#2421 Kidney injury in scleroderma: serum level of fibroblast growth factor-23, klotho and neutrophil gelatinase-associated lipocalin after iloprost infusion

Abstract

Abstract Background and Aims Systemic sclerosis (SSc) is characterized by progressive derangement of the microcirculation leading to a state of chronic tissue hypoxia with release of several inflammatory cytokines such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Renal scleroderma associated-vasculopathy is characterized by vascular damage with normal renal function and increased intrarenal stiffness, assessed by renal resistive index (RRI) Aim of this study was to evaluate at baseline serum levels of FGF-23, Klotho and NGAL in SSc patients and healthy controls (HC) and to correlate the serum levels of these markers with microvascular damage of skin and kidney. Secondary aim was to evaluate the serum levels of FGF-23, Klotho and NGAL after Iloprost infusion. Method Twenty-one SSc patients and 20 HC were enrolled. All patients had a 2-months wash-out of Iloprost infusion before of clinical, laboratory and instrumental assessment. Peripheral venous blood was collected at three different time points for SSc patients: t0 immediately before the first Iloprost infusion (after 2-months wash-out period), t1 immediately after the first Iloprost infusion and t2 the day of the next Iloprost infusion (about 14 days from the last infusion). Results SSc patients had higher serum level of FGF-23 [18.7 pg/mL (± 6.4) vs 3.6 pg/mL (± 2.2), p < 0.001], Klotho [5.1 pg/mL (±0.8) vs 2.3 pg/mL (±0.6), p < 0.001] and NGAL [20.9 pg/mL (±2.6) vs 14.5 pg/mL (±1.7), p < 0.001] compared to HC. The one-way repeated-measures ANOVA showed that mean FGF-23 [F (2,40) = 71.255, p < 0.001], Klotho [F (1.405, 28.103) = 195.095, p < 0.001] and NGAL [F (2,40) = 48.024, p < 0.001] differed significantly between time points. Conclusion SSc patients had higher FGF-23, Klotho and NGAL than HC. Our present data demonstrate that microvascular damage is associated to chronic hypoperfusion with increased circulating markers such as FGF-23, Klotho and NGAL. For the first time, we demonstrated that Iloprost infusion reduces significantly serum level of FGF-23, Klotho and NGAL and it has showed to be a key role in renal vasculopathy in SSc patients. In literature, there are no data about the modification of these serum markers before and after vasoactive treatment, especially of Iloprost infusion.