Renal elimination and eGFR prediction of proenkephalin

Proenkephalin (PENK) is assumed to be freely filtered by the glomerulus, thus potentially useful for estimating glomerular filtration rate (eGFR). Recently developed eGFR-equation based on PENK and creatinine has not been validated against existing cystatin C-based equations. This study aimed to test the hypothesis of free filtration of PENK. Also, the PENK-creatinine based eGFR-equation was validated against cystatin C. Plasma concentrations of PENK, creatinine and cystatin C were determined in arterial and renal venous blood samples collected from 70 patients undergoing transcatheter aortic valve implantation (TAVI). The renal elimination ratio (RER) of PENK (RER_PENK) was calculated and compared to the RER of creatinine (RER_crea). RER constitutes the single-pass renal elimination of a molecule, calculated as the arteriovenous concentration difference divided by the arterial concentration. For eGFR validations, the CAPA (cystatin C) and LMR (creatinine) equations were used. RER_PENK (23.7 ± 9.6%) was approximately 10% higher than RER_crea (21.4 ± 5.8%). The PENK-creatinine equation overestimated GFR by 26,1% on average, compared to the mean of the LMR and CAPA equations. The relationship between RER_PENK and RER_crea suggests free filtration and a slight degree of non-glomerular elimination of PENK. There was poor agreement between PENK and cystatin C derived eGFR-equations. PENK needs further evaluation as a predictor of GFR.