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1.
Kidney Int Rep ; 7(10): 2230-2241, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36217520

ABSTRACT

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and "death after KRT," with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

2.
BMJ Open ; 12(2): e053108, 2022 Feb 03.
Article in English | MEDLINE | ID: mdl-35115352

ABSTRACT

INTRODUCTION: Current evidence on vascular access strategies for haemodialysis patients is based on observational studies that are at high risk of selection bias. For elderly patients, autologous arteriovenous fistulas that are typically created in usual care may not be the best option because a significant proportion of fistulas either fail to mature or remain unused. In addition, long-term complications associated with arteriovenous grafts and central venous catheters may be less relevant when considering the limited life expectancy of these patients. Therefore, we designed the Optimising Access Surgery in Senior Haemodialysis Patients (OASIS) trial to determine the best strategy for vascular access creation in elderly haemodialysis patients. METHODS AND ANALYSIS: OASIS is a multicentre randomised controlled trial with an equal participant allocation in three treatment arms. Patients aged 70 years or older who are expected to initiate haemodialysis treatment in the next 6 months or who have started haemodialysis urgently with a catheter will be enrolled. To detect and exclude patients with an unusually long life expectancy, we will use a previously published mortality prediction model after external validation. Participants allocated to the usual care arm will be treated according to current guidelines on vascular access creation and will undergo fistula creation. Participants allocated to one of the two intervention arms will undergo graft placement or catheter insertion. The primary outcome is the number of access-related interventions required for each patient-year of haemodialysis treatment. We will enrol 195 patients to have sufficient statistical power to detect an absolute decrease of 0.80 interventions per year. ETHICS AND DISSEMINATION: Because of clinical equipoise, we believe it is justified to randomly allocate elderly patients to the different vascular access strategies. The study was approved by an accredited medical ethics review committee. The results will be disseminated through peer-reviewed publications and will be implemented in clinical practice guidelines. TRIAL REGISTRATION NUMBER: NL7933. PROTOCOL VERSION AND DATE: V.5, 25 February 2021.


Subject(s)
Arteriovenous Fistula , Central Venous Catheters , Aged , Clinical Protocols , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Dialysis/methods
4.
Nephrol Dial Transplant ; 37(9): 1751-1757, 2022 08 22.
Article in English | MEDLINE | ID: mdl-34383950

ABSTRACT

BACKGROUND: The aim of this study was to determine associations between characteristics of arteriovenous access (AVA) flow volume (Qa; mL/min) and 4-year freedom from cardiovascular mortality (CVM) in haemodialysis (HD) patients. METHODS: HD patients who received a primary AVA between January 2010 and December 2017 in one centre were analysed. Initial Qa was defined as the first Qa value obtained in a well-functioning AVA by a two-needle dilution technique. Actual Qa was defined as access flow at a random point in time. Changes in actual Qa were expressed per 3-month period. CVM was assessed according to the European Renal Association-European Dialysis and Transplant Association classification. The optimal cut-off point for initial Qa was identified by a receiver operating characteristics curve. A joint modelling statistical technique determined longitudinal associations between Qa characteristics and 4-year CVM. RESULTS: A total of 5208 Qa measurements (165 patients; 103 male, age 70 ± 12 years, autologous AVA n = 146, graft n = 19) were analysed. During follow-up (December 2010-January 2018, median 36 months), 79 patients (48%) died. An initial Qa <900 mL/min was associated with an increased 4-y CVM risk {hazard ratio [HR] 4.05 [95% confidence interval (CI) 1.94-8.43], P < 0.001}. After 4 years, freedom from CVM was 34% lower in patients with a Qa <900 mL/min (53 ± 7%) versus a Qa ≥900 mL/min (87 ± 4%; P < 0.001). An association between increases in actual Qa per 3-month period and mortality was found [HR 4.48/100 mL/min (95% CI 1.44-13.97), P = 0.010], indicating that patients demonstrating increasing Qa were more likely to die. In contrast, actual Qa per se was not related to survival. CONCLUSIONS: Studying novel AVA Qa characteristics may contribute to understanding excess CVM in HD patients.


