AB0124 NO EFFECTS OF HIGH DOSE 25OH-VITAMIN D SUPPLEMENTATION ON LUPUS NEPHRITIS IN AN ANIMAL MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: S. Barsotti, C. Tani, A. Kuhl, S. Pacini, S. Vagnani, M. Mosca
Journal: Annals of the Rheumatic Diseases (2020)

Background: 25OH Vitamin D (25-OH-D3) is a fat-soluble steroid-derived molecule involved in the calcium homeostasis. Low levels of 25-OH-D3 are commonly found in patients with systemic lupus erythematosus (SLE) and have been correlated to higher disease activity and severity. Several recent studies have demonstrated that high dose Vitamin D may influence several aspects of the innate and adaptive immune response and some authors hypothesized that high dose 25-OH-D3 may have a role in the treatment of SLE. Despite these observations, the immunomodulatory effect of high dose 25-OH-D3 in vivo still needs to be demonstrated. Objectives: The aim of our study was to identify the effect of 25-OH-D3 on proteinuria, survival and renal biopsy in New Zealand Black/White F1 mice (NZ), that develop a disease very similar to human SLE nephritis. Methods: We administered to 20 NZ mice a diet enriched with high dose 25-OH-D3 10,000 UI/Kg starting from 8 weeks of age. Mice were divided in 7 experimental groups (5 mice each). The first group was sacrificed before the start of the treatment (8 week of age), three groups were treated (treated mice – TM) with 25-OH-D3 and sacrificed at 16, 26 and 36 weeks of age. The other three groups were enrolled as controls and sacrificed at 16, 26 and 36 weeks of age respectively (untreated mice – UM). The parameters collected included: total urinary protein and kidney histology for the evaluation of lupus nephritis (LN): glomerulonephritis, interstitial nephritis and vascular lesions according to a 5 points scale to obtain a total score (ranging from 0 to 12). Results: In UM, proteinuria tended to increase over 1 mg/day at 12 weeks of age (1.7±0.43mg/day) and further increased until to reach a plateau after 28 weeks of age (10±2.0 mg/day). In TM, a significant increase in proteinuria over 1 mg/day was observed at 24 weeks, when the mean proteinuria was 1.7±1.33 which was lower than controls at the same age although without statistical significance (2.9±2.6); thereafter proteinuria started to increase also in treated mice and at week 30 was higher in TM compared with UM (10,3±8.8 vs 4.3±3.5 p=0.05). Figure 1. Kidney histology showed, in mice sacrificed before the start of the treatment no signs of LN. In mice sacrificed at 16 weeks minimal interstitial nephritis (score 1) was identified in 2 mice only in UM. At 26 weeks of age, a higher total LN score was identified in TM compared with UM (3.4±3.8 vs 0.4 ±0.9) with higher score for all three parameters analyzed. At 36 weeks of age, the TM group maintained a higher total LN score compared to UM (6.5±1.7 vs 6.0±2.6) with higher score for glomerulonephritis and interstitial nephritis. In the TM group, three mice spontaneously died at 26, 30 and 32 weeks of age, while in the UM only one mouse died at 36 weeks of age. Conclusion: Our data suggest that, in this animal model of SLE, 25-OH-D3 administration seems to delay the onset of proteinuria, although has no effect on the overall disease control. In addition, it may have a negative effect on renal histology and survival with earlier development of LN. Figure: Disclosure of Interests: None declared