Blood flow, ultrafiltration and solute transport rate in continuous arteriovenous haemodiafiltration: the AN-69 flat-plate haemofilter.

We measured blood flow, ultrafiltration rate and uraemic solute clearance at different dialysate flow rates during CAVHD using the AN-69 0.43 m2 flat plate haemofilter. As filter performance depends on clinical conditions and operational characteristics, data were analysed in terms of resistance to blood flow, membrane index of ultrafiltration, and diffusive mass transfer coefficients. An attempt was made to construct nomograms that may be used both to predict filter performance and to compare different haemofilters with each other.     

Treatment of acute renal failure in an infant by continuous arteriovenous hemodialysis

Continuous arteriovenous hemodialysis (CAVHD) was performed in a critically ill, oliguric infant with progressive uremia using a miniature Amicon hemofilter. Modification was made in the filter system by circulating 2.5% Dianeal peritoneal dialysis fluid into the second port of the ultrafiltrate compartment to enable the filter to function by dialysis too (CAVHD). In comparison with continuous arteriovenous hemofiltration (CAVH), CAVHD provided superior urea clearance and adequate fluid removal, allowing the simultaneous administration of parenteral nutrition. The higher solute clearances in CAVHD make the technique superior to CAVH for renal replacement therapy in critically ill infants.     

Continuous Arteriovenous Haemofiltration and Haemodiafiltration in Acute Renal Failure

Continuous arteriovenous haemofiltration (CAVH) was employedin ten patients with acute renal failure using an AN-69 platefilter. Special measures were taken to improve the efficiencyof the technique, including the use of short, large-bore cathetersfor vascular access, predilution infusion of the substitutionfluid, and moderate vacuum suction to the ultrafiltrate compartment.In five patients continuous arteriovenous haemodiafiltrationwas performed by the addition of slow dialysis at a dialysateflow of 1 litre per hour. This technically simple manoeuvreenhanced solute clearances up to 20 ml/min and obviated theneed for standard intermittent dialysis sessions in all cases. Repeated measurements of transmembrane pressure and ultrafiltrationrate permitted calculation of the in vivo membrane permeabilityindex, which showed a reproducible decline with time. With relativelylow heparin requirements an adequate filter performance couldbe maintained for over 48 h. The encouraging clinical resultsindicate that CAVHD, in spite of the invasive nature of thistechnique, may be considered a first-choice treatment for patientswith acute renal failure in the intensive care unit.     

Continuous arteriovenous haemodialysis and haemofiltration in intensive care acute renal failure patients

CAVHD and CAVH were compared regarding uraemic control in 13 critically ill intensive care patients with acute renal failure (ARF). Patients’ mean age was 60 years. Pretreatment blood urea range was 17–56 mmol/l (33–56 mmol/l in 70% of the patients). All patients received vasopressor drugs, and 92% were on artificial mechanical respiration. From the results of this study both modalities gave adequate uraemic control. There was a notable decrease in the urea and creatinine levels with CAVHD more than with CAVH. There was no statistically significant difference between the two modalities in the urea clearance. However, a significant difference (P<0.05) in creatinine was obtained with CAVHD. Our results suggest that CAVHD is a useful alternative to CAVH in ARF especially when the blood urea level is >30 mmol/l. However, a higher dialysate flow rate (e.g. 25 ml/min) should be used if the urea level is more than 40 mmol/l. CAVH should be reserved for ARF patients in whom fluid overload is a major problem.     

Continuous arteriovenous hemofiltration: in vivo functional characteristics and its dependence on vascular access and filter design

The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Introduction of percutaneous arteriovenous femoral shunt: a new access for continuous arteriovenous hemofiltration

In most critically ill unstable patients, continuous arteriovenous hemofiltration (CAVH) and continuous arteriovenous hemofiltration with dialysis (CAVHD) offer significant advantages over dialysis and ultrafiltration. Improvements in CAVH methodology have occurred since its introduction, but an ideal vascular access has yet to be designed. Scribner shunts may result in loss of a future access site, while femoral artery and vein catheterization render the patient immobilized. We have developed a percutaneous external arteriovenous femoral shunt to overcome this difficulty. The catheter consists of two single-lumen flexible polyurethane catheters with a subcutaneous Dacron cuff. A percutaneous Seldinger technique is used with a peel-away sheath to insert one catheter in the artery and one in the vein. To minimize infection and ensure durability, a 10-cm tunnel is created so that the exit of the catheters on the upper thigh is away from the groin. Like the Scribner shunt, a connecting tube is used between the catheters to maintain the patency when the shunt is not in use. Our experience with this technique is limited to seven treatments in seven patients (five CAVH, two CAVHD). Good blood flow (average, 80 mL/min), ultrafiltration rate (7 mL/min), and biochemical studies demonstrated the efficiency of the access. The average treatment was 10 days and patients were allowed to do moderate movement without resulting thrombosis or infection of the access. The major advantages of this new and efficient access for CAVH and CAVHD include simple introduction by a nephrologist, lack of potential serious complications, avoidance of sacrifice of major vessels, early ambulation and movement without compromising function, and a design for prolonged usage.     

