Renal Excretion of Antidiuretic Hormone in Healthy Subjects and Patients with Renal Failure

1984 ◽  
Vol 67 (3) ◽  
pp. 307-312 ◽  
Author(s):  
Wojciech Pruszczynski ◽  
Henri Caillens ◽  
Luc Drieu ◽  
Luc Moulonguet-Doleris ◽  
Raymond Ardaillou
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Chronic Renal Failure ◽  
Plasma Concentration ◽  
Urinary Excretion ◽  
Antidiuretic Hormone ◽  
Healthy Subjects ◽  
Excretion Rate ◽  
Urinary Excretion Rate ◽  
Fractional Clearance

1. Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease. 2. In healthy subjects studied under conditions of mild water diuresis, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 ± 0.36 pg/ml, 25.2 ± 5.5 pg/min, 7.5 ± 1.2 ml/min and 6.4 ± 1.0% (means ± sem) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied. 3. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 ± 0.19 pg/ml, 9.4 ± 2.0 pg/min, 3.4 ± 0.6 ml/min and 10.0 ± 2.9% (means ± sem) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects. 4. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 ± 0.47 pg/ml, 52.8 ± 15.8 pg/min, 9.5 ± 2.7 ml/min and 24.9 ± 4.4% (means ± sem) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure. 5. These results demonstrate that most of the filtered ADH is reabsorbed by the tubules. The reabsorptive capability is markedly diminished in patients with acute renal failure at the polyuric phase of the disease.

scholarly journals A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

2006 ◽  
Vol 281 (43) ◽  
pp. 32057-32064 ◽  
Author(s):  
Ewa M. Slominska ◽  
Elizabeth A. Carrey ◽  
Henryk Foks ◽  
Czeslawa Orlewska ◽  
Ewa Wieczerzak ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Plasma Concentration ◽  
Healthy Subjects ◽  
Human Erythrocytes ◽  
Adenosine Kinase ◽  
Atp Depletion ◽  
Mass Detection ◽  
Atp Concentration ◽  
Ribonucleoside Triphosphate

We report the identification of a hitherto unknown nucleotide that is present in micromolar concentrations in the erythrocytes of healthy subjects and accumulates at levels comparable with the ATP concentration in erythrocytes of patients with chronic renal failure. The unknown nucleotide was isolated and identified by liquid chromatography with UV and tandem mass detection, 1H nuclear magnetic resonance and infrared spectroscopy as 4-pyridone-3-carboxamide-1-β-d-ribonucleoside triphosphate (4PYTP), a structure indicating association with metabolism of the oxidized nicotinamide compounds. Subsequently, we demonstrated formation of 4PYTP in intact human erythrocytes during incubation with the chemically synthesized nucleoside precursor 4-pyridone-3-carboxamide-1-β-d-ribonucleoside (4PYR). We noted preferential accumulation of monophosphate of 4PYR (4PYMP) over 4PYTP as well as a decrease in erythrocyte ATP concentration during incubation with 4PYR. Both the 4PYR phosphorylation and ATP depletion were blocked by an inhibitor of adenosine kinase. Plasma concentration of 4PYR was detectable but very low (0.013 ± 0.006 μm) in contrast with the high daily urine excretion of this compound (26.7 ± 18.2 μmol/24 h) in healthy subjects, indicating much greater renal clearance than other nicotinamide metabolites, nucleosides, or creatinine. We also noted a 40-fold increase in 4PYR plasma concentration in patients with chronic renal failure (0.563 ± 0.321 μm). We suggest that 4PYTP formation in the erythrocytes is a hitherto unknown process aimed at sequestering potentially toxic 4PYR in a form that could be safely transported and subsequently released and excreted during passage of erythrocytes through the kidney.

scholarly journals 1287. Pharmacokinetics, Safety, and Tolerability of Nacubactam after Single Coadministration with β-Lactams in Japanese Healthy Subjects

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
Masayo Asano ◽  
Hiroki Sato ◽  
Jun Morita ◽  
Kazuya Ishiwata ◽  
Kenichiro Kondo
Keyword(s):  
Adverse Event ◽  
Urinary Excretion ◽  
Healthy Subjects ◽  
Excretion Rate ◽  
Plasma Concentrations ◽  
Concomitant Administration ◽  
Single Administration ◽  
Urinary Excretion Rate ◽  
Serious Adverse Event ◽  
Concomitant Drug

