Caveolin-1 Knock-out (KO) mice.
- 2009
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 297:2, s. 257-262
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Tidskriftsartikel (refereegranskat)abstract
- The transfer of albumin from blood to tissue has been found to be increased in caveolin-1 knock-out (KO) mice. This has been considered to reflect an increased microvascular permeability, conceivably caused by an increased endothelial production of nitric oxide (NO) in mice lacking caveolin-1. To investigate whether such an increase in endothelial NO-production would also affect the glomerular barrier characteristics, the glomerular sieving coefficients () to neutral, polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 (mol. radius 15-90 A) were determined in caveolin-1 KO mice vs. their wild-type counterparts. for Ficoll were assessed using high performance size exclusion chromatography (HPSEC) on blood and urine samples. Furthermore, the transcapillary escape rate (TER) of (125)I-labeled albumin and plasma volume (PV) were determined in both types of mice. Despite an increase in the glomerular filtration rate (GFR) in caveolin-1 KO mice (0.23+/-0.04 mL/min; n=7 vs. 0.10+/-0.02 mL/min; n=7; p<0.05) the glomerular Ficoll sieving curves were nearly identical. Furthermore, caveolin-1 KO mice showed an increased PV (6.59+/-0.42 mL/100g vs. 5.18+/-0.13 mL/100g; p<0.01) but only a tendency of an increased TER (14.69+/-1.59 %/h vs. 11.62+/-1.62 %/h; N.S.). It is concluded that in caveolin-1 KO mice the glomerular permeability was not increased, despite the presence of glomerular hyperfiltration. The present data are in line with the concept that the increased transvascular albumin leakage previously found in mice lacking caveolin-1 may be due to an elevation in systemic microvascular pressure following NO-induced precapillary vasodilatation, rather than being a consequence of an increased microvascular permeability per se. Key words: capillary permeability, nitric oxide, sieving coefficient, Ficoll, glomerular filtration rate.
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| 3. |
- Rippe, Anna, et al.
(författare)
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Disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in a mouse model of peritoneal dialysis (PD).
- 2007
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 22:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Background. This study was performed to establish a model for quantitative measurements of a number of basic peritoneal transport parameters, particularly transperitoneal clearances (Cl) of macromolecules, during mouse peritoneal dialysis. Methods. Mice were anaesthetized using 3% isofluorane inhalation anaesthesia. The right jugular vein and the left femoral artery were cannulated for infusion and sampling purposes and for registration of (mean) arterial blood pressure. Access to the peritoneal cavity occurred via a thin abdominal catheter (Ø 0.7 mm). About 2.5 ml of either 4% (n = 9) or 1.5% (n = 5) glucose containing PD-fluid were instilled intraperitoneally (i.p.). Dialysate volume was followed vs time using i.p. RISA (125I human serum albumin) as a volume marker, after correcting for RISA mass disappearance from the peritoneum, assessed separately (n = 11). Microsampling (10 µl) of plasma and dialysate was performed for determinations of glucose, haematocrit, radioactivity (RISA and 51Cr-EDTA) and Ficoll. Results. The i.p. volume vs time curves [VD(t)] were, after scaling, similar to those observed in humans (and in rats). Clearance of RISA out of the peritoneal cavity (Clout) was 9.33 ± 0.83 µl/min and the clearance of RISA to plasma (Cl->P) and the RISA clearance to the peritoneal cavity (Cl->D) were 1.49 ± 0.13 and 0.084 ± 0.008 µl/min, respectively. The peritoneal transport coefficients for 51Cr-EDTA and glucose, as well as Clout and Cl->P, were 13–17% of those previously assessed in 300 g rats, whereas Cl->D was only ~2% of that in rat. Conclusions. All peritoneal transport parameters measured, except Cl->D, scaled very well to the corresponding human data. The mechanisms of the disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in mice remain elusive and warrant further study.
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| 4. |
- Rippe, Catarina, et al.
(författare)
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Effects of glomerular filtration rate on Ficoll sieving coefficients (theta) in rats.
