Use of fractional lithium clearance in clinical and epidemiological investigation: A methodological assessment

1988 ◽  
Vol 74 (6) ◽  
pp. 651-657 ◽  
Author(s):  
P. Strazzullo ◽  
L. Iacoviello ◽  
R. Iacone ◽  
N. Giorgione
Keyword(s):  
Sodium Intake ◽  
Fractional Excretion ◽  
Lithium Carbonate ◽  
Individual Variability ◽  
Dietary Sodium ◽  
Epidemiological Investigation ◽  
Experimental Conditions ◽  
Renal Handling ◽  
Water Handling ◽  
Fractional Excretion Of Sodium

1. The fractional clearance of lithium (FCLi) has been validated in the rat under controlled experimental conditions as a reliable indicator of sodium and water handling in the proximal tubule. The purpose of the present study was to evaluate some key methodological aspects related to the use of the FCLi in clinical and epidemiological investigation. 2. FCLi was determined in healthy normotensive, or in some cases, in borderline/mild essential hypertensive subjects, by a morning urine collection obtained between 09.00 and 13.00 hours after a 300 mg oral lithium carbonate load (= 8.1 mmol of elemental lithium). 3. The ratio of intra-individual to inter-individual variance of FCLi, measured in free-living subjects on unrestricted diet, was shown to be low enough (0.33) to allow adequate characterization of individuals in a population with a single measurement, or at most with two (compared with at least four measurements needed to characterize the fractional excretion of sodium). 4. The remarkable influence of dietary sodium intake on FCLi, demonstrated under metabolic ward conditions, might explain a major portion of the observed intra-individual variability. 5. At the dosage employed in the present study, oral lithium administration did not affect the renal handling of sodium, potassium or calcium. Likewise, it did not induce any change in a series of 17 metabolic parameters and indicators of renal and liver function. 6. It is concluded that the FCLi may be a safe and useful tool for the clinical and epidemiological investigation of renal sodium and water handling. The possibility of a confounding effect of dietary sodium intake, however, should be kept in mind.

Clearance of endogenous lithium in humans: altered dietary salt intake and comparison with exogenous lithium clearance

1995 ◽  
Vol 268 (4) ◽  
pp. F718-F722 ◽  
Author(s):  
E. Folkerd ◽  
D. R. Singer ◽  
F. P. Cappuccio ◽  
N. D. Markandu ◽  
B. Sampson ◽  
...  
Keyword(s):  
Salt Intake ◽  
Sodium Intake ◽  
Lithium Concentration ◽  
Fractional Excretion ◽  
Dietary Sodium ◽  
Lithium Clearance ◽  
Dietary Salt ◽  
Renal Handling ◽  
Dietary Salt Intake ◽  
High Sodium

We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49–7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.

The Relationship of Urinary Kallikrein Activity to Renal Salt and Water Excretion

1978 ◽  
Vol 54 (1) ◽  
pp. 39-45 ◽  
Author(s):  
S. B. Levy ◽  
R. P. Frigon ◽  
R. A. Stone
Keyword(s):  
Racial Differences ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Racial Groups ◽  
Urinary Kallikrein ◽  
Experimental Conditions ◽  
Water Excretion ◽  
Water Load ◽  
Black And White ◽  
Kallikrein Activity

1. We measured urinary kallikrein (kininogenin) excretion in black and white normotensive subjects during a variety of manipulations of salt and water balance. 2. A large intravenous saline load administered while the subjects were on an unrestricted sodium diet did not significantly change urinary kallikrein activity in either racial group. 3. After several days of dietary sodium restriction both racial groups increased their urinary kallikrein activity. An intravenous water load given then further increased urinary kallikrein activity. White subjects were studied for an additional 24 h period, and urinary kallikrein activity returned to pre-water load values, indicating that the excretion of a water load in sodium-depleted subjects is associated with an increase in kallikrein excretion. 4. Black subjects excreted less kallikrein in the urine than white subjects during the initial 24 h periods of unrestricted dietary sodium intake, but there were no other significant racial differences during the other experimental conditions.

