-
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 -
BJU International Nov 2016To assess the impact of ischaemia on renal function after partial nephrectomy (PN). (Review)
Review
OBJECTIVE
To assess the impact of ischaemia on renal function after partial nephrectomy (PN).
MATERIALS AND METHODS
A literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In January 2015, the Medline and Embase databases were systematically searched using the protocol ('warm ischemia'[mesh] OR 'warm ischemia'[ti]) AND ('nephrectomy'[mesh] OR 'partial nephrectomy'[ti]). An updated search was performed in December 2015. Only studies based on a solitary kidney model or on a two-kidney model but with assessment of split renal function were included in this review.
RESULTS
Of the 1119 studies identified, 969 abstracts were screened after duplicates were removed: 29 articles were finally included in this review, including nine studies that focused on patients with a solitary kidney. None of the nine studies adjusting for the amount of preserved parenchyma found a negative impact of warm ischaemia time on postoperative renal function, unless this was extended beyond a 25-min threshold. The quality and the quantity of preserved parenchyma appeared to be the main contributors to postoperative renal function.
CONCLUSION
Currently, no evidence supports that limited ischaemia time (i.e. ≤25 min) has a higher risk of reducing renal function after PN compared to a 'zero ischaemia' technique. Several recent studies have suggested that prolonged warm ischaemia (>25-30 min) could cause an irreversible ischaemic insult to the surgically treated kidney.
Topics: Humans; Kidney; Kidney Neoplasms; Nephrectomy; Time Factors; Warm Ischemia
PubMed: 27409986
DOI: 10.1111/bju.13580 -
The Journal of Surgical Research Oct 2019Static cold storage (SCS) and hypothermic machine perfusion (HMP) are currently standard methods for renal grafts clinical preservation. Both methods are predominantly... (Comparative Study)
Comparative Study
Static cold storage (SCS) and hypothermic machine perfusion (HMP) are currently standard methods for renal grafts clinical preservation. Both methods are predominantly implemented without the active delivery of oxygen, even for donation after circulatory death-like kidneys. However, even under severe hypothermia (4°C-6°C), kidneys can consume oxygen and produce ATP. What is not established, though, is to what extent and how SCS and HMP compare in terms of oxygen. Using a porcine preclinical model of renal warm ischemia (WI) to compare SCS and HMP methods, we continuously monitored and quantified oxygen level and consumption along preservation; we also determined prepreservation and postpreservation cortical ATP level; values were given as median and [min; max] range. One-hour WI reduced ATP by ∼90% (from 3.3 [1.7; 4.5] mmol/L tissue in Controls). Oxygen consumption (QO, μmol/min per 100 g) was determined from initial solution PO decrease (SCS and HMP) and from arterio-venous difference (HMP). In SCS and HMP, PO decreased rapidly (t ∼1 h) from atmospheric levels to 52.9 [38.0; 65.9] and 8.2 [3.0, 16.0] mmHg, respectively. In HMP, QO was 2.7 [0.4; 3.9] versus 0.5 [0.0; 1.3] in SCS (P < 0.05); postpreservation ATP amounted to 5.8 [3.2; 6.5] in HMP versus 0.1 [0.0; 0.2] in SCS. Despite hypothermic conditions in SCS or HMP, donation after circulatory death-like renal grafts require oxygen. Increased oxygen consumption, restored ATP level, and improved histological profile in HMP might explain the established HMP superiority over SCS. These results establish a rational basis for the use of oxygen in hypothermic preservation. Optimal levels required for preservation and graft-type variants remain to be determined.
Topics: Adenosine Triphosphate; Allografts; Animals; Cold Temperature; Kidney; Kidney Transplantation; Male; Models, Animal; Organ Preservation; Organ Preservation Solutions; Oxygen; Oxygen Consumption; Perfusion; Swine; Warm Ischemia
PubMed: 31071608
DOI: 10.1016/j.jss.2019.04.015 -
Transplantation Reviews (Orlando, Fla.) Oct 2020To assess the impact of the learning curve of kidney transplantation on operative and postoperative complications. (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the impact of the learning curve of kidney transplantation on operative and postoperative complications.
METHODS
A literature search was systematically conducted to evaluate the significance of the learning curve on complications in kidney transplantation. Meta-analyses of the effect of the learning curve on warm ischemic time, total operating time (TOT), vascular and urological complications, postoperative bleeding, lymphocele and infection.
RESULTS
Nine studies met the inclusion criteria and 2762 patients were included in the present meta-analyses. Surgeons at the beginning of the learning curve were found to have longer TOT (mean difference 41.77 (95% CI: 4.48-79.06; P = .03) and more urological complications (risk ratio 3.93; 95% CI: 1.87-8.25; P < .01). No differences were seen in warm ischemic time, postoperative bleeding, lymphocele, and vascular complications.
CONCLUSION
Surgeons at the beginning of their learning curve have a longer TOT and more urological complications, without an effect on postoperative bleeding, lymphocele, infection and vascular complications. For interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration.
