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At least 793 records · Page 44Linked to original sources
PubMed2002

Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells overexpressing efflux transporters Pgp, cMOAT, and MRP1.

Irinotecan (CPT-11) is a water-soluble camptothecin (CPT) derivative that has been recently approved in the United States for patients as a first-line therapy in advanced colorectal cancer. Phase I clinical trials using oral CPT-11 have shown poor and variable oral bioavailability. The present study was designed to investigate the intestinal absorption and efflux mechanisms of CPT-11 using in vitro cell culture models, Caco-2 cells, and engineered Madine-Darby canine kidney (MDCK) II cells overexpressing P-glycoprotein (Pgp), canalicular multispecific organic anion transporter (cMOAT), and multidrug resistance-associated protein (MRP1). The intestinal absorptive and secretory transport of CPT-11 was investigated using Caco-2 cell monolayers. Secretory transport was concentration-dependent and saturable. The secretory efflux permeability (P(eff)) of CPT-11 decreased with decreasing temperature, with an estimated activation energy of 19.6 +/- 2.9 kcal/mol suggesting the involvement of active transporters. The involvement of potential secretory transporters was further characterized in MDCK II cells. The secretory efflux carrier permeability (P(c)) was approximately 4- and approximately 2-fold greater in MDCK II/Pgp and MDCK II/cMOAT cells than that in MDCK II/wild-type cells. Furthermore, the secretory efflux P(eff) of CPT-11 was significantly decreased by Pgp inhibitors, elacridar (GF120918) (IC50 = 0.38 +/- 0.06 microM) and verapamil (IC(50) = 234 +/- 48 microM) in MDCK II/Pgp cells and by cMOAT inhibitor 3-([(3-(2-[7-chloro-2-quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoprphyl)-thio)-methyl]-thio) propanoic acid (MK571) (IC50) = 469 +/- 60 micro;M) in MDCK II/cMOAT cells. Overall, the current study suggests that Pgp and cMOAT are capable of mediating the efflux of CPT-11 in vitro. Since both Pgp and cMOAT are expressed in the intestine, liver, and kidney, it is likely that these efflux transporters play a significant role limiting the oral absorption and disposition of this important anticancer drug.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Transport of gamma-hydroxybutyrate in rat kidney membrane vesicles: Role of monocarboxylate transporters.

Intoxication with gamma-hydroxybutyrate (GHB) is associated with coma, seizure, and death; treatment of overdoses is symptomatic. Previous studies in our laboratory have demonstrated that L-lactate and pyruvate treatment can increase the renal clearance of GHB and increase its elimination in rats, suggesting that GHB may undergo renal reabsorption mediated by monocarboxylic acid transporters (MCTs). The goals of this study were to characterize the renal transport of GHB in rats and to determine the role of MCT in its renal transport. Brush-border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from rat kidney cortex, and the uptake of L-lactate and GHB was characterized. L-Lactate and GHB undergo both pH- and sodium-dependent transport in BBM vesicles and pH-dependent transport in BLM vesicles. A simple Michaelis-Menten equation best described the pH-dependent uptake of GHB in BBM (Km, 8.0 +/- 1.8 mM; Vmax, 838 +/- 45 pmol/mg/s) and in BLM vesicles (Km, 10.5 +/- 2.6 mM; Vmax, 806 +/- 253 pmol/mg/s). mRNA of MCT1 and MCT2 was determined in rat kidney cortex using reverse transcriptase-polymerase chain reaction; using Western blot, the protein expression of MCT1 was present mainly in BLM vesicles, with weak expression in BBM vesicles, whereas that of MCT2 was exclusively in BLM vesicles. Studies with rat MCT1 gene-transfected MDA-MB231 cells demonstrated that GHB was a substrate of MCT1. The data suggest that rat MCT1 may represent an important transporter for GHB in renal tubule cells. This investigation provides evidence for the importance of MCTs in the reabsorption of the monocarboxylic acids l-lactate and GHB in the kidney.

Anesthetics, Intravenous↗
PubMed1997

Unliganded maltose-binding protein triggers lactose transport in an Escherichia coli mutant with an alteration in the maltose transport system.

