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PubMed1990

Filtration failure induced by p-aminophenol in rats is due to raised intratubular pressure and not changes in glomerular function.

1. The p-aminophenol (pAP) model of tubular necrosis displays elevated tubular pressures equivalent to 'stop-flow', with low glomerular filtration rate (GFR) but maintained blood flow and urine output. Renal function, micropuncture, and morphological studies were performed in anaesthetized rats to examine the causes of filtration failure. 2. At the height of pAP-induced renal failure proximal tubular fluid reabsorption (Jv(a] was markedly reduced while proximal and distal free-flow rates measured by tubular fluid collections during venting of the nephron were not significantly different from saline-injected controls. Renal blood flow was maintained over the 4 h observation period despite extensive and selective proximal tubular necrosis. There was no temporal relationship between increased tubular pressure and cast formation. 3. Maintained blood and tubular fluid flow rates indicate that activation of tubuloglomerular feedback plays little or no part in pAP-induced renal failure, which is apparently due to high fluid flow resistance in the region of the connecting tubule, late distal convolution or collecting ducts. Morphological appearances were consistent with compression of these segments.

Absorption↗
PubMed2006

Lean body mass-adjusted Cockcroft and Gault formula improves the estimation of glomerular filtration rate in subjects with normal-range serum creatinine.

BACKGROUND: Assessment of glomerular filtration rate (GFR) in individuals with normal-range serum creatinine is important in certain clinical situations, such as in potential living kidney donors. Accurate measurements of GFR invariably involve using an invasive method (e.g. inulin clearances), but is inconvenient. The aim of the present study was to determine whether serum creatinine-based prediction formulae adjusted for lean body mass (LBM) could improve the accuracy of GFR estimation in these subjects. METHODS: Glomerular filtration rate was determined by the clearance of technetium-99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc DTPA) from plasma in 56 subjects with normal serum creatinine. For each subject, GFR was estimated using prediction formulae +/- LBM adjustment and compared with measured GFR. Formulae analysed include Cockcroft-Gault, Levey, Gates, Mawer, Hull, Toto, Jellife and Bjornsson. RESULTS: All formulae +/- LBM adjustment underestimated measured GFR, with poor precision, poor agreement and correlation (r (2) <or= 0.25). Between 69% and 95% of the estimated GFR determined by the formulae correctly classified those with a normal measured GFR. LBM-adjusted formulae significantly improved the accuracy of GFR estimation compared with unadjusted formulae. CONCLUSION: The lean body mass-adjusted Cockcroft-Gault formula was the closest to measured GFR but is not accurate enough to replace radionuclide GFR measurement. Prediction formulae should be adjusted for LBM to improve GFR estimation.

Age Distribution↗
PubMed2006

Clinical utility of estimated glomerular filtration rates in predicting renal risk in a district diabetes population.

AIMS: To determine the utility of estimated glomerular filtration rates (eGFR) in predicting renal risk over and above currently available strategies that incorporate serum creatinine and microalbuminuria in a diabetes population. METHODS: Cross-sectional study of 4548 diabetic individuals attending a single centre over an 18-month period. Glomerular filtration rates were estimated using the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was measured using spot morning urine for albumin:creatinine ratio (ACR). SPSS was utilized for statistical analysis. RESULTS: Of the 4303 subjects with complete data, 373 (9%), 2634 (61%), 1197 (28%) and 99 (2%) individuals, respectively, had eGFR > 90, 90-60, 60-30 and < 30 ml/min per 1.73 m(2), respectively. Of those with clinically meaningful renal disease (eGFR < 60 ml/min per 1.73 m(2)), only 42% and 45%, respectively, were identified as at risk by clinical strategies utilizing serum creatinine and urine ACR individually. Even using the two together, 38% of the patients at risk would still not have been identified, since they had normal values of both. CONCLUSION: Current strategies utilizing serum creatinine and urine ACR are insufficient for the detection of renal disease in diabetes. Clinicians should consider monitoring GFR estimates in addition to assessing blood pressure, serum creatinine and urine albumin excretion in order to assess renal status and risk in adults with diabetes.

