C-Terminal Agrin Fragment - A New Fast Biomarker for Kidney Function in Renal Transplant Recipients

Abstract

Background: The C-terminal agrin fragment (CAF) is a cleavage product of agrin, the major proteoglycan of the glomerular basement membrane. This article studies if CAF could serve as a biomarker for renal function in renal transplant recipients. Material and Methods: We measured serum CAF and creatinine concentrations and calculated estimated glomerular filtration rate (eGFR) (MDRD) in 96 healthy individuals and in 110 end-stage renal disease patients undergoing kidney transplantation before and after transplantation. Correlation between CAF and creatinine concentrations/eGFR was calculated as within-patient (cWP) and between-patient correlations (cBP). Moreover, we evaluated the association of CAF with delayed graft function (DGF). The diagnostic value of CAF for early detection of DGF compared to creatinine was evaluated by receiver operating characteristics (ROC) analysis. Results: CAF concentrations strongly correlated with creatinine (r = 0.86 (cWP), r = 0.74 (cBP)) and eGFR (MDRD) (r = 0.86 (cWP), r = 0.77 (cBP)). Pre-transplant (pre-Tx) CAF concentrations were 19-fold higher than in healthy individuals (1,115.0 (258.4-3,990.0) vs. 56.6 (20.0-109.5) p<smlcap>M</smlcap>). After transplantation, CAF decreased significantly faster than creatinine (postoperative days 1-3 (POD 1-3): 562.8 (101.6-2,113.0) p<smlcap>M</smlcap>; creatinine: pre-Tx 6.9 (3.1-15.7), POD 1-3: 6.4 (1.7-12.7) mg/dl, p < 0.001). Stable concentrations were reached 1-3 months after transplantation for CAF and creatinine (CAF 145.1 (6.7-851.0) p<smlcap>M</smlcap>; creatinine 1.6 (0.7-8.0) mg/dl). CAF concentrations at POD 1-3 were significantly associated with DGF and outperformed creatinine in early detection of DGF (area under the curve (AUC) CAF 80.7% (95% CI 72.3-89.1%) vs. AUC creatinine 71.3% (95% CI 61.8-81.1%), p = 0.061). Conclusion: CAF is a promising new and fast biomarker for kidney function and may serve as a new tool for the early detection of DGF.

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

“…Indeed, agrin is expressed in the kidney and CAF22 has been related to the damage of the glomerular basement membrane 37, 38. In our study patients with renal failure as well as with dialysis were excluded.…”

Comparison of Peritoneal Low-Molecular-Weight-Protein-Removal in CCPD and CAPD Patients Based on C-Terminal Agrin Fragment Clearance

“…However, a recent cross-over study comparing high-flow CCPD and standard CAPD did not observe any significant differences in peritoneal substrate clearances for molecules up to a mass of beta 2 -microglobuline (11.8 kDa, [13]). Recently we showed that serum levels of total C-terminal agrin fragment (tCAF), a 22 k-Da protein derived from agrin, correlated with kidney function in renal transplant and CCPD patients [14,15]. The finding in the latter study was primarily due to the low contribution of peritoneal clearance to the total clearance of tCAF.…”

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

“…The COOH terminus V domain of perlecan is similar to another HS proteoglycan, agrin, which is the major proteoglycan of the glomerular basement membrane. The COOH-terminal agrin fragment is a known marker of neuronal muscular remodeling, but it has recently been shown to be a potential biomarker for renal function in renal transplant recipients (322). Like other mentioned angiogenesis inhibitors, such as arresten, canstatin, endostatin, and tumstatin, endorepellin mediates its antiangiogenesis functions through binding to ␣2␤1-integrin, a key angiogenesis receptor (376).…”