- 2006
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 69:8, s. 1326-1332
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to assess the role of diffusion and convection during filtration of Ficoll across the glomerular filter by comparing glomerular sieving coefficients ( h) to neutral fluorescein isothiocyanate ( FITC)-Ficoll 70/400 obtained at low ( hydropenic) vs raised ( normal) glomerular filtration rates (GFRs). The h for FITC-Ficoll was determined in anesthetized Wistar rats (304 +/- 18 g) following laparotomy and cannulation of the ureters, used for urine sampling. After surgery, GFR was 1.2 +/- 0.16 ml/ min (+/- s. e.), assessed using the plasma to urine clearance of FITC-inulin and Cr-51-ethylenediaminetetraacetic acid. FITC-Ficoll 70/400 was infused intravenously (i.v.) following an initial bolus dose. To raise GFR, to an average of similar to 2 ml/ min, 5 ml of serum together with glucagon ( 3 mu g/min) was given i.v. FITC- inulin and FITC- Ficoll were determined in plasma and urine using size-exclusion high-performance liquid chromatography. The h for Ficoll as a function of Stokes - Einstein radius was significantly reduced in the range of 13 - 43 angstrom when GFR was raised. The maximal h lowering effect, in relative terms, of raising GFR was obtained for a Ficoll a(e) of similar to 32 angstrom. For Ficoll(36 angstrom) (cf. albumin), h was reduced from 0.111 +/- 0.009 to 0.081 +/- 0.012 ( P<0.05; n = 7) for the GFR increment imposed. The reduction in h for Ficoll after raising GFR indicates the presence of a high diffusive component of glomerular Ficoll filtration in rats in vivo and contradicts the notion of a significant concentration polarization effect in the glomerular filter upon Ficoll molecules <50 angstrom in radius.
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| 5. |
- Rippe, Catarina, et al.
(författare)
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Nature of glomerular capillary permeability changes following acute renal ischemia/reperfusion (I/R) injury in rats.
- 2006
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 291:6, s. 1362-1368
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (theta) were obtained by analyzing Ficoll [mol.radius (a(e)) 13-85 angstrom] in urine and plasma after 20 and 60 min I/R. Furthermore, theta for human serum albumin (HSA) was estimated using a tissue uptake technique after 20 and 60 min of I/R, while clearance of HSA compared with that for neutralized HSA (nHSA) was assessed after 20 min of I/R only. Glomerular filtration rate (GFR) was measured by [Cr-51] EDTA and inulin. I/R reduced GFR and increased theta for Ficoll molecules of a(e) > 55 angstrom and theta for albumin. theta for Ficoll vs. a(e), analysed using a two-pore model, demonstrated that, despite increases in theta, the large-pore fractional ultrafiltration coefficient (alpha(L)) was unchanged after 20 min of I/R, owing to the decline in GFR, but increased after 60 min of I/R. However, the apparent alpha(L) for albumin increased already after 20 min of I/R (P < 0.005) and the nHSA/HSA clearance ratio was slightly reduced, possibly reflecting a diminished negative charge barrier. In conclusion, after 20 min of I/R, indications of a reduced charge selectivity were noted, while after 60 min of I/R, there was mainly a reduction in size selectivity, compatible with an increased formation of large pores.
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| 6. |
- Rippe, Catarina, et al.
(författare)
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Size and charge selectivity of the glomerular filter in early experimental diabetes in rats
- 2007
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 293:5, s. 1533-1538
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Tidskriftsartikel (refereegranskat)abstract
- Microalbuminuria is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size- or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at similar to 20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (C1-HSA) and neutralized albumin (C1-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using Cr-51-EDTA and [ I-125]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients (theta) for neutral FITC-Ficoll (molecular radius: 15-90 angstrom) were assessed using size exclusion chromatography. At 3 wk of diabetes, C1-HSA and C1-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of C1-HSA, whereas C1-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and C1-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores.
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| 7. |
- Rosengren, Bert-Inge, et al.
(författare)
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Transvascular protein transport in mice lacking endothelial caveolae.
- 2006
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 291:3, s. 1371-1377
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Tidskriftsartikel (refereegranskat)abstract
- Caveolae are Omega-shaped vesicular structures postulated to play a role in transvascular protein transport. Studies on mice lacking endothelial caveolae, caveolin-1 knockout (Cav-1-KO) mice, indicate increased macromolecular transport rates. This was postulated to be due to the appearance of an alternative pathway. The present study tested whether an alternative pathway had appeared in Cav-1-KO mice. Male Cav-1-KO (n=12) and male control mice (n=13) were intubated and anesthetized using 2% isoflurane. I-125-labeled albumin, I-131-labeled immunoglobulin M (IgM), and polydisperse FITC-Ficoll were administered intravenously. During tracer administration, a 90-min peritoneal dialysis dwell was performed. Clearance of tracers to dialysate and permeability-surface area product for glucose were assessed. Transvascular protein transport was higher in Cav-1-KO compared with control mice. Albumin clearance from plasma to peritoneum was 0.088 +/- 0.008 mu l/min in control and 0.179 +/- 0.012 mu l/min in Cav-1-KO (P = 0.001) mice. IgM clearance was 0.049 +/- 0.003 and 0.083 +/- 0.010 mu l/min in control and Cav-1-KO mice, respectively (P = 0.016). Ficoll clearance was increased in Cav-1-KO mice. In conclusion, the lack of caveolae in Cav-1-KO mice resulted in a marked increase in macromolecular transport. A two-pore analysis of the Ficoll clearance data revealed that the higher transport rate in Cav-1-KO mice was not compatible with the appearance of an alternative pathway for macromolecular transport. In contrast, the higher transperitoneal protein and Ficoll clearance is consistent with passive porous transport through an unperturbed two-pore system, presumably at an elevated capillary hydraulic pressure. Alternatively, the data may be explained by reductions in the selectivity of the endothelial glycocalyx, leading to an increased capillary hydraulic conductivity and large solute filtration.