Aged↗
PubMed1989

Measurement of glomerular filtration rate in adults: accuracy of five single-sample plasma clearance methods.

After an intravenous injection of a tracer that is removed from the body solely by filtration in the kidneys, the glomerular filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of urine is not needed. In the present investigation the total plasma clearance of 51Cr-EDTA (ethylenediaminetetra-acetate) was assessed from 13 blood samples taken 5-300 min post-injection in 44 adult patients with GFR greater than 15 ml min-1. In 34 of these patients the plasma clearance of 99Tcm-DTPA (diethylenetriaminepenta-acetate) was determined simultaneously. Using these clearance values as reference the accuracy of six simplified methods were studied: five single-sample methods and one five-sample method. The standard error of estimate (SEE) of the single-sample methods ranged from 4.2 to 7.5 ml min-1 using EDTA, and from 3.8 to 6.3 ml min-1 using DTPA. SEE of the five-samples method was 3.0 ml min-1 (EDTA) and 3.1 ml min-1 (DTPA). The single-sample methods given by Christensen & Groth (1986) and by Tauxe (1986) are recommended for daily use, as SEE was small even at low GFR values. In patients with GFR less than 80 ml min-1, in whom a highly accurate determination is needed, a multiple samples method is recommended, e.g., Brøchner-Mortensen (1972).

Adult↗
PubMed1993

Biocompatibility of leukocyte removal filters during leukocyte filtration of cardiopulmonary bypass perfusate.

To evaluate the biocompatibility and the efficacy of leukocyte removal filters, we performed a prospective study by using the cardiopulmonary bypass perfusate taken from the heart-lung machine for 20 patients who underwent cardiac surgery and were randomly divided into four groups according to the filters used. A leukocyte removal filter was installed in the transfusion line while the perfusate was transfused to the patients. No increases of C3a, C5a, elastase, and thromboxane were found during leukocyte filtration by polyester filters (Optima, Sepacell R500, and Pall RC100). Activation of the complement cascade was observed during filtration by the cellulose acetate filter (Cellselect) although the efficacy of the Cellselect filter was evidently higher than that of the polyester filter. These results imply that polyester leukocyte filters are superior to cellulose acetate filters in terms of biocompatibility but have a reduced efficacy. An optimal leukocyte filter providing both high efficacy and biocompatibility has yet to be developed.

Biocompatible Materials↗
PubMed1995

A high selectivity cascade filtration technique for LDL-cholesterol and Lp(a) removal.

This work proposes an improvement of the cascade filtration technique in the treatment of familial hypercholesterolemia. A model of the whole process permitted the definition of the parameters that could influence the selectivity of the fractionation: the pore size, the sieving coefficients of both fractionation and plasmapheresis membrane, and the final retentate flow rate. In vivo studies have shown that the dead-end mode for the secondary filter was not always practical because of severe membrane plugging except when a pulsatile pump was included in the extracorporeal circuit. This pump generated hydrodynamic instabilities which decreased membrane fouling and retarded the build up of the polarization concentration layer. Optimization of these specific operating conditions permitted increase in the selectivity index from 1.15 to 2.24. The performances of cascade filtration were then comparable to those of adsorption on dextran sulfate columns.

Adult↗
PubMedDate not supplied

A new centrifugal filtration device for free drug separation.

A new centrifugal membrane filtration device (Syva Corporation) has been evaluated to determine its capabilities for separation of free phenytoin for analysis. The device is a test tube-size cylinder with two compartments separated by the membrane. In serum samples from 70 patients at the Hospital of the University of Pennsylvania, free phenytoin was prepared by the new device and by equilibrium dialysis. Levels were assayed by gas chromatography and enzyme immunoassay with good agreement at all phenytoin levels. Although pH has a significant effect on the binding of some drugs to serum proteins, phenytoin binding increased to only a small extent as pH was increased from 7.0 to 7.8 (85-88.5% bound). Centrifugal filtration with this device is a reliable, fast, and easy way to prepare free drug from serum and does not include the dilution artifact inherent in equilibrium dialysis.

