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Biomedical subjects

G R Aronoff

Publications and source records attributed to G R Aronoff.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sodium kinetics in salt-sensitive and salt-resistant normotensive and hypertensive subjects.

OBJECTIVE: To test the hypotheses that sodium kinetics are not affected by blood pressure, salt sensitivity, salt resistance or race, and that the kinetics of sodium balance are not a first-order process. DESIGN, PARTICIPANTS AND INTERVENTIONS: Two studies were conducted. In the first, 18 normotensive and 36 hypertensive men and women were given sodium at 120 mmol/day for 6 days, followed by 10 mmol/day for 8 days, then 400 mmol/day for 8 more days. Salt sensitivity was defined as an increase in diastolic blood pressure from the 10 to the 400 mmol/day intake. Salt resistance was defined as no increase, or a decrease in diastolic blood pressure with the increased sodium intake. In the second study, 12 white and 12 black normotensive men ingested sodium at 10, 200 or 400 mmol/day in random order, each for 7 days. All urine was collected in both protocols. SETTING: Metabolic ward at the University of Greifswald (Greifswald, Germany; study 1), and Clinical Research Center (Indiana University, Indianapolis, Indiana, USA; study 2). MAIN OUTCOME MEASURE: In addition to conventional statistics, a pharmacokinetic analysis was carried out to determine the elimination rate constant and half-life. RESULTS: In the Greifswald study, when the sodium intake was decreased, a longer half-life was determined for the salt-sensitive than the salt-resistant hypertensive subjects. The half-life for the normotensive salt-sensitive and salt-resistant subjects did not differ. When the sodium intake was decreased, a monoexponential equation fitted the data for all subjects; when the sodium intake was increased, only data for half the subjects could be fitted to the same equation. In the Indianapolis study, black race had a significant influence upon urinary sodium excretion. Furthermore, the half-life for sodium elimination was dependent upon sodium intake; namely, the greater the intake, the longer the elimination half-life. CONCLUSIONS: The time required to reach sodium balance may increase following salt-sensitive increases in blood pressure rather than precede them. Race influences the time required to achieve salt balance. Sodium kinetics are not a first-order process.

Adult↗
PubMed1992

Therapeutic implications associated with renal studies of nabumetone.

Nonsteroidal antiinflammatory drugs (NSAID) decrease renal prostaglandins and may cause a decrease in renal blood flow, glomerular filtration, and sodium excretion. In some cases, these effects result in renal failure, edema, or hypertension. Patients with decreased effective circulating fluid volume are at greatest risk for development of these renal side effects. In addition, NSAID can cause interstitial nephritis. However, in double blind and open label controlled clinical trials, nabumetone had an effect on renal function in less than 1% of patients, regardless of sex or advanced age. Furthermore, in patients with normal or impaired renal function, single or multiple doses of nabumetone did not cause significant changes in creatinine clearance or serum creatinine values. However, with any NSAID including nabumetone, renal function should be measured before beginning therapy and periodically thereafter in patients at risk for the development of renal impairment.

Aging↗
PubMed1992

Nonsteroidal anti-inflammatory drug induced renal syndromes.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause acute renal failure from unopposed vasoconstriction or acute interstitial nephritis. NSAID induced hemodynamic renal failure is characterized by sudden oliguria, often with decreased fractional excretion of sodium, occurring in patients with decreased effective circulating fluid volume or preexisting renal disease. Allergic interstitial nephritis from NSAIDs may occur at any time during therapy with the drugs and may present as renal failure with or without the nephrotic syndrome. Although chronic renal failure has been reported, both renal syndromes usually resolve when treatment with the NSAID is discontinued. Renal function should be measured soon after initiation of therapy in patients at risk for the hemodynamic effects of the drugs and periodically thereafter. Patients should be warned about the potential toxicity of the drugs.

Acute Kidney Injury↗
PubMed1991

Low-dose recombinant human erythropoietin therapy in chronic hemodialysis patients.

