Kidney Week

Abstract: SA-PO269

1.25(OH)₂D Status in ESKD: Role of 25(OH)D and Residual Renal Function

Session Information

• Bone and Mineral Metabolism: Calcium, Magnesium, Kidney Stones
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium

Pieter Evenepoel,

• Vandewalle, Jan, University Hospitals KU Leuven, Leuven, Belgium

Jan Vandewalle,

• Bammens, Bert, University Hospitals Leuven, Leuven, Belgium

Bert Bammens,

• Claes, Kathleen, University Hospital Gasthuisberg, Leuven, Belgium

Kathleen Claes,

• Meijers, Björn Ki, UZ Leuven, Leuven, Belgium

Björn Ki Meijers,

• Naesens, Maarten, University Hospitals Leuven, Leuven, Belgium

Maarten Naesens,

• Sprangers, Ben, University of Hospitals Leuven, Leuven, Belgium

Ben Sprangers,

• Kuypers, Dirk R., University Hospitals Leuven, Leuven, Belgium

Dirk R. Kuypers,

Background

Recent insights into vitamin D regulation suggest that CKD is a state of stagnant vitamin D metabolism characterized by reduced 1.25(OH)₂D production (mediated by CYP27B1) and catabolism. The present study aimed to clarify whether this is caused by insufficient delivery of substrate or low nephron mass. As a secondary aim we investigated seasonal variation and long term trends of vitamin D levels in patients with ESKD.

Methods

We analyzed serum levels of 1.25(OH)₂D (LC MS/MS), 25(OH)D (RIA), along with other parameters of mineral metabolism (including PTH, FGF23, sclerostin), markers of inflammation in 518 adult patients (age 54.7 ± 12.8 yrs, males 60.6%) with ESKD between April 23, 2006 and December 21, 2013. Data on residual renal function (RRF) were available in 330 patients: 115 patients were anuric (24h urine output < 100 ml) and 21 patients were anephric.

Results

Median 25(OH)D and 1.25(OH)₂D levels in the overall cohort were 35.9 [24.0 – 48.6] µg/L and 26.8 [18.2 – 36.9] ng/L, respectively. 25(OH)D levels showed seasonal variation and increased by 16% along the study period (2006-2013), most probably as a result of more intense supplementation. A parallel 31% increase of 1.25(OH)₂D levels was noted. In regression analysis, only high 25(OH)D and low phosphate and sclerostin independently associated with high 1.25(OH)₂D levels. 25(OH)D was the most important determinant of 1.25(OH)₂D levels, explaining 30% of its variability. RRF did not correlate with 1.25(OH)₂D levels. Remarkably, 1.25(OH)₂D levels were only slightly lower in anephric patients (20.3 vs 27.3 ng/L, median, p=0.02). This suggests that non-renal tissues may contribute substantially to circulating 1.25(OH)₂D levels. In anuric patients, 25(OH)D levels, but not mineral metabolism hormones or inflammation were associated with 1.25(OH)₂D levels.

Conclusion

1.25(OH)₂D levels in patients with ESKD are manifestly dependent on the delivery of 25(OH)D. Extrarenal CYP27B1 activity may sustain normal 1.25(OH)₂D levels, even in anephric patients. Substrate delivery thus seems to be much more important than nephron mass in maintaining adequate 1.25(OH)₂D level. Seasonal fluctuations and long term kinetics illustrate that both vitamin D generation in the skin and nutritional vitamin D supplements contribute to 25(OH)D stores in ESKD.