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Pigment epithelium-derived factor plays role in heightened CKD risk
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Among adults with type 2 diabetes, higher levels of serum pigment epithelium-derived factor can lead to an increased likelihood of more severe stages of kidney disease, according to findings published in the Journal of Diabetes and its Complications.
“[Pigment epithelium-derived factor] is an adipokine with antioxidant, anti-inflammatory, antifibrotic and insulin-sensitizing effects,” Kelly J. Hunt, PhD, professor in the department of public health sciences at the Medical University of South Carolina in Charleston, and colleagues wrote. “Circulating levels have been associated with insulin resistance, diabetes and diabetic vascular complications. Hence, altered levels may be associated with, predict or mediate vascular damage and [pigment epithelium-derived factor] could constitute a therapeutic target and/or agent.”
Hunt and colleagues measured pigment epithelium-derived factor in 970 participants (mean age, 59.7 years; 3.1% women) from the Veterans Affairs Diabetes Trial who were recruited between 2000 and 2003 and followed until 2008. According to the researchers, initial measurements of pigment epithelium-derived factor were made using an enzyme-linked immunosorbent assay (ELISA) roughly 2 years after the overall trial initiation and then again 4 years after trial onset. The measures were taken at both points in 743 of the participants, the researchers noted. During follow-up, instances of cardiovascular events, all-cause death and kidney disease and renal dysfunction were recorded.
The researchers observed a rise in the average measure of pigment epithelium-derived factor between the first (10.5 ng/mL) and second (11 ng/mL) measurement points (P = .0092).
When looking at all-cause mortality risk, the researchers found that it was doubled for those with a pigment epithelium-derived factor level of 12 ng/mL to 27 ng/mL (HR = 2; 95% CI, 1.03-3.89) and those with a level from 8.6 ng/mL to 11.9 ng/mL (HR = 2.03; 95% CI, 1.06-3.88) compared with those with lower measures; however, this observation lost its significance in a fully adjusted model. In addition, there was no significant association between pigment epithelium-derived factor levels and CV risk.
Conversely, participants who had 12 ng/mL to 26 ng/mL of pigment epithelium-derived factor were more than three times as likely to have an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 — which the researchers categorized as stage 4 chronic kidney disease — compared with those with a pigment epithelium-derived factor measure of less than 8.6 ng/mL (HR = 3.84; 95% CI, 1.17-12.5). This finding was present with all adjustments included, as was the observation that the risk for two recordings of an eGFR of less than 60 mL/min/1.73 m2 or stage 3 CKD was more than doubled for participants with a pigment epithelium-derived factor measure of at least 12 ng/mL vs. those with a measure of less than 8.6 ng/mL (HR = 2.74; 95% CI, 1.71-4.39). The researchers added that the risk for macroalbuminuria (HR = 1.27; 955 CI, 1.02-1.59), stage 3 CKD (HR = 1.48; 95% CI, 1.28-1.73) and stage 4 CKD (HR = 1.43; 95% CI, 1.13-1.8) were all lifted when pigment epithelium-derived factor rose by 1 standard deviation. The same was true when stage 4 CKD was confirmed by two eGFR measures of less than 30 mL/min/1.73 m2 (HR = 1.8; 955 CI, 1.06-3.07).
“There is a great need for new biomarkers to stratify complication risk, and to develop and monitor new therapies,” the researchers wrote. “Our current data suggest ... that circulating [pigment epithelium-derived factor] levels may have a useful role as a biomarker for renal dysfunction in type 2 diabetes and have a future role as a therapeutic agent.” – by Phil Neuffer
Disclosures: The authors report no relevant financial disclosures.
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