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Biomedical subjects

T A Depner

Publications and source records attributed to T A Depner.

At least 55 records · Page 3Linked to original sources
PubMed1981

Four methods for determining albumin in azotemic sera evaluated.

The methods most commonly used for determination of albumin in serum depend on its binding of dyes. The binding of many drugs as well as of several dyes is impaired in azotemic sera from patients with renal failure. We therefore evaluated four methods used to measure albumin concentration in sera of patients with various degrees of renal failure, comparing results with those by the most specific method, radial immunodiffusion. The automated bromcresol green, manual immediate bromcresol green, cellulose acetate electrophoresis, 2-(4'-hydroxyazobenzene)benzoic acid binding, and Na2SO3 precipitation/biuret methods were evaluated. The correlations with results of radial immunodiffusion for azotemic sera differed from method to method but were approximately the same for each method, as in previous published reports for samples from a heterogeneous population of patients. The ratios of serum albumin concentration by these methods to albumin concentration as measured by radial immunodiffusion ranged from 0.96 to 1.13 for 29 to 41 normal and azotemic sera, but none of the ratios showed any variation beyond random scatter over a range of serum creatinine from 6.0 to 180 mg/L. Thus the choice of method to apply to azotemic sera will depend on the relative importance of accuracy, speed, cost, and technical complexity.

Autoanalysis↗
PubMed1980

Plasma protein binding in uremia: extraction and characterization of an inhibitor.

The impairment of binding drugs and other substances to serum albumin in patients with uremia can be restored to normal or near normal levels by adsorption with charcoal or synthetic polymers at pH 3. We used a nonionic poly-styrene-divinylbenzene copolymer to treat uremic plasma at pH 3. We observed a marked improvement of binding. Subsequent elution of this resin with ethanol produced a substance that, when dried and recombined with normal plasma, caused dose-dependent impairment of phenytoin and tryptophan binding. Restoration of normal binding affinity occurred after retreatment of this abnormalized plasma with resin at pH 3. Plasma and pleural fluid exudate from patients with uremia yielded, after extraction by the above technique, and inhibitor(s) of phenytoin binding in amounts averaging five times that extracted from equal volumes of normal plasma. This inhibitor (IX) is water soluble, heat stable, and dialyzable across cellophane membranes. Unlike fatty acids, which can also interfere with binding, IX partitions primarily in the water phase in solvent partition studies but undergoes a sharp transition in th pH 4 to 5 range, suggesting the presence of carboxyl group. These findings lend further support to the hypothesis that a retained ligand(s) is responsible for impaired plasma binding associated with uremia and suggests a role for organic acids known to accumulate in renal failure.

Animals↗
PubMed1980

Impaired plasma phenytoin binding in uremia. Effect of in vitro acidification and anion-exchange resin.

Phenytoin binding to uremic plasma was studied in vitro. Inhibition of binding independent of albumin concentration was demonstrated. Acidification from pH 8 to pH 3 produced a small decrease in binding by normal plasma but no change or a small increase in binding by uremic plasma. After plasma was acidified to pH 3.0, passed through an anion-exchange resin and realkalinized to pH 8, the binding by uremic plasma was restored to near normal. These studies indicate that the uremic abnormality causing impaired plasma drug binding is reversible and supports the concept that a competing ligand, tightly bound at physiologic pH, is responsible for impaired drug binding.

Albumins↗
PubMed1976

Pseudotumor of the kidney: a sequel to regional glomerulonephritis.

An unusual case of chronic renal failure associated with an abnormal intravenous urogram simulating renal neoplasm is discussed. Extensive radiographic and histologic studies support the contention that the observed mass lesion resulted from a segmental or regional compensatory hypertrophy. It is likely that this case represents a variant of unilateral glomerulonephritis with sparing of a segment or lobe of one kidney and subsequent hypertrophy of that segment as the remaining renal mass atrophied.

Adult↗
PubMed1975

Posttraumatic renal artery stenosis. Cure of hypertension by late revascularization.