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| 8. |
- Asgeirsson, Daniel, et al.
(författare)
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Glomerular sieving of three neutral polysaccharides and bikunin in rat. - Effects of molecular size and conformation.
- 2007
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 191:3, s. 237-246
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes–Einstein radius (ae) of the following polymers increases in the order: Ficoll < dextran ≤ pullulan < polyethylene oxide (PEO). We have tested the hypothesis that such an increase in 'molecular extension' will increase the molecule's glomerular permeability. Thus, we investigated the glomerular sieving coefficients (θ) of the mentioned polymers and of the negatively charged and extended protein bikunin. Methods: In anaesthetized Wistar rats, glomerular sieving curves were generated for each FITC-labelled polymer from their respective concentration in urine and plasma, determined by size exclusion chromatography. The θ for bikunin was measured using a tissue uptake technique. Results: For a molecule of ae = 55 Å (cf. IgG), θ increased in the order: Ficoll (0.00035 ± 0.000013) < dextran (0.022 ± 0.0029) < pullulan (0.033 ± 0.0024) < PEO (0.12 ± 0.0055). For ae = 36 Å (cf. albumin) the order was: Ficoll (0.076 ± 0.0061) < dextran (0.45 ± 0.037) = pullulan (0.45 ± 0.021) < PEO (0.65 ± 0.0076). θ for bikunin (0.089 ± 0.0045) was 150 times higher than that of albumin, having an equivalent ae and net negative charge. Conclusion: From these results it is concluded that for flexible and asymmetric macromolecules, their degree of glomerular hyperpermeability is proportional to their degree of 'molecular extension'. Thus, compared with globular proteins, the polysaccharides investigated, including Ficoll, were found to be hyperpermeable across the glomerular filter in vivo.
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| 9. |
- Asgeirsson, Daniel, et al.
(författare)
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Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats.
- 2006
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 291:5, s. 1083-1089
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Tidskriftsartikel (refereegranskat)abstract
- It is established that the glomerular filter sieves macromolecules based on their size, shape, and charge. Anionic proteins are thus retarded compared with their neutral or cationic counterparts. However, recent studies have indicated that charge effects are small, or even "anomalous," for polysaccharides. We therefore investigated the impact of charge on the glomerular permeability to polysaccharides by comparing sieving coefficients ({theta}; primary urine-to-plasma concentration ratio) for negatively charged, carboxymethylated (CM) FITC-Ficoll and FITC-dextran with their neutral counterparts. For these probes, {theta} were determined in anesthetized Wistar rats [269 ± 2.7 g (±SE; n = 36)], whose ureters were cannulated for urine sampling. The glomerular filtration rate was assessed using FITC-inulin. Polysaccharides were constantly infused, and after equilibration, urine was collected and a midpoint plasma sample was taken. Size and concentration determinations of the FITC-labeled polysaccharides were achieved by size-exclusion HPLC (HPSEC). For CM-Ficoll, {theta} was significantly increased (32 times at 55 Å) compared with that of uncharged Ficoll. A small increase in {theta} for CM-dextran compared with neutral dextran was also observed (1.8 times at 55 Å). In conclusion, negatively charged Ficoll relative to neutral Ficoll was found to be markedly hyperpermeable across the glomerular filter. Furthermore, negatively charged Ficoll was observed to be larger on HPSEC compared with its neutral counterpart of the same molecular weight. It is proposed that the introduction of negative charges in the "dendrimeric," cross-linked Ficoll molecule may alter its configuration, so as to make it more extended, and conceivably, more flexible, thereby increasing its glomerular permeability. charge barrier; capillary permeability; macromolecules; fractional clearance; reflection coefficients IT IS GENERALLY ACCEPTED THAT the glomerular filter discriminates among macromolecules based on their size, shape, and net charge (6, 8). With respect to charge, the permeability of anionic dextran sulfate was found to be reduced and that of cationic, diethylaminoethyl (DEAE) dextran to be increased compared with that of neutral dextran (6). However, more recent studies have indicated that sulfated dextran may be processed in the kidney (28) and desulfated during its renal passage (10), and furthermore, that it may bind to plasma proteins (17), and to membrane phospholipids (25), causing an artifactual reduction in the sieving coefficients ({theta}; i.e., the primary urine-to-plasma concentration ratios) of dextran sulfate. In addition, isolated glomerular basement membranes (GBM) have generally failed to show charge selectivity when probed with neutral and negatively charged Ficoll (7) or native (anionic) or cationized albumin (4). In line with these