Escherichia coli accumulates malto-oligosaccharides by the maltose transport system, which is a member of the ATP-binding-cassette (ABC) superfamily of transport systems. The proteins of this system are LamB in the outer membrane, maltose-binding protein (MBP) in the periplasm, and the proteins of the inner membrane complex (MalFGK2), composed of one MalF, one MalG, and two MalK subunits. Substrate specificity is determined primarily by the periplasmic component, MBP. However, several studies of the maltose transport system as well as other members of the ABC transporter superfamily have suggested that the integral inner membrane components MalF and MalG may play an important role in determining the specificity of the system. We show here that residue L334 in the fifth transmembrane helix of MalF plays an important role in determining the substrate specificity of the system. A leucine-to-tryptophan alteration at this position (L334W) results in the ability to transport lactose in a saturable manner. This mutant requires functional MalK-ATPase activity and the presence of MBP, even though MBP is incapable of binding lactose. The requirement for MBP confirms that unliganded MBP interacts with the inner membrane MalFGK2 complex and that MBP plays a crucial role in triggering the transport process.

ATP-Binding Cassette Transporters↗
PubMed2000

Hexokinase regulates kinetics of glucose transport and expression of genes encoding hexose transporters in Saccharomyces cerevisiae.

Glucose transport kinetics and mRNA levels of different glucose transporters were determined in Saccharomyces cerevisiae strains expressing different sugar kinases. During exponential growth on glucose, a hxk2 null strain exhibited high-affinity hexose transport associated with an elevated transcription of the genes HXT2 and HXT7, encoding high-affinity transporters, and a diminished expression of the HXT1 and HXT3 genes, encoding low-affinity transporters. Deletion of HXT7 revealed that the high-affinity component is mostly due to HXT7; however, a previously unidentified very-high-affinity component (K(m) = 0.19 mM) appeared to be due to other factors. Expression of genes encoding hexokinases from Schizosaccharomyces pombe or Yarrowia lipolytica in a hxk1 hxk2 glk1 strain prevented derepression of the high-affinity transport system at high concentrations of glucose.

Biological Transport↗
PubMed2002

Transport of small molecules across cell membranes: water channels and urea transporters.

How do small hydrophilic nonelectrolytes cross cell membranes? Which pathways are most important for small lipid insoluble molecules to cross cell membranes? These are questions that have been basic to membrane transport physiology for decades. More importantly, these are questions whose answers have changed significantly within the last 10 years. This review discusses the evidence that pathways other than the lipid bilayer itself exist for the transport across cell membranes of specific small hydrophilic nonelectrolytes. The description begins with briefly analyzing the relevance of well accepted basic mathematical models for transport for understanding the permeability of representative physiologically important molecules across actual cell membranes. Particular emphasis is placed on describing recently discovered proteins that facilitate the transport of some of the smallest physiologically important lipid-insoluble molecules, water, and urea. Evidence also exists for transport proteins that selectively enhance the transmembrane transport of other small lipid-insoluble molecules. Do nonselective pores for small molecules exist in cell membranes?

Animals↗
PubMed1993

Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats.

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2004

Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule.

We compared the characteristics of several cloned rabbit organic electrolyte (OE) transporters expressed in cultured cells with their behavior in intact rabbit renal proximal tubules (RPT) to determine the contribution of each to basolateral uptake of the weak acid ochratoxin A (OTA) and the weak base cimetidine (CIM). The activity of organic anion transporters OAT1 and OAT3 proved to be distinguishable because OAT1 had a high affinity for PAH (K(t) of 20 microM) and did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity for ES (K(t) of 4.5 microM) and a weak interaction with PAH (IC(50) > 1 mM). In contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated OTA, with OAT1 and OAT3 each responsible for approximately 50%: ES and PAH each reduced uptake by approximately 50%, and the combination of the two eliminated mediated OTA uptake. The weak base CIM was transported by OAT3 (K(t) of 80 microM) and OCT2 (K(t) of 2 microM); OCT1 had a comparatively low affinity for CIM, and CIM uptake by OAT1 was equivocal. Intact RPT accumulated CIM, with TEA and ES reducing CIM uptake by 20 and 75%, respectively, suggesting that OAT3 plays a quantitatively more significant role in CIM uptake in the early proximal tubule than OCT1/2. In single S2 segments of RPT, ES and TEA each blocked approximately 50% of CIM uptake. Thus the fractional contribution of different OE transporters to renal secretion is influenced by their affinity for substrate and relative expression level in RPT.

