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PubMed1979

Renal autoregulation of blood flow and filtration rate in the rabbit.

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40-110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.

Animals↗
PubMed1981

Effects of glomerular filtration dynamics on the glomerular permeability coefficient.

Studies were performed in Munich-Wistar rats (n = 24) to determine if the glomerular permeability coefficient (LpA) is affected by changes in the systemic oncotic pressure (pi A) as well as other determinants of glomerular filtration [nephron plasma flow (RPF) and glomerular hydrostatic pressure gradient (delta P)] and systemic hematocrit (Hct). Multiple regression analysis was used to separate the respective relationships of pi A, delta P, RPF, and Hct to LpA to ascertain whether the correlation of LpA to these variables was direct or mediated by some concurrently changing factor. Three two-period protocols were used to examine the changes of these determinants of filtration: 1) hydropenia to 10% body wt saline expansion (SE), 2) SE to 1% body wt of concentrated rat plasma protein (25 g/100 ml) solution (HP) with removal of 1.5% body wt whole blood, and 3) SE to 1% body wt HP with 2.5% body wt whole blood removed with reinfusion of the removed erythrocytes. Changes in LpA correlated directly with changes in pi A (P less than 0.01) and inversely with delta P (P less than 0.01). There was no direct correlation of LpA to RPF or consistent correlation of LpA to Hct.

Animals↗
PubMed1981

Measurement of nephron filtration in the dog: role of proximal intratubular pressure.

Previous studies concerning the measurement of single nephron filtration rate have shown that collections of proximal tubular fluid, in which an oil drop is held in a constant position, do not affect intratubular pressure in the early proximal tubule in the hydropenic rat. Since intratubular pressures are higher in the dog than the rat, we investigated the effect of position-controlled collections on proximal pressure and single nephron filtration rate (SNGFR) in the dog. During position-controlled collections, early proximal pressure fell 5.8 +/- 0.9 mmHg and SNGFR was 76.3 +/- 5.3 nl/min. During proximal re-collections, in which proximal pressure was maintained near the free-flow value using a long immobile oil block, SNGFR was significantly less, 44.4 +/- 5.5 nl/min. For each micropunctured kidney, SNGFR was also estimated by dividing GFR by the number of glomeruli (mean, 5.4 +/- 0.5 X 10(5)). Estimated SNGFR (50.9 +/- 6.3 nl/min) was not significantly different from pressure-controlled SNGFR but was significantly less than position-controlled SNGFR. Accordingly, in the dog, early proximal pressure decreases during position-controlled collection of proximal tubular fluid, resulting in an overestimation of SNGFR. This artifact can be avoided by controlling the intratubular pressure during collection of tubular fluid.

Animals↗
PubMed1985

Effects of Ringer fluid on regional blood flow and filtration rate in the cat kidney.

The larger subcapsular veins of the in situ cat kidney were cut open near the hilus and occluded between the slits and the common renal vein, thus permitting separation and direct measurement of venous outflows from the superficial (outer cortex) and deep (inner cortex plus medulla) drainage area. The direct recording of venous outflow in the two areas combined with plasma inulin and protein analyses provided consecutive determinations of the rate of glomerular filtration and arterial inflow of both areas. Our primary result is the demonstration of a regional difference in the renal response to extracellular isotonic volume expansion. Infusion of Ringer fluid at a moderate rate (1.0-2.0 ml X min-1) increased both blood flow (RBF) and glomerular filtration rate (GFR) in both areas; however, the RBF response was proportionately greater in the deep area and the GFR response was proportionately greater in the superficial area. Compared with a noninfused control series, statistically significant differences occurred after about 1 h of infusion. After 80 min, average RBF had increased by 33 and 20%, while average GFR had increased by 31 and 54% in the deep and in the superficial areas, respectively. To reveal direct renal effects of the Ringer fluid, the site of infusion was shifted alternately between the renal artery and the jugular vein. The results suggest that the changes in blood flow are elicited indirectly by neural or humoral mechanisms.

Animals↗
PubMed1986

Atrial natriuretic factor can increase renal solute excretion primarily by raising glomerular filtration.

