Quantifying the effects of renal impairment on plasma levels of neuroendocrine neoplasia biomarkers.
P Bech, R Ramachandran, WS Dhillo, NM Martin, KG Murphy, MA Ghatei, SR Bloom
Neuroendocrine neoplasias (NEN) account for 2% of all malignancies. There are several circulating NEN biomarkers. Chromogranin A (CgA) is regarded as the gold standard and chromogranin B (CgB) has been found to be a useful diagnostic addition to CgA measurements. The peptide product of cocaine- and amphetamine-regulated transcript (CART) is also elevated in patients with NENs, particularly pancreatic NENs.
As renal impairment or failure can increase circulating levels of CgA, CgB and CART, we determined the effect of varying degrees of renal impairment on plasma levels of NEN biomarkers in patients without NEN.
Plasma samples were collected from 106 anonymised patients with renal impairment and a control group of forty healthy subjects with normal renal function and no cancer. Renal function was determined by estimated glomerular filtration rate (eGFR).
Levels of CgA, CgB and CART increased with decreasing eGFR. CgA and CART levels were more sensitive to decreasing renal function than CgB. Highest levels of all biomarkers were observed in patients with eGFR of <15, but were not higher than 500pmol/L for CgA and CART and 232pmol/L for CgB.
Circulating levels of CgA, CgB and CART were all affected to varying degrees by renal failure. CgA and CART rose with even mild renal failure, but CgB did not, suggesting CgB may be a more reliable marker than CgA in patients with mild renal impairment. Furthermore, patients with levels >500pmol/L for CgA and CART and >232pmol/L for CgB should be investigated for NENs, even in the presence of renal failure.