findings, Schaeffer et al. (26) were unable to find (in rats in vivo) any difference between glomerular {theta} to carboxymethylated (non-sulfated) dextran or to hydroxymethyl starch (HES), both negatively charged, and their neutral counterparts. Furthermore, the HES molecules showed lower {theta} for any given Stokes-Einstein (SE) radius (cf. Ficoll) than did dextran. It was concluded that the glomerular filtration barrier restricts the transport of polysaccharide macromolecules as a function of size and configuration whereas the presence or absence of negative charge does not play any role. Further supporting these results, Guimarães et al. (18) did not find a decrease in glomerular permeability to negatively charged, carboxymethylated (CM) Ficoll compared with uncharged Ficoll, confirming a previous observation by Greive et al. (16). Instead, they found a markedly increased glomerular permeability to CM-Ficoll. In contrast to the apparent inability of the glomerular filter to discriminate between polysaccharides of different charge, there is ample evidence that, indeed, the glomerular filter selects globular proteins based on their charge. Thus anionic proteins are retarded compared with neutral and cationic proteins, as extensively reviewed by Comper and Glasgow (9) and Venturoli and Rippe (29). The reason the glomerular capillary wall exhibits low discrimination ability with respect to differently charged polysaccharides, while being able to separate proteins of different molecular charge, is obscure. However, one clue to this enigma could be the fact that carbohydrates exhibit an extended molecular configuration, with a larger SE radius, compared with that for globular proteins, for any given molecular mass (19, 29). Such an extended configuration, conceivably, generates a more flexible (compressible) structure and hence increases the molecule's permeability through the glomerular filtration barrier (29). Charge modification of a polysaccharide may lead to a further increase in molecular extension, favoring an increased flexibility and, thereby, an increased solute permeability. Could the process of charge modification of the highly cross linked and "ellipsoid" molecules of Ficoll (19) lead to conformational alterations, with increased molecular extension, increasing their permeability compared with their uncharged counterparts? If so, would the linear, "random coil," structure of dextran make it less affected by conformational changes, and thereby less hyperpermeable, when negatively charged? The present study was performed to test this hypothesis by comparing glomerular sieving coefficients to negatively charged, CM-Ficoll and -dextran vs. their uncharged molecular equivalents.
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| 10. |
- Asgeirsson, Daniel, et al.
(författare)
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Similitude of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane.
- 2009
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 196:4, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods: In anesthetized Wistar rats, FITC-Ficoll or FITC-pullulan together with (125)I-human serum albumin (RISA) or neutralized (125)I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis using conventional peritoneal dialysis fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analyzed with high performance size exclusion chromatography and a gamma counter, respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36-150 A, and for RISA and nBSA. Results: Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50+/-0.28 (muL/min; +/-SEM), tended to be lower than the clearances of Ficoll(36A) (6.55+/-0.25), pullulan(36A) (6.08+/-0.22) and nBSA (6.56+/-0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion: The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary-interstitial barrier.
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| 11. |
- Axelsson, Josefin, et al.
(författare)
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Acute hyperglycemia induces rapid, reversible increases of glomerular permeability in non-diabetic rats.
- 2010
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 298:6, s. 1306-1312
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anaesthetized Wistar rats (250-280g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (i.v.) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n=8); 2) hypertonic glucose as in 1) and a Rho-A-kinase inhibitor (Y-27632; Rho-G; n=8); 3) 20% mannitol (MANN; n=7), or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (picry) at ~320-325 mOsm/l (NaCl; n=8); 5) physiologic saline (SHAM; n=8). Fluorescein isothiocyanate (FITC)-Ficoll 70/400 was infused i.v. for at least 20 min before terminating the experiments, and plasma and urine collected to determine the glomerular sieving coefficients () for polydisperse Ficoll (mol. radius 15-80A) by high performance size exclusion chromatography. In G there was a marked increase in for Ficoll55-80A at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier be involved in these alterations. Key words: microalbuminuria, Rho-A-kinase, podocytes, endothelium.
