In vivo Visualization of Early Microcirculatory Changes following Ischemia/Reperfusion Injury in Human Kidney Transplantation

Schmitz, Volker; Schaser, K.-D.; Olschewski, Peter; Neuhaus, P.; Puhl, Gero

doi:10.1159/000107683

Cited by 38 publications

(37 citation statements)

References 48 publications

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“…Similar findings have been reported from a pilot study using the same methodology: lHbO 2 (42% vs. 52%) as well as flow (177 vs. 253 AU) was lower in patients who required postoperative hemodialysis [30]. A positive correlation between graft perfusion and postoperative function has also been shown in other studies using different methods of monitoring microcirculatory function, too [9,10,28].…”

Section: Interpretation Of Resultssupporting

confidence: 86%

“…This might be caused by an increased oxygen demand after the ischemic period and a reperfusion injury causing a no-reflow phenomenon in some microvessels [9]. Consistently, Hattori et al reported that the diameter of peritubular capillaries is decreased to two-thirds of its baseline diameter 20 min after the start of reperfusion and is not restored until 120 min thereafter [10].…”

Section: Interpretation Of Resultsmentioning

confidence: 89%

“…Only a few studies so far have looked at the microcirculation during KTx by visualizing capillary density and red blood cell (RBC) velocity; they found a positive correlation of early microvascular changes and postoperative plasma creatinine levels suggesting that microcirculatory monitoring might be able to predict early renal graft dysfunction induced by reperfusion injury [9]. In addition, RBC velocity in the early phase after reperfusion deteriorated significantly more in grafts from deceased donors compared with that of living donors [10].…”

Section: Discussionmentioning

confidence: 99%

“…Of all patients, 54% required at least one postoperative hemodialysis (median 1, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Grafts with delayed function had a longer Cit (mean 11 h 36 min) compared with those not requiring any postoperative hemodialysis (mean 7 h 45 min)(P < 0.05).…”

Section: Postoperative Kidney Functionmentioning

confidence: 98%

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Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Scheeren¹,

Martin²,

Maruschke³

et al. 2011

Transplant International

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Summary Ischemia time is a prognostic factor in renal transplantation for postoperative graft function and survival. Kidney transplants from living donors have a higher survival rate than deceased donor kidneys probably because of shorter ischemia time. We hypothesized that measurement of intraoperative kidney oxygenation (μHbO2) and microvascular perfusion predicts postoperative graft function. We measured microvascular hemoglobin oxygen saturation by reflectance spectrophotometry and microcirculatory kidney perfusion by laser Doppler flowmetry 5 and 30 min after kidney reperfusion on the organ surface in 53 renal transplant patients including 19 grafts from living donors. These values were related to systemic hemodynamics, cold ischemia time (cit), early postoperative graft function and length of hospital stay. μHbO2 improved 30 min after reperfusion compared to 5 min (from 67% to 71%, P < 0.05). μHbO2 correlated with mean arterial blood pressure and central venous pH (P < 0.01). Most importantly, μHbO2 was significantly higher in kidneys from living compared with deceased donors (74% vs. 63%) and in kidneys without vs. with biopsy‐proven postoperative rejection (71% vs. 45%, P < 0.001). Finally, μHbO2 correlated positively with cit and postoperative creatinine clearance and negatively with postoperative plasma creatinine, need for hemodialysis and length of hospital stay. Our results suggest higher oxygen extraction and thus oxygen demand of the grafts shortly after reperfusion. The intraoperative measurement of tissue oxygenation in kidney transplants is predictive of early postoperative graft function. Future studies should evaluate the potential effect of intraoperative therapeutic maneuvers to improve organ tissue oxygenation in renal transplantation.

