ACUTE PARICALCITOL ADMINISTRATION REDUCE INFLAMMATION IN CKD PATIENTS IN VIVO AND IN VITRO

Introduction and Aims: Microinflammation state is a pathologic feature of chronic kidney diseases(CKD). Recent evidence suggests that vitamin D deficiency, common in CKD patients, has a role in the modulation of immune response and inflammation. Evidence is also mounting that Paricalcitol (Pr),a synthetic vitamin D analogue, is renoprotective in different inflammatory nephropathies. Neutrophil gelatinase-associated lipocalin (NGAL),a protein with a key role in the innate immune response, is upregulated in presence of inflammation. The aim of our study was to evaluate the anti-inflammatory action in acute of Pr in CKD patients in vivo and in vitro. Methods: The study was conducted on 40 patients with IV-V stage of CKD and a control group (HS). We measured serum levels of calcium(Ca), phosphorous(P), vitamin D, parathyroid hormone(PTH), erythrocyte sedimentation rate(ESR), high-sensitivity C-reactive protein(hsCRP), interleukin-17(IL-17),interleukin-1beta (IL-1ß), interferon-gamma(IFN- ), tumour necrosis factor-alpha(TNF-!), plasmatic and urinary NGAL, albuminuria and proteinuria before and after 24 hours of an intravenous bolus of Pr 5 mcg. Human peripheral blood mononuclear cellswere isolatedand stimulated with phytohaemagglutinin. In the culture medium we measured:NGAL, IL-1ß, IL-17, TNF-! and IFN- . Results: CKD patients have alterations of Ca/P metabolism. Vitamin D values were significantly lower in these patients than in HS( p<0.0001), while the amounts of inflammatory markers such as cytokines levels were significantly higher( p<0.0001). After Pr, in CKD patients, there was a significant increase in 25(OH)D levels( p<0.005) associatedwithareductionofPTH,butnotinastatisticallysignificantway.NGALand cytokines amounts were significantly down-regulated( p<0.0001) both in vivo and in vitro. At univariate analysis,NGAL was found to be directly correlated in vivowith ESR, IL-17,INF- ,IL-1à,TNF-# and hsPCR. In vitro NGAL was found to be directly correlated with ESR, hsPCR, IL-17, IL-1à, TNF-#, while an inversion correlation was found with 25(OH)D. No significant correlation was found for albuminuria, proteinuria, PTH, Ca or P. In a multivariate model using NGAL as a dependent variable, in vivo significance was maintained for the correlation between NGAL and ESR, hsCRP,IL-17,IFN- and TNF-#. In vitro for NGAL and Vit D,IL-1à and TNF-#. Conclusions: Studies have shown an involvement of Pr in the regulation of immune and inflammatory processes. These effects appear to be mediated by non-PTH mechanisms. Pr can be used for anty-inflammatory therapeutic purposes.