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Bengt Rippe

Publications and source records attributed to Bengt Rippe.

At least 19 recordsLinked to original sources

Simulations of osmotic ultrafiltration failure in CAPD using a serial three-pore membrane/fiber matrix model.

Ultrafiltration failure (UFF) is a common complication of long-term peritoneal dialysis (PD). Functionally UFF is in most cases characterized by an enhanced peritoneal mass transfer area coefficient for glucose (PS(g)) combined with a largely unchanged peritoneal glucose osmotic conductance (L(p)Ssigma(g)). Morphologically, marked UFF occurs with fibrosis of the submesothelial zone in the peritoneum, combined with vasculopathy and vascular proliferation in deeper tissues. To computer simulate UFF, changes both in the vasculature and in the interstitium have to be taken into account. For that purpose, we used a three-pore membrane/fiber matrix serial barrier model, applying the three-pore model to the capillaries and the fiber-matrix model to the interstitium. The parameters of the three-pore model have been published previously. The interstitial fiber density was set at 0.5% (vol/vol) and the fiber radius (r(f)) at 6 A during control. If the interstitial fiber density was increased from 0.5 to 3%, and r(f) to 7.5 A (cf. collagen) while the capillary surface area was increased by 40% from control, then PS(g) increased from 9.3 to 11.5 ml/min, while the UF coefficient (L(p)S) was largely unchanged. Further increases in vascular surface area combined with further increases in fiber density caused further increments in PS(g), whereas L(p)S remained unchanged. It is concluded that a matrix of fibers coupled in series with a three-pore membrane may be used for simulating the pathophysiological alterations occurring in the peritoneum in UFF, explaining the commonly observed "uncoupling" of small solute transport (PS) from the peritoneal UF coefficient (L(p)S) in this condition.

Algorithms↗

Disproportionally low clearance of macromolecules from the plasma to the peritoneal cavity in a mouse model of peritoneal dialysis.

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 ((125)I human serum albumin) as a volume marker, after correcting for RISA mass disappearance from the peritoneum, assessed separately (n = 11). Microsampling (10 microl) of plasma and dialysate was performed for determinations of glucose, haematocrit, radioactivity (RISA and (51)Cr-EDTA) and Ficoll. RESULTS: The i.p. volume vs time curves [V(D)(t)] were, after scaling, similar to those observed in humans (and in rats). Clearance of RISA out of the peritoneal cavity (Cl(out)) was 9.33 +/- 0.83 microl/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 microl/min, respectively. The peritoneal transport coefficients for (51)Cr-EDTA and glucose, as well as Cl(out) and Cl-->P, were 13-17% of those previously assessed in 300 g rats, whereas Cl-->D was only approximately 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.

Animals↗

Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats.

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 A] 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 [51Cr]EDTA and inulin. I/R reduced GFR and increased theta for Ficoll molecules of a(e) >55 A 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.

Acute Disease↗

Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats.

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 A) 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 A). 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.

Animals↗

Transvascular protein transport in mice lacking endothelial caveolae.

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. 125I-labeled albumin, 131I-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 microl/min in control and 0.179+/-0.012 microl/min in Cav-1-KO (P=0.001) mice. IgM clearance was 0.049+/-0.003 and 0.083+/-0.010 microl/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.

Albumins↗

Increased Rho activation and PKC-mediated smooth muscle contractility in the absence of caveolin-1.

Caveolae are omega-shaped membrane invaginations that are abundant in smooth muscle cells. Since many receptors and signaling proteins co-localize with caveolae, these have been proposed to integrate important signaling pathways. The aim of this study was to test whether RhoA/Rho-kinase and protein kinase C (PKC)-mediated Ca(2+) sensitization depends on caveolae using caveolin (Cav)-1-deficient (KO) and wild-type (WT) mice. In WT smooth muscle, caveolae were detected and Cav-1, -2 and -3 proteins were expressed. Relative mRNA expression levels were approximately 15:1:1 for Cav-1, -2, and -3, respectively. Caveolae were absent in KO and reduced levels of Cav-2 and Cav-3 proteins were seen. In intact ileum longitudinal muscle, no differences in the responses to 5-HT or the muscarinic agonist carbachol were found, whereas contraction elicited by endothelin-1 was reduced. Rho activation by GTPgammaS was increased in KO compared with WT as shown using a pull-down assay. Following alpha-toxin permeabilization, no difference in Ca(2+) sensitivity or in Ca(2+) sensitization was detected. In KO femoral arteries, phorbol 12,13-dibutyrate (PDBu)-induced and PKC-mediated contraction was increased. This was associated with increased alpha(1)-adrenergic contraction. Following inhibition of PKC, alpha(1)-adrenergic contraction was normalized. PDBu-induced Ca(2+) sensitization was not increased in permeabilized femoral arteries. In conclusion, Rho activation, but not Ca(2+) sensitization, depends on caveolae in the ileum. Moreover, PKC driven arterial contraction is increased in the absence of caveolin-1. This depends on an intact plasma membrane and is not associated with altered Ca(2+) sensitivity.

