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J C Van Stone

Publications and source records attributed to J C Van Stone.

15 recordsLinked to original sources

Differences between KT/V measured during dialysis and KT/V predicted from manufacturer clearance data.

We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage renal disease patients over a period of 33 months to evaluate the accuracy of in vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87% of predicted. At all blood flows, actual clearances were significantly lower than predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted KT/V was 1.238 +/- 0.005 whereas the mean of actual measured KT/V was 16% lower or 1.024 +/- 0.005 (P less than 0.0001). At different blood flows and with different dialyzers, predicted KT/V overestimated actual values. With increasing numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V ratios progressively dropped. Prescribing dialysis treatments using manufacturer's in vitro generated clearance data can lead to marked underdialysis of patients.

Adult

The peak concentration hypothesis: a urea kinetic approach to comparing the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis.

The KT/V urea index (K, clearance; T, treatment time; V, volume of urea distribution) has become an established index of hemodialysis (HD) adequacy, values of KT/V less than 0.8 being associated with overt uremic toxicity. For the typical continuous ambulatory peritoneal dialysis (CAPD) regimen of 4 X 2 L exchanges/day, the equivalent KT/V approximately 0.6. Paradoxically, overt uremic toxicity is not commonly observed in CAPD patients with this typical therapy prescription. Application of the urea kinetic model demonstrates that HD and CAPD have the same time-averaged urea concentration at the same KT/V. However, as HD is an intermittent therapy, the urea concentration in HD exceeds the time-averaged concentration for about half the hours in the week. If uremic toxicity is related to the peak rather than the time-averaged urea concentration, a higher KT/V would be required in HD to achieve a peak concentration at or below the steady-state CAPD concentration. This peak concentration hypothesis predicts, based on the results of the National Cooperative Dialysis Study, that underdialysis with CAPD would occur at KT/V less than 0.4 for a protein intake of 1.1 gm/kg/day.

Blood Urea Nitrogen

Who should receive recombinant human erythropoietin?

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.

Anemia

Arterial-venous determinations of the "immunoreactive" angiotensin peptides in human subjects.

Simultaneous measurements of arterial and venous plasma "immunoreactive" angiotensin II and angiotensin II peptide fragments (octapeptide, heptapeptide, hexapeptide, and pentapeptide), done with high performance liquid chromatography and radioimmunoassay, were obtained in nine human subjects. Results indicate that the angiotensin II octapeptide is the major peptide fragment in both arterial and venous plasma. Approximately 80% of the "immunoreactive" angiotensin II measured in both arterial and venous plasma is the angiotensin II octapeptide fragment. The concentration of angiotensin II octapeptide in venous blood approximated the concentration of angiotensin II octapeptide measured in arterial blood. These data suggest that venous concentrations of angiotensin II octapeptide probably reflect the activity of the tissue renin angiotensin system, because its concentration was much higher than would be predicted from inactivation of arterial blood angiotensin II octapeptide in peripheral tissues.

Adult

Prescribing dialysate bicarbonate concentrations for hemodialysis patients.

A rearranged equation of Sargent and Gotch (1) was used to determine dialysate bicarbonate concentrations for hemodialysis patients. Parameters in this equation include an estimate of the acid generated by each patient between treatments, an estimate for the dialyzer dialysance for bicarbonate, ultrafiltration rate, blood flow rate and a targeted mid-dialysis plasma bicarbonate concentration of 25 mEq/L. Nine patients were studied over a 35 week period to verify this method of determining each patient's dialysate bicarbonate concentration. Prescribed dialysate bicarbonate concentrations for the nine patients varied from 29 to 38 mEq/L with five patients having a prescribed value of 35 mEq/L. After a baseline period of five weeks, five patients switched from a 37 mEq/L acetate dialysate to their prescribed dialysate bicarbonate concentration. Four patients who had already been on bicarbonate dialysis at a concentration of 35 mEq/L were dialyzed with their prescribed dialysate bicarbonate concentrations. Patients were then followed for a study period of 30 weeks. The prescribed dialysate bicarbonate concentration resulted in more normal acid/base chemistries for both groups of patients. The results also demonstrate that chronic hemodialysis patients require individualization of dialysate bicarbonate concentrations.

Acid-Base Equilibrium

Total creatine kinase and isoenzyme fractions in chronic dialysis patients.

We measured total serum creatine kinase (CK) and serum creatine kinase MB fraction (CK-MB) in 53 patients on continuous ambulatory peritoneal dialysis (CAPD) and 52 patients on maintenance hemodialysis (HD), using Scalva UV methodology for CK and electrophoresis for CK-MB. Seven of the 53 CAPD patients (13%) had an elevated total CK, and only one of these 7 patients had an elevated CK-MB greater than 5%. In contrast 22 HD patients (42%) had increased total CK values, and 6 of these 22 HD patients (27%) showed elevated CK-MB isoenzyme greater than 5%. For each sex, blacks had higher mean CK values than whites. Twenty-one out of the 43 HD patients who received intramuscular injections had elevated total CK values and 6 of these 21 patients had elevated CK-MB isoenzyme independent of the timing of injection. The increased frequency of higher total CK values in HD patients appears to be related to race and androgen administration. The modest elevations in CK-MB fraction (5 to 8%) in these patients require careful interpretation.