Controversy persists on whether atrial natriuretic factor (ANF) raises renal solute excretion simply by increasing glomerular filtration rate (GFR) or whether it directly inhibits tubular transport (independent of changes in flow rate). Free-flow micropuncture techniques were used in 10 Munich-Wistar rats. ANF caused a significant increase in single-nephron and whole-kidney GFR (41.6 +/- 1.4 to 52.7 +/- 2.3 nl/min and 0.95 +/- 0.05 to 1.24 +/- 0.09 ml/min, respectively). Although absolute proximal sodium, bicarbonate, and chloride reabsorption increased, the increment in reabsorption was less than the increase in load; therefore solute delivery out of the proximal tubule increased by approximately 30-35%. Whole-kidney electrolyte excretion also rose markedly. When single-nephron and whole-kidney GFR were reduced back to a control level by aortic constriction (40.2 +/- 1.8 nl/min and 0.93 +/- 0.05 ml/min, respectively), proximal transport reverted to normal values despite persistent ANF administration. Ninety percent of the ANF-induced natriuresis and chloruresis were simultaneously abolished when GFR was normalized. In conclusion, ANF has no direct effect on reabsorption in the superficial proximal convoluted tubule independent of changes in filtration rate. Although direct effects on more distal or deeper nephron segments are not precluded, the present data suggest that ANF can increase renal solute excretion predominantly by acutely augmenting GFR.

Animals↗
PubMed1986

Adenosine alters glomerular filtration control by angiotensin II.

This study was designed to test the hypothesis that high renal levels of adenosine (ADO) may alter glomerular filtration rate (GFR) control by angiotensin II (ANG II). In normal kidneys, ANG II infusion (20 ng X kg-1 X min-1 iv) decreased renal blood flow (RBF) to 61 +/- 3% of control, increased filtration fraction (FF) to 173 +/- 21% of control, and did not change GFR significantly. During intrarenal ADO infusion at a rate of 1.0 mumol/min, ANG II (20 ng X kg-1 X min-1 iv) decreased RBF and GFR to 61 +/- 5 and 64 +/- 6% of control, respectively. After blocking changes in tubuloglomerular feedback by occluding the ureter during mannitol diuresis, ANG II increased stop-flow pressure and postglomerular resistance (RPG) markedly but did not alter preglomerular resistance (RA), suggesting that the direct actions of circulating ANG II are confined primarily to efferent arterioles in the absence of changes in tubuloglomerular feedback. However, during intrarenal ADO infusion and inhibition of tubuloglomerular feedback, ANG II decreased stop-flow ureteral pressure and raised RA and RPG to 213 +/- 27 and 155 +/- 7% of control, respectively, while decreasing RBF to 59 +/- 5% of control. These observations suggest that ADO markedly alters the control of GFR by ANG II, possibly by causing ANG II to constrict preglomerular vessels, an effect that is not apparent in most physiological conditions but which could play a role in lowering GFR when renal ADO and ANG II levels are both elevated, as in severe renal ischemia.

Adenosine↗
PubMed1988

Contribution of dopamine 2 receptors to dopamine-induced increase in glomerular filtration rate.

The effects of the interaction of dopamine (DA) and the DA2 receptors on glomerular filtration rate (GFR) has been studied by means of micropuncture technique in adult greater than or equal to 60-day-old and young 24-day-old rats. Most of the studies were performed in rats with intact adrenergic nervous systems to allow for evaluation of the presynaptic DA2 receptors. In adult and young rats, DA and LY-171555 (LY), a selective DA2 receptor agonist, induced prompt and significant increases in the single nephron (SN) GFR. Further studies were performed only in adult rats. The LY-induced increase in SNGFR was completely abolished during DA2 receptor blockade with S-sulpiride (S-SP), while the DA-induced increase in SNGFR was attenuated but still significant during S-SP treatment. Both DA and LY significantly increased the glomerular ultra-filtration pressure (PUFAA). In rats with ganglionic blockade, the LY-induced increase of SNGFR was attenuated but still significant, whereas the DA-induced increase was less affected. The results imply that DA significantly increases GFR by interacting with the DA2 as well as with the DA1 receptors. Interaction between DA and the DA2 receptors increases PUFAA. The results do not rule out the existence of both pre- and postsynaptic renal DA2 receptors.

Animals↗
PubMed1989

Does the ultrafiltration coefficient play a key role in regulating glomerular filtration in the rat.

Various experimental maneuvers, hormones, and pharmacological agents are reported to exert their effects on glomerular filtration largely or exclusively by changing the ultrafiltration coefficient (Kf) of the filtration barrier. In light of a number of uncertainties discussed in this review, however, it is by no means certain that the Kf actually does play this central role in the physiological regulation of glomerular function.

Animals↗
PubMed1989

Effect of angiotensin II infusion on the human glomerular filtration barrier.