Renal artery stenosis causing hypertension may be the sequel of blunt nonpenetrating abdominal trauma. Early recognition of such renal artery injury is essential. In the case reported, late recognition of unilateral traumatic renal artery stenosis led to surgical correction of the lesion and lasting cure of hypertension.

Abdominal Injuries↗
PubMedDate not supplied

Uremic toxicity: urea and beyond.

Successful replacement of renal function with dialysis supports the concept that uremia is a toxic state resulting from accumulated solutes and that toxicity results from high concentrations of these solutes in body fluids. Dialyzer clearance of urea, a surrogate toxin, is the currently accepted best measure of dialysis and dialysis adequacy, but it is admittedly a compromise due to current lack of knowledge about and inability to measure more toxic solutes. This failure could be explained if uremic toxicity is actually a summation effect of multiple toxins, each at individual subtoxic levels in the patient. Other solutes could be used as surrogates to measure clearance, but urea happens to be available in high concentrations, is easily measured by all clinical laboratories, and is easily dialyzed, so changes in concentration are sensitive indicators of clearance. Measurements of creatinine clearance are confounded by the disequilibrium that occurs across red cells within the dialyzer and in the patient. Other solutes probably behave more like creatinine than urea, so urea stands out as uniquely diffusible, a property that actually spoils its effectiveness as a surrogate toxin, especially when applied to more frequent and continuous dialysis. Accumulation of other solutes may correlate better with toxic uremic symptoms and the residual syndrome. More studies are needed to examine the kinetics of other solutes, their generation rates, and their distribution volumes to provide clinicians with more knowledge and tools to optimize dialysis treatments. Examination of the effectiveness of solute removal in patients dialyzed more frequently may provide significant insight into the pathogenesis of uremia.

Humans↗
PubMedDate not supplied

Catheter performance.

Venous catheters differ from peripheral arteriovenous (AV) access devices in many important ways. This discussion focuses on their performance as a conduit for blood flow between the patient and the dialyzer and on how catheter function is both limited and enhanced relative to the more common peripheral accesses. Catheter flow is limited by the high resistance inherent in the extended length of venous catheters relative to dialysis needles, but the high rate of flow in central veins also diminishes the opportunity for access recirculation. Cardiopulmonary recirculation is absent in patients with catheter access unless the patient also has a peripheral access. In the latter case, the same detrimental effect on urea clearance is seen regardless of which access device is used. Flow-dependent recirculation through circuits other than the peripheral AV access reduces the efficiency of dialysis (regardless of the type of access, catheter, or peripheral AV device used) across both catheters and peripheral AV devices. The inside diameter of the catheter plays a sensitive role in determining catheter resistance to flow. Slight increases in diameter under the same pressure head are associated with large increases in flow. Negative pressure at the catheter inflow port generated by the blood pump is magnified relative to peripheral devices, predisposing to partial collapse of the pump tubing segment and erroneous blood flow readings by the pump motor speed indicator. Setting a limit on prepump negative pressure can minimize this error. Future applications of dialysis may require lower pump speeds, which would allow more liberal use of catheter access if their potential for infection and clotting can be reduced.

Blood Flow Velocity↗
PubMedDate not supplied

Catheter related bacterial infections mimic reactions to exogenous pyrogens during hemodialysis.

Pyrogenic reactions are characterized by fever, chills, hypotension, or a combination of these developing during or shortly after hemodialysis in a previously asymptomatic patient. The temporal association with treatment implicates exposure of the patient's blood to bacterial pyrogens from contaminated dialysate or a reused dialyzer. Routine body temperature monitoring is recommended to detect these exposures. The current study was prompted by the appearance of several symptomatic febrile episodes in patients who were asymptomatic and afebrile before treatment with high-flux hemodialysis. During a 6 month period, temperatures were measured with a digital oral thermometer before and after 9,605 high-flux hemodialyses in 163 patients. Elevations above 100 degrees F (37.8 degrees C) were observed during or after 33 dialyses in 15 patients. In 18 of these dialyses, the temperature was also elevated before treatment began. Four patients who had no symptoms or fever before dialysis accounted for febrile reactions during 11 of the remaining 15 dialysis treatments. Fever was accompanied by rigors during most of the episodes. Subsequent blood cultures grew Enterococcus faecalis (two), Enterobacter cloacae (two), and Pseudomonas aeruginosa and cepacia (one). All four patients had indwelling silastic double lumen venous catheters (PermCaths), all responded to intravenous antibiotics, and all required eventual removal of the catheter. The apparent precipitation of sepsis by dialysis indicates that shear forces caused by high pulsatile blood flow through the catheter may dislodge organisms that have colonized the lumen. Intraluminal instillation of antibiotics is suggested as a preventative measure.