The Effect of Papillectomy on Renal Function in the Rat during Hydropenia and after an Acute Saline Load

1972 ◽  
Vol 50 (7) ◽  
pp. 662-673 ◽  
Author(s):  
D. R. Wilson
Keyword(s):  
Renal Function ◽  
Partial Nephrectomy ◽  
Sodium Excretion ◽  
Free Water ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Renal Handling ◽  
Water Excretion ◽  
Fractional Excretion Of Sodium

The effect of unilateral papillectomy on renal function in the rat was compared with the effect of partial nephrectomy which produced a similar decrease in glomerular filtration rate (G.F.R.) in the presence of an intact papilla. Under hydropenic conditions the kidney with papillectomy had a higher urine flow rate, sodium excretion rate, fractional sodium excretion, and osmolar clearance, while urine osmolality was lower. After an acute saline load the differences in sodium and water excretion disappeared, and fractional excretion of sodium and water were significantly higher in both types of kidney damage than in the contralateral control kidney. Free water reabsorption was lower in the papillectomized kidney after saline loading. Thus removal of the papilla resulted in abnormalities in the renal handling of salt and water which varied with the state of hydration of the animal and which were distinct from the effects of a reduction in G.F.R. by partial nephrectomy. It was concluded that the site of nephron loss, whether mainly in the renal medulla or in the cortex, may be another factor, in addition to G.F.R. and tubular reabsorption, which influences sodium and water excretion by the moderately damaged kidney.

Atrial Natriuretic Peptide-Cyclic Gmp Relationships in Normal Humans: Effects of Dietary Sodium Intake

1993 ◽  
Vol 85 (1) ◽  
pp. 13-17 ◽  
Author(s):  
G. A. Sagnella ◽  
N. D. Markandu ◽  
M. G. Buckley ◽  
D. R. J. Singer ◽  
G. A. MacGregor
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cyclic Gmp ◽  
Sodium Intake ◽  
Fractional Excretion ◽  
Dietary Sodium ◽  
High Sodium ◽  
High Sodium Intake ◽  
Normotensive Subjects ◽  
Atrial Natriuretic

1. The present study was designed to investigate the relationships between circulating atrial natriuretic peptide, plasma and urinary cyclic GMP and sodium excretion under basal conditions and in response to changes in dietary sodium intake. 2. Measurements of plasma atrial natriuretic peptide and plasma and urinary (24 h collections) cyclic GMP, sodium and creatinine were made in (i) 30 normotensive subjects on their normal sodium intake and (ii) 12 subjects on the 5th day of a low and on the 5th day of a high sodium intake. 3. Plasma cyclic GMP, urinary cyclic GMP and fractional excretion of cyclic GMP in 30 normotensive subjects on their normal sodium intake were (means ± SEM) 5.4 ± 0.5 pmol/ml, 434.5 ± 31.8 pmol/min and 86.9 ± 8.6%, respectively. There were significant correlations between urinary cyclic GMP and its corresponding filtered load (r = 0.55) and between the renal clearance of cyclic GMP and that of creatinine (r = 0.44), but there were no significant associations between circulating atrial natriuretic peptide and plasma cyclic GMP or the fractional excretion of cyclic GMP or between urinary sodium and the fractional excretion of cyclic GMP. 5. Plasma atrial natriuretic peptide was significantly raised on the 5th day of the high sodium intake compared with the low sodium intake (10.6 ± 1.6 versus 4.2 ± 0.9 pg/ml; P <0.05). Similarly, there were increases in urinary cyclic GMP excretion (692.3 ± 43.4 versus 427.4 ± 41.9 pmol/min, P <0.05), but there were no significant differences in the fractional excretion of cyclic GMP. 6. As neither plasma nor urinary cyclic GMP was strongly associated with circulating levels of atrial natriuretic peptide, the present study suggests that other factors may be more important than circulating atrial natriuretic peptide as determinants of extracellular cyclic GMP.

scholarly journals Defective renal water handling in transgenic mice over-expressing human CD39/NTPDase1

2012 ◽  
Vol 303 (3) ◽  
pp. F420-F430 ◽  
Author(s):  
Yue Zhang ◽  
Kaiya L. Morris ◽  
Shannon K. Sparrow ◽  
Karen M. Dwyer ◽  
Keiichi Enjyoji ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Free Water ◽  
Fractional Excretion ◽  
Urinary Concentration ◽  
Free Water Clearance ◽  
Water Handling ◽  
Fractional Excretion Of Sodium ◽  
Urinary Concentrating Ability

