-
Urologia Internationalis 2021Donors' health and safety are mandatory in the living-donor kidney transplantation procedure. Laparoscopic live donor nephrectomy (LLDN) provides an increase in donor...
OBJECTIVE
Donors' health and safety are mandatory in the living-donor kidney transplantation procedure. Laparoscopic live donor nephrectomy (LLDN) provides an increase in donor numbers with its benefits and becomes a standard of care. We aimed to explain the results, complication rates, tips, and tricks of the largest number of LLDN case series ever performed in the literature.
MATERIALS AND METHODS
Between August 2012 and December 2019, 2,477 live donor case files were analyzed retrospectively. Age, gender, hospitalization times, body mass index, warm ischemia times, operation times, numbers of arteries, side of the kidneys, and complications were noted.
RESULTS
1,421 (57.4%) of 2,477 donors were female (p = 0.007). Operation times and warm ischemia times were found longer in right-sided LLDN and donors with multiple renal arteries (p = 0.046, <0.001, and <0.001, respectively). Obesity (BMI >30 kg/m2) did not affect warm ischemia times while prolonging the operation times (p = 0.013). Hospitalization times and numbers of complications were higher in obese donors.
CONCLUSIONS
LLDN seems to be a reliable solution with fewer complications and higher satisfaction rates. We hope to illuminate the way with tips and trick points for beginner transplant surgeons based on the experience obtained from 2,477 LLDN cases.
Topics: Adult; Female; Hospitals, High-Volume; Humans; Laparoscopy; Living Donors; Male; Middle Aged; Nephrectomy; Postoperative Complications; Retrospective Studies; Tissue and Organ Harvesting
PubMed: 33207353
DOI: 10.1159/000511377 -
The Journal of Thoracic and... Nov 2017The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP)...
Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism.
OBJECTIVE
The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia.
METHODS
Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity.
RESULTS
EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmHO, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmHO, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration.
CONCLUSIONS
Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.
Topics: Adenosine A2 Receptor Antagonists; Animals; Disease Models, Animal; Extracorporeal Circulation; Lung; Lung Transplantation; Organ Preservation; Organ Preservation Solutions; Reperfusion; Swine; Warm Ischemia
PubMed: 28483262
DOI: 10.1016/j.jtcvs.2017.02.072 -
International Journal of Molecular... Apr 2024Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike... (Review)
Review
Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.
Topics: Humans; Heart Transplantation; Organ Preservation; Tissue and Organ Procurement; Animals; Perfusion; Tissue Donors; Energy Metabolism
PubMed: 38673737
DOI: 10.3390/ijms25084153 -
Transplantation Feb 2017Bruton tyrosine kinase (Btk) is a central player in multiple signaling pathways of lymphoid and myeloid cells. Myeloid cells are crucial early effectors in organ...
BACKGROUND
Bruton tyrosine kinase (Btk) is a central player in multiple signaling pathways of lymphoid and myeloid cells. Myeloid cells are crucial early effectors in organ ischemia-reperfusion (IR) injury. BTKB66 is a selective, irreversible inhibitor of Btk. In this study, we hypothesized that Btk inhibition would reduce hepatocellular injury in a murine model of liver warm hepatic IR.
METHODS
First, BTKB66 was tested in in vitro models of lipopolysaccharide-mediated neutrophil and macrophage activation. Then, to assess its efficacy in vivo, BTKB66 was administered orally to mice for 7 days before subjecting them to 90 minutes of warm hepatic ischemia followed by reperfusion for 6 or 24 hours. Clinical and pathologic features in the livers, including AST, ALT, and a panel of cytokines and chemokines, were examined.
RESULTS
BTKB66 potently inhibited lipopolysaccharide-mediated activation of bone marrow-derived neutrophils and macrophages in vitro. It also reduced the severity of IR injury as determined by AST and ALT levels, as well as immune cell infiltrates. BTKB66 significantly decreased hepatic markers of sterile inflammation, such as C-X-C motif chemokine 1, C-X-C motif chemokine 2, and C-X-C motif chemokine 10, in parallel with depression of serum markers of the myeloid cell activation, such as CCL5, CCL11, and C-X-C motif chemokine 5.