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| 12. |
- Axelsson, Josefin, et al.
(författare)
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Effects of early endotoxemia and dextran-induced anaphylaxis on the size-selectivity of the glomerular filtration barrier in rats.
- 2009
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 296:2, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anaesthetized Wistar rats, the left ureter was catheterized for urine collection, while simultaneously, blood access was achieved. Endotoxemia was induced by Lipopolysaccharide (LPS) from E. Coli, and glomerular permeability assessed at 60, 90 (ENDO-(60)/90; n=7) and 120 min (ENDO-120; n=7). Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min (ANA-5; n=8) and 40 min (ANA-40; n=9). Sham animals, were followed for either 5 or 120 min. The glomerular sieving coefficients () to FITC-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). 2 h after start of the LPS infusion, but not at 60 or 90 min, for Ficoll70A had increased markedly (from 2.91 x 10(-5) +/- 6.33 x 10(-6) to 7.78 x 10(-5) +/- 6.21 x 10(-6) (P<0.001)). In anaphylaxis there was a large increase in for Ficolls >60 A in mol. radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter. Key words: capillary permeability, Ficoll, sieving coefficient, albumin.
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| 13. |
- Axelsson, Josefin, et al.
(författare)
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Loss of size-selectivity of the glomerular filtration barrier in rats following laparotomy and muscle trauma.
- 2009
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 297, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- Post-traumatic microalbuminuria may be caused by either charge- or size-selective alterations in the glomerular filtration barrier, or both, and/or to a reduction in proximal tubular protein reabsorption (PTR). This study was performed to elucidate the pathophysiology of the increases in glomerular permeability occurring in rats exposed to laparotomy or to laparotomy and muscle trauma. In anaesthetized Wistar rats (250-280 g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats were exposed to trauma by laparotomy (L) (n=8), or by a combination of L and muscle trauma (MT), induced by topical blunt injury of the abdominal muscles bilaterally. After L muscles were crushed using a hemostatic forceps at either 2x2 sites ("small" MT; n=9), or at 2x5 sites ("large" MT; n=9). Sham groups (n=16), not exposed to laparotomy, were used as controls. The glomerular sieving coefficients () to polydisperse, fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 13-80A) were determined at 5 or 60 min after L and (L + MT), respectively, from plasma and urine samples, and analyzed by high performance size-exclusion chromatography (HPSEC). A tissue uptake technique was used to assess for (125)I-serum albumin. L, with or without MT, increased for Ficoll55-80A and albumin rapidly and markedly. -Ficoll70A thus increased approximately threefold, and for albumin significantly, for all trauma groups. According to the "two-pore model" of glomerular permeability these changes reflect an increase in the number of large pores in the glomerular filter without any primary changes in the charge-selective properties of the filter. Key words: microalbuminuria, glomerular sieving coefficients, albumin, Ficoll.
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| 14. |
- Axelsson, Josefin, et al.
(författare)
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mTOR inhibition with temsirolimus causes acute increases in glomerular permeability, but inhibits the dynamic permeability actions of puromycin aminonucleoside.
- 2015
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 308:10, s. 1056-1064
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of the mammalian target of rapamycin (mTORi) can produce de novo proteinuria in kidney transplant patients. On the other hand, mTORi has been shown to suppress disease progression in several animal models of kidney disease. In the present study we investigated whether glomerular permeability can be acutely altered by the mTORi, temsirolimus, and whether mTORi can affect acute purumycin aminonucleoside (PAN) or angiotensin II (AngII) induced glomerular hyperpermeability. In anaesthetized Wistar rats, the left ureter was cannulated for urine collection, while simultaneously, blood access was achieved. Temsirolimus was administered as a single dose i.v. 30 min before the start of the experiments in animals infused with PAN or AngII or in non-exposed animals. Polydispersed FITC-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA infusion was given during the whole experiment. Measurements of Ficoll in plasma and urine were performed sequentially before the temsirolimus injection (baseline) and at 5, 15, 30, 60 and 120 min after the start of the experiments. Urine and plasma samples were analyzed by high performance size exclusion chromatography (HPSEC) to assess glomerular sieving coefficients (θ) for Ficoll10-80Å. Temsirolimus per se increased baseline glomerular permeability to Ficoll50-80Å 45 min after its administration, a ROS dependent phenomenon. PAN caused a rapid and reversible increase in glomerular permeability, peaking at 5 min, and again at 60-120 min, which could be blocked by the ROS scavenger, tempol. mTORi abrogated the second permeability peak induced by PAN. However, it had no effect on the immediate AngII or PAN induced increases in glomerular permeability.
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| 15. |
- Axelsson, Josefin, et al.
