BACKGROUND: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration. STUDY DESIGN: 4 observational studies in patients and 2 pharmacokinetic studies in rodents. SETTING & PARTICIPANTS: 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session. PREDICTOR: First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality. OUTCOMES & MEASUREMENTS: Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay. RESULTS: In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (beta = -0.72; P