To test the hypothesis that low-dose recombinant human erythropoietin (r-HuEpo) would be effective and safe therapy for the anemia of end-stage renal failure, we studied 37 chronic hemodialysis patients for 3 months before and 6 months after beginning treatment with r-HuEpo, 3,000 U, administered initially intravenously (IV) three times weekly. Hematocrit increased from a mean of 25.2 vol% into the target range (mean, 32.2 vol%, a 28% increase) by 4 months. Transfusion requirements were dramatically reduced. Eight patients (22%) had exacerbated or new development of hypertension, while in trials using higher doses this occurred in 35%. Vascular access thrombosis, dialyzer clotting, and seizures were not seen more frequently during r-HuEpo therapy. Dialyzer reuse was not affected. Low-dose r-HuEpo therapy is effective in most hemodialysis patients and may be associated with less adverse effects because of the slower increase in blood viscosity. As targets are reached, downward dosage adjustments need to be smaller when using an initial low-dose regimen.

Adolescent↗
PubMed1991

Regulation of atrial natriuretic peptide release in normal humans.

Atrial volume, pressure, and heart rate are considered the most important modulators of atrial natriuretic peptide (ANP) release, although their relative role is unknown. Continuous positive-pressure breathing in normal humans may cause atrial pressure and atrial volume to go in opposite directions (increase and decrease, respectively). We utilized this maneuver to differentially manipulate atrial volume and atrial pressure and evaluate the effect on ANP release. Effective filling pressure (atrial pressure minus pericardial pressure) was also monitored, because this variable has been proposed as another modulator of ANP secretion. We measured right atrial (RA) pressure, RA area, esophageal pressure (reflection of pericardial pressure), and RA and peripheral venous ANP in seven healthy adult males at rest and during continuous positive-pressure breathing (19 mmHg for 15 min). Continuous positive-pressure breathing decreased RA area (mean +/- SE, *P less than 0.05) 13.6 +/- 1.1 to 10.5 +/- 0.8* cm2, increased RA pressure 4 +/- 1 to 16 +/- 1* mmHg, increased esophageal pressure 2 +/- 1 to 12 +/- 1* mmHg, and increased effective filling pressure 2 +/- 0 to 4 +/- 1* mmHg. RA ANP increased from 67 +/- 17 to 91 +/- 18* pmol/l and peripheral venous ANP from 43 +/- 4 to 58 +/- 6* pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Renal and hemodynamic effects of atrial natriuretic peptide in patients with cirrhosis.

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 microgram/kg/min. The infusions lasted for 2 hours and were flanked by both baseline and recovery periods. There was a significant effect of placebo on urinary sodium and chloride excretion rates but no effect on urine flow rate. In response to anaritide, the urine flow rate increased at 0.03, 0.06, 0.075, and 0.100 microgram/kg/min. The sodium and chloride excretion rates increased at all doses except the highest dose. There was no definite effect of anaritide on urinary potassium, calcium, and phosphate excretion rates. There was also no significant effect on creatinine clearance. The mean arterial pressure decreased in response to the 0.060, 0.075, and 0.100 microgram/kg/min doses. In addition, five of the patients receiving the highest dose (0.300 microgram/kg/min) had decreases in their systolic pressures to 90 mm Hg or less. In conclusion, anaritide is natriuretic and diuretic in patients with cirrhosis complicated by ascites and/or edema. Its effect, however, on arterial pressure may limit its therapeutic potential in this patient population.

Atrial Natriuretic Factor↗
PubMed1990

Interactions of ceftazidime and tobramycin in patients with normal and impaired renal function.

