Lymphocyte Function in Human Acute Kidney Injury

Weller, Sophie Joanne; Varrier, Matt; Ostermann, Marlies

doi:10.1159/000478538

Cited by 26 publications

(20 citation statements)

References 28 publications

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“…Lymphocytes are the main components of adaptive immunity, which also play a significant role in the development and maintenance of AKI, directly by cellular damage and indirectly by producing pro-inflammatory cytokines [30–38]. Natural killer T cells are presumed to induce renal injury as they are directly cytotoxic and release pro-inflammatory cytokines and activate macrophages and neutrophils [39].…”

Section: Pathophysiology Of Akimentioning

confidence: 99%

Complete blood count in acute kidney injury prediction: a narrative review

Gameiro

Lopes

2019

Ann. Intensive Care

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Acute kidney injury (AKI) is a complex syndrome defined by a decrease in renal function. The incidence of AKI has raised in the past decades, and it is associated with negative impact in patient outcomes in the short and long term. Considering the impact of AKI on patient prognosis, research has focused on methods to assess patients at risk for developing AKI, diagnose subclinical AKI, and on prevention and treatment strategies, for which it is crucial an understanding of pathophysiology the of AKI. In this review, we discuss the use of easily available parameters found in a complete blood count to detect patients at risk for developing AKI, to provide an early diagnosis of AKI, and to predict associated patient outcomes.

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Section: Pathophysiology Of Akimentioning

confidence: 99%

Complete blood count in acute kidney injury prediction: a narrative review

Gameiro

Lopes

2019

Ann. Intensive Care

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“…During ATN, neutrophils and natural killer T (NKT) cells first emerge at injured sites ( Fig. 2B ) [ 44 ]. Whether NKT cells directly damage tubule cells remains under debate [ 45 ].…”

Section: The Immune System In the Early Injury Phase Of Atnmentioning

confidence: 99%

Immune mechanisms in the different phases of acute tubular necrosis

Kundert

Platen

Iwakura

et al. 2018

Kidney Res Clin Pract.

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Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.

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“…Describing this early immune response pathway could have an important impact on future research, including the development of novel therapeutic interventions. Current data suggest that T cells play a key role in the initiation and propagation of the immune reaction in experimental AKI [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response

Göcze

Ehehalt²,

Zeman³

et al. 2018

Crit Care

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BackgroundBasic science data suggest that acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI) is an inflammatory process involving the adaptive immune response. Little is known about the T-cell contribution in the very early phase, so we investigated if tubular cellular stress expressed by elevated cell cycle biomarkers is associated with early changes in circulating T-cell subsets, applying a bedside-to-bench approach.MethodsOur observational pilot study included 20 consecutive patients undergoing endovascular aortic repair for aortic aneurysms affecting the renal arteries, thereby requiring brief kidney hypoperfusion and reperfusion. Clinical-grade flow cytometry-based immune monitoring of peripheral immune cell populations was conducted perioperatively and linked to tubular cell stress biomarkers ([TIMP-2]•[IGFBP7]) immediately after surgery. To confirm clinical results and prove T-cell infiltration in the kidney, we simulated tubular cellular injury in an established mouse model of mild renal IRI.ResultsA significant correlation between tubular cell injury and a peripheral decline of γδ T cells, but no other T-cell subpopulation, was discovered within the first 24 hours (r = 0.53; p = 0.022). Turning to a mouse model of kidney warm IRI, a similar decrease in circulating γδ T cells was found and concomitantly was associated with a 6.65-fold increase in γδ T cells (p = 0.002) in the kidney tissue without alterations in other T-cell subsets, consistent with our human data. In search of a mechanistic driver of IRI, we found that the damage-associated molecule high-mobility group box 1 protein HMGB1 was significantly elevated in the peripheral blood of clinical study subjects after tubular cell injury (p = 0.019). Correspondingly, HMGB1 RNA content was significantly elevated in the murine kidney.ConclusionsOur investigation supports a hypothesis that γδ T cells are important in the very early phase of human AKI and should be considered when designing clinical trials aimed at preventing kidney damage.Trial registrationClinicalTrials.gov, NCT01915446. Registered on 5 Aug 2013.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2094-x) contains supplementary material, which is available to authorized users.

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Lymphocyte Function in Human Acute Kidney Injury

Cited by 26 publications

References 28 publications

Complete blood count in acute kidney injury prediction: a narrative review

Complete blood count in acute kidney injury prediction: a narrative review

Immune mechanisms in the different phases of acute tubular necrosis

Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response

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