Circadian Changes in Plasma Phosphate Concentration, Urinary Phosphate Excretion, and Cellular Phosphate Shifts

Kemp, Graham J.; Blumsohn, Aubrey; Morris, B W

doi:10.1093/clinchem/38.3.400

Cited by 46 publications

(24 citation statements)

References 2 publications

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“…Our findings could also represent an effect of dapagliflozin on the Nampt/NAD + pathway, which regulates the circadian rhythm of phosphate (25). The nadir of this circadian rhythm occurs around 8:00-11:00 AM (26)(27)(28), coinciding with sample collection in this study. Our results may therefore reflect attenuation of the circadian rhythm rather than a consistent effect over time.…”

Section: Discussionsupporting

confidence: 64%

Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

Jong¹,

Petrykiv²,

Laverman³

et al. 2018

CJASN

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Background and objectives The sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear. Design, setting, participants, & measurements We performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable reninangiotensin-aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR$45 ml/min per 1.73 m 2 , and glycosylated hemoglobin$7.2% and ,11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) levels. Results Thirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH) 2 D decreased by 212% (225% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment. Conclusions Dapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

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Section: Discussionsupporting

confidence: 64%

Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

Jong¹,

Petrykiv²,

Laverman³

et al. 2018

CJASN

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“…Variation in the urinary excretion of phosphate is expected in relation to food intake. However, even in constant conditions (food intake taken as hourly snacks, constant light and rest) important variations in phosphate excretion have been observed (37,40). This data suggests that phosphate excretion is controlled by an endogenous mechanism independent of food intake or other systemic cues.…”

Section: Phosphatementioning

confidence: 96%

Circadian regulation of renal function

Firsov

Bonny

2010

Kidney International

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Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms.

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“…15,16 Plasma Pi concentrations and renal Pi excretion display significant daily oscillations in animals [17][18][19] as well as in humans. 12,13,[20][21][22][23] The daily oscillation of plasma Pi levels in nocturnal rodents (rats) is roughly inverse to that in humans. 14,[17][18][19][20]24 In humans and rodents, plasma Pi levels are decreased during the active phase and increased in the resting phase.…”

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confidence: 99%