Angiotensin II (ANG II) infusion has been reported to impair barrier size selectivity and exacerbate proteinuria in the rat. To examine whether this is also true of humans, we infused a pressor dose of ANG II into seven healthy controls and seven nephrotic patients. A prompt depression of glomerular filtration rate (GFR) and renal plasma flow was observed in each group (P less than 0.01). Surprisingly, the excretion rates of albumin (5.3 +/- 1.6 to 2.8 +/- 0.3 in controls and 4,791 +/- 1,244 to 3,833 +/- 800 micrograms/min in nephrotics) and immunoglobulin G (1.5 +/- 0.4 to 0.8 +/- 0.2 and 305 +/- 87 to 255 +/- 94 micrograms/min, respectively) fell significantly during ANG II infusion. Fractional clearances of dextrans of broad size distribution (radii 34-54 A) were uniformly elevated by ANG II infusion in controls but tended to decline in nephrotics. A heteroporous model of the glomerular capillary wall revealed ANG II to have a negligible effect on membrane-pore structure. However, the depressed GFR lowered the rate at which macromolecule-rich filtrate was formed through a subset of nondiscriminatory pores from 272 to 176 microliters/min in controls and from 394 to 334 microliters/min in nephrotics. We conclude that, in striking contrast to the rat, pressor ANG II infusion has little or no influence on barrier size selectivity in humans but exerts an antiproteinuric effect by lowering the filtered protein load.

Adult↗
PubMed1991

Analysis of pulsatile pressures and flows in glomerular filtration.

Previous mathematical models of glomerular filtration have ignored the pulsatility of the glomerular capillary pressure, using only steady-state equations and time-averaged pressures and flows. Because the actual pressure pulses are rapid and of large amplitude and because the governing equations are nonlinear, it is questionable whether the effects of the pressure pulses average out in the manner that has been assumed. We have developed a model that includes sinusoidal variations in the glomerular transcapillary hydraulic pressure (delta P) and the afferent arteriolar plasma flow rate over each cardiac cycle. The analysis suggests that the previously ignored time derivatives in the luminal mass balance equations are not negligible. The amplitude of the oscillations in delta P was found to be sufficient to reverse the direction of the transmural fluxes over part of each cardiac cycle, at the more efferent locations in a capillary. However, the time-averaged values of single-nephron glomerular filtration rate and sieving coefficients for macro-molecules from the pulsatile model differed from that for a steady-state formulation by less than 0.1 and less than or equal to 10%, respectively. We conclude that use of the usual steady-state assumption introduces negligible errors in calculating glomerular membrane parameters from experimental data.

Animals↗
PubMed2001

Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules.

The effect of shape on the transglomerular passage of solutes has not been hitherto systematically studied. We perfused isolated rat kidneys to determine the fractional clearances (theta) at various filtration rates for four molecules of different shapes but with similar Stokes-Einstein radii (aSE = 34-36 A). The theta for hyaluronan, bikunin, and Ficoll36 A were 66, 16, and 11%, respectively, at a glomerular filtration rate (GFR) of 0.07 ml x min(-1) x g wet wt(-1) and decreased to 46, 14, and 7%, respectively, on a fivefold increase in GFR. Under the same conditions, theta for albumin increased from 0.15 to 0.74%, and similar behavior was observed for larger Ficolls (aSE >45 A). Pore analysis showed that the "apparent neutral" solute radii of Ficoll, albumin, bikunin, and hyaluronan were 35, 64, 33, and 24 A, respectively, despite similar aSE. In addition, the properties of the glomerular filter changed with increasing GFR and hydrostatic pressure. We conclude that elongated shape, irrespective of size and charge, drastically increases the transglomerular passage of a solute, an effect that is related to its frictional ratio.

Albumins↗
PubMed1985

Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes.

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.

Animals↗
PubMed1991

Filtration-assisted exchange transfusion using alpha alpha Hb, an erythrocyte substitute.

A method for improving the efficiency of exchange transfusion to evaluate hemoglobin- (Hb) based erythrocyte substitutes is described. The method uses a continuous-flow hollow-fiber plasma separation filter to remove the erythrocytes while returning 75% of the plasma. The removed volume was replaced with a 14-g/dl solution of human Hb cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb). Filtration of 2.76 blood vol in anesthetized swine resulted in a 95% reduction of hematocrit and produced a plasma Hb concentration of 7.63 g/dl. Hyperoncotic Hb solutions cause volume expansion, which reduces the efficiency of exchange but provides hemodynamic stability in the face of decreasing blood viscosity and subsequent intravascular volume loss with Hb redistribution. Filtration-assisted exchange transfusion is rapid, conserves valuable modified Hb, and ensures continuous adequate oxygen delivery.