Continuous arteriovenous renal replacement systems for critically ill children

Five different arteriovenous renal replacement systems were used to treat 23 critically ill oliguric or anuric children. Slow continuous ultrafiltration (SCU) was carried out for 8 patient days, continuous arteriovenous haemofiltration (CAVH) for 40, suction-supported CAVH for 56, continuous or intermittent arteriovenous haemodiafiltration (AVHDF) for 3, and continuous arteriovenous haemodialysis (CAVHD) for 24 days. SCU allowed excellent control of fluid overload in 4 patients within 47±17 h. Urea clearances ranged from 5.6±2.1 ml/min per m² (spontaneous CAVH) to 15.3±3.7 ml/min per m² (CAVHD) and enabled good control of azotaemia. Ultrafiltration rates of the different filters ranged from 1.6±0.3 to 11.5±2.4 ml/min per m². The only serious complication was a femoral artery thrombosis in a 1.5-year-old boy. Minor side-effects were local bleeding at the entrance site of the arterial catheter and transient hypotension during suction-supported CAVH. Of 23 patients, 8 died because of progressive multiple organ system failure, a mortality of 35%.     

Continuous arteriovenous hemofiltration: an in vitro simulation and mathematical model

In vitro and mathematical models of continuous arteriovenous hemofiltration (CAVH) have been developed. Human erythrocytes resuspended in normal saline containing 5% bovine albumin were used to perfuse the circuit from a gravity driven pressure source. Membrane hydraulic permeability was observed to decline from 31.2 x 10(-5) +/- 11.9 x 10(-5) cm/(min.mm Hg) before use to 12.3 x 10(-5) +/- 3.3 x 10(-5) (mean +/- SD) after use. This fall occurred during the first one to two hours whether perfused with blood or 5% albumin alone. Pressure-flow relationships of each circuit component, measured with 40% sucrose as a calibration medium, conformed to Poiseuille's equation. Use of high resistance blood access on the venous end of the circuit resulted in a low blood flow rate and high filtration fraction. The same access, when placed on the arterial end, produced both low blood flow rate and low filtration fraction. These results were a consequence of pressure distribution within the circuit as demonstrated by measurements of perfusion, prefilter, and postfilter pressures. The importance of negative pressure applied to the filter chamber in order to maintain favorable Starling forces, when the system was operated with a small bore arterial access, was demonstrated by similar methods. Enhancement of urea clearance by predilution was verified. Model simulations suggest that predilution will be of less benefit or even detrimental for other solutes which fail to distribute across the erythrocyte membrane. Comparison of results with predictions of a mathematical model demonstrated good agreement, but with some tendency to overestimate filtrate production. The latter was attributed to neglect of concentration polarization of plasma proteins in model development.     

Continuous arteriovenous hemodiafiltration in the acute treatment of hyperammonaemia due to ornithine transcarbamylase deficiency

BACKGROUND: Acute hyperammonemia caused by urea cycle disorder is a medical emergency for which immediate managements should be taken to minimize permanent brain damage. Among different enzyme defects, ornithine transcarbamylase deficiency (OTC) is one of the most common enzyme defect in urea cycle disorders. We utilized continuous renal replacement therapy techniques in the acute treatment of hyperammonemia due to ornithine transcarbamylase deficiency. PATIENTS AND METHODS: Three male neonates with elevated serum ammonia levels were shown, based on urine organic acid analysis and serum amino acid studies, to have OTC deficiency. Administration of sodium benzoate and sodium phenylacetate for activating alternative nitrogen waste pathway were used associated with protein restriction. Other modalities, including blood exchange transfusion, peritoneal dialysis, continuous renal replacement therapy were utilized in an attempt to lower serum ammonia concentration. RESULTS: We report the successful use of continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), continuous arteriovenous hemodiafiltration (CAVHDF) in the acute management of hyperammonemia due to OTC deficiency. We also compared the ammonia clearance between peritoneal dialysis, exchange transfusion, CAVH, CAVHD and CAVHDF. It demonstrated the evidence that CAVHDF provides the best ammonia clearance. CONCLUSION: Continuous renal replacement therapy including CAVH, CAVHD, and CAVHDF may be the alternative techniques for acute management of hyperammonemia in inborn error of metabolism when dialysis machine is not available. Our data suggests CAVHDF provides the best ammonia clearance.     