Animals↗
PubMed2002

Urea transporters are distributed in endothelial cells and mediate inhibition of L-arginine transport.

Our laboratory previously reported that uremic levels of urea inhibit L-arginine (L-Arg) transport into endothelial cells. The present study further investigated this effect. We measured L-Arg transport in cultured bovine aortic endothelial cells with normal or high urea (25 mM). The urea transport inhibitor phloretin abolished the inhibitory effect of urea on L-Arg transport, suggesting a role for urea transporters (UTs). We screened bovine aortic endothelial cells and several other endothelial cell types for the presence of UTs by using Western blot analysis. UT-B was present in all endothelial cells, irrespective of species or location of derivation, whereas UT-A distribution was variable and sparse. UT-B was also abundant in rat aorta, mesenteric blood vessels, and spinotrapezius muscle, whereas UT-A distribution was, again, variable and sparse. Chronic elevation of urea had variable, inconsistent effects on UT abundance. This study showed that urea must enter endothelial cells, probably by UT-B, to inhibit L-Arg transport. In view of the wide distribution of UT-B in rat vasculature, elevated blood urea nitrogen may lead to endothelial L-Arg deficiency in vivo.

Animals↗
PubMed2000

Importance of valine at position 152 for the substrate transport and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding of dopamine transporter.

Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 through 186 (encompassing the third transmembrane domain) is responsible for the substrate transport and cocaine analog binding. The present study has been carried out to determine the specific amino acid(s) conferring DAT functions by interchanging the amino acid residues in the corresponding region between human and bovine DAT. As described previously, the DA, MPP(+) transport, and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding almost disappeared in chimera hb3 in which the region from residues 133 through 186 of bovine DAT was substituted into human DAT. Replacement of isoleucine, residue 152 of chimera hb3 (bovine DAT sequence), with valine, the human DAT residue at the identical position, remarkably restored the substrate transport and CFT binding to 76% to 98% of the human DAT values. Similarly, substitution of isoleucine for valine at position 152 in the human DAT reduced the substrate transport and CFT binding by 57% to 97%. Among other amino acids tested at position 152 of the chimera hb3, only alanine resulted in small but significant increases in the DAT functions ranging from 16 to 34%. Thus, valine at position 152 plays a crucial role for molecular mechanisms underlying the interactions of DA, MPP(+), and CFT with human DAT.

Amino Acid Sequence↗
PubMed2002

Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines.

Selective blockers of the norepinephrine transporter (NET) inhibit dopamine uptake in the prefrontal cortex. This suggests that dopamine in this region is normally cleared by the somewhat promiscuous NET. We have tested this hypothesis by comparing the effects of inhibitors selective for the three monoamine transporters with those of a nonspecific inhibitor, cocaine, on uptake of 3H-dopamine into synaptosomes from frontal cortex, caudate nucleus, and nucleus accumbens from wild-type, NET, and dopamine transporter (DAT) knock-out mice. Dopamine uptake was inhibited by cocaine and nisoxetine, but not by GBR12909, in frontal cortex synaptosomes from wild-type or DAT knock-out mice. At transporter-specific concentrations, nisoxetine and GBR12909 failed to block dopamine uptake into frontal cortex synaptosomes from NET knock-out mice. The efficacy of cocaine at the highest dose (1 mm) was normal in DAT knock-out mice but reduced by 70% in NET knock-out mice. Nisoxetine inhibited dopamine uptake by 20% in caudate and nucleus accumbens synaptosomes from wild-type and DAT knock-out mice but had no effect in those from NET knock-out mice. Cocaine failed to block dopamine uptake into caudate or nucleus accumbens synaptosomes from DAT knock-out mice. Cocaine and GBR12909 each inhibited dopamine uptake into caudate synaptosomes from NET knock-out mice, but cocaine effectiveness was reduced in the case of nucleus accumbens synaptosomes. Thus, whereas dopamine uptake in caudate and nucleus accumbens depends primarily on the DAT, dopamine uptake in frontal cortex depends primarily on the NET. These data underscore the fact that which transporter clears dopamine from a given region depends on both the affinities and the local densities of the transporters.