Animals↗
PubMed1992

Alterations of filtration coefficients in pulmonary edema of different pathogenesis.

Different pathomechanisms in the development of pulmonary edema are being discussed. We investigated the effect of pathogenetically varying forms of edema on lung vascular barrier function in isolated cell-free perfused rabbit lungs. As an index of permeability, capillary filtration coefficients (Kfc) were determined from the slope of lung weight change over periods of stepwise venous pressure elevation (5, 7.5, and 10 mmHg) before (controls) and 60 min after edema induction. Edema was induced by venous congestion (n = 6), by application of arachidonic acid in the presence of diclofenac sodium (n = 6), and by elastase application (n = 6). Control values ranged from 0.28 to 0.51 ml.min-1 x mmHg-1 x 100 g-1. Kfc was significantly enhanced after edema induction up to 243% of control value in the hydrostatic edema, 357% in the arachidonic acid edema, and 594% in the elastase edema. When the alterations in capillary filtration due to the different types of edema were compared, Kfc was significantly higher in the proteinase edema, indicating an irreversibly damaged barrier function. These data exemplify different pathophysiological characteristics due to the pathogenesis of interstitial edema formation.

Airway Resistance↗
PubMed1999

Preparation of leukodepleted platelet concentrates from pooled buffy coats: prestorage filtration with Autostop BC.

BACKGROUND AND OBJECTIVES: Our requirements for leukocyte-depleted platelet concentrates (LD-PC) for an adult patient are: platelets >240x10(9), leukocytes <5x10(6), volume of 150-400 ml; and at the end of storage a pH between 6.8 and 7.4 and presence of the swirling effect. Our aim was to develop a standardized, semiautomated method for the production of LD-PC, by pooling of buffy coats (BC), and prestorage leukoreduction by filtration. MATERIALS AND METHODS: Whole blood was collected in Top and Bottom systems, and separated automatically with the Compomattrade mark G3 equipment into a red cell concentrate, a plasma and a BC. Subsequently, a pool of 5 BC was made, and 200 g plasma from one of the donors was added. Then, after soft spin centrifugation, the platelet rich plasma was leukocyte depleted by filtration using the Autostoptrade markBC filter, and stored in a 1,000 ml polyolefin platelet storage bag. RESULTS: BC (n = 60) had a volume of 51+/-2 ml (mean +/- SD) with a hematocrit of 0.44+/-0.03 l/l and contained 80+/-5% of the platelets and 74+/-12% of the leukocytes of the whole blood. Routinely prepared LD-PC (n = 15,037) contained a median of 341x10(9) platelets (range 49-599x10(9)), with only 104/15,037 (0.7%) containing fewer than 240x10(9) platelets; the median volume was 263 ml (range 134-373 ml). In 118/917 (13%) LD-PC leukocytes were observed in the Nageotte hemocytometer, but only twice exceeding 1x10(6) leukocytes per unit, and none exceeding 5x10(6) (median <0. 6x10(6); range <0.6-1.41x10(6)). Storage experiments of the LD-PC (n = 12) revealed adequate oxygenation and maintenance of pH and swirling effect up to 9 days. CONCLUSIONS: This method warrants with 99% confidence that LD-PC contain more than 240x10(9) platelets; with 97.5% confidence that 100% of the LD-PC contain <5x10(6) leukocytes, and with 95% confidence that more than 99% of the LD-PC contain fewer than 1x10(6) leukocytes; these LD-PC can be stored satisfactorily for up to 9 days.

Automation↗
PubMed2000

Evaluation of leukocyte-depleted platelet concentrates obtained by in-line filtration.

BACKGROUND AND OBJECTIVES: The use of leukocyte-depleted platelet concentrates (PCs) is justified, yet questions remain regarding their properties. We have assessed the in vitro quality of WBC-reduced PCs obtained by using a new in-line filter. MATERIALS AND METHODS: Twenty blood units were randomized for standard component preparation, or for processing including in-line leukodepletion of platelet-rich plasma using an ATS(TM) PL Pall filter. The resultant PCs were compared during storage for several in vitro platelet quality parameters, content of cytokines and anaphylatoxins, and coagulation markers. RESULTS: In-line filtration of platelet-rich plasma through ATS PL was highly efficient rendering PCs with 99.93% less white blood cells (WBCs) than standard PCs. During storage for up to 9 days, leukocyte-depleted units displayed platelet content, biochemical parameters, and platelet surface expression of glycoproteins Ibalpha, IIb/IIa, CD62 and CD63, similar to those of standard units. However, in-line leukocyte-reduced PCs displayed no significant accumulation of IL-6 and IL-8 during storage in contrast to standard units. Moreover, while storage promoted complement activation with C3a and C4a liberation in both WBC-reduced PCs and standard units, the concentration of these anaphylatoxins after the 9-day storage period was higher in the former group. Finally, all units, standard and leukocyte-reduced, displayed a similar storage-promoted rise in TGF-beta(1), and a mild prolongation of activated partial thromboplastin and prothrombin times. CONCLUSION: In-line filtration during component preparation appears as an easy and effective procedure for obtaining prestorage leukocyte-depleted PCs. During subsequent blood bank storage, these WBC-reduced PCs display, in comparison with standard PCs, normal in vitro platelet properties, decreased accumulation of cytokines IL-6 and IL-8, and increased complement activation.

