Comparative evaluation of fractional excretion of sodium following saline infusion in transplanted kidneys and in isolated perfused kidneys in conditions of previous high or low dietary sodium intake

1976 ◽  
Vol 361 (2) ◽  
pp. 121-126 ◽  
Author(s):  
A. Nizet
1988 ◽  
Vol 74 (6) ◽  
pp. 651-657 ◽  
Author(s):  
P. Strazzullo ◽  
L. Iacoviello ◽  
R. Iacone ◽  
N. Giorgione

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.


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

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.


The Lancet ◽  
1985 ◽  
Vol 326 (8466) ◽  
pp. 1208-1211 ◽  
Author(s):  
GiuseppeA. Sagnella ◽  
AngelaC. Shore ◽  
Nirmalad. Markandu ◽  
GrahamA. Macgregor

1995 ◽  
Vol 268 (4) ◽  
pp. F718-F722 ◽  
Author(s):  
E. Folkerd ◽  
D. R. Singer ◽  
F. P. Cappuccio ◽  
N. D. Markandu ◽  
B. Sampson ◽  
...  

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.


1986 ◽  
Vol 70 (5) ◽  
pp. 477-484 ◽  
Author(s):  
C. Guarner ◽  
I. Colina ◽  
F. Guarner ◽  
J. Corzo ◽  
J. Prieto ◽  
...  

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.


1987 ◽  
Vol 253 (5) ◽  
pp. F868-F873
Author(s):  
C. A. Gaillard ◽  
H. A. Koomans ◽  
A. J. Rabelink ◽  
E. J. Mees

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.


2004 ◽  
Vol 287 (6) ◽  
pp. F1204-F1212 ◽  
Author(s):  
Jian Song ◽  
Xinqun Hu ◽  
Min Shi ◽  
Mark A. Knepper ◽  
Carolyn A. Ecelbarger

Dietary fructose, NaCl, and/or saturated fat have been correlated with mean arterial pressure (MAP) rises in sensitive strains of rats. Dysregulation of sodium and/or water reabsorption by the kidney may contribute. Using radiotelemetry and parallel semiquantitative immunoblotting, we examined the effects of various diets on MAP and the regulation of abundance of the major renal sodium and water transport proteins in male Sprague-Dawley rats. In study 1, rats (∼275 g) were fed one of four diets for 4 wk ( n = 6/group): 1) control, 2) 65% fructose, 3) control + added NaCl (2.59%), or 4) fructose + NaCl. In study 2, 5% butter (fat) was added to the above four diets. Both fat and NaCl, but not fructose, caused modest rises in MAP (5–10 mmHg) and increased the day-to-night ratio in diastolic blood pressure. NaCl or fructose increased kidney size. Creatinine clearance was increased by salt or fat, and fractional excretion of sodium was decreased by fat. In study 1, high NaCl markedly reduced plasma renin and aldosterone and its regulated proteins in whole kidney, i.e., the thiazide-sensitive Na-Cl cotransporter and the α- and γ (70-kDa band)-subunits of the epithelial sodium channel. These effects were blunted by fat. Fructose increased the abundance of the sodium phosphate cotransporter, whereas it decreased the bumetanide-sensitive Na-K-2Cl cotransporter and aquaporin-2. Overall, doubling of dietary fat appeared to impair dietary sodium adaptation, i.e., blunt the downregulation of aldosterone-mediated effects, thus allowing blood pressure to rise at an accelerated rate.


2003 ◽  
Vol 285 (6) ◽  
pp. F1198-F1209 ◽  
Author(s):  
Jakob Nielsen ◽  
Tae-Hwan Kwon ◽  
Jeppe Praetorius ◽  
Young-Hee Kim ◽  
Jørgen Frøkiær ◽  
...  

Lithium-induced nephrogenic diabetes insipidus is associated with increased renal sodium excretion in addition to severe urinary concentrating defects. However, the molecular basis for this altered renal sodium excretion remains undefined. The amiloride-sensitive sodium channel (ENaC) is expressed in the renal connecting tubule and collecting duct and is essential in renal regulation of body sodium balance and blood pressure. We hypothesized that dysregulation of ENaC subunits may be responsible for the increased sodium excretion associated with lithium treatment. Lithium treatment for 28 days resulted in severe polyuria, increased fractional excretion of sodium, and increased plasma aldosterone concentration. Immunoblotting revealed that lithium treatment induced a marked decrease in the protein abundance of β-ENaC and γ-ENaC in the cortex and outer medulla. Moreover, immunohistochemistry and laser confocal microscopy demonstrated an almost complete absence of β-ENaC and γ-ENaC labeling in cortical and outer medullary collecting duct, which was not affected by dietary sodium intake. In contrast, immunohistochemistry showed increased apical labeling of all ENaC subunits in the connecting tubule and inner medullary collecting duct in rats on a fixed sodium intake but not in rats with free access to sodium. Except for a modest downregulation of the thiazide-sensitive Na-Cl cotransporter, the key renal sodium transporters upstream from the connecting tubule (including the α1-subunit of Na-K-ATPase, type 3 Na/H exchanger, and Na-K-2Cl cotransporter) were unchanged. These results identify a marked and highly segment-specific downregulation of β-ENaC and γ-ENaC in the cortical and outer medullary collecting duct, chief sites for collecting duct sodium reabsorption, in rats with a lithium-induced increase in fractional excretion of sodium.


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