Is Transforming Growth Factor (TGF)β1 a Possible Early Tool and Therapeutic Target in Kidney Transplant Recipients?

Background: Kidney transplantation is the best therapy for end-stage renal disease. After transplantation kidney graft survival may be limited by delayed graft function, rejection events, graft fibrosis, etc. In pos-transplant protocol biopsies, an increase in macrophage infiltration in the renal parenchyma correlates with the severity of renal dysfunction. Likewise, macrophage infiltration precedes the production of TGFβ and fibrosis, so this could have a prognostic value for subsequent graft survival. This study aimed to evaluate a possible correlation between serum and renal tissue TGFβ1 levels with interstitial fibrosis in a prospective cohort of kidney transplant patients from January 2022 to September 2023 Methods: Forty patients (19 living-donor kidney transplant and 21 deceased-donor kidney transplant) underwent protocol biopsies at three months and one-year pos-transplant. Banff 2022 was employed for histologic evaluation, renal tissue TGFβ1 levels were measured by immunohistochemistry and serum levels by the ELISA technique at both time points. Subsequently, the correlation of serum and renal TGFβ1 levels with interstitial fibrosis/tubular atrophy in protocol biopsies was performed. Results: Age group was 21- 61 years in living-donor kidney transplant and 24-75 in deceased-donor (p=0.028). Cold ischemia time was 83.5 ± 57.8 minutes in living-donor kidney transplant, and 793.6 ± 249.3 in deceased-donor (p=<0.001). Glomerular filtration rate (CKD-EPI 2021) at 3 and 12 months postransplant was not significantly different. Twelve patients had subclinical kidney allograft rejection, the most frequent was humoral. Kidney graft survival was 100% at 12 months. The results showed a positive correlation between TGFβ1 expression levels in the intersticium and the presence of IFTA at three months post-transplant. (p=0.005). For the year post-transplant, the interstitial increase in TGFβ1 levels had a tendency correlation with the rise in fibrosis in the biopsy (p=0.070). A tendency was observed in patients who did not develop rejection to have lower serum levels or lower intensity of TGFβ1 expression in biopsy(p=0.037). Conclusion: TGFβ1 serum levels no correlates with IFTA but TGFβ1 expression levels correlates with IFTA degree and rejection in biopsies at three months pos-transplant.