We studied the in vivo interaction of ceftazidime and tobramycin in normal volunteers and anuric patients given each drug separately or both drugs in combination. Kinetic analysis of plasma concentration data showed minor changes in the disposition of these agents when they were given concurrently. However, the resulting clearance of both tobramycin and ceftazidime was unchanged when these drugs were given concurrently. The volume of distribution of tobramycin at steady state was increased by 20% in normal volunteers when given with ceftazidime. The increase in distribution was accompanied by a slight decrease in ceftazidime elimination rate. No additional alteration in dosing over those necessary to adjust for a decrease in renal function is necessary when giving this combination.

Adult↗
PubMed1990

The treatment of anemia with low-dose recombinant human erythropoietin.

Recombinant human erythropoietin is effective therapy for the anemia of chronic renal failure. Hypertension, seizures, dialysis access thromboses, and clotted dialyzers have been reported as problems associated with the use of this drug. To test the hypothesis that low-dose erythropoietin is effective and safe, we gave 37 chronic hemodialysis patients this compound (3,000 units, i.v.) three times each week for 3 months. Before and for 3 months during therapy, we measured hemoglobin, hematocrit, blood transfusions, blood pressure, access thromboses, seizures, and clotted dialyzers. After 2 months of treatment, mean hemoglobin concentration and mean hematocrit increased significantly. Five patients had no increase in either value. In 4 of these 5 nonresponders, blood loss accounted for treatment failure. Neither blood pressure nor the incidence of access thromboses, seizures, and clotted dialyzers changed during the 3 months of therapy. We conclude that recombinant human erythropoietin is effective as treatment for the anemia of chronic renal failure at much lower doses than have been reported previously. The low incidence of adverse events may be related to the low dose used.

Anemia↗
PubMed1990

Atrial natriuretic peptide and the renin-aldosterone axis during exercise in man.

Under non-exercise conditions, atrial natriuretic peptide (ANP) elevation suppresses plasma renin activity (PRA) and aldosterone (PA). A similar effect of ANP on PRA-PA during exercise has been suggested but not demonstrated. We measured ANP, PRA, PA, plasma potassium (K+), and changes in plasma volume (PV) and blood volume (BV) at rest and during incremental cycle ergometer exercise to exhaustion in ten healthy males. Plasma concentrations (mean +/- SE) of hormones and electrolytes increased (P less than 0.05) during exercise: ANP (68 +/- 14 to 207 +/- 48 pg.ml-1), PA (11.2 +/- 2.2 to 18.8 +/- 3.4 ng.dl-1), PRA (5.1 +/- 1.1 to 8.2 +/- 1.6 ng.ml-1.90 min-1), and K+ (4.2 +/- 0.1 to 5.5 +/- 0.1 mEq). PV and BV declined, reaching maximal deflections from baseline during the 100% stage (12.9 +/- 1.5 and 8.4 +/- 0.8% decreases, respectively). There were positive correlations between ANP and PRA (r = 0.58; P less than 0.01), ANP and PA (r = 0.56; P less than 0.01), and PRA and PA (r = 0.80; P less than 0.001). Increases in K+ did not correlate with increases in PA. The fall in PV correlated with elevations in PRA (r = -0.67; P less than 0.01) and PA (r = -0.58; P less than 0.01), and the fall in BV correlated with elevations in PRA (r = -0.62; P less than 0.01) and PA (r = -0.44; P less than 0.02). ANP production was related to exercise intensity (gauged by heart rate response; r = 0.58; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The effect of oxygen on sodium excretion in hypoxemic patients with chronic obstructive lung disease.