Centrifugation↗
PubMed2005

Prestorage leukoreduction and low-temperature filtration reduce hemolysis of stored red cell concentrates.

BACKGROUND: Universal prestorage leukoreduction in Canada created the perception that stored red cells (RBCs) are more hemolyzed than their unfiltered predecessors. A pool-split design tested the effects of leukoreduction on hemolysis of stored RBCs. STUDY DESIGN AND METHODS: Two ABO-matched units were pooled, divided, and then processed into leukoreduced (LR) and nonleukoreduced (NLR) units with the Pall LT-WB or RC-PL systems and sampled during standard processing and storage for testing of sterility, counts, hemolysis, and osmotic fragility. RESULTS: Room temperature (RT) filtration of 10 pairs of LT-WB-LR and -NLR units showed significantly different percentage of hemolysis (0.39%) and osmotic fragility (0.643%) at 42 days. Cold-stored and -filtered units (2 days at 4 degrees C before processing) were less hemolyzed, but showed a similar proportional decrease of hemolysis in LR units (0.13% vs. 0.25% at 42 days). RBCs from RC-PL systems showed the lowest hemolysis although there was a filtration effect (0.05% vs. 0.12%, 42 days). Osmotic fragility paralleled hemolysis. Segment samples gave inaccurate results. Two-day prefiltration cold storage reduced hemolysis from 0.36 to 0.07 percent (42 days, p < 0.001). RT-LR hemolysis became significantly higher by Day 10 and 4 degrees C LR by Day 12. NLR units showed hemolysis by Day 7. LR units filtered cold were less hemolyzed (p < 0.05) than RT-LR but osmotic fragility was unchanged. CONCLUSIONS: LR-RBCs prepared by any of three methods (LT-WB, RT or cold; RC-PL), filtered at 4 degrees C, were less hemolyzed during storage than nonfiltered concentrates: 4 degrees C leukoreduction is beneficial for RBCs and does not cause hemolysis or enhance fragility.

Blood Preservation↗
PubMed1984

Glomerular filtration rate during lithium therapy. A longitudinal study.

In order to investigate the side effect of lithium on renal function the glomerular filtration rate (GFR) was measured before (to) and after a mean of 16.5 months (t1) (range 12-25 months) lithium treatment in 13 consecutive patients aged 32-67 years (mean age 46 years). The patients had a normal renal function before the treatment was started; none of them had previously been treated with lithium. During treatment GFR (ml/min) fell from 101.9 to 98.3 which was not significant. However, standard-GFR (ml/min/1.73 m2) fell from 88.4 to 84.8 (P less than 0.05) mainly due to a significant rise in body weight and estimated surface area during treatment. No significant changes appeared in plasma creatinine. It is concluded that lithium therapy for a mean of 16.5 months does not affect the glomerular filtration rate; but considerably longer observations of GFR during lithium therapy should be done by means of a reliable GFR measurement method.

Adult↗
PubMed1977

The investigation of collagen induced platelet aggregation by the screen filtration pressure technique.

A modification of the screen filtration pressure technique has been developed to allow platelet response to collagen to be measured. Using a commercial collagen suspension this method has been found to be both simple to perform and to give highly reproducible results. Changes in platelet response to collagen after administration of acetylsalicyclic acid were clearly detected and this suggests that collagen screen filtration pressure may provide a sensitive method for evaluating the effect of platelet release inhibiting drugs.

Aspirin↗
PubMed1991

Leukocyte removal filtration of platelet concentrates. A study of platelet loss using 111In-labelled platelets and dynamic gamma camera scintigraphy.

111In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the "dead space" volume within the filter. It is concluded that radiolabelled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction.

Blood Platelets↗
PubMed1983

Development of glomerular filtration rate and excretion of beta 2-microglobulin in neonates during gentamicin treatment.

