SSc patients with scleroderma renal crisis have high PIGF levels

Protein may serve as tool for evaluating long-term dialysis risk, said researchers by Katherine Poinsatte | January 21, 2025

​Scleroderma (SSc) patients who’ve had a scleroderma renal crisis, a life-threatening complication of SSc, have higher levels of placental growth factor (PIGF), protein that stimulates blood vessel growth, in their blood than those who haven’t had one, a study in France shows.

Among French patients who’d had a scleroderma renal crisis, higher PIGF levels were also found in those who reached end-stage kidney failure compared with SSc patients who didn’t need dialysis, which is a treatment to clean the blood.

“Serum [blood] PlGF may identify the risk of [scleroderma renal crisis] occurrence among SSc patients with a good specificity and represents a potential tool for long-term dialysis risk evaluation,” the researchers wrote. The study, “Pilot Study of diagnostic performances of vascular biomarkers soluble fms-like tyrosine kinase and placental growth factor in scleroderma renal crisis,” was published in Kidney International Reports. 
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In a scleroderma renal crisis, abrupt blood pressure changes and acute kidney failure augurs a risk of of chronic kidney disease and dialysis. One of the few clinically measurable risk factors for developing scleroderma renal crisis is the presence of antibodies against RNA polymerase III. No biomarker has been able to help predict kidney prognosis after a scleroderma renal crisis, however.
PIGF has been found at higher levels in SSc patients with pulmonary hypertension, a condition where blood pressure in the lungs is abnormally high, compared with people with SSc but without pulmonary hypertension.

PIGF protein may be SSc biomarker
The researchers hypothesized that PIGF could likewise serve as a biomarker to help determine the risk of scleroderma renal crisis and compared 27 SSc patients with a history of scleroderma renal crisis against 24 patients who hadn’t had one.

Those with a history of scleroderma renal crisis were more likely to have diffuse systemic scleroderma, have thicker skin, and showed significantly higher blood levels of creatinine, which can signal kidney damage.

Results showed that 37% of the SSc patients who’d had a scleroderma renal crisis tested positive for anti-RNA polymerase III antibodies, while only 13% without scleroderma renal crisis had the self-reactive antibodies, a statistically significant difference.

Median PIGF levels were significantly higher in SSc patients who’d had a scleroderma renal crisis compared with those hadn’t had a scleroderma renal crisis — 42.1 vs. 18.5 picograms (pg) per milliliter of blood serum.

Similar differences were seen between SSc patients who had a scleroderma renal crisis and healthy control donors, and with control groups of patients with hemolytic uremic syndrome, a condition that damages blood vessels in the kidneys, or malignant hypertension, which is when sudden increases in blood pressure raise the risk of organ damage. In contrast, PIGF levels didn’t differ between patients with or without self-reactive antibodies against RNA polymerase III.

Patients who had high levels of PIGF, defined as above 26.5 pg per milliliter, were more likely to have diffuse forms of SSc and to have telangiectasia, that is, small, widened blood vessels near the surface of the skin.

The scientists also measured the diagnostic accuracy of PIGF measurement for scleroderma renal crisis diagnosis. A threshold of 24.5 pg per milliliter was associated with a specificity of 95% and a sensitivity of 67%. Specificity refers to the ability to rule out a diagnosis, while sensitivity refers to the ability to correctly identify people with a given condition.

Among those who’d had scleroderma renal crisis, higher PIGF levels were associated with a higher risk for chronic kidney disease and an increased risk of long-term dialysis after a median follow-up of six years.
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“Our study reports that high PlGF levels are associated with [scleroderma renal crisis] and the risk of kidney failure. These findings suggest that PlGF could serve as a valuable biomarker for [scleroderma renal crisis] renal prognosis,” wrote the researchers, who said more studies, including blood analysis before a scleroderma renal crisis, are needed to validate using PlGF as a reliable diagnostic biomarker for the complication in clinical practice.