In advanced chronic obstructive lung disease (COLD), sodium retention is common, associated with reduction in renal plasma flow (RPF) and stimulation of the renin-aldosterone (PRA-PA) system, two abnormalities due to or influenced by hypercapnia: the independent role of hypoxemia in perturbing sodium homeostasis is unknown. In five stable patients with COLD (FEV1 = 0.9 +/- 0.21, mean +/- SE) with mild edema, during two weeks of a low sodium diet (one week on room air: pH = 7.39 +/- 0.02; PaO2 = 55 +/- 4 mm Hg; PaCO2 = 49 +/- 4 mm Hg; and one week on O2: pH = 7.38 +/- 0.01; PaO2 = 72 +/- 6 mm Hg; PaCO2 = 52 +/- 4 mm Hg) we monitored sodium balance, systemic and renal hemodynamics, plasma sodium and potassium, PRA, PA, and atrial natriuretic hormone (ANH). During air breathing, patients uniformly showed a depression of RPF despite normal cardiac output; plasma hormone levels did not differ from controls but there was elevation (greater than 2 SD above the normal mean) of PRA in four patients, PA in two patients, and ANH in two of five patients. During O2 breathing, urinary sodium increased significantly from 67 +/- 7 to 102 +/- 10 mEq/24 h. Surprisingly, the patients experienced a small but significant weight gain (0.6 +/- 0.1 kg). None of the other variables was affected by O2 therapy. The following conclusions were reached: in advanced COLD, correction of hypoxemia results in sodium diuresis, indicating that hypoxemia (in the presence of hypercapnia) contributes to sodium retention. The mechanism for this beneficial effect of O2 will require further investigation.

Aldosterone↗
PubMed1990

Effect of positive and negative pressure breathing on sodium and water excretion.

Positive and negative pressure breathing purportedly alter renal sodium and water excretion by modifying hemodynamics and/or hormonal regulators of sodium and water homeostasis. To test this hypothesis we monitored hemodynamic and hormonal responses in seven normal men to (1) continuous positive pressure breathing (19 +/- 1 mm Hg for 30 minutes) after water loading (urine volume = 15 +/- 1 ml/min); and (2) continuous negative pressure breathing (11 +/- 1 mm Hg for 30 minutes) after maintenance water ingestion (urine volume = 4 +/- 1 ml/min), in random order. Each study was repeated on a control day without pressure breathing. Results were as follows (mean +/- SE, p less than 0.05): (1) continuous positive pressure breathing decreased urinary sodium from 0.28 +/- 0.07 to 0.17 +/- 0.04 mEq/min, increased atrial natriuretic peptide from 34.2 +/- 4.9 to 48.5 +/- 6.9 pg/ml, and had no effect on osmolar and free water clearances, cardiac output, plasma renin activity, or plasma aldosterone and plasma arginine vasopressin levels; and (2) continuous negative pressure breathing increased free water clearance from 0.6 +/- 0.7 to 4.5 +/- 1.2 ml/min, urine volume from 4.0 +/- 0.8 to 8.9 +/- 1.3 ml/min, and cardiac output from 5.1 +/- 0.4 to 7.0 +/- 0.6 L/min in a proportional manner (r = 0.40, p less than 0.01) and had no effect on osmolar clearance, urinary volumes of sodium and potassium, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of oral calcium, potassium, digoxin, and nifedipine on natriuresis in normal humans.

Many factors influence renal sodium excretion and blood pressure. We tested the independent effects of dietary calcium (Ca; 500 mg twice daily), potassium (KCl; 20 mEq three times daily), sodium-potassium dependent ATPase inhibition (digoxin), calcium channel blockade (nifedipine), and placebo, on acute natriuresis in 14 normal subjects while receiving 150 mEq/d sodium diets and 2 L normal saline intravenously over four hours. Each subject received each regimen in random sequence. Sodium balance before infusion was not different among the regimens. Plasma renin activity (PRA) was increased in subjects receiving nifedipine, while the plasma aldosterone concentration (PA) was not different among the regimens. None of the regimens influenced the clearance of inulin or paraaminohippurate (PAH) either before or after saline infusion. Only KCl and nifedipine affected sodium excretion compared to controls. KCl and nifedipine increased the amount of sodium excreted after the infusion was terminated. In the case of nifedipine, this natriuresis was sufficient to increase the 24-hour sodium excretion on that day to above that of the other regimens. The data support the notion that potassium and nifedipine may decrease blood pressure by facilitating sodium excretion. Nifedipine may also uncouple renin from aldosterone. Oral calcium supplementation and sodium-potassium dependent ATPase inhibition did not facilitate natriuresis.