Continuous arteriovenous haemofiltration in the newlyborn with acute renal failure and congenital heart disease

Newlyborn infants with congenital heart disease who develop acute renal failure are particularly difficult to treat. There are often complex associated medical problems and the mortality is high. Continuous arteriovenous haemofiltration (CAVH) provides a slow and gentle removal of fluid, together with the possibility of correcting metabolic abnormalities. We used CAVH in six newlyborn infants all with severe congenital heart disease, who developed acute renal failure early in life. In four patients it was necessary to insert a blood pump into the circuit to maintain adequate blood flow. CAVH alone, with or without a blood pump, was unable to reduce the plasma urea and creatinine, and in three of the infants, dialysis across the filter was required. CAVH was effective in controlling fluid balance. Although mortality remains high we feel CAVH has an important role in selected patients.     

Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Pharmacokinetics of cefuroxime and ceftazidime in patients with acute renal failure treated by continuous arteriovenous haemodialysis.

To determine appropriate doses of cefuroxime and ceftazidime for septic patients with acute renal failure (ARF) treated by continuous arteriovenous haemodialysis (CAVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received cefuroxime 500 mg (n = 11) or 750 mg (n = 1), or ceftazidime 500 mg (n = 9) i.v. 12-hourly and all studies were done at steady-state. For cefuroxime, volume of distribution (Vdarea) was 22.8 +/- 3.5 l, terminal elimination half-life (t1/2) 12.6 +/- 2.2 h and total body clearance (TBC) 22.3 +/- 3.0 ml/min (mean +/- SEM). Mean sieving coefficient (SC) was 0.90 +/- 0.12 and filter clearances at Qd 1 and 2 l/h were 14.0 +/- 2.3 and 16.2 +/- 3.4 ml/min respectively. For ceftazidime, Vdarea was 31.1 +/- 6.5 l, t1/2 14.7 +/- 3.3 h, and TBC 24.8 +/- 0.8 ml/min. Mean SC was 0.86 +/- 0.03, and filter clearances at Qd 1 and 2 l/h 13.1 +/- 1.2 and 15.2 +/- 1.5 ml/min. Satisfactory plasma concentrations of both antibiotics were maintained in all patients during treatment. These data suggest that cefuroxime 500-750 mg and ceftazidime 500 mg 12-hourly are suitable doses for patients with ARF treated by CAVHD.     

CONTINUOUS ARTERIOVENOUS HEMODIAFILTRATION IN THE ACUTE TREATMENT OF HYPERAMMONAEMIA DUE TO ORNITHINE TRANSCARBAMYLASE DEFICIENCY

Background. Acute hyperammonemia caused by urea cycle disorder is a medical emergency for which immediate managements should be taken to minimize permanent brain damage. Among different enzyme defects, ornithine transcarbamylase deficiency (OTC) is one of the most common enzyme defect in urea cycle disorders. We utilized continuous renal replacement therapy techniques in the acute treatment of hyperammonemia due to ornithine transcarbamylase deficiency.

Patients and methods. Three male neonates with elevated serum ammonia levels were shown, based on urine organic acid analysis and serum amino acid studies, to have OTC deficiency. Administration of sodium benzoate and sodium phenylacetate for activating alternative nitrogen waste pathway were used associated with protein restriction. Other modalities, including blood exchange transfusion, peritoneal dialysis, continuous renal replacement therapy were utilized in an attempt to lower serum ammonia concentration.

Results. We report the successful use of continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), continuous arteriovenous hemodiafiltration (CAVHDF) in the acute management of hyperammonemia due to OTC deficiency. We also compared the ammonia clearance between peritoneal dialysis, exchange transfusion, CAVH, CAVHD and CAVHDF. It demonstrated the evidence that CAVHDF provides the best ammonia clearance.

Conclusion. Continuous renal replacement therapy including CAVH, CAVHD, and CAVHDF may be the alternative techniques for acute management of hyperammonemia in inborn error of metabolism when dialysis machine is not available. Our data suggests CAVHDF provides the best ammonia clearance.     