Subject(s)
Arteriovenous Shunt, Surgical , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Proportional Hazards Models , ROC Curve , Regional Blood Flow , Renal Dialysis/methods
6.
Ned Tijdschr Geneeskd ; 1642020 11 05.
Article in Dutch | MEDLINE | ID: mdl-33331724

ABSTRACT

A novel endovascular technique allows percutaneous creation of arteriovenous fistulas for hemodialysis. The proximal radial artery is cannulated through the perforating vein in the cubital fossa using ultrasound guidance. A fused anastomosis between these blood vessels is created using heat and pressure. This results in an arteriovenous fistula that can be regarded as an alternative for a surgically created brachiocephalic fistula. In our early experience, this new technique is safe and successful. Moreover, no complications due to high-flow fistulas have been reported with this technique to date. Nevertheless, the intervention rate and the cost effectiveness of the new endovascular technique need to be compared to traditional open surgery before it can be considered standard clinical care.


Subject(s)
Arteriovenous Fistula , Catheterization, Peripheral/methods , Endovascular Procedures/methods , Radial Artery/surgery , Veins/surgery , Aged , Anastomosis, Surgical , Arteriovenous Shunt, Surgical/methods , Female , Humans , Male , Middle Aged , Renal Dialysis/methods , Time Factors , Treatment Outcome
7.
Clin Breast Cancer ; 17(4): 316-321, 2017 07.
Article in English | MEDLINE | ID: mdl-28202253

ABSTRACT

BACKGROUND: Up to 90% of patients undergoing breast cancer surgery suffer from seroma formation, which can cause discomfort and various complications after mastectomy. This retrospective observational cohort study aimed to elucidate whether flap fixation with fibrin sealant (ARTISS) tissue glue reduces seroma formation and seroma aspiration after mastectomy when compared with flap fixation using Vicryl sutures and when compared with a conventional wound closure technique. METHODS: All patients undergoing mastectomy due to invasive breast cancer or ductal carcinoma in situ were eligible for inclusion. From May 2012 to March 2013, all patients undergoing mastectomy in 2 large breast cancer centers were treated using flap fixation with Vicryl sutures. From September 2013 to March 2014, all patients undergoing mastectomy were treated with flap fixation using ARTISS tissue glue. The data were retrospectively analyzed and compared with a "drain-only" group that was not treated with flap fixation (May 2011-March 2012). RESULTS: A total of 230 women who underwent mastectomy were retrospectively analyzed in this trial; 88 patients were included in the drain-only group (DO), 92 patients were included in the flap fixation group using Vicryl sutures (FF-1), and 50 patients were included in the flap fixation group using ARTISS tissue glue (FF-2). There was significantly less seroma formation in the group after flap fixation using sutures (P = .006). There were significantly fewer patients who required seroma aspiration in the FF-1 group (P = .001) and the FF-2 group (P = .001) after undergoing mastectomy and sentinel node biopsy or modified radical mastectomy. CONCLUSION: This study suggests that flap fixation after mastectomy using ARTISS tissue glue or sutures reduces postoperative seroma aspiration. As a result, flap fixation might lead to less patient discomfort. A randomized, prospective trial should be performed to verify these results.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Mastectomy/adverse effects , Postoperative Complications/prevention & control , Seroma/prevention & control , Surgical Flaps/statistics & numerical data , Tissue Adhesives/therapeutic use , Aged , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Drainage , Female , Fibrin Tissue Adhesive/therapeutic use , Follow-Up Studies , Humans , Middle Aged , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Seroma/etiology , Sutures/statistics & numerical data
8.
Ann Vasc Surg ; 29(3): 586-93, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25595104