Adrenergic alpha-Agonists↗

Simple cystatin C-based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan-Barratt prediction equations for children.

BACKGROUND: Serum creatinine is the most commonly used marker for estimation of glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR marker, several prediction equations including several parameters are being used, with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan-Barratt equations being the ones most widely accepted for estimation of relative GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these GFR prediction equations for adults and children might be replaced by simple prediction equations based on plasma concentrations of cystatin C. METHODS: Data from 536 patients (0.3-93 years), consecutively referred for determination of GFR by an invasive gold standard procedure, were used for the analysis. Calculations of bias (median percentage of error), correlation (adjusted R(2)), and percentage of estimates within 30% and 50% of measured GFR were used in the comparisons. RESULTS: A cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or better than the simplified MDRD, the Schwartz, and the Counahan-Barratt prediction equations for the adult (> or =18 years) and juvenile groups of the investigated cohort. Age did not influence the cystatin C-based prediction equation for adults, whereas gender did, but with a factor close to unity (0.948 for females). CONCLUSION: A GFR prediction equation based solely on cystatin C (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction equation for adults and the Schwartz and Counahan-Barratt prediction equations for children.

Adolescent↗

Lung edema formation during cold perfusion: important differences between rat and porcine lung.

BACKGROUND: The aim of this study was to investigate the effect of different perfusion pressures on edema formation during cold flush perfusion with the 2 most commonly used preservation solutions in clinical lung transplantation: Euro-Collins and Perfadex solutions. METHODS: Isolated rat and porcine lungs were perfused for 3 minutes at 4 degrees C to 8 degrees C at a pressure of either 10, 15 or 20 mm Hg. Weight gain was recorded continuously. Weight gain per minute was calculated after the first phase of rapid weight gain was completed. RESULTS: In the rat model, perfusion pressure of 10 mm Hg resulted in a macro- and microscopically apparent edema, irrespective of the type of preservation solution. Perfusion pressures of 10, 15 and 20 mm Hg have weight gains of 100%, 150% and 350%, respectively, after 3 minutes of perfusion. The corresponding weight gain per minute was 18%, 31% and 84% of the initial weight. There were no statistically significant differences in weight gain between the different solutions at equal perfusion pressure. In the porcine model the flow was extremely low at 10 mm Hg and no weight gain was registered, whereas the weight gain per minute at 15 and 20 mm Hg was 1.0% and 2.1% of the initial weight. CONCLUSIONS: In porcine lungs, cold perfusion at 20 mm Hg gives minimal edema formulation, whereas in rat lungs the edema formation is deleterious, irrespective of the solution used.

Animals↗

Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability.

Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by "crowding" experiments or measurements of intrinsic viscosity, suggest that the Ficoll molecule exhibits a rather open, deformable structure and thus deviates from an ideally hard sphere. This is also indicated from the relationship between (log) in vitro SE radius and (log) molecular weight (MW). Whereas globular proteins seem to behave in a way similar to hydrated hard spheres, polydisperse dextran and Ficoll exhibit in vitro SE radii that are much larger than those for compact spherical molecules of equivalent MW. For dextran, this can be partially explained by a high-molecular-size asymmetry. However, for Ficoll the explanation may be that the Ficoll molecule is more flexible (deformable) than are globular proteins. An increased compressibility of Ficoll and an increased deformability and size asymmetry for dextran may be the explanation for the fact that the permeability of the GCW is significantly higher when assessed using polysaccharides such as Ficoll or dextran compared with that obtained using globular proteins as molecular size probes. We suggest that molecular deformability, besides molecular size, shape, and charge, plays a crucial role in determining the glomerular permeability to molecules of different species.

Dextrans↗

Increased glomerular albumin permeability in old spontaneously hypertensive rats.

