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BJU International Aug 2023To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients...
OBJECTIVES
To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia.
PATIENTS AND METHODS
Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia.
RESULTS
In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score.
CONCLUSIONS
The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.
Topics: Humans; Kidney Neoplasms; Nephrectomy; Kidney; Warm Ischemia; Ischemia; Glomerular Filtration Rate; Retrospective Studies
PubMed: 37017637
DOI: 10.1111/bju.16023 -
World Journal of Urology Apr 2023The lack of a reliable and reproducible technique to ensure a constantly low temperature of the graft during kidney transplantation (KT) may be a cause of renal... (Review)
Review
PURPOSE
The lack of a reliable and reproducible technique to ensure a constantly low temperature of the graft during kidney transplantation (KT) may be a cause of renal nonfunction. The aim of this review was to assess all the methods and devices available to ensure hypothermia during vascular anastomosis in KT.
METHODS
A literature search was conducted through May 2022 using PubMed/Medline, Cochrane Library, Embase and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The review protocol was registered on PROSPERO (CRD42022326550).
RESULTS
A total of 20 studies reporting on four hypothermia techniques met our inclusion criteria. Simple instillation of cold serum is not sufficient, the graft reaching up to 33 ℃ at the end of warm ischemia time (WIT). Plastic bags filled with ice slush have questionable efficiency. The use of a gauze jacket filled with ice-slush was reported in 12/20 studies. It ensures a graft temperature up to 20.3 ℃ at the end of WIT. Some concerns have been linked to potentially inhomogeneous parenchymal cooling and secondary ileus. Novel devices with continuous flow of ice-cold solution around the graft might overcome these limitations, showing a renal temperature below 20 ℃ at all times during KT.
CONCLUSION
The gauze filled with ice slush is the most common technique, but several aspects can be improved. Novel devices in the form of cold-ischemia jackets can ensure a lower and more stable temperature of the graft during KT, leading to higher efficiency and reproducibility.
Topics: Humans; Kidney Transplantation; Warm Ischemia; Hypothermia, Induced; Hypothermia; Ice; Reproducibility of Results
PubMed: 36826486
DOI: 10.1007/s00345-023-04328-9 -
Urologia Internationalis 2015To analyze current evidence comparing the safety and outcomes of regional and global ischemia for partial nephrectomy (PN). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To analyze current evidence comparing the safety and outcomes of regional and global ischemia for partial nephrectomy (PN).
MATERIALS AND METHODS
A systematic search of the PubMed and Web of Science databases was conducted in May 2014 to identify studies comparing the safety and outcomes of regional and global ischemia for PN. A systematic review and meta-analysis was also performed.
RESULTS
Six retrospective observational studies were selected for the analysis, including 363 patients who underwent PN (162 regional ischemia and 201 global ischemia cases). Operation times were not statistically different [weighted mean difference (WMD) = 20.35 min, 95% CI: -0.28-40.97, p = 0.05], but estimated blood loss was significantly higher in the regional ischemia group (WMD = 52.04 ml, 95% CI: 14.30-89.78, p = 0.007) than in the global ischemia group. Complication rates [odds ratio (OR) = 1.16; 95% CI: 0.63-2.15, p = 0.63] and blood transfusion rates (OR = 1.85; 95% CI: 0.86-4.01, p = 0.12) of the two groups were not significantly different. The regional ischemia group showed better postoperative renal function (WMD = 4.23 ml/min, 95% CI: 2.61-5.85, p < 0.00001) than the global ischemia group, and all cases in the regional ischemia group showed negative margins.
CONCLUSIONS
Regional ischemia is as safe to perform as global ischemia, and the former leads to better postoperative renal functions than the latter. These findings support the application of regional ischemia for PN.
Topics: Blood Loss, Surgical; Blood Transfusion; Bloodless Medical and Surgical Procedures; Chi-Square Distribution; Humans; Nephrectomy; Odds Ratio; Operative Time; Reperfusion Injury; Risk Factors; Time Factors; Treatment Outcome; Warm Ischemia
PubMed: 25427979
DOI: 10.1159/000367997 -
Investigative and Clinical Urology Sep 2020This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the deterioration in renal function in patients with cT1 renal tumors.