CONCLUSIONS
BTKB66 treatment ameliorated hepatocellular injury in a well-established model of liver partial warm ischemia and in situ reperfusion. These findings confirm that neutrophil recruitment and activation play an essential role in IR stress, and that targeting Btk activity may provide a useful approach for preventing hepatocellular damage and improving outcomes in liver transplantation.
Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; Apoptosis; Biomarkers; Cells, Cultured; Chemotaxis, Leukocyte; Cytokines; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Liver; Liver Diseases; Liver Transplantation; Macrophage Activation; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Neutrophil Activation; Perfusion; Phosphorylation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Reperfusion Injury; Signal Transduction; Time Factors; Warm Ischemia
PubMed: 27820779
DOI: 10.1097/TP.0000000000001552 -
Transplant International : Official... 2022Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value...
Normothermic Regional Perfusion and Hypothermic Oxygenated Machine Perfusion for Livers Donated After Controlled Circulatory Death With Prolonged Warm Ischemia Time: A Matched Comparison With Livers From Brain-Dead Donors.
Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value of abdominal normothermic regional perfusion (A-NRP) associated with dual hypothermic oxygenated machine perfusion (D-HOPE) in controlled DCD LT, prospectively collected data on LTs performed between January 2016 and July 2021 were analyzed. Outcome of controlled DCD LTs performed using A-NRP + D-HOPE ( = 20) were compared to those performed with grafts procured after brain death (DBD) ( = 40), selected using propensity-score matching. DCD utilization rate was 59.5%. In the DCD group, median functional WIT, A-NRP and D-HOPE time was 43, 246, and 205 min, respectively. Early outcomes of DCD grafts recipients were comparable to those of matched DBD LTs. In DCD and DBD group, incidence of anastomotic biliary complications and ischemic cholangiopathy was 15% versus 22% ( = 0.73) and 5% versus 2% ( = 1), respectively. One-year patient and graft survival was 100% versus 95% ( = 0.18) and 90% versus 95% ( = 0.82). In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.
Topics: Brain; Brain Death; Death; Graft Survival; Humans; Liver; Organ Preservation; Perfusion; Retrospective Studies; Tissue Donors; Warm Ischemia
PubMed: 35529593
DOI: 10.3389/ti.2022.10390 -
The Annals of Thoracic Surgery Aug 2006
Topics: Adrenergic beta-Agonists; Albuterol; Animals; Cyclic AMP; Lung; Rats; Salmeterol Xinafoate; Warm Ischemia
PubMed: 16863746
DOI: 10.1016/j.athoracsur.2006.02.064 -
Annals of Surgery Jan 2000To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify...
OBJECTIVE
To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes.
SUMMARY BACKGROUND DATA
Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before.
METHODS
Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage.
RESULTS
After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte-vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues.
CONCLUSIONS
This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte-vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R.
Topics: Animals; Biomarkers; Blood Flow Velocity; Carrier Proteins; Cell Membrane Permeability; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Intestinal Mucosa; Intestine, Small; Leukocytes; Male; Microcirculation; Myelin P2 Protein; Neoplasm Proteins; Nerve Tissue Proteins; Rats; Rats, Inbred Lew; Reperfusion Injury
PubMed: 10636108
DOI: 10.1097/00000658-200001000-00014 -
International Braz J Urol : Official... 2021To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia.
PURPOSE
To quantitatively evaluate the possible long-term protective effects of quercetin during renal warm ischemia.
MATERIALS AND METHODS
Male rats were allocated into 4 groups: sham (S), sham quercetin (SQ), ischemia (I), and ischemia quercetin (IQ). Groups SQ and IQ received quercetin (50mg/kg) before and after surgery. Groups I and IQ had their left renal vessels clamped for 60 minutes. All animals were euthanized four weeks after the procedure, and serum urea and creatinine levels were measured. Renal weight and volume, cortex-non-cortex area ratio (C-NC), cortical volume (CV), glomerular volumetric density (Vv[glom]), volume-weighted glomerular volume (VWGV) and number of glomeruli per kidney (N[glom]) were evaluated by stereological methods. Results were considered statistically significant when p < 0.05.
