Pilot Study of Diagnostic Performances of Vascular Biomarkers Soluble fms-Like Tyrosine Kinase and Placental Growth Factor in Scleroderma Renal Crisis

Abstract

Introduction

Scleroderma renal crisis (SRC) is a major vascular complication of systemic sclerosis (SSc), associated with high morbidity and mortality. In this retrospective study, we evaluated the potential prognostic and diagnostic roles of angiogenesis molecules, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt1/PlGF ratio as biomarkers in SRC.

Methods

Sera samples from 27 patients with a history of SRC (SSc-SRC+) were collected following event occurence. Biomarker levels were assessed using an electrochemiluminescence immunoassay and compared with age- and sex-matched patients with SSc-SRC− (n = 24), hemolytic uremic syndrome (HUS) (n = 27), malignant hypertension (MHT) (n = 22), and donors (n = 61). Areas under the receiver-operating-characteristic curves (AUC) were used to evaluate diagnostic accuracy. Long-term dialysis risk was evaluated using a Cox model.

Results

The median (interquartile range [IQR]) PlGF (pg/ml) was significantly higher in the serum of patients with SSc-SRC+ (42.1 [21.4–51.8]) compared with donors (14.7 [11.8–17.9]), those with SSc-SRC− (18.5 [14.7–21.5]) (P < 0.0001), those with HUS (22.8 [19.5–29.6]), and those with MHT (25.5 [17.2–39.3]) (P < 0.0001). In a multivariate regression adjusting for multiple confounders, PlGF was associated with higher SRC risk with an odds ratio of 1.08 [1.01–1.22], (P = 0.034). A PlGF level above 24.5 pg/ml revealed an AUC of 0.81 (confidence interval [0.68–0.94]), a specificity of 95%, and a sensitivity of 67% for SRC diagnosis. Eleven patients with SSc-SRC+ reached end-stage kidney failure with significantly higher PlGF (42.9 [22.4–78.2]) compared with patients who were dialysis-free (19.7 [15.6–29.7], P = 0.03).

Conclusion

Serum PlGF may identify the risk of SRC occurrence among patients with SSc with a good specificity and represents a potential tool for long-term dialysis risk evaluation.