BACKGROUND: Severe long-standing hypertension is associated with an increased urinary protein excretion. METHODS: To investigate the mechanisms of this proteinuria, we measured the glomerular clearances and calculated the glomerular sieving coefficients (theta) for neutral albumin (theta(o-alb)) and for native albumin (theta(alb)) in spontaneously hypertensive rats (SHR) at the ages of 3, 9 and 14 months, in comparison with age-matched normal control Wistar rats (NCR). The hypothesis was that increases in the glomerular permeability of both negatively charged and neutral albumin would indicate a preferential size-selective dysfunction of the glomerular capillary wall (GCW), while an increased permeability to negatively charged albumin, as compared with neutral albumin, predominantly would indicate a charge-selectivity dysfunction of the GCW. A tissue (renal) uptake technique together with urinary sampling was used to assess theta. The glomerular filtration rate was assessed using the plasma to urine clearance of (51)Cr-EDTA. RESULTS: The theta(alb) in SHR increased 2.6 times at 14 months of age as compared with at 3 months, while there was no significant change of theta(alb) in NCR with age. Furthermore, the increased theta(alb) in old SHR correlated significantly with an increase in theta(o-alb) (r = 0.86, P<0.001), suggesting that albuminuria in old SHR primarily results from an increased number of rather unselective ('large') pores in the glomerular filter. CONCLUSIONS: In old age, but not at a young age, hypertensive rats develop proteinuria as a result of dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of more unselective pores.

Age Factors↗

Transvascular passage of macromolecules into the peritoneal cavity of normo- and hypothermic rats in vivo: active or passive transport?

During the last decades there has been a debate regarding whether transvascular protein transport is an active (transcytosis) or a passive (porous) process. To separate cooling-sensitive transcytosis from passive transport processes between blood and peritoneal fluid, we induced hypothermia in rats in vivo, reducing their body temperature to 19 degrees C. Control rats were kept at 37 degrees C. Either human albumin, or IgG, or IgM, or LDL, radiolabeled with (125)I, was given intra-arterially together with (51)Cr-EDTA. During tracer administration, a 2-hour peritoneal dialysis dwell was performed. Clearance of the tracers to dialysate, and the permeability-surface area coefficient (PS) for (51)Cr-EDTA and glucose were assessed. During cooling, mean arterial blood pressure (MAP) was reduced to 40% of control and plasma viscosity increased by 48.5%, while peritoneal blood flow was reduced to 10%. At 19 degrees C, clearance of albumin to dialysate fell from 9.30 +/- 1.62 (SEM) to 3.13 +/- 0.28 microl/min (p < 0.05), clearance of IgG from 6.33 +/- 0.42 to 2.54 +/- 0.12 microl/min (p < 0.05), clearance of IgM from 3.65 +/- 0.33 to 1.10 +/- 0.12 microl/min (p < 0.05), and clearance of LDL from 3.54 +/- 0.20 to 0.73 +/- 0.06 microl/min (p < 0.05). The fall in PS for (51)Cr-EDTA was from 0.320 +/- 0.01 to 0.075 +/- 0.003 ml/min (p < 0.05), and that for glucose from 0.438 +/- 0.02 to 0.105 +/- 0.01 ml/min (p < 0.05). Tissue cooling reduced large solute transport largely in proportion to the cooling-induced reductions of MAP (to 40%), and the concomitant increase in viscosity (to 67%), i.e. to approximately 20-30% (0.40 x 0.67) of control, though LDL clearance was reduced further. The fall in small solute PS, in excess of the viscosity effect, mirrored the fall in peritoneal blood flow occurring during hypothermia. In conclusion, the good correlation of predicted to calculated changes suggests that the overall transendothelial macromolecular passage in vivo occurs passively, and not due to active processes.

Albumins↗

Acute peritoneal dialysis in rats results in a marked reduction of interstitial colloid osmotic pressure.

The aim of this study was to investigate whether the interstitial colloid osmotic pressure (COP(i)) of peritoneum is of importance for peritoneal fluid reabsorption during peritoneal dialysis (PD). For testing this hypothesis, a method to isolate interstitial fluid from the peritoneal membrane and to measure the interstitial COP(i) in the normal peritoneum and directly after the initiation of PD needed to be developed and validated. Eighteen female rats were anesthetized subcutaneously in the neck region with fentanyl-midazolam (1:1). Nylon wicks were implanted postmortem by means of a plastic catheter in the tissue just underneath the peritoneal surface. The characteristics of this fluid were compared with that isolated from wicks that were implanted in intermuscular spaces in hindlimb muscle and back subcutis. All wicks were removed after 20 min and centrifuged. The wick fluid was collected and analyzed in a colloid osmometer constructed for submicroliter samples, and interstitial fluid COP was compared with that of plasma. PD was initiated by injecting 20 ml of 3.86% glucose-containing PD fluid (Dianeal) into the peritoneal cavity, over a dwell time of 4 h. Control rats received no PD. The ratio of COP(i) to that of plasma (COP(p)) during control was 0.65 +/- 0.05 in peritoneum, 0.53 +/- 0.04 in muscle, and 0.59 +/- 0.05 in skin. After a PD dwell, the ratio was 0.29 +/- 0.03 in peritoneum, 0.54 +/- 0.08 in muscle, and 0.41 +/- 0.06 in skin. Thus, the COP ratio in peritoneum fell by 55% (P = 0.014) and in skin by 30% (P = 0.03), whereas the COP ratio in muscle was unchanged. The results suggest that acute PD results in a marked fall of the COP(i) in the peritoneal membrane, shifting the Starling equilibrium toward an absorptive state. The effect was restricted to the peritoneal membrane and, to some extent, the skin. It is speculated that the increase in peritoneal hydrostatic pressure after PD causes an increase in interstitial tissue volume, with primarily a dilution of interstitial colloids.

