*Purpose: Previous reports from a number of studies indicate that renal allograft recipients who have inflammatory infiltrates within areas of interstitial fibrosis with tubular atrophy (i-IFTA) on biopsy are at higher risk of developing progressive renal dysfunction. Connective tissue growth factor (CTGF) is a soluble cysteine-rich protein that is physiologically important for proliferation, differentiation, adhesion, wound repair, and angiogenesis. It also plays a role in chronic disease where it is associated with tissue fibrosis. Moreover, several studies have demonstrated that CTGF is increased in the urine of adult allograft recipients with IFTA or T cell-mediated acute rejection (AR). It is not known, however, if its level varies with the presence of inflammation in areas of fibrosis, and no study has evaluated its utility as a biomarker in pediatric recipients. We hypothesized that urinary CTGF (uCTGF) levels might differ based on the extent of i-IFTA and thus allow for the identification of patients at higher risk of progressive allograft dysfunction.

*Methods: We collected urine samples from pediatric renal allograft recipients who underwent surveillance or indication biopsy at two centers up to three months prior to biopsy. uCTGF levels prior to biopsy were correlated with allograft histologic findings. uCTGF was measured by indirect sandwich ELISA. Urinary creatinine was measured via the colorimetric Jaffe reaction. uCTGF levels were normalized to urine creatinine (Cr) and compared in patients with normal biopsies and those with IFTA, borderline or acute T cell-mediated rejection (AR), and i-IFTA. Data was log-transformed and non-parametric rank sum and area under the ROC curve (AUC) analyses were used to evaluate biomarker performance.

*Results: Biopsy histology was reported as normal (n=19), AR (n=16), IFTA (n=11), or i-IFTA (n=8). We find that uCTGF/Cr is not significantly associated with IFTA alone (p=0.2), but distinguishes patients with normal biopsies from those with biopsies showing i-IFTA (p=0.02), or biopsies with AR (p=0.03). Receiver operator characteristic curves demonstrate that uCTGF/Cr performs well as a biomarker of i-IFTA (AUC 0.783 [0.611, 0.0955]).

*Conclusions: This pilot study suggests that creatinine-normalized urinary CTGF levels could help distinguish pediatric patients with intragraft inflammation in areas of scarring who are at risk of developing progressive renal allograft failure. These findings warrant additional evaluation of urinary CTGF in larger cohort trials to determine its efficacy in the routine biomarker monitoring of pediatric transplant recipients.

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