MATERIALS AND METHODS
We conducted a systematic review that included patients over 18 years of age who underwent PN with or without warm ischemia for cT1 renal tumors. The primary outcome was impaired renal function. A search strategy was performed in MEDLINE, EMBASE, LILACS, CENTRAL, the article reference lists, and the unpublished literature to reach saturation of the information. We assessed the risk of bias with the methodological index for nonrandomized studies (MINORS) tool, and we performed a meta-analysis according to the type of variable.
RESULTS
We found a total of 5,682 articles, of which 14 met the inclusion criteria. Seven studies evaluated renal function, identifying a difference in means (MD) of 3.50 (95% confidence interval [CI], 1.16 to 5.83), favoring no ischemia. We did not find any significant differences regarding intraoperative bleeding or operative time (MD, 55 mL; 95% CI, -33.16 to 144.08; and MD, 1.87; 95% CI, -20.47 to 24.21; respectively).
CONCLUSIONS
In this study, PN without ischemia showed a decrease in deterioration of the estimated glomerular filtration rate compared with warm ischemia.
Topics: Humans; Kidney Neoplasms; Neoplasm Staging; Nephrectomy; Treatment Outcome; Warm Ischemia
PubMed: 32869563
DOI: 10.4111/icu.20190313 -
Biochimica Et Biophysica Acta.... Feb 2017Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used...
BACKGROUND
Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate immune parameters as endpoints.
METHODS
Mice (C57Bl/6J) were subjected to sham surgery, 30min, or 60min of partial hepatic ischemia. Liver function was measured after 24h using intravital microscopy and spectroscopy. Innate immune activity was assessed at 6 and 24h of reperfusion using mRNA and cytokine arrays. Liver inflammation and function were profiled in two patient cohorts subjected to I/R during liver resection to validate the preclinical results.
RESULTS
In mice, plasma ALT levels and the degree of hepatic necrosis were strongly correlated. Liver function was bound by a narrow damage threshold and was severely impaired following 60min of ischemia. Severe ischemia (60min) evoked a neutrophil-dominant immune response, whereas mild ischemia (30min) triggered a monocyte-driven response. Clinical liver I/R did not compromise liver function and displayed a cytokine profile similar to the mild I/R injury model.
CONCLUSIONS
Mouse models using ≤30min of ischemia best reflect the clinical liver I/R injury profile in terms of liver function dynamics and type of immune response.
GENERAL SIGNIFICANCE
This short duration of ischemia therefore has most translational value and should be used to increase the prospects of developing effective interventions for hepatic I/R.
Topics: Adaptive Immunity; Animals; Cytokines; Disease Models, Animal; Humans; Immunity, Innate; Inflammation; Liver; Male; Mice, Inbred C57BL; Reperfusion Injury; Warm Ischemia
PubMed: 27989959
DOI: 10.1016/j.bbadis.2016.10.022 -
American Journal of Transplantation :... May 2022Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary...
Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.
Topics: Death; Heart; Heart Arrest; Heart Transplantation; Humans; Perfusion; Tissue Donors; Tissue and Organ Procurement; Warm Ischemia
PubMed: 35114047
DOI: 10.1111/ajt.16987 -
Clinical Science (London, England :... Aug 2015Ischaemia/reperfusion injury is an important cause of liver damage during surgical procedures such as hepatic resection and liver transplantation, and represents the... (Review)
Review
Ischaemia/reperfusion injury is an important cause of liver damage during surgical procedures such as hepatic resection and liver transplantation, and represents the main cause of graft dysfunction post-transplantation. Molecular processes occurring during hepatic ischaemia/reperfusion are diverse, and continuously include new and complex mechanisms. The present review aims to summarize the newest concepts and hypotheses regarding the pathophysiology of liver ischaemia/reperfusion, making clear distinction between situations of cold and warm ischaemia. Moreover, the most updated therapeutic strategies including pharmacological, genetic and surgical interventions, as well as some of the scientific controversies in the field are described.
Topics: Animals; Cold Ischemia; Cytoprotection; Hepatectomy; Humans; Liver; Liver Diseases; Liver Transplantation; Reperfusion Injury; Risk Factors; Signal Transduction; Warm Ischemia
PubMed: 26014222
DOI: 10.1042/CS20150223 -
Urology Dec 2014To assess renal functional deterioration after partial nephrectomy with warm and cold ischemia using (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scintigraphy... (Comparative Study)
Comparative Study
OBJECTIVE
To assess renal functional deterioration after partial nephrectomy with warm and cold ischemia using (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scintigraphy parameters.
