Delayed kidney graft function: from mechanism to translation

Abstract

In as many as 50% of cases the immediate post-kidney transplant course is complicated by delayed graft function that is most commonly related to ischemia and reperfusion injury. In addition to the acute complications related to renal failure and the associated economic impact of prolonged hospitalization, the development of delayed graft function is associated with an increased risk of chronic allograft nephropathy and shortened allograft survival. Challenges in understanding its mechanisms include the complexity, as contributors are derived from both the donor and the recipient. This acute kidney injury is modulated and caused by a complex interplay of events that lead to hypoxic and ischemic injury as well as to altered repair mechanisms. New therapies primarily seek to suppress the inflammatory homing of adaptive immune cells to the kidney, limit cell death, and/or interrupt detrimental signaling of necrosis. Although there are several promising novel targets and innovative therapeutics available, many challenges remain in their translation from bench to bedside. Identifying organs at risk and clearly defined end points will be critical in designing interventional trials.

A molecular signature for delayed graft function

“…A higher incidence of DGF has been associated with the use of allografts from older extended criteria donors (ECD, age >60, or >50 with two of the following: a history of high blood pressure, a creatinine ≥1.5, or death resulting from a stroke), donation after cardiac death donors (DCD) and increased allograft biological age (Mallon, Summers, Bradley, & Pettigrew, 2015; McGuinness et al, 2016; Menke, Sollinger, Schamberger, Heemann, & Lutz, 2014; Mundt, Yard, Kramer, Benck, & Schnulle, 2015; Schroppel & Legendre, 2014). The extent to which donor and recipient‐related characteristics influence the magnitude of IRI and/or DGF occurrence, beyond accepted clinical risk factors for DGF, remains to be proven (Menke et al, 2014; Mundt et al, 2015; Schroppel & Legendre, 2014), particularly in the context of allograft repair, or regeneration pathways, activated in response to IRI.…”

“…The extent to which donor and recipient‐related characteristics influence the magnitude of IRI and/or DGF occurrence, beyond accepted clinical risk factors for DGF, remains to be proven (Menke et al, 2014; Mundt et al, 2015; Schroppel & Legendre, 2014), particularly in the context of allograft repair, or regeneration pathways, activated in response to IRI. Increased demand for organ donation, coupled with increasing chronological age and associated comorbidities in the donor population, has necessitated the use of organs that have been previously deemed as marginal for clinical use (Morrissey & Monaco, 2014; Nagaraja et al, 2015).…”

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“…[1][2][3][4]6,19,20 Predisposing factors are age, obesity, alcoholism, smoking, multiple operations, foreign body implantation, wound infection, hematoma, technical error, and unsuitable suture material. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In addition, medical illnesses such as chronic renal failure, liver insufficiency, infection, and pulmonary diseases are known risk factors.…”

“…[1][2][3][4][5][6][9][10][11][12][13][14][15][16][17] The average cost of initial hospitalization for patients undergoing deceased donor renal transplant, who develop DGF, is approximately $25 000 higher per patient. [17][18][19][20][24][25][26][27][28] When the clinical manifestations of DGF, such as increased rate of acute rejection and worse graft survival, are taken into account, the economic impact is expanded. 19,20,27 Delayed graft function is thus associated with lower graft survival, longer hospital stay, higher costs, and increased psychologic and significant medical sequelae.…”

Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use

“…Следовательно, есть основания полагать, что ДП может найти применение в кли-нической практике, например, при трансплантации почек, когда имеется ишемическое и реперфузионное повреждение этого ор-гана [28]. Наиболее частым проявлением подобного поврежде-ния (у 50% пациентов) служит «отсроченная функция трансплан-тата» (ОФТ) [29]. В первом рандомизированном исследовании не удалось обнаружить улучшения функции почки после ДИП в раннем периоде после трансплантации [30].…”