Optimization of Hemofilters for the Development of Implantable Artificial Kidneys

The concept of developing an implantable artificial kidney demands, in addition to the regeneration of endogenous filtrate, a small hemofilter with a high filtration rate. Conventional capillary filters are limited in their capacity to yield adequate filtrate, even if the number of capillaries is increased. To improve filter design so as to modify flow conditions for filtration rate augmentation, it is necessary to consider such factors as blood flow through a single capillary, wall shear rate, and transmembrane pressure (ptm) in in vivo applications, where such biological considerations as blood pressure, blood flow, and flow characteristics of blood are important. These requirements lead to a completely new filter type, the "curl filter," characterized by a large effective filtration surface in a relatively small number of hollow fibers in which optimal flow conditions prevail.     

Operating characteristics of pediatric continuous arteriovenous hemofiltration in an animal model

Continuous arteriovenous hemofiltration (CAVH) is an increasingly popular technique in the care of critically ill children. The operating characteristics of the available circuits are largely unknown. Prior to introducing CAVH into our pediatric intensive care unit, we investigated the performance of three CAVH circuits: CAVH with postfilter dilution, CAVH with prefilter dilution (CAVH_pre) and CAVH with dialysis counterflow. Using a neonatal lamb model, we measured filter blood flow (Q_B), ultrafiltrate rate (Q_U), arterial, venous and ultrafiltrate compartment pressure, oncotic pressure, plus urea levels in blood and ultrafiltrate fluid for the three CAVH circuit designs. Transmembrane pressure and urea clearance were calculated for various values of Q_B after varying a clamp on the arterial side of the circuit. The major finding, applicable to all circuits, was the wide variability of Q_B. Constant attention was required in order to obtain a consistent Q_B. Fluid clearance was effective with all three circuits. Urea clearance averaged 5–10 ml/min and was principally dependent on Q_U and independent of Q_B. The addition of dialysis counterflow did not increase urea clearance. The most convenient circuit we tested was CAVH_pre, but the problem of unstable Q_B is common to all unpumped arteriovenous filtrate circuits. It is a major limiting factor in the practical application of this technology to critically ill children.     

Fat contamination of pericardial suction blood and its influence on in vitro capillary-pore flow properties in patients undergoing routine coronary artery bypass grafting

OBJECTIVE: Neurologic dysfunction after cardiopulmonary bypass might be due to arterial microembolization. Pericardial suction blood is a possible source of embolic material. Our aim was to determine the capillary-pore flow ability of pericardial suction blood. METHODS: Pericardial suction blood from patients undergoing coronary bypass was collected, and pericardial suction blood and venous blood were sampled at the end of cardiopulmonary bypass and before reinfusion of pericardial suction blood. Pericardial suction blood was (n = 10) or was not (n = 10) prefiltered through a 30-microm cardiotomy screen filter before capillary in vitro analysis. Additionally, in 8 patients the plasma viscosity was measured, and in 5 of these patients, pericardial suction blood capillary deposits were evaluated by using a microscopy-imprint method and fat staining. Capillary flow was tested through 5-microm pore membranes. Tested components were plasma, plasma-eliminated whole-blood resuspension, and leukocyte/plasma-eliminated erythrocyte resuspension. Initial filtration rate and clogging slope expressed the blood-to-capillary interaction. RESULTS: The plasma-flow profile of pericardial suction blood was highly impaired, with a 47% reduction in initial filtration rate (P <.001) and a 142% steeper clogging slope flow deceleration (P <.01). This difference was not due to a change in pericardial suction blood viscosity, such as by free hemoglobin, which corresponded to 5.7% of the erythrocytes. There were no differences in resuspended whole blood or erythrocytes. The cardiotomy filter had no effect. Microscopy suggested the presence of capillary fat deposits in pericardial suction blood that were not seen with venous plasma (P <.05). The pericardial suction blood volume was 458 +/- 42 mL and contained 95.6 +/- 9.3 g/L hemoglobin. CONCLUSIONS: The pericardial suction blood plasma capillary flow function was highly impaired by liquid fat. Pericardial suction blood hemoglobin appears worth recovering after fat removal, despite profound hemolysis.     

Haemodynamic effects of arteriovenous and venovenous haemofiltration in piglets

The aim of this study was to compare the early haemodynamic effects of continuous arteriovenous haemofiltration (CAVH) with those of continuous venovenous haemofiltration(CVVH) in normal and endotoxic piglets, within the framework of a two-period cross-over trial. Sixteen domestic piglets (weight 6–18 kg) underwent 1 h of CAVH followed by 1 h of CVVH or 1 h of CVVH followed by 1 h of CAVH. Six were pre-treated with a graded endotoxin infusion to simulate clinical sepsis. The main measurements included: heart rate; mean arterial (MAP), pulmonary artery, central venous and pulmonary artery occlusion pressures; thermodilution cardiac output; and calculated systemic (SVRI) and pulmonary vascular resistance indexes. Each measurement was performed immediately before and 30 min after commencement of each technique of filtration. Commencement of haemofiltration in normal piglets caused minimal haemodynamic effects. In endotoxic piglets, commencement of filtration, whether CAVH or CVVH, caused a haemodynamic change which was significantly more pronounced in the first filter (SVRI –39%, MAP –32%) than the second filter (SVRI +22%, MAP +0.9%) (SVRI,P=0.01, first filter vs. second) (MAP,P=0.009 first filter vs. second). In conclusion, there were no significant differences between the early haemodynamic effects of CAVH and CVVH in normal or endotoxic piglets. The haemodynamic effects of either technique may become more significant in the presence of sepsis.     