ABSTRACT

BACKGROUND: Ambulatory Muller phlebectomy for varicose veins can be performed under local anesthesia. However, subcutaneous injection of local tumescent anesthetics may cause discomfort because of acidity of the solution. Addition of sodium bicarbonate lowers the acidity of anesthetic solutions, which might cause less pain. The objective of this study was to study whether alkalinization of the local anesthetic solution with sodium bicarbonate 1.4% decreases perioperative pain during Muller phlebectomies. METHODS: It is a double-blind single-center randomized controlled trial. In all, 101 patients scheduled for ambulatory Muller phlebectomy were randomized to receive either local anesthesia with alkalinized solution (lidocaine 1% and epinephrine in sodium bicarbonate 1.4%) or standard solution (lidocaine 1% and epinephrine in saline 0.9%). Primary outcome was pain during injection of local anesthetics with the use of the Visual Analogue Scale (VAS). Secondary outcomes were peroperative and postoperative pain, use of analgesics, patient satisfaction, return to function, and complications. RESULTS: Patients receiving subcutaneous injection of local anesthetics diluted in sodium bicarbonate 1.4% experienced significantly less pain during injection compared with patients treated with standard anesthetic solution (VAS, 1.75 ± 1.8 vs. 3.55 ± 2.2, P < 0.00). Peroperative and postoperative pain, complication rates, use of analgesics, patient satisfaction, return to function, and complications did not differ between the 2 groups (P > 0.10). CONCLUSIONS: Alkalinization of local anesthetic solution with sodium bicarbonate 1.4% significantly improves patient comfort during injection of local tumescent anesthesia.


Subject(s)
Anesthesia, Local , Anesthetics, Local/administration & dosage , Lidocaine/administration & dosage , Pain/prevention & control , Varicose Veins/surgery , Vascular Surgical Procedures/methods , Adult , Aged , Analgesics/therapeutic use , Anesthesia, Local/adverse effects , Anesthetics, Local/adverse effects , Anesthetics, Local/chemistry , Double-Blind Method , Female , Humans , Hydrogen-Ion Concentration , Injections, Subcutaneous , Kaplan-Meier Estimate , Lidocaine/adverse effects , Lidocaine/chemistry , Male , Middle Aged , Netherlands , Pain/chemically induced , Pain/diagnosis , Pain Measurement , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Patient Satisfaction , Prospective Studies , Recovery of Function , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/chemistry , Time Factors , Treatment Outcome , Varicose Veins/diagnosis , Vascular Surgical Procedures/adverse effects
9.
Transplantation ; 95(9): 1100-4, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23492990

ABSTRACT

BACKGROUND: Kidney donation after cardiac death leads to vascular damage as a result of warm ischemia, affecting renovascular circulating volume. Novel ultrasound dilution techniques may be used to measure renovascular circulating volumes during hypothermic machine perfusion of donor kidneys. METHODS: Renovascular circulating volumes of machine-perfused porcine kidneys were repeatedly measured by ultrasound dilution at different perfusion pressures (30, 40, 50, and 60 mm Hg), durations of perfusion (1 and 24 hr), and warm ischemia times (15 and 45 min). Validity of ultrasound dilution was assessed by comparing volume changes after clamping of renal artery branches. RESULTS: Repeatability of ultrasound dilution measurements of renovascular circulating volumes was good (mean coefficient of variation, 7.6%). Renovascular circulating volumes significantly increased with higher perfusion pressures, remained constant over time, and significantly decreased with longer warm ischemia times. Changes in ultrasound dilution measurements after renal artery branch clamping did not correlate with changes in actual perfused volumes. CONCLUSIONS: Ultrasound dilution is a reproducible method to assess renovascular circulating volumes in machine-perfused kidneys, which is susceptible to changes in warm ischemia times. Future studies should evaluate the value of renovascular volume in pretransplantation kidney viability testing.