(författare)
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Rapid, dynamic changes in glomerular permeability to macromolecules during systemic Angiotensin II (AngII) infusion in rats.
- 2012
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 303:6, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- The actions of systemic angiotensin II (AngII) infusions on glomerular permeability were investigated in vivo. In anaesthetized Wistar rats (250-280g) the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused i.v. with either of four doses of AngII (16 ng/kg/min (Lo-AngII; n=7), 230 ng/kg/min (Lo-Int-AngII; n=8), 910 ng/kg/min (Hi-Int-AngII; n=7), or 1.82 μg/kg/min (Hi-AngII; n=8)), or with the calcium channel blocker, nimodipine, together with the Hi-Int-AngII dose (n=6), respectively, and with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60 and 120 min and analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. In AngII groups there was a rapid, marked increase in glomerular permeability (θ) to Ficoll molecules >34Å, which was completely abrogated by the AngII-blocker, candesartan. The permeability increase was reversible within 15-60 min, but some increases remained even after 60 min. For the highest AngII doses given GFR decreased transiently, concomitant with marked increases in MAP. Nimodipine blocked the hemodynamic AngII actions, whereas the glomerular permeability response remained unchanged. According to a two-pore model and a log-normal distributed pore model the AngII induced increases in glomerular permeability are compatible with an increased number of "large pores" in the glomerular filter, and, to some extent, an increase in the dispersity of the small pore radius.
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| 16. |
- Axelsson, Josefin, et al.
(författare)
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Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo
- 2011
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 301:4, s. 708-712
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Tidskriftsartikel (refereegranskat)abstract
- Axelsson J, Sverrisson K, Rippe A, Fissell W, Rippe B. Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo. Am J Physiol Renal Physiol 301: F708-F712, 2011. First published July 20, 2011; doi:10.1152/ajprenal.00183.2011.-The glomerular filtration barrier (GFB) is commonly conceived as a negatively charged sieve to proteins. Recent studies, however, indicate that glomerular charge effects are small for anionic, carboxymethylated (CM) dextran vs. neutral dextran. Furthermore, two studies assessing the glomerular sieving coefficients (theta) for negative CM-Ficoll vs. native Ficoll have demonstrated an increased glomerular permeability for CM-Ficoll (Asgeirsson D, Venturoli D, Rippe B, Rippe C. Am J Physiol Renal Physiol 291: F1083-F1089, 2006; Guimaraes M, Nikolovski J, Pratt L, Greive K, Comper W. Am Physiol Renal Physiol 285: F1118-F1124, 2003.). The CM-Ficoll used, however, showed a larger Stokes-Einstein radius (a(e)) than neutral Ficoll, and it was proposed that the introduction of negative charges in the Ficoll molecule had made it more flexible and permeable. Recently, a negative FITC-labeled CM-Ficoll (CMI-Ficoll) was produced with a conformation identical to that of neutral FITC-Ficoll. Using these probes, we determined their theta:s in anesthetized Wistar rats (259 +/- 2.5 g). After blood access had been achieved, the left ureter was cannulated for urine sampling. Either polysaccharide was infused (iv) together with a filtration marker, and urine and plasma were collected. Assessment of theta FITC-Ficoll was achieved by high-performance size-exclusion chromatography (HPSEC). CMI-Ficoll and native Ficoll had identical elugrams on the HPSEC. Diffusion of anionic Ficoll was significantly reduced compared with that of neutral Ficoll across the GFB for molecules of a(e) similar to 20-35 angstrom, while there were no charge effects for Ficoll of a(e) similar to 35-80 angstrom. The data are consistent with a charge effect present in "small pores," but not in "large pores," of the GFB and mimicked those obtained for anionic membranes in vitro for the same probes.
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| 17. |
- Axelsson, Josefin, et al.
(författare)
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Scavengers of reactive oxygen species, paracalcitol, RhoA and Rac-1 inhibitors and tacrolimus inhibit angiotensin II induced actions on glomerular permeability.