Topics: Humans; Kidney Transplantation; Learning Curve; Lymphocele; Postoperative Complications; Warm Ischemia
PubMed: 32624245
DOI: 10.1016/j.trre.2020.100564 -
Transplantation Proceedings 2021One of the cornerstone research models used in our laboratories is the induction of ischemic injury through cold ischemia followed by warm ischemia to donor kidneys to...
One of the cornerstone research models used in our laboratories is the induction of ischemic injury through cold ischemia followed by warm ischemia to donor kidneys to mimic the clinical realities of transplantation. The experimental design of the present study included bilateral nephrectomies on the day of syngeneic kidney transplant, with serum creatinine measured 24 hours postoperatively to measure acute function. Cold ischemia time in these experiments was always 30 minutes, and warm ischemia time was not standardized but always recorded. It became apparent that some transplanted kidneys that should have displayed injury were producing close to normal serum creatinine levels on postoperative day 1. In reviewing our data, we found a potential correlation between warm ischemia time and serum creatinine, in particular a significant proportion of low serum creatinine results (0.48 ± 0.26 mg/dL vs 1.99 ± 1.11 mg/dL; P < .05) was associated with warm ischemia times that were significantly shorter than our historical average (29.2 ± 2.7 min vs 35.7 ± 2.2 min; P < .05). The kidneys with lower serum creatinine also displayed lower apoptosis and brush border injury scores and fewer tubular casts. Therefore, we concluded that establishing a minimum warm ischemia time was just as important as standardized cold ischemia time to ensure consistent injury in this model.
Topics: Animals; Cold Ischemia; Creatinine; Disease Models, Animal; Ischemia; Kidney; Kidney Transplantation; Male; Mice; Warm Ischemia
PubMed: 33168203
DOI: 10.1016/j.transproceed.2020.08.010 -
Journal of Endourology May 2018Nephron-sparing surgery, especially through a minimally invasive approach, is increasingly being performed for incidentally detected renal masses with excellent...
Nephron-sparing surgery, especially through a minimally invasive approach, is increasingly being performed for incidentally detected renal masses with excellent outcomes. Tumors in central location remain a surgical challenge during nephron-sparing surgery. In this chapter, we discuss the minimally invasive management of these tumors, which include complex hilar tumors and endophytic central tumors, with a focus on surgical technique. The key to management of these tumors is to maintain good preoperative hydration, achieving adequate exposure of tumor, and the use of intraoperative ultrasound to plan the resection plane. Individual vessels may be ligated as they enter close to the tumor. Careful renorrhaphy is essential, especially in hilar tumors, which have major blood vessels at the base of the tumor. Selective use of near infrared fluorescence imaging, on-demand ischemia, early unclamping, enucleoresection techniques, and intracorporeal hypothermia may help minimize, or reduce the effect of warm ischemia.
Topics: Hemostasis; Humans; Ischemia; Kidney Neoplasms; Minimally Invasive Surgical Procedures; Nephrectomy; Nephrons; Organ Sparing Treatments; Patient Positioning; Postoperative Period; Preoperative Period; Robotic Surgical Procedures; Ultrasonography; Video Recording; Warm Ischemia
PubMed: 29774822
DOI: 10.1089/end.2018.0046 -
The Journal of Heart and Lung... Sep 2021Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft...
Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation.
BACKGROUND
Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP).
METHODS
Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1β, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined.
RESULTS
Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs.
CONCLUSIONS
The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Cold Ischemia; Cytokines; Disease Models, Animal; Extracorporeal Circulation; Inflammation; Lung; Lung Transplantation; Organ Preservation; Perfusion; Rats; Rats, Sprague-Dawley; Tissue Donors; Warm Ischemia
PubMed: 34193360
DOI: 10.1016/j.healun.2021.05.015 -
BioMed Research International 2023Donor lung ventilation and inflation during the warm ischemia could attenuate ischemia-reperfusion injury (IRI) after lung transplantation. Hydrogen sulfide (HS), as a...
Comparison of Inflation and Ventilation with Hydrogen Sulfide during the Warm Ischemia Phase on Ischemia-Reperfusion Injury in a Rat Model of Non-Heart-Beating Donor Lung Transplantation.