Subject(s)
Hypothermia, Induced/methods , Kidney/blood supply , Organ Preservation/methods , Animals , Perfusion , Reproducibility of Results , Swine , Warm Ischemia
10.
Clin Transplant ; 27(3): E295-301, 2013.
Article in English | MEDLINE | ID: mdl-23464536

ABSTRACT

To reduce the growing waiting list for kidney transplantation, we explored the limits of kidney transplantation from donors after cardiac death by liberally accepting marginal donor kidneys for transplantation. As the percentage of primary non-function (PNF) increased, we evaluated our transplantation program and implemented changes to reduce the high percentage of PNF in 2005, followed by a second evaluation over the period 2006-2009. Recipients of a kidney from a donor after cardiac death between 1998 and 2005 were analyzed, with PNF as outcome measure. During the period 2002-2005, the percentage of PNF increased and crossed the upper control limits of 12% which was considered as unacceptably high. After implementation of changes, this percentage was reduced to 5%, without changing the number of kidney transplantations from donors after cardiac death. Continuous monitoring of the quality of care is essential as the boundaries of organ donation and transplantation are sought. Meticulous donor, preservation, and recipient management make extension of the donor potential possible, with good results for the individual recipient. Liberal use of kidneys from donors after cardiac death may contribute to a reduction in the waiting list for kidney transplantation and dialysis associated mortality.


Subject(s)
Death , Graft Survival , Kidney Diseases/mortality , Kidney Transplantation/methods , Tissue and Organ Procurement , Female , Follow-Up Studies , Humans , Kidney Diseases/surgery , Kidney Transplantation/mortality , Male , Middle Aged , Prognosis , Survival Rate , Waiting Lists
11.
Ann Clin Biochem ; 50(Pt 2): 140-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23431486

ABSTRACT

BACKGROUND: Preservation of deceased donor kidneys by hypothermic machine perfusion results in superior transplant outcomes as compared with static cold storage and provides the opportunity to measure biomarkers of cellular injury in perfusate samples. Identification of biomarkers predicting early graft dysfunction so far has met with limited success. METHODS: Two-dimensional difference gel electrophoresis and mass spectrometry were used to explore the proteome of perfusate samples from machine-perfused human donor kidneys (N = 18) and to discover novel biomarkers of ischaemic acute kidney injury. RESULTS: Thirty-two protein spots were successfully identified, representing 19 unique proteins that were derived from renal tissue and from residual plasma in the renal microcirculation. Two unidentified protein spots were significantly up-regulated, whereas one protein spot--identified as haptoglobin--was significantly down-regulated in the perfusate of ischaemically injured kidneys from donors after cardiac death as compared with kidneys from brain-dead donors who had not suffered warm ischaemic injury. Furthermore, two protein spots were up-regulated in kidneys that never functioned after transplantation, whereas one spot was up-regulated--identified as α1-antitrypsin--in kidneys with delayed graft function. CONCLUSIONS: We provide the first description of the renal perfusate proteome and present preliminary evidence of differentially expressed biomarkers in human donor kidneys with different levels of acute ischaemic injury. Their diagnostic value for the selection of marginal kidneys in clinical transplantation should be determined in future studies.


Subject(s)
Kidney Transplantation , Kidney/metabolism , Perfusion , Proteome/metabolism , Tissue Donors , Biomarkers/metabolism , Female , Humans , Male , Middle Aged , Proteome/analysis , Proteomics , Tissue Preservation
12.
Transplantation ; 95(4): 603-10, 2013 Feb 27.
Article in English | MEDLINE | ID: mdl-23296150

ABSTRACT

BACKGROUND: Donation after cardiac death (DCD) increases the number of donor kidneys but is associated with more primary nonfunction (PNF) and delayed graft function (DGF). It has been suggested that biomarkers in the preservation solution of machine perfused kidneys may predict PNF, although evidence is lacking. METHODS: We analyzed the diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, lactate dehydrogenase (LDH), heart-type fatty acid binding protein, redox-active iron, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin to predict PNF and DGF in 335 DCD kidneys preserved by hypothermic machine perfusion at our center between 1 January 1997 and 1 January 2008. The diagnostic accuracy of these biomarkers to predict PNF was evaluated with the area under the receiver operating characteristics curves. Additionally, the risk of DGF and graft failure was assessed. RESULTS: LDH and IL-18 concentrations were associated with PNF (odds ratio [95% confidence interval], 1.001 [1.000-1.002]; P=0.005 and 1.001 [1.000-1.002]; P=0.003, respectively) in a multivariate analysis; the diagnostic accuracy for PNF was "poor" for all biomarkers but increased to "fair" for redox-active iron and IL-18 in a multivariate analysis (area under the receiver operating characteristics curves, 0.701 and 0.700, respectively). LDH and IL-18 concentrations were associated with DGF; biomarker concentration was not associated with 1-year graft survival. CONCLUSIONS: The diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, LDH, heart-type fatty acid binding protein, redox-active iron, IL-18, and neutrophil gelatinase-associated lipocalin to predict viability of DCD kidneys varies from "poor" to "fair". Therefore, DCD kidneys should not be discarded because of high biomarker perfusate concentration.