Adult↗
PubMedDate not supplied

Clinical measurement of blood flow in hemodialysis access fistulae and grafts by ultrasound dilution.

Blood flow is a fundamental property of the hemodialysis access device. Periodic monitoring of flow could be useful for detection of impending access failure and prevention of underdialysis, but simple measurements of access flow during hemodialysis are not currently available. Flow in peripheral arteriovenous fistulas and grafts was examined using an indicator dilution technique while the patient's blood lines were reversed. The indicator was a bolus of normal saline detected by an ultrasound flow sensor clamped onto the patient's blood line. The ultrasound sensor measured blood flow in the tubing using an established transit-time method and simultaneously detected saline dilution of the blood from changes in the average cross sectional velocity of an ultrasound beam that illuminated the blood flowing through the tubing. Access flow was measured 110 times in 25 patients, 16 with loop grafts and 9 with native fistulas. Measured access flow ranged from 125 to 2860 ml/min. The mean error of duplicate measurements within patients was 5.0 +/- 3.8%. To assess the adequacy of saline mixing with the blood, access flow was measured at three dialyzer blood flow rates. In paired studies, no significant difference was observed in access flow measured at two lower dialyzer blood flow rates when compared to flow measured at 350 ml/min. A comparison with access flow measured by a duplex color Doppler technique in seven patients gave a mean error of 9.2 +/- 7.2% in paired studies. These data show that blood flow in peripheral arteriovenous grafts and fistulas can be measured accurately during hemodialysis using ultrasound velocity dilution.

Blood Flow Velocity↗
PubMedDate not supplied

Hemodialysis access recirculation measured by ultrasound dilution.

The most widely used clinical method for measuring recirculation in the access device is based on urea dilution. The three simultaneous blood samples required during hemodialysis interrupt the treatment, and results of chemical analysis are often delayed for several days. Alternatively, detecting recirculation by dilution of arterial blood caused by a bolus of normal saline injected into the venous blood line has several advantages. In this study, an ultrasound sensor clamped onto the arterial line entering the dialyzer was used to detect such dilution from a reduction in sound velocity observed in the saline diluted blood. Within the target range, the change in ultrasound velocity (ultrasound dilution) is linearly correlated with the dilution of whole blood by normal saline. The same sensor was also used to measure flow in the blood line using an established ultrasound transit-time method. During 34 hemodialyses in 28 patients, only 3 patients had detectable recirculation measured by ultrasound dilution. To further evaluate the sensitivity of the new method the dialysis lines were reversed during hemodialysis in the 25 patients with no recirculation. After this, all had detectable recirculation ranging from 10 to 60%. The mean error of duplicate measurements was 3.9 +/- 2.8%. Recirculation by ultrasound dilution correlated closely with recirculation measured by urea dilution (r = 0.9156, p < 001). The data suggest that the ultrasound dilution method is both sensitive and accurate. Ease of use and immediate availability of results added to the clinical usefulness of this method for evaluating the integrity of the hemodialysis access.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Amino acid losses during hemodialysis: effects of high-solute flux and parenteral nutrition in acute renal failure.

