Circadian variation of mineral and bone parameters in end-stage renal disease

Hariprasad Trivedi
Aniko Szabo
Shi Zhao
Tom Cantor
Hershel Raff, Aurora Health Care

Endocrine Research Laboratory, Aurora St. Luke’s Medical Center, Aurora Research Institute


BACKGROUND: Mineral and bone parameters are actively managed in end-stage renal disease (ESRD). However, whether these undergo circadian variation is not known. We investigated the circadian variation of mineral and bone parameters in patients on long-term hemodialysis.

METHODS: Seventeen ESRD patients on long-term hemodialysis and eight volunteers without kidney disease were enrolled. Subjects had all medications that affect calcium-phosphate-parathyroid hormone balance (phosphate binders, vitamin D analogues, and calcimimetics) discontinued. Thereafter, for a period of 5 days, subjects consumed a diet controlled in calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve 2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total 25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23).

RESULTS: In the ESRD patients plasma phosphate demonstrated significant circadian variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P = 0.009) also varied significantly during the circadian period; for ionized calcium peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a significant circadian variation. Only phosphate (P < 0.0001) and PTH (P = 0.00008) demonstrated circadian variation in the control group.

CONCLUSIONS: Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit a circadian variation in patients with ESRD. Knowledge of these phenomena is pertinent for the interpretation of clinical testing.