Subject(s)
Kidney Transplantation , Organ Preservation Solutions/chemistry , Organ Preservation/methods , Perfusion , Acute-Phase Proteins/analysis , Adult , Biomarkers/analysis , Delayed Graft Function/etiology , Delayed Graft Function/metabolism , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins/analysis , Female , Glutathione Transferase/analysis , Graft Survival , Humans , Interleukin-18/analysis , Iron/analysis , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , L-Lactate Dehydrogenase/analysis , Lipocalin-2 , Lipocalins/analysis , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nephrectomy , Odds Ratio , Organ Preservation/adverse effects , Oxidation-Reduction , Perfusion/adverse effects , Predictive Value of Tests , Proportional Hazards Models , Proto-Oncogene Proteins/analysis , ROC Curve , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
Nephrol Dial Transplant ; 28(1): 220-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23197676

ABSTRACT

BACKGROUND: Although acceptable outcomes have been reported in kidney transplantation from donation after cardiac death (DCD), little is known about kidney transplantation from paediatric DCD. The objective of this study was to compare the outcome of kidney transplantation using paediatric DCD with the outcome of paediatric donation after brain death (DBD). METHODS: Recipients from DCD and DBD donors <18 years of age transplanted in the Netherlands between January 1981 and July 2006 were included in this study. Ninety-one patients were transplanted with kidneys from paediatric DCD donors and 405 patients received grafts from paediatric DBD donors. RESULTS: Grafts from DCD donors were associated with higher percentage of primary non-function (9 versus 2%, P < 0.01) and delayed graft function (48 versus 8%, P < 0.001) compared with DBD donor grafts. Estimated glomerular filtration rate did not differ between groups (57 ± 17 versus 58 ± 21 mL/min at 1 year and 62 ± 14 versus 57 ± 22 mL/min at 5 years, respectively). After correction for confounding variables, the risk of graft failure was higher in the DCD group [hazard ratio 2.440 (95% confidence interval (CI) 1.280-4.650; P = 0.007]. Patient survival, however, was similar between groups [hazard ratio 1.559 (95% CI 0.848-2.867; P = 0.153)]. CONCLUSIONS: Paediatric DCD kidneys represent a valuable source of donor kidneys that has not been fully utilized. Although transplantation of paediatric DCD kidneys is associated with a higher risk of graft failure than transplantation of paediatric DBD kidneys, results are comparable with adult donors. We therefore conclude that paediatric DCD kidneys can be safely added to the donor pool.


Subject(s)
Brain Death , Death , Delayed Graft Function/epidemiology , Graft Survival , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Tissue and Organ Procurement/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male , Netherlands , Retrospective Studies , Tissue Donors , Treatment Outcome
14.
Ned Tijdschr Geneeskd ; 156(50): A5057, 2012.
Article in Dutch | MEDLINE | ID: mdl-23231871

ABSTRACT

'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease). Acute kidney injury occurs as a result of the combination of reduced perfusion in the kidney, systemic inflammation, and the administration of nephrotoxic drugs. Patients with chronic renal damage, advanced age, diabetes mellitus or heart failure are at an increased risk of acute kidney injury. In the short term, acute kidney injury leads to a markedly increased risk of death; the long-term effect of acute kidney injury is a permanent loss of renal microcirculation which could result in chronic renal disease. Certain biomarkers in the urine offer new possibilities for detecting acute kidney injury in its early stage. Treatment of patients with acute kidney injury is currently supportive in nature. The optimisation of a patient's haemodynamics results in a reduction of the occurrence of acute kidney injury during extensive surgical procedures. A promising treatment aimed at preventing acute kidney injury is called 'remote ischaemic pre-conditioning'.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/complications , Acute Kidney Injury/therapy , Disease Progression , Humans , Kidney/pathology , Kidney/physiopathology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/prevention & control , Prognosis , Renal Replacement Therapy , Risk Factors
15.
Ned Tijdschr Geneeskd ; 156(14): A4559, 2012.
Article in Dutch | MEDLINE | ID: mdl-22475240