Albumins↗

Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys.

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; (51)Cr-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) A, and the "unrestricted pore area over diffusion path length" (A(0)/DeltaX) 1.84 +/- 0.43 x 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.

Albumins↗

Mass transfer of calcium across the peritoneum at three different peritoneal dialysis fluid Ca2+ and glucose concentrations.

BACKGROUND: In peritoneal dialysis, the rate of ultrafiltration has been predicted to be a major determinant of peritoneal calcium (Ca2+) removal. Hence, dialysis fluid glucose concentration should be an important factor governing the transperitoneal Ca2+ balance. The aim of this study was to test the effect of various dialysate glucose levels and selected dialysate Ca2+ levels on Ca2+ removal in peritoneal dialysis patients. METHODS: Patients (N = 8) received, during a 7-week period, 2 L of lactate (30 mmol/L)/bicarbonate (10 mmol/L)-buffered peritoneal dialysis solutions containing either 1.5% glucose and 1.0 mmol/L Ca2+ or 2.5% glucose and 1.6 mmol/L Ca2+, or 4% glucose and 2.5 mmol/L Ca2+, respectively, provided in a three-compartment bag (trio system). Patients underwent standardized (4-hour) dwells, one for each of the three dialysates to assess permeability-surface area product (PS) or mass transfer area coefficients (MTAC) for ionized and "freely diffusible" Ca2+, lactate, glucose, bicarbonate, phosphate, creatinine, and urea. RESULTS: There was a clear-cut dependence of peritoneal Ca2+ removal on the rate of ultrafiltration. For large peritoneal to dialysate Ca2+ gradients (2.5 mmol/L Ca2+ in 4% glucose) a close fit of measured to simulated data was predicted by the three-pore model using nonelectrolyte equations. For low transperitoneal Ca2+ concentration gradients, however, directly measured Ca2+ data agreed with the simulated ones only when the peritoneal Ca2+ PS was set lower than predicted from pore theory (6 mL/min). CONCLUSION: There was a marked ultrafiltration dependence of transperitoneal Ca2+ transport. Nonelectrolyte equations could be used to simulate peritoneal ion (Ca2+) transport provided that the transperitoneal ion concentration gradients were large. Based on our data 1.38 mmol/L Ca2+ in the dialysis fluid would have created zero net Ca2+ gain during a 4-hour dwell for 1.5% glucose, whereas 1.7 and 2.2 mmol/L Ca2+ would have been needed to produce zero Ca2+ gain for 2.5% glucose and 3.9% glucose, respectively.

Biological Transport↗

Blood flow limitation in vivo of small solute transfer during peritoneal dialysis in rats.

The aim of this study was to determine whether or to what extent transperitoneal flux of small solutes is reduced at low blood flows during peritoneal dialysis (PD) in rats. Peritoneal blood flow reductions were achieved by bleeding anesthetized (300 g) rats by 25% of their blood volume. After bleeding, a 2 h PD dwell was started using standard PD fluid. The permeability-surface area product (PS) for (51)Cr-EDTA and glucose were assessed, as well as the transperitoneal clearance (Cl) of albumin. Control animals were not bled. After bleeding, peritoneal blood flow declined from 145 +/- 17 perfusion units (PU) to 59 +/- 12 PU (P = 0.001). Concomitant with this reduction, PS for (51)Cr-EDTA fell from 0.284 +/- 0.01 ml/min to 0.216 +/- 0.01 ml/min (P = 0.006) and PS for glucose from 0.338 +/- 0.02 ml/min to 0.294 +/- 0.01 ml/min (P = 0.046). Mean arterial BP (MAP) dropped from 133 +/- 4 mmHg to 61 +/- 5 mmHg (P = 0.008). Cl of albumin fell largely in proportion to the estimated capillary hydrostatic pressure drop, i.e., from 6.1 +/- 0.7 microl/min to 2.3 +/- 0.3 microl/min (P = 0.001). The results demonstrate that the transperitoneal clearances of small solutes are blood flow limited during PD, when peritoneal perfusion is markedly reduced. The level of flow limitation was, however, much lower than expected and observed in other tissues. Albumin transport, which is not blood flow limited, was reduced largely in proportion to the calculated capillary hydrostatic pressure decrease.

Animals↗

Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy.

BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall.

Adult↗