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The Cochrane Database of Systematic... May 2024Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Waiting lists for kidney transplantation continue to grow. Live kidney donation significantly reduces waiting times and improves long-term outcomes for recipients. Major disincentives to potential kidney donors are the pain and morbidity associated with surgery. This is an update of a review published in 2011.
OBJECTIVES
To assess the benefits and harms of open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), hand-assisted LDN (HALDN) and robotic donor nephrectomy (RDN) as appropriate surgical techniques for live kidney donors.
SEARCH METHODS
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 31 March 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing LDN with ODN, HALDN, or RDN were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Thirteen studies randomising 1280 live kidney donors to ODN, LDN, HALDN, or RDN were included. All studies were assessed as having a low or unclear risk of bias for selection bias. Five studies had a high risk of bias for blinding. Seven studies randomised 815 live kidney donors to LDN or ODN. LDN was associated with reduced analgesia use (high certainty evidence) and shorter hospital stay, a longer procedure and longer warm ischaemia time (moderate certainty evidence). There were no overall differences in blood loss, perioperative complications, or need for operations (low or very low certainty evidence). Three studies randomised 270 live kidney donors to LDN or HALDN. There were no differences between HALDN and LDN for analgesia requirement, hospital stay (high certainty evidence), duration of procedure (moderate certainty evidence), blood loss, perioperative complications, or reoperations (low certainty evidence). The evidence for warm ischaemia time was very uncertain due to high heterogeneity. One study randomised 50 live kidney donors to retroperitoneal ODN or HALDN and reported less pain and analgesia requirements with ODN. It found decreased blood loss and duration of the procedure with HALDN. No differences were found in perioperative complications, reoperations, hospital stay, or primary warm ischaemia time. One study randomised 45 live kidney donors to LDN or RDN and reported a longer warm ischaemia time with RDN but no differences in analgesia requirement, duration of procedure, blood loss, perioperative complications, reoperations, or hospital stay. One study randomised 100 live kidney donors to two variations of LDN and reported no differences in hospital stay, duration of procedure, conversion rates, primary warm ischaemia times, or complications (not meta-analysed). The conversion rates to ODN were 6/587 (1.02%) in LDN, 1/160 (0.63%) in HALDN, and 0/15 in RDN. Graft outcomes were rarely or selectively reported across the studies. There were no differences between LDN and ODN for early graft loss, delayed graft function, acute rejection, ureteric complications, kidney function or one-year graft loss. In a meta-regression analysis between LDN and ODN, moderate certainty evidence on procedure duration changed significantly in favour of LDN over time (yearly reduction = 7.12 min, 95% CI 2.56 to 11.67; P = 0.0022). Differences in very low certainty evidence on perioperative complications also changed significantly in favour of LDN over time (yearly change in LnRR = 0.107, 95% CI 0.022 to 0.192; P = 0.014). Various different combinations of techniques were used in each study, resulting in heterogeneity among the results.
AUTHORS' CONCLUSIONS
LDN is associated with less pain compared to ODN and has comparable pain to HALDN and RDN. HALDN is comparable to LDN in all outcomes except warm ischaemia time, which may be associated with a reduction. One study reported kidneys obtained during RDN had greater warm ischaemia times. Complications and occurrences of perioperative events needing further intervention were equivalent between all methods.
Topics: Nephrectomy; Humans; Living Donors; Robotic Surgical Procedures; Laparoscopy; Randomized Controlled Trials as Topic; Kidney Transplantation; Length of Stay; Pain, Postoperative; Operative Time; Tissue and Organ Harvesting; Warm Ischemia
PubMed: 38721875
DOI: 10.1002/14651858.CD006124.pub3 -
BMC Urology May 2024Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of...
BACKGROUND
Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of robotic nephron-sparing surgery (NSS) for treating RSAML.
METHODS
We retrospectively evaluated 15 patients with RSAMLs who were treated with robotic NSS at the Department of Urology of Tongji hospital, ranging from November 2018 to September 2022. Renal vessels and ureter were dissected. The outer part of RSAML was resected. The rest of tumor was removed by bluntly grasp, curettage and suction. Absorbable gelatin sponges were filled in the renal sinus. The preoperative parameters, operative measures and postoperative outcomes were all collected. Follow-up was performed by ultrasonography and estimated glomerular filtration rate (eGFR).
RESULTS
Robotic NSS was successfully performed in all the patients, without any conversion to open surgery or nephrectomy. The mean operation time was 134.13 ± 40.56 min. The mean warm ischemia time was 25.73 ± 3.28 min. The median estimated blood loss was 100 [50, 270] ml and 1 patient required blood transfusion. The mean drainage duration was 5.77 ± 1.98 days. The median postoperative hospital stay was 6.90 [5.80, 8.70] days. Two patients experienced postoperative urinary tract infection (Clavien-Dindo Grade II). During the median follow-up of 25.53 ± 15.28 months, patients received 91.18% renal function preservation. No local recurrence occurred in all the patients.