Administration, Oral↗
PubMed1989

Atrial natriuretic peptide, renin and aldosterone in obstructive lung disease and heart failure.

Elevations of atrial natriuretic peptide (ANP) in congestive heart failure (CHF) and chronic obstructive lung disease (COLD) are presumably due to atrial hypertension, while secondary hyperaldosteronism in these patients is thought to result from diminished renal perfusion. The responsiveness of the ANP and renin (PRA)-aldosterone (PA) systems to acute increases in right atrial pressure has not been studied in these patients, but in normals a reciprocal relationship between ANP with PRA and PA has been shown. The authors monitored venous pressure (VP, reflective of right atrial pressure), ANP, PRA and PA in 15 stable COLD patients, seven stable CHF patients and three normal controls at baseline and after elevation of VP by antishock trousers. Inflation of the trousers resulted in increased VP and ANP (p less than 0.05): control ANP, 84 +/- 17 to 108 +/- 23 pg/ml; COLD ANP, 176 +/- 5 to 200 +/- 7; and CHF ANP, 388 +/- 20 to 499 +/- 37. PRA and PA were not suppressed by increasing ANP levels and the delta ANP/delta VP ratio was similar among groups. No intergroup differences in resting PRA and PA were noted, but PRA was higher (p = 0.007) and PA tended to be higher (p = 0.08) in a sub-group of six edematous patients, as compared with non-edematous patients and controls. These findings: (1) confirm previously reported ANP differences between COLD and CHF; (2) indicate that the ANP system remains responsive to physiologic manipulations in COLD and CHF; and (3) demonstrate that ANP and the PRA-PA axis are not reciprocally related in either group.

Aged↗
PubMed1988

Nizatidine disposition in subjects with normal and impaired renal function.

To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night.

Adult↗
PubMed1988

Facilitation of natriuresis with nifedipine in normal humans.

We tested the effect of dietary potassium (KCl, 20 mEq three times daily), calcium (Ca, 500 mg twice daily), sodium-potassium-dependent ATPase inhibition (digoxin), calcium channel blockade (nifedipine), and placebo on acute natriuresis in 14 normal subjects who received 2 L normal saline intravenously over 4 h. Plasma renin activity (PRA) was increased in subjects receiving nifedipine, while plasma aldosterone (PA) concentrations were not different among the regimens. Only KCl and nifedipine affected sodium excretion compared to controls. KCl and nifedipine increased the amount of sodium excreted after the infusion was terminated. In the case of nifedipine, this natriuresis was sufficient to increase the 24 h sodium excretion on that day to above that of the other regimens.

Adolescent↗
PubMed1987

Effect of acute renal failure on insulin disposition in the isolated perfused rat kidney.

The renal disposition of insulin in acute renal failure has not been evaluated. We used the isolated perfused rat kidney to test the hypothesis that acute renal failure (ARF) decreases renal insulin clearance. We used warm ischemia for 45 min, uranyl nitrate 5 mg/kg, ureter ligation, and nonfiltering kidneys as methods of inducing ARF. Comparisons were made with normal control kidneys. The concentrations of insulin in perfusate and urine was determined by radioimmunoassay. Acute renal failure caused significant reductions in glomerular filtration rate, sodium and potassium reabsorption, and an increased urine pH. Warm ischemia and uranyl nitrate toxicity caused a 50% decrease in the renal clearance of insulin. Nonfiltering kidneys cleared insulin at a rate 90% decreased from controls. Ureteral ligation caused a 32% decrease in insulin clearance. Filtration was necessary for insulin to be cleared from perfusate. We conclude that ARF decreased renal insulin clearance through a decrease in insulin uptake from both the tubular lumen and peritubular surface.

Acute Kidney Injury↗