Genetic susceptibility to delayed graft function following kidney transplantation: a systematic review of the literature

Abstract

Delayed graft function (DGF) is defined as the need for dialysis within 7 days following kidney transplantation (KTx). DGF is associated with increased costs, higher risk for acute rejection and decreased long-term graft function. Renal ischaemia/reperfusion (I/R) injury plays a major role in DGF occurrence. Single nucleotide polymorphisms (SNPs) in certain genes may aggravate kidney susceptibility to I/R injury, thereby worsening post-transplant outcomes. The present article proposes an extensive review of the literature about the putative impact of donor or recipient SNPs on DGF occurrence in kidney transplant recipients (KTRs). Among 30 relevant PubMed reports, 16 articles identified an association between 18 SNPs and DGF. These polymorphisms concern 14 different well-known genes and one not-yet-identified gene located on chromosome 18. They have been categorized into five groups according to the role of the corresponding proteins in I/R cascade: (i) oxidative stress, (ii) telomere shortening, (iii) chemokines, (iv) T-cell homeostasis and (v) metabolism of anti-inflammatory molecules. The remaining 14 studies failed to demonstrate any association between the studied SNPs and the occurrence of DGF. A better understanding of the genetic susceptibility to renal I/R injury may help prevent DGF and improve clinical outcomes in KTRs.

A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China

“…However, delayed graft function (DGF), a major early complication after renal transplantation, has seriously affected long-term survival of the recipients [ 2 , 3 ]. Among the many factors causing DGF, donor risks such as age and serum creatinine (sCr) level are crucial for donor and renal evaluation [ 4 ].…”

The Impact of Hematological Indices on the Occurrence of Delayed Graft Function (DGF) of Transplanted Kidney

“…In the present study, DGF occurred in 39.45% of the recipients. Based on the studies conducted thus far, it is only possible to isolate factors that increase the risk of delayed transplanted kidney function, the most important being cold and warm ischemia time, HLA compatibility, donor DBD (Donation after Brain Death), recipient BMI, donor weight, immunosuppressive induction treatment used, and duration of dialysis [3][4][5]25,26]. In most cases, the haematological indices described in the literature are used to assess the prognosis of patients with cancer or cardiovascular disease.…”

“…The immediate function of the transplanted kidney occurs in about half of the recipients, while in the remaining individuals, the function of the transplanted kidney may progressively appear, in which case we speak of Delayed Graft Function (DGF), the incidence of which is lowest after transplantation of a kidney from a living donor (4-10%) [1] and increases up to 53-69% after transplantation of a kidney from a DCD (Donation after Cardiac Death) donor [2]. The risk of DGF can be influenced by a variety of both immunologic and nonimmunologic factors, the most important of which are as follows: donor age, cold and warm ischemia times, HLA (Human Leukocyte Antigen) compatibility, the immunosuppressive induction treatment, and the duration of dialysis therapy [3][4][5]. Algorithms have been created to estimate the risk of DGF, including the Irish nomogram [6], the Jeldres DGF nomogram [7], the Irish nomogram DGF calculator [8], and DGFS [9].…”

Comprehensive assessment of deceased donor kidneys with clinical characteristics, pre-implant biopsy histopathology and hypothermic mechanical perfusion parameters is highly predictive of delayed graft function

“…Ideally, kidneys will be neither wasted nor used in poor condition. Of course, it is difficult to achieve this, and additional in-depth evaluation systems, such as molecular markers, irrigation fluid culture, susceptibility-weighted imaging and other information, need to be further investigated to improve quality of organ transplantation [28][29][30][31].…”