Animals↗
PubMed2004

Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells.

Recent studies have shown that the mammalian high-affinity copper transporter encoded by Ctr1 is involved in the uptake of cisplatin. However, the roles of hCtr1 in cisplatin-sensitive and cisplatin-resistant mammalian cells have not been investigated. Here, we show that, of five cisplatin-resistant cell lines, only one (SR2) exhibited substantial reduction in hCtr1 expression as compared with that in its sensitive line small cell lung cancers (SCLC), whereas copper efflux transporters ATP7A and ATP7B were not significantly altered. SR2 exhibited cross-resistance to carboplatin but not to oxaliplatin. Transfection of expression hemagglutinin-tagged hCtr1 cDNA into SCLC and SR2 cells enhanced the uptake of copper, cisplatin, carboplatin, and oxaliplatin, suggesting that hCtr1 transporter can transport these platinum-based drugs. Whereas increased sensitivities to all these platinum drugs were observed in hCtr1-transfected SCLC cells, increased sensitivities to cisplatin and carboplatin but not to oxaliplatin were observed in hCtr1-transfected SR2 cells. These results suggest that SR2 acquired an additional unique intracellular resistance mechanism to oxaliplatin. Finally, using hCtr1 deletion mutants, we showed that the NH2-terminal domain of hCtr1 was involved in transporting all these platinum-based antitumor agents. These results collectively show the importance of hCtr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant variants.

Antineoplastic Agents↗
PubMed1986

Regulation of hexose transporters in chicken embryo fibroblasts: stimulation by the phorbol ester TPA leads to increased numbers of functioning transporters.

As has been observed with many types of cultured cells, chicken embryo fibroblasts (CEF) when exposed to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) develop a 3- to 4-fold increase in hexose transport activity in 4 h. This increase in transport activity occurred despite a modest decline of 20% in [3H]leucine incorporation into acid insoluble fractions. Cycloheximide largely, but not completely, blocked the increase in transport activity during TPA exposure. The effects of TPA were somewhat similar to those of glucose starvation induced enhancement of hexose transport activity. Furthermore, with TPA there was no additive effect to that produced by glucose starvation. Plasma membrane enriched fractions were prepared from CEF treated with or without TPA. Membranes prepared from TPA exposed cells had a two-fold enhancement of stereospecific D-glucose transport activity as well as D-glucose inhibitable [3H]cytochalasin B binding as compared to the membranes from control CEF. There was no effect on transport when membranes were exposed to TPA in vitro. These results provide strong evidence that TPA exposure leads to an increase in the number of functioning transporters, an effect largely requiring protein synthesis.

5'-Nucleotidase↗
PubMed1996

Radioligand binding and autoradiographic visualization of adenosine transport sites in human inferior vagal ganglia and their axonal transport along rat vagal afferent neurons.