ABSTRACT

We report on 3 male patients aged 57, 47, and 53, who each sustained an unstable straddle injury during low-energy pelvic trauma while horseback riding. All 3 patients were haemodynamically stable; radiography revealed diastasis of the pubic symphysis in each case. In two patients, the sacroiliac joints were intact but the third patient showed widening of the right sacroiliac joint. In this patient, the pelvis was initially fixated with osteosynthesis screws and dynamic compression plates; however, arthrodesis of the right sacroiliac joint was performed due to its non-union one year after the injury. Fractures of the pelvic ring are relatively rare and are typically associated with high-energy trauma. Immediate surgical treatment is necessary for patients with fractures of the pelvic ring for the stabilisation of haemorrhagic shock, identification of soft-tissue injuries and fixation of the pelvis.


Subject(s)
Athletic Injuries/diagnosis , Fracture Fixation, Internal/methods , Pelvic Bones/injuries , Pelvic Bones/surgery , Animals , Athletic Injuries/diagnostic imaging , Athletic Injuries/surgery , Bone Plates , Bone Screws , Horses , Humans , Male , Middle Aged , Pelvic Bones/diagnostic imaging , Radiography
16.
Crit Care Med ; 40(3): 766-9, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21983365

ABSTRACT

OBJECTIVE: Organ donation after cardiac death increases the number of donor organs. In controlled donation after cardiac death donors, the period between withdrawal of life-sustaining treatment and cardiac arrest is one of the parameters used to assess whether organs are suitable for transplantation. The objective of this study was to identify donation after cardiac death donor characteristics that affect the interval between withdrawal of life-sustaining treatment and cardiac death. DESIGN: Prospective multicenter study of observational data. PATIENTS: All potential donation after cardiac death donors in The Netherlands between May 2007 and June 2009 were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 242 potential donation after cardiac death donors, 211 entered analysis, 76% of them died within 60 mins, and 83% died within 120 mins after withdrawal of life-sustaining treatment. The median time to death was 20 mins (range 1 min to 3.8 days). Controlled mechanical ventilation, use of norepinephrine, absence of reflexes, neurologic deficit as cause of death, and absence of cardiovascular comorbidity were associated with death within 60 and 120 mins. The use of analgesics, sedatives, or extubation did not significantly influence the moment of death. In the multivariable logistic regression analysis, controlled mechanical ventilation remained a risk factor for death within 60 mins, and norepinephrine administration and absence of cardiovascular comorbidity remained risk factors for death within 120 mins. The clinical judgment of the intensivist predicted death within 60 and 120 mins with a sensitivity of 73% and 89%, respectively, and a specificity of 56% and 25%, respectively. CONCLUSION: Despite the identification of risk factors for early death and the additional value of the clinical judgment by the intensivist, it is not possible to reliably identify potential donation after cardiac death donors who will die within 1 or 2 hrs after life-sustaining treatment has been withdrawn. Consequently, a donation procedure should be initiated in every potential donor.


