Diagnostic significance of TGF-β1 in kidney recipients with graft dysfunction

Abstract

Development of minimally invasive diagnosis techniques for complications in recipients, based on analysis of the levels of molecular and genetic biomarkers, is an urgent task facing modern transplantology. Transforming growth factor beta 1 (TGF-β1), which has multiple effects in the body, among the potential indicators of complications.Objective: to assess the diagnostic significance of serum TGF-β1 in kidney recipients with graft dysfunction.Materials and methods. The study included 129 kidney recipients aged 17 to 68 years and 35 healthy subjects. Serum TGF-β1 levels in the recipients were determined by immunoenzyme technique.Results. Kidney recipients included 95 patients with laboratory and clinical signs of graft dysfunction, who underwent biopsy of the transplanted kidney, followed by morphological examination, and 34 recipients with normal graft function. Serum TGF-β1 levels in the kidney recipients were significantly higher than in their healthy counterparts (p = 0.00001); it did not correlate with most blood test parameters; with the glomerular filtration rate (GFR). Kidney recipients with graft dysfunction had significantly higher TGF-β1 levels than other recipients (p = 0.018). In recipients with graft dysfunction, morphological study revealed the following: acute tubular necrosis (ATN, n = 11), acute T-cell mediated rejection (ACR, n = 26), acute antibody-mediated rejection (AMR, n = 35), non-immune-mediated nephrosclerosis with signs of calcineurin inhibitor nephrotoxicity (CNI nephrotoxicity, n = 13), and recurrent glomerulonephritis (chronic graft rejection, n = 10). Recipients with immune-mediated graft injury (ACR, AMR and chronic rejection) had higher serum TGF-β1 levels than recipients with graft dysfunction resulting from other causes, p < 0.0001. Kidney recipients with serum TGF-β1 levels above the threshold value of 94.3 ng/mL had a higher risk of immune-mediated graft dysfunction than other kidney recipients (RR = 2.2 ± 0.22 [95% CI 1.46–3.46]) with 77.5% test sensitivity and 60.3% specificity.Conclusion. The calculated threshold serum TGF-β1 level in kidney recipients can be considered as an auxiliary indicator of graft dysfunction resulting from acute or chronic rejection.