Fibroblast growth factor 23 is associated with fractional excretion of sodium in patients with chronic kidney disease

2018 ◽  
Vol 34 (12) ◽  
pp. 2051-2057 ◽  
Author(s):  
Hong Xu ◽  
Ali Hashem ◽  
Anna Witasp ◽  
Rik Mencke ◽  
David Goldsmith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Sodium Excretion ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Fibroblast Growth ◽  
Fractional Excretion Of Sodium ◽  
Renal Sodium Handling ◽  
Sodium Handling

Abstract Background Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin–angiotensin–aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients. Methods This was a cross-sectional study encompassing 180 CKD patients Stage 1–5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis. Results The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman’s rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship. Conclusions FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.

[PP.30.05] BLOOD PRESSURE IN RELATION TO 24-HOUR URINARY SODIUM EXCRETION AND RENAL SODIUM HANDLING

2016 ◽  
Vol 34 ◽  
pp. e308
Author(s):  
K. Stolarz-Skrzypek ◽  
A. Bednarski ◽  
A. Franczyk ◽  
M. Folta ◽  
H. Barton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Renal Sodium Handling ◽  
Sodium Handling

scholarly journals Fibroblast Growth Factor 23 and Blood Pressure in Older Adults

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 236-243
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Antihypertensive Medications ◽  
Incident Hypertension ◽  
Blood Pressures ◽  
The Mean ◽  
Fgf 23

FGF-23 (fibroblast growth factor 23) regulates phosphorus and vitamin D. Elevated FGF-23 is associated with incident hypertension in young- and middle-aged adults, but there is limited data in older adults. Serum FGF-23 was measured using an intact ELISA assay in 2496 participants of the Healthy Aging and Body Composition Study. The association between FGF-23 and prevalent hypertension (self-reported and confirmed by use of antihypertensive medications) and number of antihypertensive medications was determined. The associations between FGF-23 and incident hypertension, and diastolic and systolic blood pressure trajectories were evaluated over 10 years. Models were adjusted for demographics, estimated glomerular filtration rate and albuminuria, cardiovascular disease risk factors, and measures of mineral metabolism. The mean (SD) age was 75 (3) years, with 51% women, and 40% black participants. The prevalence of hypertension at baseline was 75% and the mean systolic and diastolic blood pressures were 134 (21) mm Hg and 70 (12) mm Hg, respectively. The majority of participants without hypertension at baseline developed incident hypertension (576 of 1109 or 52%). In adjusted models, each 2-fold higher FGF-23 was associated with prevalent baseline hypertension (odds ratio=1.46 [1.24–1.73]) and greater number of blood pressure medications (IRR=1.14 [1.08–1.21]) but not with baseline diastolic or systolic blood pressure. In fully adjusted longitudinal analyses, a 2-fold higher FGF-23 was associated with incident hypertension (hazard ratio=1.18 [1.03–1.36]) and worsening systolic blood pressures (β=0.24 [0.08–0.40] mm Hg per year increase), but not with diastolic blood pressures (β=0.04 [−0.04 to 0.12] mm Hg per year increase). Higher FGF-23 concentrations are associated with prevalent and incident hypertension as well as rising systolic blood pressures in community-living older adults.

Role of atrial natriuretic peptide in volume-expansion natriuresis

1986 ◽  
Vol 251 (2) ◽  
pp. R310-R313 ◽  
Author(s):  
T. R. Schwab ◽  
B. S. Edwards ◽  
D. M. Heublein ◽  
J. C. Burnett
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Urinary Sodium ◽  
Right Atrial ◽  
Fractional Excretion Of Sodium

Studies were performed to investigate the role of circulating atrial natriuretic peptide (ANP) in acute volume-expansion natriuresis. Sham-operated (SHAM, n = 6) and right atrial appendectomized (ATRX, n = 12) anesthetized rats underwent acute volume expansion with isoncotic albumin. After equilibration and control periods, volume expansion increased urine flow rate, urinary sodium excretion, fractional excretion of sodium, and circulating ANP. Absolute increases in urine flow rate (delta 46 +/- 4 SHAM; delta 25 +/- 5 microliter/min ATRX), urinary sodium excretion (delta 9.48 +/- 1.01 SHAM; delta 4.77 +/- 1.03 mueq/min ATRX), fractional excretion of sodium (delta 3.16 +/- 0.53 SHAM; delta 1.65 +/- 0.32% ATRX), and ANP (delta 303.3 +/- 35.9 SHAM; delta 156.6 +/- 26.0 pg/ml ATRX) were significantly reduced by right atrial appendectomy. No significant differences in mean arterial pressure, central venous pressure, or glomerular filtration rate during volume expansion were observed between groups. These studies support the hypothesis that right atrial appendectomy in the rat attenuates acute volume expansion-induced increases in circulating ANP and urinary sodium excretion and that the natriuresis of acute volume expansion is mediated in part by an increase in circulating ANP.

Response to atrial natriuretic peptide in dogs with hypovolemic acute pancreatitis

1989 ◽  
Vol 256 (2) ◽  
pp. F211-F217
Author(s):  
M. Levy ◽  
P. Cernacek
Keyword(s):  
Blood Pressure ◽  
Acute Pancreatitis ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Volume ◽  
Sodium Excretion ◽  
Fractional Excretion ◽  
Fractional Excretion Of Sodium ◽  
Acute Renal Insufficiency ◽  
Atrial Natriuretic

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.

scholarly journals Ubiquitin COOH-terminal hydrolase L1 deletion is associated with urinary α-klotho deficiency and perturbed phosphate homeostasis

2018 ◽  
Vol 315 (2) ◽  
pp. F353-F363 ◽  
Author(s):  
Naomi C. Boisvert ◽  
Chet E. Holterman ◽  
Alexey Gutsol ◽  
Josée Coulombe ◽  
Wanling Pan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Sodium Phosphate ◽  
Fibroblast Growth Factor 23 ◽  
Fractional Excretion ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Wild Type ◽  
Phosphate Homeostasis ◽  
Renal Brush Border Membrane

Loss of ubiquitin COOH-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1−/− mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels was similar to wild-type levels. Plasma parathyroid hormone and fibroblast growth factor 23 levels were not different; however, fibroblast growth factor 23 mRNA levels were significantly increased in femur homogenates from Uchl1−/− mice. Full-length and soluble α-klotho levels were comparable in kidneys from wild-type and Uchl1−/− mice; however, soluble α-klotho was reduced in Uchl1−/− mice urine. Consistent with unchanged components of 1,25(OH)2D3 metabolism (i.e., CYP27B1 and CYP24A1), sodium-phosphate cotransporter 2b protein levels were not different in ileum brush borders from Uchl1−/− mice, suggesting that the intestine is not the source of hyperphosphatemia. Nonetheless, when Uchl1−/− mice were fed a low-phosphate diet, plasma phosphate, urinary phosphate, and fractional excretion of phosphate were significantly attenuated and comparable to levels of low-phosphate diet-fed wild-type mice. Our findings demonstrate that Uchl1-deleted mice exhibit perturbed phosphate homeostasis, likely consequent to decreased urinary soluble α-klotho, which can be rescued with a low-phosphate diet. Uchl1−/− mice may provide a useful mouse model to study mild perturbations in phosphate homeostasis.

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