Ectonucleoside triphosphate diphosphohydrolase-1 hydrolyzes extracellular ATP and ADP to AMP. Previously, we showed that CD39 is expressed at several sites within the kidney and thus may impact the availability of type 2 purinergic receptor (P2-R) ligands. Because P2-Rs appear to regulate urinary concentrating ability, we have evaluated renal water handling in transgenic mice (TG) globally overexpressing hCD39. Under basal conditions, TG mice exhibited significantly impaired urinary concentration and decreased protein abundance of AQP2 in the kidney compared with wild-type (WT) mice. Urinary excretion of total nitrates/nitrites was significantly higher in TG mice, but the excretion of AVP or PGE2 was equivalent to control WT mice. There were no significant differences in electrolyte-free water clearance or fractional excretion of sodium. Under stable hydrated conditions (gelled diet feeding), the differences between the WT and TG mice were negated, but the decrease in urine osmolality persisted. When water deprived, TG mice failed to adequately concentrate urine and exhibited impaired AVP responses. However, the increases in urinary osmolalities in response to subacute dDAVP or chronic AVP treatment were similar in TG and WT mice. These observations suggest that TG mice have impaired urinary concentrating ability despite normal AVP levels. We also note impaired AVP release in response to water deprivation but that TG kidneys are responsive to exogenous dDAVP or AVP. We infer that heightened nucleotide scavenging by increased levels of CD39 altered the release of endogenous AVP in response to dehydration. We propose that ectonucleotidases and modulated purinergic signaling impact urinary concentration and indicate potential utility of targeted therapy for the treatment of water balance disorders.

Renal prostaglandins in cirrhosis of the liver

1986 ◽  
Vol 70 (5) ◽  
pp. 477-484 ◽  
Author(s):  
C. Guarner ◽  
I. Colina ◽  
F. Guarner ◽  
J. Corzo ◽  
J. Prieto ◽  
...  
Keyword(s):  
Renal Failure ◽  
Urinary Excretion ◽  
Sodium Intake ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Bed Rest ◽  
Control Group ◽  
Fractional Excretion Of Sodium ◽  
Cirrhotic Patients ◽  
The Relationship

1. Urinary prostaglandin excretion was studied in 42 patients with liver cirrhosis and in nine control subjects on restricted sodium intake and on bed rest. Creatinine clearance (CCr), sodium excretion (UNaV), plasma renin activity (PRA) and plasma aldosterone were also evaluated. 2. Patients without ascites and ascitic patients without renal failure showed increased urinary excretion of immunoreactive 6-ketoprostaglandin F1α (i6-keto-PGF1α), prostaglandin E2 (iPGE2) and thromboxane B2 (iTXB2) when compared with controls, while immunoreactive PGF2α (iPGF2α) levels did not differ from those in the control group. Patients with functional renal failure (FRF) presented a significant reduction of vasodilator prostaglandins but urinary excretion of iTXB2 was higher than in controls. 3. On the whole, cirrhotic patients with higher urinary excretion of prostaglandins had normal or nearly normal PRA and aldosterone levels. i6-keto-PGF1α and iPGE2 inversely correlated with PRA and aldosterone. 4. The relationship between i6-ketoPGF1α and CCr was found to be highly significant in cirrhotic patients but not in the control group. On the other hand, iPGE2 significantly correlated with UNaV and with the fractional excretion of sodium (FENa). 5. We concluded that: (a) enhanced renal prostaglandin synthesis in cirrhosis, inversely related to PRA and aldosterone, may be dependent on volume status; and (b) preserved renal function in these patients is associated with the ability to synthesize prostacyclin and PGE2.

scholarly journals Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niels Van Regenmortel ◽  
Lynn Moers ◽  
Thomas Langer ◽  
Ella Roelant ◽  
Tim De Weerdt ◽  
...  
Keyword(s):  
Fluid Therapy ◽  
Sodium Intake ◽  
Free Water ◽  
Daily Practice ◽  
Fluid Retention ◽  
Dietary Sodium ◽  
Renal Handling ◽  
Maintenance Fluid ◽  
Sodium Load ◽  
Maintenance Fluid Therapy

