P0722VITAMIN D-DEFICIENT RATS RECOVER RENAL ALTERATIONS AFTER VITAMIN D REPLACEMENT FOLLOWING ISCHEMIA-REPERFUSION INJURY

Abstract

Abstract Background and Aims Several studies have been linking vitamin D deficiency (VDD) as a non-traditional risk factor to acute kidney injury (AKI). It has been shown that VDD associated with AKI potentiates the injury and may accelerate the progression of kidney disease. Conversely, some lines of evidence have been describing that vitamin D sufficiency can be considered as a renal protective factor. Thus, we aimed to verify the effect of vitamin D replacement (R) on the renal disease progression post ischemia-reperfusion injury (IRI) in vitamin D deficient rats. Method We performed bilateral 45 min IRI on day 30 in all animal groups. Male Wistar rats were randomized into three groups: 1- IRI (fed a standard diet for 120 days); 2- VDD+IRI (fed a vitamin D-free diet for 120 days); and 3- VDD+IRI+R (fed a vitamin D-free diet for 30 days and just after IRI, on day 31, we reintroduced the standard diet for more 90 days). We evaluated inulin clearance (Cin); mean arterial pressure (MAP); renal blood flow (RBF); plasma levels of Vitamin D2+D3 [25(OH)D] and Parathormone (PTH) by ELISA. In addition, we performed histomorphometrical studies for CD3+ cells, fibronectin and vimentin as well as the fractional interstitial area (FIA). Moreover, we run qPCR studies and immunoblotted for vitamin D receptor (VDR) and Klotho. All the results are described in table 1. Results Vitamin D replacement restored the plasma levels of 25(OH)D and PTH in VDD+IRI+R group. Also, VDD+IRI+R presented an improvement of renal function and hemodynamic parameters. In addition, we observed more evident alterations in tubulointerstitial compartment, featuring interstitial expansion (renal fibrosis and inflammatory cell infiltrates) and fibronectin and vimentin expression in VDD+IRI rats. These alterations were recovered by vitamin D replacement. Concerning VDR and Klotho data, our results revealed a decreased expression of these targets in VDD+IRI group. On the other hand, vitamin D replacement retrieved the expression of VDR and Klotho. Conclusion Our study suggests that vitamin D replacement improved the recovery of renal function, hemodynamics, inflammatory and morphological alterations. In addition, vitamin D replacement was able to reestablish the expression of VDR and Klotho in IRI-AKI associated with vitamin D deficiency. Thus, it is recommendable that vitamin D levels should be observed as well as its reposition should be taken into account in renal patients.