Subject(s)
Death , Heart Arrest , Tissue Donors , Withholding Treatment , Advanced Cardiac Life Support , Female , Forecasting , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Time Factors , Tissue and Organ Procurement
17.
Transplantation ; 92(3): 296-302, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21709605

ABSTRACT

BACKGROUND: Novel interventions that protect against ischemia and reperfusion injury are needed to improve early graft function after kidney transplantation. Propofol, a widely used anesthetic, has proven an efficient membrane-targeted antioxidant and cytoprotective agent. METHODS: The cytoprotective effects of propofol and its reaction intermediate dipropofol on hypothermic proximal tubular epithelial cells were compared with other phenolic antioxidants. For delivery of propofol into kidney grafts, a water-soluble cyclodextrin complex of propofol was prepared. The therapeutic effects of this propofol formulation were studied in a porcine autotransplantation model using 45 min of warm ischemia and 22 hr of hypothermic preservation. RESULTS: Propofol and dipropofol effectively protected tubular cells from hypothermic injury in vitro. Delivery of propofol to porcine kidneys was achieved by adding the cyclodextrin complex of propofol to the preservation solution during machine perfusion. This preservation strategy significantly prevented lipid peroxidation and tended to attenuate the increase in renovascular resistance during the early reperfusion period after autologous kidney transplantation. The antioxidant effects of propofol were followed by a modest improvement in renal function in the first 10 days after transplantation. Treatment with propofol during organ preservation did not reduce neutrophil infiltration into the graft. CONCLUSION: We consider propofol to be a promising renoprotective agent that may attenuate hypothermic and ischemic acute kidney injury in renal transplantation. The novel application of cyclodextrin carrier systems enabled delivery of the water-insoluble propofol to the graft during hypothermic preservation.


Subject(s)
Antioxidants/pharmacology , Kidney Transplantation/methods , Kidney Tubules, Proximal/drug effects , Organ Preservation Solutions/pharmacology , Propofol/pharmacology , Alkanes/pharmacology , Anesthetics, Intravenous/pharmacology , Animals , Cells, Cultured , Chemistry, Pharmaceutical , Cyclodextrins/pharmacology , Drug Carriers/pharmacology , Hypothermia/drug therapy , Kidney Tubules, Proximal/cytology , Male , Oxidative Stress/drug effects , Phenols/pharmacology , Reperfusion Injury/prevention & control , Solubility , Sus scrofa , Transplantation, Autologous , Water
18.
Free Radic Res ; 45(6): 699-706, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21449636

ABSTRACT

F(2)-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F(2)-isoprostanes are biologically active compounds that signal through the thromboxane A(2) (TP) receptor; infusion of F(2)-isoprostanes reduces glomerular filtration in the kidney by constricting afferent arterioles. This study investigated whether endogenous F(2)-isoprostanes contribute to the pathogenesis of ischemic acute kidney injury, which is associated with oxidative stress and reduced glomerular filtration. TP receptor knockout mice-that lack F(2)-isoprostanes and thromboxane A(2) signalling-and wild-type control mice underwent 30 min of renal ischemia and 24 h of reperfusion. Kidney dysfunction, histological injury and the number of infiltrated neutrophils were similar between the two mouse strains, whereas TP receptor knockout mice had significantly more apoptotic cells and tissue lipid peroxidation than their wild-type counterparts. F(2)-isoprostanes and thromboxane B(2) were readily detectable in urine collections after surgery. The findings indicate that F(2)-isoprostanes and thromboxane A(2) signalling do not contribute critically to the pathogenesis of ischemic acute kidney injury and more generally provide evidence against a prominent role for F(2)-isoprostanes signalling in exacerbating acute disease states associated with oxidative stress.


Subject(s)
Acute Kidney Injury/metabolism , Kidney/metabolism , Receptors, Thromboxane/metabolism , Reperfusion Injury/metabolism , Signal Transduction , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Animals , Antioxidants , Blood Urea Nitrogen , Creatine/blood , F2-Isoprostanes/metabolism , Gene Deletion , Glomerular Filtration Rate , Kidney/blood supply , Kidney/pathology , Kidney/physiopathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Thromboxane/genetics , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Thromboxane A2/metabolism
19.
Ann Surg ; 253(3): 598-604, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21248631