Ten infants of different gestational ages (GA) and postnatal ages (PNA), treated with gentamicin, were compared with 10 control patients of similar GA and PNA to evaluate the possible nephrotoxic effects of this drug. Changes in the glomerular filtration rate (GFR) and the fractional excretion of beta 2-microglobulin in urine (FE beta) were used as indicators of renal dysfunction. In the control infants there was a postnatal increase in the GFR that was higher in full-term than in preterm infants. The FE beta decreased logarithmically as a function of both the GA and the PNA. The GFR was statistically lower in 5/10 and 6/10 of the patients on the first and the last days of gentamicin treatment (GT) respectively. Three weeks after GT, 8/10 had a normal GFR. The FE beta was statistically higher in 4/10 of the patients on their first day of GT and 7/10 on their last day of GT. Three weeks after GT, 9/10 of the patients had a normal FE beta for their postnatal and gestational ages. It is concluded that GT influences filtration and proximal reabsorption in GT infants by decreasing the GFR and increasing the FE beta. However, the observed renal dysfunction seemed to be reversible.

Beta-Globulins↗
PubMed1990

Reduced glomerular filtration and elevated urinary protein excretion in diabetic ketoacidosis.

Glomerular filtration rate (GFR) was measured by two methods in 9 children with diabetic ketoacidosis (DKA), directly by true creatinine clearance and indirectly by means of serum beta-2-microglobulin levels. We found significantly reduced GFR in the first hours of DKA. The rapid improvement in GFR after fluid and electrolyte replacement indicates that volume depletion is the major cause of low filtration rate. In spite of the reduced GFR we observed pronounced albuminuria and low molecular weight (LMW) proteinuria. We conclude that the pathological albuminuria and microalbuminuria in DKA are caused not by glomerular hyperfiltration but by tubular dysfunction.

Adolescent↗
PubMed2003

Effects of enzyme replacement therapy with agalsidase alfa on glomerular filtration rate in patients with Fabry disease: preliminary data.

UNLABELLED: Progressive deposition of globotriaosylceramide results in severe complications involving the kidney, heart and brain in both hemizygous male and heterozygous female patients with Fabry disease. Analysis of renal data from FOS--the Fabry Outcome Survey--suggests that enzyme replacement therapy with agalsidase alfa can significantly improve renal function in patients with Fabry disease, at least in those with a mild decrease in glomerular filtration rate, and may also be able to slow down the natural decline in renal function in patients with a moderate reduction in glomerular filtration rate. CONCLUSION: Initial results from the large cohort of patients within FOS indicate that treatment with agalsidase alfa has beneficial effects on kidney function in patients with Fabry disease.

Fabry Disease↗
PubMed1997

Efficacy of filtration leukocytapheresis on rheumatoid arthritis with vasculitis.

The present study was designed to determine the efficacy of filtration leukocytapheresis (LCAP) in the treatment of rheumatoid arthritis (RA) with vasculitis. Nine RA patients with vasculitis were studied by the Malignant RA Collaborative Group formed by 8 clinical centers. A total of 7 filtration LCAP procedures using the Cellsorba column (Asahi Medical Co., Ltd., Tokyo, Japan) were performed with 1 week intervals between treatments. During each apheresis procedure, 3,000 ml of blood was filtered and returned to the patient at a flow rate of 50 ml/min for 60 min. In addition to the amelioration of arthritis, the improvement of extraarticular symptoms associated with rheumatoid vasculitis such as polyneuritis, skin ulcers, digital gangrene and rheumatoid nodules was obtained. In contrast, no improvement was observed in interstitial pneumonia or lung fibrosis. LCAP could be an optional modality for the treatment of RA with vasculitis.

Adult↗
PubMed1980

Effect of isotonic volume expansion on glomerular filtration rate and renal hemodynamics in the developing rat kidney.