- 2013
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 305:3, s. 237-243
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Tidskriftsartikel (refereegranskat)abstract
- Systemic infusions of angiotensin II (AngII) rapidly induce large, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor(s), AngII generates reactive oxygen species (ROS) and produces Ca(2+) influx into cells, leading to activation of a plethora of signaling cascades, including e.g. calcineurin, and small GTPases, such as Rac-1 and RhoA. In the present study we sought to interact with some of these cascades in order to test potential novel antiproteinuric agents. In anaesthetized Wistar rats the left urether was cannulated for urine collection, and blood access was achieved. Rats were infused with AngII (16 ng/kg/min) alone, or together with the ROS scavengers, TEMPOL or dimethylthiourea (DMTU), or the D-vitamin analog, paracalcitol, the RhoA-kinase inhibitor, Y-27632, the Rac-1 inhibitor, NSC-23766, or the calcineurin inhibitor, tacrolimus. FITC-Ficoll-70/400 (mol.radius 10-80Å) and (51)Cr-EDTA were infused throughout the experiment. Plasma and urine samples were taken during baseline and at 5 and 15 min after the start of the infusions and analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ) for Ficoll10-80Å. AngII infusion into rats caused marked increases in glomerular permeability to large Ficoll molecules (Ficoll50-80Å), which were abrogated by the ROS scavenger TEMPOL and partly by DMTU. Paracalcitol, RhoA and Rac-1 inhibition, and, to some extent, tacrolimus, but not prostacyclin, could also inhibit the glomerular permeability actions of AngII. Our data suggest that cellular ROS generation and active Ca(2+) signaling are involved in AngII induced increases in glomerular permeability.
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| 18. |
- Axelsson, Josefin, et al.
(författare)
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Size-selectivity of a synthetic high-flux and a high cut-off dialyzing membrane compared to that of the rat glomerular filtration barrier
- 2012
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Ingår i: Journal of Membrane Science. - : Elsevier BV. - 0376-7388. ; 413, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the size-selectivity of two different synthetic dialyzing membranes, having widely differing sieving properties, with respect to their handling of polydispersed fluorescein isothiocyanate (FITC)-Ficoll, FITC-dextran and of proteins, i.e. I-125-human serum albumin (RISA) and I-125-myoglobin (Myo). Are Ficoll and dextran, compared to proteins, "hyperpermeable" across synthetic dialyzing membranes, similar to their behavior across the glomerular filtration barrier (GFB)? A high-flux membrane (HF-Revaclear (R); n = 12) and a high cut-off membrane (HCO; n = 14) in capillary mini-dialyzers were perfused with diluted horse serum. The perfusate contained polydisperse FITC-Ficoll 70/400 or FITC-dextran (mol radius 13-80 angstrom), FITC-Inulin, and, in some experiments, RISA/Myo. After a priming period, sampling of filtrate occurred, and a midpoint plasma sample taken. Filtrate-to-plasma concentration ratios (theta) vs. molecular radius (a(e)) were assessed using HPLC for Ficoll and dextran. Size-selectivity for Ficoll increased in the order: HF-Revaclear (R) < rat glomerulus < HCO. Although the HCO filter showed the highest cut-off, this occurred at the expense of a high permeability to albumin and large Ficoll molecules and a high degree of dispersity of (small) pore radii, as assessed using a log-normal + shunt distributed pore model. According to a two-pore model, the fractional hydraulic conductance accounted for by large pores (alpha(L)) was 8.58 +/- 0.93 x 10(-3) and 1.51 +/- 0.88 x 10(-3) for the HCO and the HF-Revaclear (R), respectively, compared to 4.1 +/- 0.80 x 10(-5) for the rat glomerulus. In conclusion, the HCO filter investigated showed a high theta for myoglobin, similar to that of the GFB. However, the number of large pores was markedly higher and the pore size heterogeneity markedly larger than for the GFB. Membrane permeability was dependent on molecular species and increased in the order: proteins < Ficoll < dextran. (C) 2012 Published by Elsevier B.V.
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| 19. |
- Axelsson, Josefin, et al.
(författare)
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Transient and sustained increases in glomerular permeability following ANP infusion in rats.
- 2011
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Ingår i: American Journal of Physiology-Renal Physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 300, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- The present study was performed to investigate the effects of systemic atrial natriuretic peptide (ANP) infusion on the glomerular permeability to macromolecules in rats. In anaesthetized Wistar rats (250-280g) the left urether was cannulated for urine collection while simultaneously blood access was achieved. Rats were continuously infused i.v. with ANP, 30 ng/min/kg (Lo-ANP; n=8) or 800 ng/min/kg (Hi-ANP; n=10) or 0.9% NaCl (SHAM; n=16), respectively, and with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 (mol.radius 13-90Å) and (51)Cr-EDTA for 2 h. Plasma and urine samples were taken at 5, 15, 30, 60 and 120 min of ANP infusion, and analyzed by high performance size exclusion chromatography (HPLC) for determination of glomerular sieving coefficients () for Ficoll. GFR was also assessed ((51)Cr-EDTA). In Hi-ANP there was a rapid (within 5 min), but bimodal, increase in glomerular permeability. to high MW Ficoll thus reached a maximum at 15 min, after which returned to near control at 30 min, to again increase moderately at 60 and 120 min. In Lo-ANP there was also a rapid, reversible increase in glomerular , returning to near control at 30 min, followed by just a tendency of a sustained increase in permeability, but with a significant increase in "large pore" radius. In conclusion, in Hi-ANP there was a rapid increase in glomerular permeability, with an early, partly reversible permeability peak, followed by a (moderate) sustained increase in permeability. In Lo-ANP animals, only the initial permeability peak was evident. In both Lo-ANP and Hi-ANP the glomerular sieving pattern observed was found to mainly reflect an increase in the number and radius of "large pores" in the glomerular filter.