Adult

The amount of sodium removed by hemodialysis.

The amount of sodium removed by hemodialysis was estimated, without using radioisotopes, as the change in total osmotically active cations, which is the product of the serum sodium concentration and urea-space. The extracellular and total body fluid volumes were measured using 35SO4 and 3H2O, respectively, in five stable hemodialysis patients under four different conditions. Urea-space determined, based on urea kinetics, was consistent with total body fluid volume measured by 3H2O. The amount of sodium removal, estimated as the change in the product of the serum (Na+) and urea-space, was equal to the change in the sodium content, which is the product of the serum (Na+) and extracellular fluid volume measured by 35SO4. Sodium removal may be divided into two components, diffusion and ultrafiltration.

Blood

Effect of erythropoietin on anemia of peritoneally dialyzed anephric rats.

The effect of erythropoietin on anemia was studied in anephric rats undergoing peritoneal dialysis. Both the number of bone marrow red cell precursors and plasma iron turnover were markedly depressed in untreated peritoneally dialyzed anephric animals when compared to peritoneally dialyzed sham-operated control rats. Anephric rats receiving 2 U of erythropoietin per day for 12 days had greater than threefold more bone marrow red cell precursors and a twofold larger plasma iron turnover than did the saline injected anephric rats. There was no significant difference in either bone marrow red cell precursors or plasma iron turnover in the erythropoietin-treated anephric rats when compared to the nonuremic controls. Although the rats receiving erythropoietin for 12 days had a significantly higher hematocrit (29.5%) than the saline injected uremic rats did (19.0%), the hematocrit was significantly lower than that found in nonuremic control animals, either receiving erythropoietin (48.1%) or not receiving erythropoietin (41.6%). Our data suggests that erythropoietin is potentially a useful agent for the treatment of anemia of chronic renal failure.

Anemia

Hemodialysis with glycerol dialysate.

Glycerol has a rate and volume of distribution similar to urea. Thirty-six mM glycerol in the dialysate prevents the fall in serum osmolality but does not decrease symptoms or improve the vascular stability of patients on chronic hemodialysis. We suggest that the benefits of mannitol, sodium and glucose in preventing or reversing symptoms during chronic dialysis are due to their extracellular distribution.

Animals

Effects of potassium chloride on plasma renin activity during sodium restriction in normal man.

Previous studies have suggested that large intakes of potassium (K) will suppress plasma renin activity (PRA) in normal man. The effect of more modest intakes of K on PRA is unclear. The present study was designed to compare the PRA in 11 normal volunteers maintained on an electrolyte-free diet (7000 J), with and without the addition of 50 mEq/day of potassium chloride (7000 J + KCl), well within the limits of usual dietary consumption. Control recumbent and 2 hr of upright PRA determinations were made by radioimmunoassay prior to the initiation of either the 7000 J diet or the 7000 J + KCl diet and on the fourth day of the diet, at a time when urinary sodium, K, and chloride excretions were near intakes. Mean (+/- S.E.M.) PRA's are indicated in Table II. There are significant (p less than 0.01) differences between (1) all respective recumbent and upright posture positions and (2) before and after the administration of 7000 J and 7000 J + KCl. However, there are no significant differences between (1) control periods or (2) before and after the addition of KCl to the electrolyte-free diet. We conclude from these studies that K, given in modest amounts, has no inhibiting effect on PRA.

Adult

Pharmacokinetics of acetaminophen elimination by anephric patients.

The pharmacokinetics of acetaminophen elimination were determined in five surgically anephric and five physiologically anephric patients on an interdialysis day, and in three normal adult volunteers. There was no significant difference in the biologic half-life and no apparent difference in the volume of distribution of acetaminophen between the three groups of subjects but the anephrics, unlike the normal subjects, showed pronounced accumulation of acetaminophen glucuronide and sulfate in plasma. The apparent volume of distribution for conjugated acetaminophen is considerably smaller than that for the unmetabolized drug even though neither acetaminophen nor its glucuronide or sulfate is significantly bound to plasma proteins. The results of this study indicate that the kidneys do not contribute significantly to the elimination of acetaminophen in man. Sin ce acetaminophen is eliminated largely by conjugation with glucuronic acid and sulfate, it can be concluded that the kidneys do not contribute significantly to the formation of these metabolites.

Acetaminophen

Hemodialysis and chloroquine poisoning.

The use of hemodialysis in the treatment of chloroquine intoxication was investigated. The in vitro and in vivo clearances of chloroquine were adequate (in vitro 53.4 ml. per minute, in vivo 57 ml. per minute). However, dialysis did not reduce the mortality in dogs. Eight milligrams per kilogram were uniformly fatal with or without dialysis whereas 5 mg. per kilogram were not fatal in any dog. Less than 5 per cent of administered chloroquine was removed during 6 hours of dialysis. Red cell chloroquine averaged 4 times serum values. Hemodialysis is ineffective in the treatment of chloroquine intoxication probably because chloroquine rapidly becomes intracellular after administration.

Animals