Investigação da relação do polimorfismo de nucleotídeo único (rs187238) no gene da interleucina-18 e do tempo de isquemia fria com a função do enxerto em receptores de transplante renal de um Hospital Universitário de Fortaleza

Abstract

Renal dysfunction is a common complication among recipients of organs from deceased donors and can be caused by ischemia-reperfusion injury, which affects the therapeutic success of the transplant. Cold ischemia time (CIT) refers to the period of organ transport, from its removal from the donor to its implantation in the recipient. Prolonged periods of CIT can influence renal graft survival, causing irreversible renal injury. In the search for early biomarkers of renal function, urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) may be potential predictors of graft dysfunction. IL-18 is a proinflammatory cytokine that may be involved in modulating the immune response related to acute kidney injury. The single nucleotide polymorphism rs187238 (-137G/C), located in the gene for this interleukin, is known to cause an increase in the expression of this cytokine, which may influence the individual's inflammatory profile. The present study sought to investigate the influence of the rs187238 polymorphism and CIT on graft function in kidney transplant recipients. The work is structured in three articles. The first is a narrative review on the influence of CIT on delayed graft renal function. The other articles are cross-sectional studies including renal allograft recipients from a university hospital in Fortaleza between 2023 and 2025. These studies evaluated the influence of CIT, urinary IL-18 levels, and rs187238 polymorphism genotypes on graft renal function one month after transplantation. It was observed that prolonged periods of cold ischemia are related to longer hospital stays and graft renal dysfunction, reflected in higher serum creatinine levels, lower estimated glomerular filtration rate (eGFR), and higher urinary NGAL levels. Urinary IL-18 levels and rs187238 polymorphism genotypes had no influence on clinical parameters of renal function one month post-transplant. It is concluded that urinary IL-18 is not characterized as a biomarker of renal injury in this period, and its rs187238 polymorphism did not impact the markers of renal function of the allograft. In addition, the findings demonstrate that CIT can determine the patient's prognosis and the therapeutic success of the transplant.