ABSTRACT

OBJECTIVE: To provide an integrated insight into the kinetics of tubular injury, inflammation, and oxidative stress after human kidney transplantation. BACKGROUND: Tissue injury due to ischemia and reperfusion is an inevitable consequence of kidney transplantation. Tubular epithelial injury, inflammation, and oxidative stress play major roles in the pathophysiology of acute kidney injury in small animals, but it remains to be established whether this paradigm holds true for human kidney transplantation. METHODS: Markers of tubular injury, inflammation, and oxidative stress were compared between recipients of kidneys from donors after cardiac death (DCD; N = 8) with prolonged ischemia and recipients of living donor kidneys with minimal ischemia (N = 8). RESULTS: In the early postoperative period, creatinine clearance and tubular sodium reabsorption were profoundly reduced in DCD kidneys, coinciding with significantly increased urinary concentrations of tubular injury markers (neutrophil gelatinase-associated lipocalin, N-acetyl-ß--glucosaminidase, and cystatin C) and an 18-fold increase in renal production of cytokeratin-18, indicating extensive necrotic cell death. Tubular injury in DCD kidneys was followed by greater systemic inflammatory activity and oxidative stress in the postoperative period (measured with 17-plex cytokine arrays and as plasma F2-isoprostanes, respectively). In contrast, no evidence of oxidative damage to either of the 2 kidney types was found in the early reperfusion period. CONCLUSIONS: These findings establish the relevance of observations in animal models for human kidney transplantation and form the basis for development of novel therapies to improve early graft function and expand the use of donor kidneys with prolonged ischemia.


Subject(s)
Kidney Function Tests , Kidney Transplantation/physiology , Kidney Tubular Necrosis, Acute/physiopathology , Kidney Tubules/blood supply , Kidney Tubules/physiopathology , Reperfusion Injury/physiopathology , Urothelium/physiopathology , Acetylglucosaminidase/urine , Acute-Phase Proteins/urine , Adolescent , Adult , Creatinine/urine , Cystatin C/urine , Female , Humans , Keratin-18/urine , Lipocalin-2 , Lipocalins/urine , Living Donors , Male , Middle Aged , Oxidative Stress/physiology , Proto-Oncogene Proteins/urine , Systemic Inflammatory Response Syndrome/physiopathology , Young Adult
20.
J Surg Res ; 171(1): 283-90, 2011 Nov.
Article in English | MEDLINE | ID: mdl-20421113

ABSTRACT

BACKGROUND: Restoring metabolism to an organ after hypothermic storage and before transplantation could reverse some of the detrimental effects of ischemic injury. This may be particularly beneficial for kidneys from non-heart-beating (NHBD) donors that sustain significant periods of warm and cold ischemic injury. This pilot study assessed the feasibility of a short period of normothermic preservation (NP) in a porcine autotransplant model. METHODS: Kidneys were subjected to 30 min of warm ischemia, then preserved by hypothermic machine perfusion (HMP) for 22 h or 20 h HMP followed by 2 h of NP using autologous blood. Kidneys were then re-implanted, a contralateral nephrectomy performed, and renal function measured over 10 d. RESULTS: Post-transplant, 4/6 animals survived in the NP group compared with 5/6 in the HMP group (P = 1.00). Creatinine levels fell below 250 µmol/L in all four of the surviving animals in the NP group compared with 2/5 in the HMP group (P = 0.608). There was no difference in levels of renal function (peak creatinine, HMP = 1736 ± 866 versus NP = 1553 ± 516 µmol/L; P ≥ 0.990). Levels of lipid peroxidation were significantly lower 60 min post-transplant in the NP group (NP = 477 ± 118.0 versus HMP = 671 ± 99.4 pg/mL; P = 0.026). CONCLUSION: A period of NP at the end of the renal preservation period in NHB kidneys is a feasible method of kidney preservation. NP could prove to be a useful technique to predetermine graft function and allow pre-transplant modification of organs.


Subject(s)
Graft Survival/physiology , Kidney Transplantation , Kidney/physiology , Organ Preservation/methods , Reperfusion Injury/prevention & control , Animals , Biomarkers/metabolism , Blood Transfusion, Autologous , Feasibility Studies , Kidney Function Tests , Models, Animal , Nephrectomy , Oxidative Stress/physiology , Perfusion/methods , Pilot Projects , Sus scrofa , Temperature , Transplantation, Autologous
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