1,25D/25D RATIO TO ASSESS THE OVERALL BALANCE OF VITAMIN D HYDROXYLASES (D-OH-ases)

INTRODUCTION AND AIMS

Anabolic and/or catabolic vitamin D-OH-ases (1-alpha, 24- and 25- OH-ases), differently regulated in variable clinical conditions, are responsible for fluctuating 1,25D levels. The overall balance could thus affect sensitivity to insufficiency and/or deficiency: 1,25D levels will be less dependent from vitamin D stores in cases with more efficient activity.

We hypothesized that the ratio between the active hormone, 1,25D, and its precursor, 25D, could represent an indirect tool to estimate the overall balance of vitamin D-OH-ases activity.

METHODS

We studied two CKD populations, CRF on conservative therapy and renal TX pts, who presumably are developing or, respectively, recovering from secondary hyperparathyroidism. 70 CRF and 80 TX, naïve to vitamin D therapy, were selected to be comparable for age (58±15 vs. 54±10 y), renal function (eGRF 45±22 vs 46±15 ml/min) and 25D levels (23±11 vs 26±11 ng/ml). 300 normal subjects (N; age 45±14 y; eGFR 113±14 ml/min; 25D 25±13 ng/ml) were the controls (Figura 1),

RESULTS

1,25D levels were 24±13, 42±15 and 50±16 pg/ml respectively in CRF, TX and N (p<.001).

The ratio 1,25D/25D was 1,4±1,0 in CRF, 2.0±1,4 in TX, and 3.0±2,4 in N (p<.0001).

In the subgroup with 25D≥20 ng/ml, the ratio was 0.9±0.5 in CRF; 1.4±0.6 in TX and 2.0±0.5 in N (p<.0001).

In the subgroup with 25D<20 ng/ml it was 2.2±1.2 in CRF; 3.4±1.6 in TX and 4.0±3.3 in N (p<.001) (Figura 2) .

In each of the populations (CRF, TX and N), the ratio was different between the two storage conditions (p<.001).

The ratio correlated negatively with 25D in each population (p<.0001), with r values definitely increasing with the use of non-linear models in N (from 0.556 to 0.774) and in TX (from 0.692 to 0.812), but not in CRF (from 0.648 to 0.692) (Figura 3) (Figura 4).

CONCLUSIONS

In our experience the ratio 1,25D/25D, as expected in feed-back systems, is negatively correlated with the substrate, has higher values in case of deficiency, and shows an exponential increment in N and in TX. CRF patients with the lowest values, can be regarded as more sensitive to vitamin D insufficiency or deficiency.