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Section: Interpretation Of Resultssupporting

confidence: 86%

Section: Interpretation Of Resultsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Postoperative Kidney Functionmentioning

confidence: 98%

See 2 more Smart Citations

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Scheeren¹,

Martin²,

Maruschke³

et al. 2011

Transplant International

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show abstract

“…In rodent models of ischemic acute kidney injury, it has been demonstrated that the peritubular microcirculation suffers endothelial injury and functional impairment after reperfusion (5, 44), which has recently been observed in humans as well (13,21,31). The endothelium is covered by the glycocalyx, a dynamic network of proteoglycans and glycoproteins that determines vascular permeability, transduces shear stress to the endothelium, and prevents interaction of leukocytes and platelets with the vascular wall (29).…”

mentioning

confidence: 99%

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Snoeijs¹,

Vink²,

Voesten³

et al. 2010

American Journal of Physiology-Renal Physiology

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Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury. ischemia-reperfusion injury; endothelial glycocalyx KIDNEY TRANSPLANTATION IS inevitably associated with ischemia and reperfusion injury. Depending on the severity of injury, 20 -80% of recipients of deceased donor kidneys require dialysis treatment in the first week after transplantation, which is referred to as delayed graft function (26). This condition complicates patient management and is associated with a 40% increased rate of graft loss in kidneys from donors after brain death (45). Liberal use of donations after cardiac death greatly expands the number of available donor kidneys and may even eliminate transplant waiting lists (37). However, kidneys from these donors suffer extensive ischemic injury from circulatory arrest until organ preservation, which almost invariably leads to delayed graft function after transplantation. More importantly, up to 15-25% of these kidneys will never regain function, unnecessarily exposing recipients to the risks of major surgery and immunological sensitization (43).Adequate reperfusion is essential for functional recovery of donor kidneys and prevents ongoing ischemic tissue injury after revascularization. In rodent models of ischemic acute kidney injury, it has been demonstrated that the peritubular microcirculation suffers endothelial injury and functional impairment after reperfusion (5, 44), which has recently been observed in humans as well (13,21,31). The endothelium is covered by the glycocalyx, a dynamic network of proteoglycans and glycoproteins that determines vascular permeability, transduces shear stress to the endothelium, and prevents interaction of leukocytes and platelets with the vascular wall (29). Loss of endothel...

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Generation of neutrophil extracellular traps in patients with acute liver failure is associated with poor outcome

et al. 2021

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Background and Aims: Acute liver failure (ALF) is characterized by significant changes in the hemostatic system and by systemic inflammation. The formation of neutrophil extracellular traps (NETs), in which an activated neutrophil expels its DNA, histones, and granular enzymes, such as myeloperoxidase (MPO), has been associated with immune-mediated and thrombotic diseases. We hypothesized that formation of NETs in patients with ALF contributes to progression of disease. Approach and Results:A total of 676 patients with ALF (international normalized ratio [INR], ≥1.5) or severe acute liver injury (ALI; INR, ≥2.0) were recruited from the U.S. ALF Study Group Registry between 2011 and 2018, of whom 308 patients (45.6%) had acetaminophen-induced ALF. Up to 21 days after admission, 483 patients (71.5%) survived without liver transplantation (LT). Levels of cell-free DNA (cfDNA) and the specific NET marker MPO-DNA complexes were measured in plasma samples obtained on admission and compared to levels in healthy controls. In addition, liver tissue obtained at transplantation of 20 ALF patients was stained for NETs. Levels of cfDNA were 7.1-fold, and MPO-DNA complexes 2.5-fold, higher in patients with ALF compared to healthy controls. cfDNA levels were not associated with 21-day transplant-free survival, but were higher in those patients with more-severe disease on admission, as reflected by various laboratory and clinical parameters. MPO-DNA levels were 30% higher in patients with ALF who died or required urgent LT. Liver tissue of ALF patients stained positive for NETs in 12 of 18 evaluable patients.

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In vivo Visualization of Early Microcirculatory Changes following Ischemia/Reperfusion Injury in Human Kidney Transplantation

Cited by 38 publications

References 48 publications

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Generation of neutrophil extracellular traps in patients with acute liver failure is associated with poor outcome

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