Urinary connective tissue growth factor as a biomarker chronic allograft nephropathy in a rat model

Abstract

To determine whether urinary connective tissue growth factor (CTGF) can be a molecular marker for chronic allograft nephropathy (CAN) in a rat model. F344 rat renal grafts were orthotopically transplanted into Lewis rats (n = 24). Lewis rats underwent sham operation as control group (n = 12). Kidney grafts were harvested at Weeks 4, 8, 12 and 16 respectively. Serum creatinine (SCr) was measured. The CAN grades were evaluated according to the Banff 97 schema. The expressions of CTGF in kidney, serum and urine were determined by Western blot and competitive indirect ELISA. Spearman correlation analysis was used to compare CTGF expression and the development of CAN. The expression of CTGF in the graft group was markedly elevated in comparison with the control group. Statistics analysis of CTGF protein in kidney detected by Western blot showed significant differences between these five groups (0.33 ± 0.05 for control, 0.55 ± 0.02 for Week 4, 0.80 ± 0.03 for Week 8, 0.90 ± 0.03 for Week 12 and 1.14 ± 0.11 for Week 16, P < 0.01). Both urine and serum CTGF increased by Week 4 and maintained a high level up to Week 16. The urinary CTGF of renal allografts was (2.9 ± 0.7), (12.9 ± 3.6), (32.3 ± 11.4) and (31.0 ± 8.9) ng/mg creatinine for Weeks 4, 8, 12 and 16 respectively. The urinary levels were positively correlated with SCr, Banff scores and expression of CTGF in the graft kidney (r = 0.848, 0.874, 0.747, all P < 0.01). CTGF plays a significant role in the pathological changes of CAN after kidney transplantation. Urinary CTGF has the potential as a biomarker for predicting the clinical course of CAN.