The present study has employed membrane-binding studies and in vitro autoradiography to demonstrate the presence of adenosine transport sites in human inferior vagal ganglia using [3H]nitrobenzylthioinosine ([3H]NBMPR), a potent inhibitor of adenosine transport. In addition, [3H]NBMPR was used to determine whether adenosine transport sites are subject to axonal transport along the rat vagus nerve. Binding of [3H]NBMPR to human inferior vagal ganglia membranes was saturable and reversible. Saturation experiments revealed a single class of high affinity-binding sites with a Kd of 93.73 +/- 23.13 pM and Bmax of 413.50 +/- 50.40 fmol/mg protein. In displacement experiments, the adenosine transport inhibitor dipyridamole was the most potent displacer of [3H]NBMPR binding (Ki = 42.7 +/- 28.0 nM). Adenosine itself was able to fully displace [3H]NBMPR binding with a Ki of 115.0 +/- 34.0 microM. The A1/A2a adenosine receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) was able to fully displace [3H]NBMPR binding in only one experiment at a concentration of 100 microM, yielding an affinity 1000-fold higher than its affinity for adenosine receptors. All competition curves obtained from displacement experiments displayed monophasic profiles, indicating the presence of a single class of [3H]NBMPR binding sites. Incubation of human inferior vagal ganglia sections with [3H]NBMPR (0.7 nM) revealed dense binding which appeared to be consistent with the distribution of neuronal cell bodies in this tissue. Following unilateral ligation of the vagus nerve in the rat, accumulation of [3H]NBMPR binding sites occurred both proximal and distal to the vagal ligatures. These results suggest that [3H]NBMPR binds with high affinity to a single class of adenosine transport sites, and that these sites are present on vagal afferent neurons in the human and undergo bidirectional axonal transport along the rat vagus nerve.

Adenosine↗
PubMed1990

Visualization of transport-related configurations of the nuclear pore transporter.

The transport of macromolecules between the cytoplasm and nucleus of the cell is mediated by the nuclear pore complex (NPC). In this study, details of the central transporter assembly within NPCs have been examined by cryoelectron microscopy, image processing, and classification analysis. The NPC transporter in isolated amphibian nuclei appears to adopt a minimum of four transport-related configurations including: (a) a putative closed form with a 90-100 A diameter central pore, (b) a docked form with material aligned over the pore, (c) an open form with substrates apparently caught "in transit," and (d) an open form with an enlarged pore. This data confirms previous observations on NPC transporters labeled with nucleoplasmin-gold (Akey, C.W., and D.S. Goldfarb. 1989. J. Cell Biol. 109:971-982) and allows a working model of the central NPC transporter to be proposed. The model is comprised of two supramolecular irislike assemblies which open asynchronously to provide an expanded pore for translocation while maintaining transport fidelity.

Animals↗
PubMed2001

Function and regulation of monoamine transporters: focus on the norepinephrine transporter.

Presynaptic norepinephrine transporters (NETs) mediate the rapid clearance of norepinephrine from synaptic spaces. NET is a member of the Na+ and Cl- -coupled neurotransmitter transporter gene family, which also includes the serotonin and dopamine transporters. Recent studies reveal that these transporter molecules might be a dynamic component of synaptic plasticity, rather than a constitutive determinant of neurotransmitter levels in synaptic spaces. Recognition that cellular signaling molecules and transporter ligands, including cocaine, amphetamines, and antidepressants, can modify transporter intrinsic activity, trafficking, phosphorylation, and protein levels suggests opportunities for revealing unknown mechanisms of drug action. Control of these properties of transporter function may allow for the development of new strategies to modulate monoaminergic neurotransmission and identify regulatory pathways that may be compromised in psychiatric, neurologic, and neurodegenerative disorders.

Journal Article↗
PubMed1979

Transmembrane effects of irreversible inhibitors of anion transport in red blood cells. Evidence for mobile transport sites.

Experiments were designed to determine whether band 3, the anion transport protein of the red cell membrane, contains a mobile element that acts as a carrier to move the anions across a permeability barrier. The transport site-specific, nonpenetrating irreversible inhibitor 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS) was found to be effective only when applied extracellularly. It was used to sequester transport sites on the extracellular side of the membrane in intact cells. The membranes were then coverted into inside-out vesicles. The number of anion transport sites available on the cytoplasmic side of the vesicle membranes was then estimated by measuring the binding of N-(-4-azido-2-nitrophenyl)-2-aminoethyl-sulfonate (NAP-taurine), a photoreactive probe. Pretreatment with DIDS from the extracullular side substantially reduced the binding of NAP-taurine at the cytoplasmic side. Since NAP-taurine does not appear to penetrate into the intravesicular (normally extracellular) space, a transmembrane effect is apparently involved. About 70% of the DIDS-sensitive NAP-taurine binding sites are located in band 3, with the remainder largely in a lower molecular weight (band 4) region. A similar pattern of reduction in NAP-taurine binding is produced by high concentrations of Cl-, but this anion has little or no effect in vesicles from cells pretreated with DIDS. Thus the DIDS-modulated sites seem to be capable of binding either NAP-taurine or Cl. It is suggested that band 3 contains a mobile transport element that can be recruited to the extracellular surface by DIDS, thus becoming unavailable to NAP-taurine at the cytoplasmic face of the membrane. The results are consistent with a model of carrier-mediated transport in which the movement of the transport site is associated with a local conformational change in band 3 protein.