BACKGROUND: During standard hemodialysis, amino acid losses are substantial, amounting to 6 to 9 g per treatment. When these nutritional supplements are infused during dialysis, losses are increased, but a net positive balance can be achieved if the infusion rate is high enough. High-flux dialyzers, used with increasing frequency in modern dialysis centers because of their more permeable synthetic membranes, should cause further amino acid losses; however, the increase has not been measured, and the effect on plasma levels has not been examined. Assessment of net balance requires measurement of blood concentrations as well as of clearance. METHODS: To quantitate the effect of high-flux dialysis on amino acid balance, we measured clearances, plasma levels, and losses of individual amino acids during hemodialysis in patients with acute renal failure who required daily parenteral nutrition. RESULTS: Nearly all predialysis amino acid levels in plasma were within the normal range, probably because of control of uremia with prior dialyses and from continuous infusion. In paired studies, clearances were higher (150 +/- 15 mL/min vs 107 +/- 11 mL/min, p < .01), and levels fell more at mid-dialysis with high-flux membranes (28% +/- 5%) than with conventional cellulosic membranes (4 +/- 5%, p < .05). Mean losses of amino acid were 5.2 +/- 0.6 g per conventional dialysis, representing 60% of the total infused, and 7.3 +/- 1.8 g per high-flux dialysis, or 80% of the simultaneous infusion. Fractional losses decreased at higher infusion rates, but losses of individual amino acids varied from one fourth to more than 10 times the amount infused. Compared with other small solutes, plasma levels were relatively well maintained even during high-flux dialysis, a factor that enhanced removal by the dialyzer. Total balance depended more on the infusion rate than on the dialysis membrane. CONCLUSIONS: These studies show that positive balance can be achieved with concurrent infusion during dialysis, especially at higher amino acid delivery rates. High-flux dialysis causes a greater disturbance of amino acid equilibrium than conventional dialysis does, but 24-hour gains far exceeded losses in the dialysate for most of the amino acids.

Acute Kidney Injury↗
PubMedDate not supplied

High venous urea concentrations in the opposite arm. A consequence of hemodialysis-induced compartment disequilibrium.

Resistance to urea diffusion among body fluid compartments diminishes the therapeutic effectiveness of hemodialysis. Cell membrane or capillary wall resistance is thought to be responsible for hemodialysis-induced urea disequilibrium. The authors examined the possibility that reduced blood flow might contribute to urea disequilibrium in the arm opposite the blood access site. Blood samples were taken simultaneously from a vein in the arm opposite the access site and from the arterial port after occluding the access graft between the needle sites for 1 min. Venous urea nitrogen levels from the opposite arm averaged 10% higher after 5 min, 26% higher after 60 min, and 36% higher after 120 min of dialysis. A three-compartment model of urea kinetics that includes a blood flow term accurately predicted all measured urea nitrogen concentrations in both arms. These data suggest that the opposite arm often behaves as a compartment with high resistance to urea diffusion. Slow diffusion from this compartment is partially due to reduced blood flow/compartment volume, and results in a delayed fall in venous blood urea nitrogen (BUN).

Arm↗
PubMedDate not supplied

Effectiveness of low dose erythropoietin: a possible advantage of high flux hemodialysis.

Recombinant human erythropoietin (EPO) was administered to 32 stable out-patients with end-stage renal disease (ESRD) on a priority basis three times a week. All patients underwent dialysis with polysulfone hollow fiber dialyzers. Mean time-averaged blood urea nitrogen (BUN) value was 50 +/- 12 mg/dl, and Kt/V for urea was 1.20 +/- 0.34/dialysis. The initial dose of EPO was 2,800 +/- 950 U/dialysis (45 +/- 17 U/kg/dialysis). The maintenance dose averaged 2,500 U/dialysis. Within the mean time of observation, 15 +/- 4 weeks, all but one patient responded to EPO by eliminating transfusion requirements, and 29 of 32 achieved the target hematocrit of 30-33%. For patients with hematocrits below 25% before EPO, the increase averaged 1.6 +/- 0.8%/week. The dose of EPO was lower and the hematocrit response was higher than reported previously. The rate of increase in hematocrit did not correlate with small molecular weight solute removal. Mean red blood cell survival was 52 +/- 18 days. No adjustments in blood pressure (BP) medications or dry weight were required to control BP. These data and earlier experiences with recovery from the anemia of ESRD after more effective dialysis suggest that the bone marrow response to EPO may be augmented by high flux hemodialysis.

Adolescent↗
PubMedDate not supplied

Pressure effects on roller pump blood flow during hemodialysis.