The intraoperative measure of runoff resistance in the canine hindlimb

Long-term survival of femoro-popliteal grafts has been predicted on both graft function and distal vascular bed resistance. The purpose of this study was to demonstrate peripheral resistance as a function of the inherent elasticity (distensibility) of the distal vascular bed. The use of saline perfusate and maintenance of physiologic pressure will supplant such other factors as fluid viscosity, vasomotor tone, blood pressure, and tube dimensions. Our model consisted of Javid shunt insertion in the femoral artery of 13 female dogs distal to an occlusive tie. Saline was perfused in incremental fashion every 30 sec over a 5-min period; femoral pressure measurements were taken at each flow rate (Q) (cc/min). Results show that mean femoral pressure (MFP) varies with Q less than 125 (P less than 0.005) and Q greater than 200 (P less than 0.001). Furthermore, mean resistance (MR) declined precipitously with Q greater than 125 cc/min but at higher Q the MR plateaued (P less than 0.0001). We interpret these results to indicate that at Q less than 125 vasomotor tone is the predominant factor in MR and that saline perfusion abrogated this factor at 125 greater than Q less than 200. At Q greater than 200, MR declined only slightly and, therefore, MFP varied directly with Q indicating that vessel elasticity is the predominant feature of MR after vasomotor tone ablation and that pressure varies directly with flow in a distensible system. Pressure-flow graphs could be obtained prior to femoro-popliteal reconstruction via this quick, simple technique and rapid rises in pressure should indicate poor distal runoff.     

Narrow-pore flow behavior of blood cells in cardioplegic suspension

Cardioplegia alters the ionic composition of the myocardium and also the blood in a way that may influence the cellular capillary flow behavior. We measured changes in RBC volume and narrow-pore flow resistance of blood cardioplegia versus crystalloid medium. Potassium, magnesium and sodium as osmotic control caused an expected cell shrinkage and reduced the flow resistance through 3 microm pores; however, stressing the osmosis further resulted in increased resistance. No major effects were seen with the 5 microm filters. Twenty percent blood cells in the cardioplegic medium caused a 360% increase in 5 microm pore resistance. There were no obvious additional filterability effects of the cardioplegic additives other than their osmotic patterns. There may be a theoretical advantage in having a cell-free medium in terms of flow resistance. Using blood cardioplegia, a limited hypertonicity may be beneficial in reducing the capillary flow resistance of RBC.     

Theoretical analysis of pathogenetic mechanisms in experimental acute renal failure

A network thermodynamic model of glomerular dynamics has been employed to determine the degree of change in individual glomerular vascular resistances, hydraulic conductivity and proximal tubule pressure that, singly or in concert, could lower GFR to the degree expected in experimental acute renal failure (ARF). In both the rat and dog, the analysis shows that filtration failure is not achieved until preglomerular resistance (RA) is increased at least twofold or postglomerular resistance (RE) is decreased by 74% or more with all other determinants held at control values. Tubular obstruction alone will not provide failed filtration until tubule pressure is increased to 30 to 40 mm Hg in the rat and 44 mm Hg in the dog. A much smaller change in tubular pressure can contribute greatly to the development of filtration failure, however, when occurring in association with major change in individual vascular resistances. Glomerular capillary resistance must be increased to a value more than twice the normal sum of RA and RE (greater than fivefold in the dog), and glomerular capillary hydraulic conductivity lowered to below 5% of control, as isolated changes, before full filtration failure is approached. There is no reason to believe that most forms of ARF relate to only a single abnormality, however, and the effect of concomitant changes in individual resistances, hydraulic conductivity and proximal tubule pressure on glomerular filtration and blood flow is presented in the text and figures. A possible mechanism by which altered blood viscosity at the efferent arteriole may contribute to ARF is discussed and quantified. The degree of change in any determinant required to exert a given effect on filtration is independent of etiology, thus rendering the results of this analysis equally valid for any other pathological event which causes a significantly reduced GFR in the rat or dog.