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| 20. |
- Dolinina, Julia, et al.
(författare)
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Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species
- 2016
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 311:5, s. 984-990
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with eitherL-NAME orL-NAME together with the superoxide scavenger Tempol, or together withL-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h.L-NAME increased θ for Ficoll70Å from 2.27 ± 1.30 ˟ 10-5 to 8.46 ± 2.06 ˟ 10-5 (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed withL-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo byL-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.
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| 21. |
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| 22. |
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| 23. |
- Krawczyk, Katarzyna K., et al.
(författare)
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Assessing the contribution of thrombospondin-4 induction and ATF6α activation to endoplasmic reticulum expansion and phenotypic modulation in bladder outlet obstruction
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Phenotypic modulation of smooth muscle cells is a hallmark of disease. The associated expansion of endoplasmic reticulum (ER) volume remains unexplained. Thrombospondin-4 was recently found to promote ATF6α activation leading to ER expansion. Using bladder outlet obstruction as a paradigm for phenotypic modulation, we tested if thrombospondin-4 is induced in association with ATF6α activation and ER expansion. Thrombospondin-4 was induced and ATF6α was activated after outlet obstruction in rodents. Increased abundance of spliced of Xbp1, another ER-stress sensor, and induction of Atf4 and Creb3l2 was also seen. Downstream of ATF6α, Calr, Manf, Sdf2l1 and Pdi increased as did ER size, whereas contractile markers were reduced. Overexpression of ATF6α, but not of thrombospondin-4, increased Calr, Manf, Sdf2l1 and Pdi and caused ER expansion, but the contractile markers were inert. Knockout of thrombospondin-4 neither affected bladder growth nor expression of ATF6α target genes, and repression of contractile markers was the same, even if ATF6α activation was curtailed. Increases of Xbp1s, Atf4 and Creb3l2 were similar. Our findings demonstrate reciprocal regulation of the unfolded protein response, including ATF6α activation and ER expansion, and reduced contractile differentiation in bladder outlet obstruction occurring independently of thrombospondin-4, which however is a sensitive indicator of obstruction.
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| 24. |
- Lund, Ulla, et al.
(författare)
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Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys
- 2003
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Ingår i: American Journal of Physiology: Renal, Fluid and Electrolyte Physiology. - : American Physiological Society. - 0363-6127. ; 284:6, s. 1226-1234
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Tidskriftsartikel (refereegranskat)abstract
- The size and charge-selective properties of the glomerular barrier are partly controversial. Glomerular sieving coefficients (theta) for proteins have rarely been determined noninvasively before in vivo. Therefore, theta was assessed vs. glomerular filtration rate (GFR; Cr-51-EDTA clearance) in intact rats for radiolabeled myoglobin, kappa-dimer, neutral horseradish peroxidase (nHRP), neutral human serum albumin (nHSA), and native albumin (HSA). To obtain theta, glomerular tracer clearance, assessed from the 7- to 8-min kidney uptake of protein, was divided by the GFR. The data were fitted with a two-pore model of glomerular permeability, where the small-pore radius was 37.35 +/- 1.11(SE) Angstrom, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 . 10(6) cm. Although seemingly horizontal for nHRP and nHSA, the log theta vs. GFR curves showed slightly negative slopes for the proteins investigated in the GFR interval of 2-4.5 ml/min. Strong negative ( linear) correlations between ( log) theta and GFR were obtained for myoglobin (P = 0.002) and HSA (P = 0.006), whereas they were relatively weak for nHRP and nHSA and nonsignificant for kappa-dimer. theta for nHSA was markedly higher than that for HSA. In conclusion, there were no indications of increases in theta vs. GFR, as indicative of concentration polarization, for the proteins investigated at high GFRs. Furthermore, the glomerular small-pore radius assessed from endogenous (neutral) protein sieving data was found to be smaller than previously determined using dextran or Ficoll as test molecules.
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| 25. |
- Morelle, Johann, et al.
(författare)
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Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane
- 2018
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 29:7, s. 1875-1886
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Tidskriftsartikel (refereegranskat)abstract
- Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.
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