CONCLUSIONS
Robotic NSS for RSAML is a complicated procedure that demands technical expertise and a well-designed strategy is critical in the operation. Treating RSAML with modified robotic NSS is safe, effective and feasible.
Topics: Humans; Robotic Surgical Procedures; Kidney Neoplasms; Female; Retrospective Studies; Adult; Male; Middle Aged; Organ Sparing Treatments; Angiomyolipoma; Nephrons; Nephrectomy
PubMed: 38715034
DOI: 10.1186/s12894-024-01492-x -
Annals of Hepatology 2024Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation,...
INTRODUCTION AND OBJECTIVES
Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors.
PATIENTS AND METHODS
12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq.
RESULTS
Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response.
CONCLUSIONS
In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI.
Topics: Liver Transplantation; Reperfusion Injury; Humans; DNA Methylation; Liver; Male; Middle Aged; Female; Epigenesis, Genetic; Gene Expression Profiling; Transcriptome; Adult; Aged
PubMed: 38710471
DOI: 10.1016/j.aohep.2024.101506 -
Physiological Research Apr 2024An analytical method for studying DNA degradation by electrophoresis after cell lysis and visualization of DNA fragments with fluorescent dye, comet assay, was used to...
An analytical method for studying DNA degradation by electrophoresis after cell lysis and visualization of DNA fragments with fluorescent dye, comet assay, was used to evaluate the viability of the endothelial layer of human arterial grafts with the aim of identifying the procedure that will least damage the tissue before cryopreservation. Four groups of samples were studied: cryopreserved arterial grafts that were thawed in two different ways, slowly lasting 2 hours or rapidly for approx. 7 minutes. Arterial grafts that were collected as part of multiorgan procurement with minimal warm ischemia time. Cadaveric grafts were taken as part of the autopsy, so they have a more extended period of warm ischemia. The HeadDNA (%) parameter and others commonly used parameters like TailDNA (%). TailMoment, TailLength, OliveMoment, TailMoment to characterize the comet were used to assess viability in this study. The ratio of non-decayed to decayed nuclei was determined from the values found. This ratio for cadaveric grafts was 0.63, for slowly thawed cryopreserved grafts 2.9, for rapidly thawed cryopreserved grafts 1.9, and for multi-organ procurement grafts 0.68. The results of the study confirmed the assumption that the allografts obtained from cadaveric donors are the least suitable. On the other hand, grafts obtained from multiorgan donors are better in terms of viability monitored by comet assay. Keywords: Arterial grafts, Cryopreservation, Cadaveric, Multiorgan procurement, Viability, Comet assay.
Topics: Humans; Cryopreservation; Comet Assay; Cadaver; Arteries; Graft Survival
PubMed: 38710053
DOI: 10.33549/physiolres.935055 -
In Vivo (Athens, Greece) 2024Acute and chronic kidney diseases are a major contributor to morbidity and mortality worldwide, with no specific treatments currently available for these. To enable...
BACKGROUND/AIM
Acute and chronic kidney diseases are a major contributor to morbidity and mortality worldwide, with no specific treatments currently available for these. To enable understanding the pathophysiology of and testing novel treatments for acute and chronic kidney disease, a suitable in vivo model of kidney disease is essential. In this article, we describe two reliable rodent models (rats and mice) of efficacious kidney injury displaying acute to chronic kidney injury progression, which is also reversible through novel therapeutic strategies such as ischemic preconditioning (IPC).
MATERIALS AND METHODS
We utilized adult male Lewis rats and adult male wildtype (C57BL/6) mice, performed a midline laparotomy, and induced warm ischemia to both kidneys by bilateral clamping of both renal vascular pedicles for a set time, to mimic the hypoxic etiology of disease commonly found in kidney injury.
RESULTS
Bilateral ischemia reperfusion injury caused marked structural and functional kidney injury as exemplified by histology damage scores, serum creatinine levels, and kidney injury biomarker levels in both rodents. Furthermore, this effect displayed a dose-dependent response in the mouse model.
CONCLUSION
These rodent models of bilateral kidney IRI are reliable, reproducible, and enable detailed mechanistic study of the underlying pathophysiology of both acute and chronic kidney disease. They have been carefully optimised for single operator use with a strong track record of training both surgically trained and surgically naïve operators.
Topics: Animals; Reperfusion Injury; Disease Models, Animal; Mice; Rats; Male; Kidney; Acute Kidney Injury; Biomarkers; Rats, Inbred Lew; Mice, Inbred C57BL; Ischemic Preconditioning; Creatinine
PubMed: 38688639
DOI: 10.21873/invivo.13538 -
Transplantation Apr 2024This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death...