Abstract Background A single administration of nacubactam (NAC) with concomitant β-lactams in Japanese healthy subjects was conducted to assess pharmacokinetics (PK), safety, and tolerability of NAC in coadministration with cefepime (FEP), aztreonam (ATM), meropenem (MEM), or piperacillin (PIP). Methods The administration period included Period I, Period II, and Period III where NAC alone, concomitant drug alone, NAC and concomitant drug were administered by 1hour-IV infusion in each period. The dose of each drug tested was 2 g of NAC, FEP, ATM, MEM and 4 g of PIP and 8 subjects were administered in each cohort (32 subjects in total). Results Plasma NAC concentrations and NAC urinary excretion rate after coadministration with each concomitant drug were similar to those of administration of NAC alone. The PK parameter of NAC showed the similar value both after administration of NAC alone and after concomitant administration with each concomitant drug. Based on these findings, it was confirmed that coadministration of NAC with FEP, ATM, MEM or PIP did not affect the PK of NAC. Plasma concentrations and urinary excretion rate of FEP, ATM, MEM or PIP after coadministration of each concomitant drug with NAC were similar to those of administration of each concomitant drug alone. The PK parameter of each β-lactam tested showed the similar value both after administration of β-lactam alone and after concomitant administration with NAC. Based on these finding, it was confirmed that coadministration of each concomitant drug with NAC did not affect the PK of FEP, ATM, MEM and PIP. As for the safety, there was no serious adverse event, all of TEAEs reported were mild in severity and judged to be “not related”. Conclusion It was confirmed that single coadministration of NAC with FEP, ATM, MEM, or PIP did not affect the both PKs of NAC and β-lactams, and was safe and well-tolerated in Japanese healthy subjects. Disclosures Masayo Asano, BS, Meiji Seika Pharma Co., Ltd. (Employee) Hiroki Sato, BS, Meiji Seika Pharma Co., Ltd. (Employee) Jun Morita, PhD, Meiji Seika Pharma Co., Ltd. (Employee) Kazuya Ishiwata, MS, Meiji Seika Pharma Co., Ltd. (Employee) Kenichiro Kondo, PhD, Meiji Seika Pharma Co., Ltd. (Employee)

scholarly journals Effect of an acute oral protein load on renal acidification in healthy humans and in patients with chronic renal failure.

1997 ◽  
Vol 8 (5) ◽  
pp. 784-792
Author(s):  
N G de Santo ◽  
G Capasso ◽  
G Malnic ◽  
P Anastasio ◽  
L Spitali ◽  
...  
Keyword(s):  
Renal Failure ◽  
Metabolic Acidosis ◽  
Chronic Renal Failure ◽  
Urinary Excretion ◽  
Healthy Subjects ◽  
Tubular Reabsorption ◽  
Renal Tubules ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance

The effect of a meat load on the renal handling of acid-base balance was studied in ten healthy subjects (GFR by inulin clearance = 98.5 +/- 8.14 ml.min-1.1.73 m-2) and in ten patients affected by chronic renal failure (CRF) (GFR = 39.9 +/- 5.3 ml.min-1.1.73 m-2). After the meat load (2 g.kg-1 body weight of cooked unsalted red meat), GFR increased by 26.9% (peak value) over baseline in healthy subjects and by 32% in CRF patients. The acid-base status of the healthy subjects was in the normal range, whereas the CRF patients disclosed a slight metabolic acidosis. After a meat load, there was, in the healthy subjects, an increase in the filtered load of bicarbonate coupled to an enhanced tubular reabsorption and urinary excretion. The time course between bicarbonate load and urinary excretion was coincident. In CRF patients, the increase of bicarbonate tubular load after the meal was associated with an increase in tubular reabsorption but not in urinary excretion of this anion. The relationship between bicarbonate load and reabsorption was linear in both groups up to the highest filtered loads. Baseline titratable acidity (TA) and ammonium (NH4+) excretion (expressed per ml GFR) were increased in CRF patients as compared with control subjects, but no changes were found after the meat load in both groups in these experimental conditions. The data indicate that the renal tubules contribute to the maintenance of acid-base balance both in healthy subjects and in CRF patients by reabsorbing most of the additional bicarbonate load. The transient, but significant, increase in bicarbonate excretion observed in healthy subjects could be related to the increased tubular load of bicarbonate. In CRF patients, tubular bicarbonate reabsorption was more complete, possibly because of the stimulation of H+ secretion by the mild metabolic acidosis. TA and NH4+ did not participate in tubular compensation of the increased buffer load.

