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 (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF. LIMITATIONS: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted. CONCLUSION: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session.
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 (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF. LIMITATIONS: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted. CONCLUSION: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session.
Authors: K G F Gerritsen; N Bovenschen; T Q Nguyen; D Sprengers; M P Koeners; A N van Koppen; J A Joles; R Goldschmeding; R J Kok Journal: J Cell Commun Signal Date: 2016-09-19 Impact factor: 5.782
Authors: Claire H den Hoedt; Maaike K van Gelder; Muriel P Grooteman; Menso J Nubé; Peter J Blankestijn; Roel Goldschmeding; Robbert Jan Kok; Michiel L Bots; Marinus A van den Dorpel; Karin G F Gerritsen Journal: Toxins (Basel) Date: 2019-05-13 Impact factor: 4.546
Authors: Sandra Rayego-Mateos; José Luis Morgado-Pascual; Carolina Lavoz; Raúl R Rodrigues-Díez; Laura Márquez-Expósito; Antonio Tejera-Muñoz; Lucía Tejedor-Santamaría; Irene Rubio-Soto; Vanessa Marchant; Marta Ruiz-Ortega Journal: Biomolecules Date: 2022-02-03