BACKGROUND
This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death (DCD) hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model.
METHODS
Thirty-two male Lewis rats were divided into 2 groups: the control group and the exosome group. The donor-heart rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 90 min, and then transplanted into recipients via abdominal heterotopic heart transplantation. Vehicle or exosome was added into the perfusate of normothermic EVHP in the control or exosome group. We evaluated left ventricular graft function, myocardial inflammation, and myocardial apoptosis of the donor heart 1.5 h after heart transplantation. Furthermore, we investigate the alternation of myocardial gene expression in the donor hearts between both groups by transcriptome sequencing.
RESULTS
The treatment with exosome significantly enhanced cardiac function through increasing left ventricular developed pressure, dp/dtmax, and dp/dtmin of DCD hearts at 90 min after heart transplantation compared with the control group. The myocardial cells in the exosome group exhibited an orderly arrangement without obvious edema. Furthermore, exosome added into perfusate in the exosome group significantly attenuated the level of inflammatory response and apoptosis. Transcriptome sequencing and RT-qPCR showed the phosphoinositide 3-kinase/protein kinase B pathway was activated after exosome treatment.
CONCLUSIONS
Normothermic EVHP combined with exosome can be a promising and novel DCD heart preservation strategy, alleviating myocardial ischemia-reperfusion injury in the DCD heart.
PubMed: 38685203
DOI: 10.1097/TP.0000000000005040 -
Transplantation Apr 2024Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes...
Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia-reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain.
BACKGROUND
Ischemia-reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation.
METHODS
Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors.
RESULTS
Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT).
CONCLUSIONS
Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.
PubMed: 38685198
DOI: 10.1097/TP.0000000000005042 -
Journal of Robotic Surgery Apr 2024The study aims to assess the available literature and compare the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) for posterior-lateral renal... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of the perioperative outcomes of robot-assisted laparoscopic transperitoneal versus retraperitoneal partial nephrectomy for posterior-lateral renal tumors: a systematic review and meta-analysis.
The study aims to assess the available literature and compare the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) for posterior-lateral renal tumors using transperitoneal (TP) and retroperitoneal (RP) approaches. Systematically searched the Embase, PubMed, and Cochrane Library databases for literature. Eligible studies were those that compared TP-RAPN and RP-RAPN for posterior-lateral renal tumors. The data from the included studies were analyzed and summarized using Review Manager 5.3, which involved comparing baseline patient and tumor characteristics, intraoperative and postoperative outcomes, and oncological outcomes. The analysis included five studies meeting the inclusion criteria, with a total of 1440 patients (814 undergoing RP-RAPN and 626 undergoing TP-RAPN). Both groups showed no significant differences in age, gender, BMI, R.E.N.A.L. score, and tumor size. Notably, compared to TP-RAPN, the RP-RAPN group demonstrated shorter operative time (OT) (MD: 17.25, P = 0.01), length of hospital stay (LOS) (MD: 0.37, P < 0.01), and lower estimated blood loss (EBL) (MD: 15.29, P < 0.01). However, no significant differences were found between the two groups in terms of warm ischemia time (WIT) (MD: -0.34, P = 0.69), overall complications (RR: 1.25, P = 0.09), major complications (the Clavien-Dindo classification ≥ 3) (RR: 0.97, P = 0.93), and positive surgical margin (PSM) (RR: 1.06, P = 0.87). The systematic review and meta-analysis suggests RP-RAPN may be more advantageous for posterior-lateral renal tumors in terms of OT, EBL, and LOS, but no significant differences were found in WIT, overall complications, major complications, and PSM. Both surgical approaches are safe, but a definitive advantage remains uncertain.
Topics: Female; Humans; Male; Blood Loss, Surgical; Kidney Neoplasms; Laparoscopy; Length of Stay; Nephrectomy; Operative Time; Peritoneum; Postoperative Complications; Robotic Surgical Procedures; Treatment Outcome
PubMed: 38683492
DOI: 10.1007/s11701-024-01963-1 -
Frontiers in Surgery 2024[This corrects the article DOI: 10.3389/fsurg.2021.808733.].
[This corrects the article DOI: 10.3389/fsurg.2021.808733.].
PubMed: 38680215
DOI: 10.3389/fsurg.2024.1411863 -
The Journal of Thoracic and... Apr 2024Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary...
OBJECTIVE
Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model.
METHODS
A porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared.
RESULTS
After transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function.
CONCLUSIONS
Treatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant.
PubMed: 38678474
DOI: 10.1016/j.jtcvs.2024.03.001