Direct Proportionality of Urinary Excretion Rate and Serum Level of Tetracycline in Human Subjects

Nature ◽  
1963 ◽  
Vol 198 (4879) ◽  
pp. 450-453 ◽  
Author(s):  
T. CHULSKI ◽  
R. H. JOHNSON ◽  
C. A. SCHLAGEL ◽  
J. G. WAGNER
Keyword(s):  
Serum Level ◽  
Urinary Excretion ◽  
Excretion Rate ◽  
Human Subjects ◽  
Urinary Excretion Rate ◽  
Direct Proportionality

Compartmental transfer of mercury released from amalgam

1997 ◽  
Vol 16 (11) ◽  
pp. 667-672 ◽  
Author(s):  
S. Halbach ◽  
L. Kremers ◽  
H. Willruth ◽  
A. Mehl ◽  
G. Welzl ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Urinary Excretion ◽  
Total Mercury ◽  
Excretion Rate ◽  
Absorbed Dose ◽  
Correlation Coefficients ◽  
Urinary Excretion Rate ◽  
Amalgam Fillings

The number of amalgam-covered surfaces and the occlusal area of the fillings, the concentrations of total mercury in plasma, erythrocytes and urine, the urinary excretion rate, and the absorbed daily doses estimated by two separate methods from intra-oral Hg emission were determined in 29 volunteers with a low amalgam load. The transfer ofHg from the fillings via the oral cavity and blood to urinary excretion was evaluated by multiple correla tions between these variables. In addition, the combina tion of variables most representative of the entire compartmental transfer of amalgam Hg was determined. Urinary excretion (1), Hg concentration in plasma (2) and absorbed dose (3) were most closely correlated to each other, followed by correlations with the variables of the fillings (4). Correlation coefficients were 0.75 for variables 1 vs 2 and 2 vs 3, and 0.49 for variables 3 vs 4. It was concluded that variables 1-3 best reflected the transfer of mercury from amalgam fillings throughout the organism and that they were relatively insensitive to dietary mercury. The determination of total mercury in plasma and of its urinary excretion rate appears, under practical aspects, most suitable for the investigation of Hg uptake from amalgam.

Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure

2006 ◽  
Vol 44 (1) ◽  
Author(s):  
Elżbieta Kimak ◽  
Andrzej Książek ◽  
Janusz Solski
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Chronic Renal Failure ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Healthy Subjects ◽  
Linear Regression Analysis ◽  
Multivariate Linear Regression Analysis ◽  
Post Transplant ◽  
Transplant Patients ◽  
Lipoprotein Composition

AbstractStudies were carried out in 183 non-dialyzed, 123 hemodialysis, 81 continuous ambulatory peritoneal dialysis and 35 post-transplant patients and in 103 healthy subjects as a reference group. Lipids and apolipoprotein (apo)AI and apoB were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE-triglyceride-rich lipoprotein (TRL) in the non-high-density lipoprotein (non-HDL) fraction from apoCIIInonB and apoEnonB in the HDL fraction in four groups of patients with chronic renal failure (CRF) and healthy subjects. Multivariate linear regression analysis was used to investigate the relationship between triglyceride (TG) or HDL-cholesterol (HDL-C) concentrations and lipoproteins. Dyslipidemia varied according to the degree of renal insufficiency, the type of dialysis and therapy regime in CRF patients. Lipoprotein disturbances were manifested by increased TG, non-HDL-C and TRL concentrations, and decreased HDL-C and apoAI concentrations, whereas post-renal transplant patients showed normalization of lipid and lipoprotein profiles, except for TG levels and total apoCIII and apoCIIInonB. The present study indicates that CRF patients have disturbed lipoprotein composition, and that hypertriglyceridemia and low HDL-C concentrations in these patients are multifactorial, being secondary to disturbed lipoproteins. The method using anti-apoB antibodies to separate apoB-containing lipoproteins in the non-HDL fraction from non-apoB-containing lipoproteins in HDL can be used in the diagnosis and treatment of patients with progression of renal failure or atherosclerosis. The variability of TG and HDL-C concentrations depends on the variability of TRL and cholesterol-rich lipoprotein concentrations, but the decreases in TG and increases in HDL-C concentrations are caused by apoAI concentration variability. These relationships, however, need to be confirmed in further studies.