METHODS
Open partial nephrectomy was performed in 59 patients with warm ischemia and 64 patients with cold ischemia. (99m)Tc-MAG3 renal scintigraphy was performed and effective renal plasma flow was calculated to evaluate split renal function. In addition, regional (99m)Tc-MAG3 uptake was analyzed in the surgically unaffected parts to evaluate ischemic damage.
RESULTS
The mean tumor size in the warm and cold ischemia groups was 2.9 and 3.2 cm, respectively, and the mean ischemic time was 24.2 minutes (range, 8-46 minutes) and 26.7 min (range, 8-58 minutes), respectively. One week after surgery, effective renal plasma flow in the operated kidney decreased to 66.2% (from 160.2 to 105.4 mL/min/1.73 m(2)) in the warm ischemia group and to 77.4% (from 152.3 to 116.6 mL/min/1.73 m(2)) in the cold ischemia group. Regional (99m)Tc-MAG3 uptake changed to 89.2% of baseline in the warm ischemia group and 101.5% of baseline in the cold ischemia group. When the ischemic time was ≥ 25 minutes, regional (99m)Tc-MAG3 uptake in the warm ischemia group did not recover to the baseline level at 6 months. Multiple regression analyses demonstrated a significant correlation between ischemic time and the decrease in regional (99m)Tc-MAG3 uptake in the warm ischemia group, but not in the cold ischemia group.
CONCLUSION
Warm ischemia for ≥ 25 minutes caused long lasting diffuse damage throughout the operated kidney, whereas cold ischemia for up to 58 minutes prevented ischemic injury to the renal remnant.
Topics: Chi-Square Distribution; Cohort Studies; Cold Ischemia; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Function Tests; Kidney Neoplasms; Male; Multivariate Analysis; Nephrectomy; Postoperative Care; Postoperative Complications; Radionuclide Imaging; Regression Analysis; Retrospective Studies; Technetium Tc 99m Mertiatide; Time Factors; Treatment Outcome; Warm Ischemia
PubMed: 25432829
DOI: 10.1016/j.urology.2014.08.040 -
Transplantation Jun 2021Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia... (Review)
Review
Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation.
Topics: Hepatectomy; Humans; Liver Transplantation; Organ Preservation; Perfusion; Time Factors; Tissue Donors; Tissue Survival; Tissue and Organ Harvesting; Warm Ischemia
PubMed: 34048418
DOI: 10.1097/TP.0000000000003819 -
Transplantation Proceedings Sep 2014The aim of our study was to retrospectively evaluate the impact of ischemia time and other clinical factors on the development of liver allograft primary nonfunction...
The aim of our study was to retrospectively evaluate the impact of ischemia time and other clinical factors on the development of liver allograft primary nonfunction (PNF). We enrolled 531 consecutive liver transplantations from 1998 to 2013, identifying 10 PNF (1.9%). PNF was found to be statistically related to 4 different variables: donor age>60 years (P=.01), female donor gender (P=.01), total ischemia time>10 hours (P=.03) and infusion of more than 30 fresh frozen plasma units during surgery (P=.02). The study focused on the clinical impact of total ischemia time. We grouped total ischemia time into 4 groups (Group 1: ≤7.5 hours; Group 2: between 7.5 and 10 hours; Group 3: between 10 and 12 hours; Group 4: >12 hours) and 2 groups (assigning a cut-off value of 10 hours): both these grouping systems significantly influenced the development of PNF and 1-year graft survival, with limited impact on long-term survival. We split total ischemia time in a "technical time," "hepatectomy time," and "warm ischemia time." Only the first 2 components were found to be statistically related to PNF development with P=.02 and P=.003, respectively. Further studies should focus on these aspects of PNF.
Topics: Adult; Aged; Aged, 80 and over; Female; Graft Survival; Humans; Linear Models; Liver Transplantation; Logistic Models; Male; Middle Aged; Outcome Assessment, Health Care; Primary Graft Dysfunction; Retrospective Studies; Survival Analysis; Warm Ischemia
PubMed: 25242773
DOI: 10.1016/j.transproceed.2014.07.040