Accurate measurement of blood flow during hemodialysis is essential to avoid underdialysis. When blood roller pumps are pushed to the high-flow rates demanded by high performance dialyzers, flow may be overestimated. This study examined the effect of inflow (Pa) and outflow (Pv) pressures induced by hemodialysis roller pumps on flow in vitro and in vivo. Blood flow was measured volumetrically, and with an ultrasonic flow probe, whereas Pa was adjusted from -50 to -400 torr and Pv from 50 to 300 torr. Only Pa influenced flow. At -200 torr, true flow measured volumetrically averaged 8.5% +/- 1.3% less than the blood pump revolutions per minute (RPM) meter reading. At -400 torr, the difference was 33.0% +/- 1.9%. There was no visible indication that flow was reduced to less than pump meter readings. Pv, hematocrit, and the source of pump tubing had no significant effect. Flow measured with an ultrasonic transit-time probe during routine hemodialysis in 64 patients was 9.0% +/- 2.7% less than pump meter readings when Pa varied from -180 to -220 torr. Blood pump meter readings greater than 400 ml/min were usually inaccurate because of low Pa. Prepump monitoring of arterial inflow pressure can prevent hidden reductions in blood flow that decrease dialysis efficiency.

Blood Flow Velocity↗
PubMedDate not supplied

Modeling urea kinetics with two vs. three BUN measurements. A critical comparison.

Hemodialysis urea modeling usually requires three BUN measurements, C1, C2, and C3 (3-BUN), to determine urea generation rate (G) and volume of urea distribution (V) from dVC/dt = f(C, V, G). We eliminated the requirement for C3 by modifying the algorithm to generate a periodic solution to the equations describing C1 and C2 (2-BUN). During 156 consecutive dialyses in 37 patients there were no differences in V or G by the two methods: V = 38.3 +/- 1.3 L, G = 6.35 +/- 0.22 mg/min (2-BUN); V = 37.9 +/- 1.3 L, G = 6.08 +/- 0.23 mg/min (3-BUN). Theoretic analysis showed that transient departure from a constant protein intake produces greater errors in average G determined by the 3-BUN model than by the 2-BUN model. We compared predicted predialysis BUN values to measured predialysis BUN (mg/dl) at two days, one week and two months following the modeled dialysis. The 2-BUN method accurately predicted C3 in 156 studies: r = 0.90, mean error 6.8 +/- 6.0% (SD). Prediction of predialysis BUN at one week was less accurate for both methods: mean error 10.4 +/- 7.1% (2-BUN), 16.0 +/- 10.7% (3-BUN). At 2 months, the correlation between measured and calculated predialysis BUN fell to 0.59 (2-BUN) and 0.65 (3-BUN). Deviations from predicted BUN increased with time regardless of the model; no clear advantage of either method was seen at longer time intervals. Computer CPU time required to calculate V and G remained under 1 sec for the 2-BUN method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Comparison of binding by concentrated peritoneal dialysate and serum.

Major advances in dialysis therapy have occurred over the last decade, yet various abnormalities persist in end-stage renal disease (ESRD) patients. The etiology of these residual defects remains largely unknown. We are currently testing the hypothesis that some of these abnormalities are due to retention of small molecular weight, protein bound toxins, which are poorly dialyzable. We sought an alternative to blood as a source of bound toxins. Spent peritoneal dialysate (PD) was tested as a source. With use of a series of filtration devices, PD albumin content was increased about 35-fold. Evidence of bound ligands was shown by two methods. Salicylate binding by patients' sera and concentrated PD (n = 8) were markedly reduced, unbound salicylate being 14.9 +/- 5.1% (SD) and 15.8 +/- 4.9% at albumin concentrations of 3.30 +/- 1.04 and 3.23 +/- 0.84 g/dl. Serum from eight normal subjects, diluted to 2.95 g/dl albumin, had 7.4 +/- 1.1% unbound salicylate. HPLC analysis of deproteinized concentrated dialysate was compared to ultrafiltrates of the same fluid. Numerous bound peaks were seen, particularly in the late eluting peaks. Spent PD is a rich source of protein bound ligands for further study.

Blood Volume↗