Relationship of Transforming Growth Factor-βl and Arginase-1 Levels with Long-term Survival after Kidney Transplantation

Abstract

In this study, we compared the serum levels of transforming growth factor-pi (TGF-β1), interleukin-10 (IL-10), and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs). We then evaluated the relationship between these levels and graft function. Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation). All patients had stable kidney function. The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017. The plasma levels of TGF-β1, IL-10, and arginase-1 were analyzed using enzyme-linked immunosorbent assays (ELIS A). The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs. The time elapsed since transplantation was positively correlated with the levels of TGF-β1 and arginase-1 in the LTSKTRs. The estimated glomerular filtration rate was positively correlated with the TGF-β1 level, and the serum creatinine level was negatively correlated with the TGF-β1 level. Higher serum levels of TGF-pi and arginase-1 were found in LTSKTRs than in STSKTRs, and we found that TGF-β1 was positively correlated with long-term graft survival and function. Additionally, TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation. On the basis of these findings, TGF-β1 and arginase-1 may play important roles in determining long-term graft survival. Thus, we propose that TGF-pi and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival.

A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation

“…In line with our results, the minor alleles of these TGFB1 polymorphisms have also been suggested to lead to lower levels of TGF-β1 [ 30–32 ]. Furthermore, Du et al reported that long-term survival kidney transplant recipients had higher TGF-β1 levels than short-term survival kidney transplant recipients [ 18 ]. Serum TGF-β1 levels positively correlated with long-term graft survival and function.…”

“…In contrast, genetic deficiency of TGF-β1 in mice leads to multiorgan inflammation (including that of the kidney) [ 17 ]. In the context of these findings, Du et al found that TGF-β1 plasma levels were positively associated with long-term graft survival in kidney transplant recipients [ 18 ]. Finally, local TGF-β1 expression in the kidney allograft during rejection has been associated with a favourable outcome [ 19 , 20 ].…”

Relationship between the microenvironment and survival in kidney transplantation: a bibliometric analysis from 2013 to 2023

“…In kidney transplantation, TGF-β1 has been a topic of interest and most investigators believe that TGF-β1 affects allograft survival in different ways ( 37 ). It has been shown that TGF-β1 cells are closely associated with the short-term prognosis of clinical kidney transplantation.…”

TGF‐β1–p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications

“…Indeed, mice engineered to express epithelial-targeted, inducible, constitutively active TGF-b receptor I exhibit acute tubular injury and apoptosis, phenotypic dedifferentiation, synthesis of profibrotic factors, and interstitial inflammatory cell recruitment (45). In transplant-associated renal ischemia/ reperfusion injury, TGF-b1 initiates early repair and regeneration but in the setting of chronic inflammation drives continual matrix deposition and remodeling, leading to fibrotic disease, compromised renal function, and eventual organ rejection (46). Excessive ECM accumulation also provides a source of damage-associated molecular pattern ligands for the inflammatory response TLR (47)(48)(49)(50).…”