Anaphylatoxins↗
PubMed2003

Cystatin C as an endogenous marker of glomerular filtration rate in renal transplant patients.

BACKGROUND: Serum creatinine is the most common endogenous marker used to estimate the glomerular filtration rate (GFR). However, creatinine depends considerably on muscle mass, and its tubular secretion increases, especially in chronic renal failure. Cystatin C is a 13-kD protease inhibitor which is produced by all nucleated cells and is independent of muscle mass and sex. Cystatin C is eliminated by glomerular filtration and metabolized by proximal tubular cells. Its measurement has been proposed as an alternative and more sensitive marker of GFR than creatinine in patients with slight to moderately decreased GFR. METHODS: We investigated serum cystatin C levels in comparison with creatinine as a single measurement for estimation of GFR in 173 patients after renal transplantation. GFR was calculated as creatinine clearance according to standard equations. RESULTS: Serum creatinine correlated well with cystatin C (r = 0.84; p < 0.0001). No significant differences were obtained for the comparison of the linear correlation of 1/creatinine with creatinine clearance (r = 0.77; p < 0.0001) and for the linear correlation of 1/cystatin C with creatinine clearance (r = 0.73; p < 0.0001). However, we found a significant advantage of cystatin C in detecting a clinical relevant reduction of kidney function (GFR <70 ml/min; p = 0.0047, McNemar test). CONCLUSION: Cystatin C is an alternative marker for the assessment of GFR in renal allograft recipients that may be superior to creatinine.

Adult↗
PubMed2005

Assessing suitability for renal donation: can equations predicting glomerular filtration rate substitute for a reference method in the Indian population?

BACKGROUND: Accurate measurement of donor renal function has important long-term implications for both the donor and recipient. As the use of recommended filtration markers is limited by cumbersome and costly techniques, renal function is typically estimated using 24-hour urinary creatinine clearance (urine-CrCl). Prediction equations used for rapid bedside estimation of glomerular filtration rate (GFR) are simple and overcome the inaccuracies of urinary collection and, if validated, can expedite the donor workup besides reducing the cost. We assessed the suitability of urine-CrCl and prediction equations for evaluating potential Indian renal donors. METHODS: 173 consecutive renal donors were enrolled. The predictive capabilities of the Cockcroft and Gault equation for creatinine clearance (CrCl) corrected for body surface area (CG-CrCl), CG-CrCl corrected for GFR (CG-GFR), MDRD-1, MDRD-2 and urine-CrCl were evaluated with 99mTc-diethylenetriaminepentaacetic acid (DTPA)-GFR as reference GFR. RESULTS: The study population had a mean age of 44.1 years with 74% being females. Mean DTPA-GFR was 83.85 ml/min/1.73 m2. The median percent absolute difference was most with urine-CrCl and least with CG-GFR (21.84 and 13.82). The Pearson's correlation varied from 0.08 to 0.26 (urine-CrCl and MDRD-1). The precision was most with MDRD-1 and least with urine-CrCl (0.07 and 0.01). The bias was least with CG-GFR and most with MDRD-2 (1.34 and 17.16). The number of subjects with predicted GFR values within 30% of DTPA was most with MDRD-1 (86%) and least with urine-CrCl (69%). The sensitivity for selecting a donor with a GFR of > or = 80/ml/min/1.73 m2 was the most with CG-GFR (65.7%), while specificity was maximum with MDRD-2 (90.1%). CONCLUSION: Our results in potential Indian renal donors show that of all the prediction equations MDRD-1 is the most precise and accurate, while CG-GFR is the least biased. However, the poor correlation and level of error exhibited by these equations makes them suboptimal for donor evaluation.

Adult↗