Donor lung ventilation and inflation during the warm ischemia could attenuate ischemia-reperfusion injury (IRI) after lung transplantation. Hydrogen sulfide (HS), as a kind of protective gas, has demonstrated the antilung IRI effect. This study is aimed at observing the different methods of administering HS in the setting of warm ischemia, ventilation, and inflation on the lung graft from a rat non-heart-beating donor. After 1 h of cardiac arrest, donor lungs in situ were inflated with 80 ppm HS (FS group), ventilated with 80 ppm HS (VS group), or deflated (control group) for 2 h. Then, the lung transplantation was performed after 3 h cold ischemia. The rats without ischemia and reperfusion were in the sham group. Pulmonary surfactant in the bronchoalveolar lavage fluid was measured in donor lung. The inflammatory response, cell apoptosis, and lung graft function were assessed at 3 h after reperfusion. The lung injury was exacerbated in the control group, which was attenuated significantly after the HS treatment. Compared with the FS group, the pulmonary surfactant in the donor was deteriorated, the lung oxygenation function was decreased, and the inflammatory response and cell apoptosis were increased in the graft in the VS group ( < 0.05). In conclusion, HS inflation during the warm ischemia phase improved the function of lung graft via regulating pulmonary surfactant stability and decreased the lung graft IRI via decreasing the inflammatory response and cell apoptosis.
Topics: Rats; Animals; Warm Ischemia; Hydrogen Sulfide; Pulmonary Surfactants; Lung; Lung Transplantation; Reperfusion Injury; Respiration
PubMed: 36778057
DOI: 10.1155/2023/3645304 -
Transplantation Proceedings Dec 2023The limitation of ischemia times, which damages the organs and impacts transplant outcomes, is a drawback of controlled donation after circulatory death. (Observational Study)
Observational Study
BACKGROUND
The limitation of ischemia times, which damages the organs and impacts transplant outcomes, is a drawback of controlled donation after circulatory death.
METHODS
The aim of the study was to analyze the influence of preservation and ischemia times on overall survival and both censured graft survival and overall graft survival. This was an observational and retrospective study of patients undergoing liver transplantation with grafts from controlled donation after circulatory death between November 2013 and November 2022.
RESULTS
Sixty-five patients were included in the study. Twenty percent (12 patients) developed early graft dysfunction according to Olthoff's classification, and 7 patients (11.6%) scored ≥7 points according to the Model for Early Allograft Function Scoring scale. Five patients (7.6%) met the criteria for primary graft failure. The retransplantation rate was 9.2% (6 cases). Fifty patients (76.9%) remained alive, and 15 patients (23.1%) died. When analyzing overall survival based on the main preservation and ischemia times, we observed that the best results occurred in the group with a functional warm ischemia time <12 minutes, with a survival rate at 1, 3, and 5 years of 95.8%, 87.1%, and 87.1%, respectively (P = .043). Regarding the analysis of censured graft survival based on the main preservation and ischemia times, we found that the worst results occurred in the group with a cold ischemia time ≥6 hours, with a survival rate of around 48% at 3 and 5 years (P = .047).
CONCLUSIONS
High-risk patients have lower overall and graft survival in the short and long term in grafts from controlled donation after circulatory death.
Topics: Humans; Retrospective Studies; Transplant Recipients; Ischemia; Tissue Donors; Warm Ischemia; Graft Survival; Death; Tissue and Organ Procurement
PubMed: 37813786
DOI: 10.1016/j.transproceed.2023.08.033 -
Annals of Transplantation Jul 2019BACKGROUND Prolonged cold ischemia is an established risk factor for poor early graft function (EGF). However, warm ischemia incurring during graft implantation has...
BACKGROUND Prolonged cold ischemia is an established risk factor for poor early graft function (EGF). However, warm ischemia incurring during graft implantation has received little attention regarding its possible detrimental effect on EGF. The aim of our study was to examine the impact of recipient warm ischemia time on EGF. MATERIAL AND METHODS The data of 102 consecutive kidney transplants were analyzed to determine the association between duration of graft implantation time (IT) and EGF. Recipient IT groups were (GI) up to 45 min, (GII) 45-60 min, and (GIII) >60 min. EGF was categorized as immediate (IGF), slow (SGF), or delayed graft function (DGF). In recipients with IGF, graft function was further assessed by time needed for reduction in serum creatinine by 50% (SC50) of pre-transplant value, and serum creatinine on day 7 (SCD7). RESULTS Of a total of 102 recipients, 55 (55%) were in GI, 33 (32%) were in GII, and 14 (13%) were in GIII. Factors prolonging IT were recipient body mass index (BMI) (p=0.02) and multiple arteries in donor kidneys (p<0.01). No recipients in GI had DGF or SGF, while 2 in GII had DGF, and 5 patients in GIII had poor EGF. SC50 was significantly longer in GIII and GII versus GI (40.8±42.4 and 32.8±20.4 vs. 22.2±17.2 [p=.02, p≤.01]), respectively. Mean SCD7 was also significantly higher in GIII and GII versus GI. The mean last serum creatinine was comparable among all groups. CONCLUSIONS IT of more than 45 min was a risk factor for poor EGF, but achieved statistical significance only when it exceeded 60 min. Longer IT also significantly slowed the fall in SC50, and led to a higher SCD7. However, poor EGF and suboptimal early SC trends had little long-term effect on serum creatinine.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Transplant Recipients; Treatment Outcome; Warm Ischemia; Young Adult
PubMed: 31332156
DOI: 10.12659/AOT.916012