Abnormal Diurnal Patterns of Parathyroid Hormone are Associated with Sustained Mild Hypercalcemia in Non-Dialyzed Chronic Kidney Disease.

BACKGROUND: Plasma PTH levels are normally high during the night and early morning and lowest at approximately 10 am (the PTH circadian rhythm). Our objective was to examine the relationship between the PTH circadian rhythm and calcium-phosphorus metabolism in non-dialyzed, chronic kidney disease (CKD) patients. METHODS: The characteristics of twenty-eight subjects comprised: male, 23; diabetic patients, 16; mean age, 71.1 +/- 10.5 years; mean eGFR, 18.3 +/- 8.1 mL/min/1.73 m2. Under a protein-restricted diet, plasma intact PTH (iPTH) was measured at 7 am (iPTH7), 10 am (iPTH10), and 10 pm (iPTH22). Serum concentrations of calcium (Ca), phosphate (Pi), 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25[OH]2D), and fibroblast growth factor (FGF)-23 were measured at 7 am. A normal iPTH rhythm was defined as when both iPTH7 and iPTH22 exceeded iPTH10. When iPTH10 was equal to, or exceeded either iPTH7 or iPTH22, or both, the rhythm was considered abnormal. RESULTS: Median levels of iPTH7, iPTH10, and iPTH22 were 92.5 [IQR: 60.8-152.01, 85.5 [61.0-144.5], and 95.5 164.3-160.5] pg/mL, respectively. Sixteen subjects showed an abnormal iPTH rhythm. There was no significant difference between groups in age, eGFR, iPTH7, iPTH10, iPTH22, Pi, 25-OH1D, 1,25(OH)2D, or FGF-23. However, the abnormal group showed significantly higher mean levels of corrected Ca as compared to the normal group (9.50 +/- 0.42 vs. 9.18 +/- 0.28; p = 0.032). CONCLUSIONS: Abnormal diurnal patterns of PTH are associated with sustained mild hypercalcemia in nondialyzed chronic kidney disease patients. This abnormal rhythm was not associated with Pi or FGF-23, and this may be an independent risk factor for CKD-mineral and bone disorder.

Continuous Hemodiafiltration with an AN69ST Hemofilter (AN69ST-CHDF) as FGF-23-Lowering Therapy.

BACKGROUND: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Continuous hemodiafiltration (CHDF) is often performed for the treatment of the aforementioned acute illnesses. We have previously reported that an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has a greater capacity for in vitro FGF-23 adsorption than polysulfone and polymethyl methacrylate membranes. However, reports related to the influence of AN69ST-CHDF on serum FGF-23 levels in acute illness are lacking. In this study, we investigated the effect of AN69ST-CHDF on circulating FGF-23 concentrations in clinical practice. METHODS: Subjects comprised six inpatients who underwent AN69ST-CHDF for an acute illness. Blood samples for the measurement of serum FGF-23 were collected at 0, 3, and 12 hours post-treatment. Blood samples were also drawn from the extracorporeal circuit at the inlet and outlet of the hemofilter 3 hours after CHDF initiation, in order to calculate the clearance of serum FGF-23. RESULTS: Three and 12 hours after the start of AN69ST-CHDF, circulating FGF-23 levels decreased from baseline values with a marginal statistical significance (p = 0.0625 and 0.0938, respectively). An FGF-23 clearance of 27.5 [interquartile range: 19.4 - 29.2] mL/minute 3 hours after the initiation of AN69ST-CHDF was achieved. CONCLUSIONS: Our results suggest that AN69ST-CHDF can be a novel FGF-23 lowering therapy for acute illnesses requiring acute blood purification.