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

## TL;DR

This study explores how two vascular biomarkers, PlGF and sFlt-1, can help diagnose and predict outcomes in patients with scleroderma renal crisis.

## Contribution

The study introduces PlGF as a novel biomarker with high specificity for diagnosing scleroderma renal crisis and predicting dialysis risk.

## Key findings

- PlGF levels were significantly higher in patients with scleroderma renal crisis compared to controls and other kidney disease groups.
- A PlGF level above 24.5 pg/ml showed 95% specificity and 67% sensitivity for diagnosing scleroderma renal crisis.
- Higher PlGF levels were associated with increased risk of end-stage kidney failure in these patients.

## Abstract

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.

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.

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).

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.