RESULTS
Serum urea levels in group I increased by 10.4% in relation to group S, but no differences were observed among the other groups. The C-NC of group I was lower than those of all other groups, and group IQ had similar results to sham groups. The Vv[glom] and N[glom] of group I were lower than those of group S (33.7% and 28.3%, respectively) and group IQ had no significant difference compared to the S group.
CONCLUSIONS
Quercetin was effective as a nephroprotective agent in preventing the glomerular loss observed when the kidney was subjected to warm ischemia. This suggests that this flavonoid may be used preventively in kidney surgery, when warm ischemia is necessary, such as partial nephrectomy.
Topics: Animals; Kidney; Kidney Glomerulus; Male; Nephrectomy; Quercetin; Rats; Rodentia; Warm Ischemia
PubMed: 33848072
DOI: 10.1590/S1677-5538.IBJU.2020.0358 -
Central European Journal of Urology 2024The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM),... (Review)
Review
INTRODUCTION
The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM), estimated blood loss (EBL) and estimated GFR reduction while also suggesting the optimal dosage scheme.
MATERIAL AND METHODS
A systematic review was performed using Medline (PubMed), ClinicalTrials.gov, and Cochrane Library (CENTRAL) databases, in concordance with the PRISMA statement. Studies in English regarding the use of indocyanine green in partial nephrectomy were reviewed. Reviews and meta-analyses, editorials, perspectives, and letters to the editors were excluded.
RESULTS
Individual ICG dose was 5 mg in most of the studies. The mean warm ischemia time (WIT) on each study ranged from 11.6 minutes to 27.2 minutes. The reported eGFR reduction ranged from 0% to 15.47%. Lowest mean EBL rate was 48.2 ml and the highest was 347 ml. Positive surgical margin rates were between 0.3% to 11%.
CONCLUSIONS
Indocyanine green seems to be a useful tool in partial nephrectomy as it can assist surgeons in identifying tumor and its related vasculature. Thereby, warm ischemia time can be reduced and, in some cases, selective ischemia can be implemented leading to better renal functional preservation.
PubMed: 38645804
DOI: 10.5173/ceju.2023.155 -
BJU International Feb 2023To provide a narrative review of the major advances regarding ischaemia and functional recovery after partial nephrectomy (PN), along with the ongoing controversies. (Review)
Review
OBJECTIVE
To provide a narrative review of the major advances regarding ischaemia and functional recovery after partial nephrectomy (PN), along with the ongoing controversies.
METHODS
Key articles reflecting major advances regarding ischaemia and functional recovery after PN were identified. Special emphasis was placed on contributions that changed perspectives about surgical management. Priority was also placed on randomized trials of off-clamp vs on-clamp cohorts.
RESULTS
A decade ago, 'Every minute counts' was published, showing strong correlations between duration of ischaemia and development of acute kidney injury (AKI) and chronic kidney disease after clamped PN. This reinforced perspectives that ischaemia was the main modifiable factor that could be addressed to improve functional outcomes and helped spur efforts towards reduced or zero ischaemia PN. These approaches were associated with strong functional recovery and some peri-operative risk, although they were generally safe in experienced hands. Further research demonstrated that, when parenchymal volume changes were incorporated into the analyses, ischaemia lost statistical significance, and percent parenchymal volume saved proved to be the main determinant. Cold ischaemia was confirmed to be highly protective, and limited warm ischaemia also proved to be safe. The reconstructive phase of PN, with avoidance of parenchymal devascularization, appears to be most important for functional outcomes. Randomized trials of on-clamp vs off-clamp PN have shown minimal impact of ischaemia on functional recovery.
CONCLUSIONS
The past decade has witnessed great progress regarding functional recovery after PN, with many lessons learned. However, there are still unanswered questions, including: What is the threshold of warm ischaemia at which irreversible ischaemic injury begins to develop? Are some cohorts at increased risk for AKI or irreversible ischaemic injury? and Which patients should be prioritized for zero-ischaemia PN?
Topics: Humans; Kidney; Kidney Neoplasms; Nephrectomy; Warm Ischemia; Ischemia; Acute Kidney Injury; Glomerular Filtration Rate; Retrospective Studies
PubMed: 35835519
DOI: 10.1111/bju.15848