Abstract Purpose Iatrogenic fluid overload is a potential side effect of intravenous fluid therapy in the hospital. Little attention has been paid to sodium administration as a separate cause of harm. With this narrative review, we aim to substantiate the hypothesis that a considerable amount of fluid-induced harm is caused not only by fluid volume, but also by the sodium that is administered to hospitalized patients. Methods We show how a regular dietary sodium intake is easily surpassed by the substantial amounts of sodium that are administered during typical hospital stays. The most significant sodium burdens are caused by isotonic maintenance fluid therapy and by fluid creep, defined as the large volume unintentionally administered to patients in the form of dissolved medication. In a section on physiology, we elaborate on the limited renal handling of an acute sodium load. We demonstrate how the subsequent retention of water is an energy-demanding, catabolic process and how free water is needed to excrete large burdens of sodium. We quantify the effect size of sodium-induced fluid retention and discuss its potential clinical impact. Finally, we propose preventive measures, discuss the benefits and risks of low-sodium maintenance fluid therapy, and explore options for reducing the amount of sodium caused by fluid creep. Conclusion The sodium burdens caused by isotonic maintenance fluids and fluid creep are responsible for an additional and avoidable derailment of fluid balance, with presumed clinical consequences. Moreover, the handling of sodium overload is characterized by increased catabolism. Easy and effective measures for reducing sodium load and fluid retention include choosing a hypotonic rather than isotonic maintenance fluid strategy (or avoiding these fluids when enough free water is provided through other sources) and dissolving as many medications as possible in glucose 5%.

Effect of colchicine on urinary phosphate and regulation by parathyroid hormone

1976 ◽  
Vol 231 (1) ◽  
pp. 61-65 ◽  
Author(s):  
TP Dousa ◽  
CG Duarte ◽  
FG Knox
Keyword(s):  
Alkaline Phosphatase ◽  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Fractional Excretion ◽  
Renal Handling ◽  
Fractional Excretion Of Sodium ◽  
Cytoplasmic Microtubules ◽  
Fractional Excretion Of Phosphate ◽  
Sodium And Potassium

The possible role of cytoplasmic microtubules in the renal handling of phosphate and its regulation by parathyroid hormone (PTH) was evaluated with colchicine, a microtubule-disrupting agent. Colchicine-treated rats were thyroparathyroidectomized (TPTX) and subsequently infused with PTH. Treatment with a total dose of 1 mg colchicine had no effect on glomerular filtration rate or fractional excretions of sodium and potassium. Fractional excretion of phosphate in colchicine-treated TPTX rats was significantly higher compared with TPTX controls. After PTH infusion, control rats responded with increases in fractional excretion of phosphate and urinary cyclic AMP but colchicine-treated rats had variable and insignificant changes in both parameters. Fractional excretion of sodium and potassium did not change significantly after PTH. Renal cortical activities of cyclic AMP phosphodiesterase, soluble alkaline phosphatase, cytochrome oxidase, leucine aminopeptidase, or basal adenylate cyclase were not significantly affected by colchicine treatment. On the other hand, stimulation of adenylate cyclase by a submaximal dose of PTH was markedly decreased in colchicine-treated rats, and the activity of membrane-bound alkaline phosphatase was also significantly decreased. The binding of radioactive colchicine in renal cortical extracts from rats treated with colchicine was significantly diminished. These results suggest that disruption of cytoplasmic microtubules in renal cortical cells interferes with phosphate transport and its regulation by PTH.

Effects of indomethacin on renal response to atrial natriuretic peptide

1987 ◽  
Vol 253 (5) ◽  
pp. F868-F873
Author(s):  
C. A. Gaillard ◽  
H. A. Koomans ◽  
A. J. Rabelink ◽  
E. J. Mees
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Free Water ◽  
Fractional Excretion ◽  
Lithium Clearance ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
Water Clearance

We studied the effect of alpha-human natriuretic peptide (ANP, 100 micrograms iv) on renal sodium handling in eight healthy subjects before and after 7 days of indomethacin (50 mg 3 times a day). Sodium intake was 100 mmol/day. Prior to indomethacin, ANP caused a fourfold rise in sodium excretion over the first 20 min and a threefold rise in fractional sodium excretion. The clearance studies, performed during maximal water diuresis, showed increased fractional free water clearance and lithium clearance. Indomethacin caused marked sodium retention. Complete escape did not occur until the sixth day, when cumulative balance was 244 mmol (range 176-337). By this time renin and aldosterone were suppressed and fractional lithium and free water clearance reduced. The natriuretic effect of ANP was not attenuated, and the fractional excretion of sodium and chloride rose even more than without indomethacin. The reduction in lithium and free water clearance under indomethacin tended to be reversed by ANP. These data suggest that the natriuretic effect of ANP is not mediated by or dependent on renal prostaglandins. Indomethacin and ANP appear to have opposite effects on sodium excretion, maximal free water clearance, and lithium clearance.

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