Binding Sites↗
PubMed1968

Ion transport characteristics of grape root lipids in relation to chloride transport.

Ion transport properties of grape root lipids were measured as liquid-membrane permeability. Phosphatidylcholine exchanged chloride very slowly against carbonate and bicarbonate but more rapidly against nitrate, phosphate, and sulfate. Exchange of chloride against nitrate was rather low for the phosphatidylcholine and phosphatidylethanolamine lipid fractions; monogalactose diglyceride was by far the most effective chloride transporter studied. Comparison between the lipid composition of the roots of the 5 grape rootstocks and the chloride transport capacity of the specific membranes strongly suggests that, indeed, the chloride transport capacity of the lipids present in the membranes of the root cells accounts for the observed differences in chloride transport to the leaves. Whereas monogalactose diglyceride had a high chloride transport capacity, compared with phosphatidylcholine, the reverse was true for exchange of sodium against potassium. Thus, phosphatidylcholine has more the properties of a cation exchanger, and monogalactose diglyceride those of an anion transporter.

Journal Article↗
PubMed2004

Free-water transport in fast transport status: a comparison between CAPD peritonitis and long-term PD.

BACKGROUND: Ultrafiltration failure (UFF) in continuous ambulatory peritoneal dialysis (CAPD) is a transient phenomenon during acute peritonitis and a permanent complication in long-term peritoneal dialysis (PD). The high solute transport rates during acute peritonitis are probably caused by an increased number of perfused peritoneal capillaries. Long-term PD is associated with an increased number of peritoneal microvessels, leading to an enlargement of the anatomic vascular surface area. This leads to high mass transfer area coefficients (MTAC) and to UFF. Impaired conductance to glucose, leading to a reduction in free-water transport, may be a contributing factor to UFF in long-term PD. We hypothesized that UFF during acute peritonitis is, in the absence of permanent structural changes, only caused by an increased vascular surface area, while in long-term patients it is often the result of an increased surface area in combination with an impaired conductance to glucose. Therefore, the peritoneal transport parameters of patients with acute peritonitis were compared to those in long-term PD patients. METHODS: A standard peritoneal permeability analysis (SPA) was done in 10 PD patients during the first 48 hours after the diagnosis of peritonitis. The results were compared to those obtained in 10 long-term PD patients matched for the MTAC creatinine. In addition, the results of 8 peritonitis patients were compared with SPA results of 8 recently started PD patients, matched for MTAC creatinine. RESULTS: Peritonitis patients had a deeper maximal dip in D/P sodium, corrected for diffusion, than long-term patients (0.058 vs. 0.039, P < 0.05). Most parameters of peritoneal fluid transport were not different, except that t50 (i.e., the time to reach 50% of the maximum transcapillary ultrafiltration) was reached earlier during the dwell in peritonitis than in long-term PD-128 versus 175 minutes, P < 0.05. This confirmed the difference in the shape of the intraperitoneal volume versus time curve, which was blunted in the long-term patients. No differences were found for the parameters of solute transport between peritonitis patients and recently started patients. CONCLUSION: In contrast to patients with long-term PD, the osmotic conductance to glucose is unaffected in peritonitis, despite the lower net ultrafiltration caused by high solute transport. This implies that impaired free- water transport in chronic PD must be regarded as a contributing factor to UFF.

Acute Disease↗