Young rats (20-24 days) and adult rats (40-45 days) were studied during hydropenia and volume expansion with regard to glomerular filtration rate (GFR) and the determinants of GFR. During hydropenia, GFR and renal blood flow (RBF) were significantly lower in younger than in adult rats both in absolute terms and when related to bodyweight. Equivalent degrees of volume expansion (6% of b.wt.) resulted in a much more pronounced increase in GFR and RBF in younger than in older rats. This suggests that the high renal vascular resistance in hydropenic young rats is primarily due to vasoconstriction. The relationship between the filtration rate of superficial nephrons and the total GFR was the same in hydropenic and volume expanded rats in both age groups. The tubular stop flow pressure, the calculated hydrostatic glomerular capillary pressure and ultrafiltration pressure in the afferent part of the glomerular capillaries was slightly lower in hydropenic young rats than in hydropenic adult rats. The pressures did not rise after volume expansion. It is concluded that the marked increase in GFR in volume expanded young rats is mainly due to increased renal plasma flow.

Animals↗
PubMed1980

Simultaneous measurements of capillary filtration and diffusion capacities during graded infusions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) into the rat hindquarter vascular bed.

The relationships between capillary diffusion capacity (PS) for Cr-EDTA respective capillary filtration capacity (CFC) and vascular resistance during graded intraarterial infusions of NA and 5-HT into the artificially constant flow perfused rat hindquarter vascular bed were investigated. During maximal vasodilatation PS for Cr-EDTA was some 5.5--5.7 ml/min x 100 g, CFC some 0.04 ml/min x mmHg x 100 g, while vascular resistance was 2.8 mmHg x ml-1 x min x 100 g (PRU100) and isogravimetric capillary pressure 12.8 mmHg on an average. Setting out from maximal vasodilatation, increasing doses of NA and 5-HT produced graded reductions in capillary surface area as reflected by progressive decreases in both PS for Cr-EDTA and CFC. These changes occurred simultaneously with progressive increases in both pre- and postcapillary resistances, causing elevations in both arterial and capillary hydrostatic pressures and hance in capillary fluid filtration at constant flow. Capillary hydrostatic pressure increased maximally to 45 mmHg (calculated for NA) and vascular resistance to some 21 mmHg x ml-1 x min x 100 g on an average. PS for Cr-EDTA decreased maximally to some 0.7--1 ml/min x 100 g for both NA and 5-HT and furthermore, the relationships between PS for Cr-EDTA and PRU100 for NA respective 5-HT were almost identical. This was taken to indicate that capillary surface area for nutritional exchange is affected similarly by both drugs. However, the CFU-PRU100 relationship was shifted towards some 30--50% higher CFC values for 5-HT than for NA at almost every level of vasoconstriction. This might suggest that 5-HT besides reducing capillary surface area also induced moderate increases in capillary permeability though increases in number and/or radius of large pores (gaps) (cf. Rippe, Kamiya & Folkow 1978). Even during NA-induced vasoconstriction, when virtually no changes in capillary permeability occurred, PS for Cr-EDTA was reduced to a relatively greater extent than CFC, the discrepancy being most pronounced during marked vasoconstriction. The significance of this finding is discussed.

Animals↗
PubMed1984

The influence of tubulo-glomerular feedback on the autoregulation of filtration rate in superficial and deep glomeruli.

Single nephron glomerular filtration rate (SNGFR) of superficial and juxtamedullary nephrons were measured at normal and reduced perfusion pressure in the left kidney of young Sprague Dawley rats. Perfusion pressure was lowered by constricting the aorta proximal to the branching of the left renal artery. The influence of the tubulo-glomerular feedback mechanism on SNGFR was quantitated by measuring SNGFR during intact and interrupted urine flow to the macula densa region. By using a modified Hanssen technique, SNGFR was measured under free-flow conditions. In other experiments, the urine flow to the distal nephron was blocked by a micropuncture technique, which was used for collection of the tubular fluid for measuring the filtration rate. All nephron populations autoregulated SNGFR from 70-80 to 130 mmHg, which was the upper limit of this investigation, when urine flow throughout the nephron was intact. The autoregulation in this pressure range was lost when tubular fluid was prevented from reaching the distal nephron. It was shown that the influence of negative feedback on SNGFR by the macula densa mechanism at normal blood pressure is greater in deep nephrons than in superficial ones.

Animals↗