scholarly journals Pregnancy Enhances the Angiotensin (Ang)-(1–7) Vasodilator Response in Mesenteric Arteries and Increases the Renal Concentration and Urinary Excretion of Ang-(1–7)

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3338-3343 ◽  
Author(s):  
Liomar A. A. Neves ◽  
Aleck F. Williams ◽  
David B. Averill ◽  
Carlos M. Ferrario ◽  
Michael P. Walkup ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Excretion Rate ◽  
Virgin Female ◽  
Cardiovascular Regulation ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Resistance Arteries ◽  
Urinary Excretion Rate ◽  
Response Curves ◽  
Mesenteric Vessels

Abstract The vasoactive effect of angiotensin (Ang)-(1–7) in mesenteric resistance arteries together with its plasma and kidney concentration and urinary excretion was assessed in pregnant and virgin rats. Mesenteric arteries (230–290 μm) were mounted in a pressurized myograph system and Ang-(1–7) concentration-dependent response curves (10−10–10−5m) were determined in arteries preconstricted with endothelin-1 (10−7m). The Ang-(1–7) response was investigated in vessels with and without pretreatment with the Ang-(1–7) antagonist [d-[Ala7]-Ang-(1–7)] (10−7m). Ang-(1–7) caused a significantly enhanced, concentration-dependent dilation of mesenteric vessels (EC50 = 2.7 nm) from pregnant compared with virgin female rats. d-[Ala7]-Ang-(1–7) eliminated the vasodilator effect of Ang-(1–7). There was no significant change in plasma concentration of Ang-(1–7) in pregnant animals. On the other hand, 24 h urinary excretion and kidney concentration of Ang-(1–7) were significantly higher in pregnant animals. The increased mesenteric dilation to Ang-(1–7) with enhanced kidney concentration and 24 h urinary excretion rate of Ang-(1–7) suggests an important role for this peptide in cardiovascular regulation during pregnancy.

Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A

1986 ◽  
Vol 251 (4) ◽  
pp. F581-F587 ◽  
Author(s):  
N. Perico ◽  
A. Benigni ◽  
C. Zoja ◽  
F. Delaini ◽  
G. Remuzzi
Keyword(s):  
Urinary Excretion ◽  
Cyclosporin A ◽  
Chronic Treatment ◽  
Excretion Rate ◽  
Thromboxane A2 ◽  
Significant Negative Correlation ◽  
Progressive Increase ◽  
Urinary Excretion Rate ◽  
Acid Clearance ◽  
Selective Increase

Animals and humans undergoing a chronic treatment with cyclosporin A (CyA) show a reduction in glomerular filtration rate (GFR). The cause of this abnormality has not been established. Since CyA interferes with arachidonic acid (AA) metabolism in various cells, we wished to determine whether alterations in renal AA metabolites contribute to deteriorating renal function in rats on CyA. We show that chronic CyA treatment induces a progressive increase in the renal synthesis of thromboxane (TX) A2. This is a selective abnormality in that CyA does not influence the renal synthesis of prostaglandin E2 (PGE2) and prostacyclin (PGI2). A significant negative correlation has been found between TXB2 urinary excretion rate and inulin clearance. No correlation has been observed between TXB2 excretion and p-aminohippuric acid clearance. The withdrawal of CyA is followed by a normalization of both TXB2 urinary excretion rate and GFR. The administration of a selective TXA2 inhibitor, UK-38,485, resulted in a significant reduction in urinary excretion of TXB2 accompanied by a significant increase in GFR. We conclude that chronic treatment with CyA in rats is associated with a selective increase in renal TXA2 synthesis and suggest that this abnormality may play a role in the reduction of GFR.

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