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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potential donation after cardiac death donors who will die within 1 or 2 hrs after life-sustaining treatment has been withdrawn.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. [ABSTRACT FROM AUTHOR]

Introduction: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice., Methods: The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups., Discussion: As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Clinical guidelines provide recommendations on the minimal blood vessel diameters required for arteriovenous fistula creation but the evidence for these recommendations is limited. We compared vascular access outcomes of fistulas created in agreement with the ESVS Clinical Practice Guidelines (i.e. arteries and veins >2 mm for forearm fistulas and >3 mm for upper arm fistulas) with fistulas created outside these recommendations., Methods: The multicenter Shunt Simulation Study cohort contains 211 hemodialysis patients who received a first radiocephalic, brachiocephalic, or brachiobasilic fistula before publication of the ESVS Clinical Practice Guidelines. All patients had preoperative duplex ultrasound measurements according to a standardized protocol. Outcomes included duplex ultrasound findings at 6 weeks after surgery, vascular access function, and intervention rates until 1 year after surgery., Results: In 55% of patients, fistulas were created in agreement with the ESVS Clinical Practice Guidelines recommendations on minimal blood vessel diameters. Concordance with the guideline recommendations was more frequent for forearm fistulas than for upper arm fistulas (65% vs 46%, p  = 0.01). In the entire cohort, agreement with the guideline recommendations was not associated with an increased proportion of functional vascular accesses (70% vs 66% for fistulas created within and outside guideline recommendations, respectively; p  = 0.61) or with decreased access-related intervention rates (1.45 vs 1.68 per patient-year, p  = 0.20). In forearm fistulas, however, only 52% of arteriovenous fistulas created outside these recommendations developed into a timely functional vascular access., Conclusions: Whereas upper arm arteriovenous fistulas with preoperative blood vessel diameters <3 mm had similar vascular access function as fistulas created with larger blood vessels, forearm arteriovenous fistulas with preoperative blood vessel diameters <2 mm had poor clinical outcomes. These results support that clinical decision-making should be guided by an individual approach., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Central venous catheters (CVC) remain a commonly used vascular access option in haemodialysis, despite guidelines advising to preferably use arteriovenous fistulae. Compared to younger patients, the risk-benefit ratio of CVC in older patients might be more beneficial, but previous studies mainly focussed on catheter-related bacteraemia and/or assessed tunnelled CVC (TCVC) only. This study's aim was to compare all catheter-related infections and malfunctions in older patients with younger patients using all CVC subtypes., Materials and Methods: We used data from DUCATHO, a multicentre observational cohort study in The Netherlands. All adult patients in whom a CVC was placed for haemodialysis between 2012 and 2016 were included. The primary endpoint was the occurrence of catheter-related infections, comparing patients aged ⩾70 years with patients aged <70 years (reference). As secondary endpoints, catheter malfunctions and catheter removal due to either infection or malfunction were assessed. Using Cox proportional hazards and recurrent events modelling, hazard ratios (HR) with 95% confidence intervals (CI) were calculated with adjustment of prespecified confounders. Additionally, endpoints were assessed for non-tunnelled CVC (NTCVC) and TCVC separately., Results: A total of 1595 patients with 2731 CVC (66.5% NTCVC, 33.1% TCVC) were included. Of these patients, 1001 (62.8%) were aged <70 years and 594 (37.2%) ⩾70 years. No statistically significant difference was found for the occurrence of catheter-related infections (adjusted HR 0.80-95% CI 0.62-1.02), catheter malfunction (adjusted HR 0.94-95% CI 0.75-1.17) and catheter removal due to infection or malfunction (adjusted HR 0.94-95% CI 0.80-1.11). Results were comparable when assessing NTCVC and TCVC separately., Conclusion: Patients aged ⩾70 to <70 years have a comparable risk for the occurrence of catheter-related infections and catheter malfunction. These findings may help when discussing treatment options with older patients starting haemodialysis and may inform the current debate on the best vascular access for these patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney., Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125 I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson's correlation coefficient and linear regression were used to assess relations between parameters., Results: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 μm 2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.β = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.β = 0.31, p = 0.01) and at five years (St.β = 0.30, p = 0.01) after donation, independent of age., Conclusions: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors., (© 2023. The Author(s).)

Objective: Although observational cohort studies report that interventions to achieve functionality are clinically successful in 85% of patients, the proportion of newly created autologous arteriovenous fistulas that result in functional vascular access typically is only 70 - 80%. To address this discrepancy, the selection and outcomes of interventions to achieve functionality in a multicentre prospective cohort study were analysed., Methods: The Shunt Simulation Study enrolled 222 patients who needed a first arteriovenous fistula in nine dialysis units in The Netherlands from 2015 to 2018 and followed these patients until one year after access creation. In this observational study, the technical and clinical success rates of interventions to achieve functionality based on lesion and intervention characteristics were analysed and the clinical outcomes of arteriovenous fistulas with assisted and unassisted functionality were compared., Results: For patients who were on dialysis treatment at the end of the study, unassisted fistula functionality was 54% and overall fistula functionality was 78%. Thirty-four per cent of arteriovenous fistulas required an intervention to achieve functionality, 68% of which eventually became functional. Seventy-five per cent of these interventions were percutaneous balloon angioplasties of vascular access stenoses. Patients with clinically successful interventions to achieve functionality had larger pre-operative vein diameters (2.8 ± 1.0 mm vs. 2.3 ± 0.6 mm, p = .036) and less often presented with thrombosed fistulas than patients with unsuccessful interventions (7% vs. 43%, p = .006). Arteriovenous fistulas with assisted functionality had similar secondary patency as fistulas with unassisted functionality (100% and 98% at six months, p = .44), although they required more interventions to maintain function (2.6 vs. 1.7 per year; rate ratio 1.52, 95% CI 1.04 - 2.18, p = .032)., Conclusion: Interventions to achieve functionality were needed in about a third of newly created arteriovenous fistulas. Most thrombosed fistulas were abandoned, and when selected for thrombectomy rarely reached clinical success. On the other hand, interventions to achieve functionality of patent fistulas had high clinical success rates and therefore can be done repeatedly until the fistula has become functional., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Arteriovenous grafts (AVGs) are the second best option for haemodialysis access when native arteriovenous fistulae placement is not possible, because they have a lower patency owing to neointimal hyperplasia at the venous anastomosis. This review aimed to evaluate the effect of geometric graft modification to the graft-vein interface on AVG patency., Data Sources: The MEDLINE and Embase (OvidSP) databases were systematically searched for relevant studies analysing the effect of geometrically modified AVGs on graft patency and stenosis formation (last search July 2019)., Review Methods: Data regarding AVG type, patency, and graft outlet stenosis was extracted for further evaluation. Data were pooled in a random effects model to estimate the relative risk of graft occlusion within one year. Follow up, number of patients, and relevant patient characteristics were extracted for the quality assessment of the included studies using Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. The quality of the evidence was determined according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system., Results: Search strategies produced 2772 hits, of which eight articles met predetermined inclusion criteria. Overall, the included articles had low to moderate risk of bias. In total, 414 expanded polytetrafluoroethylene AVGs (232 geometrically modified and 182 standard) were analysed, comprising two modified AVG types: a prosthetic cuff design (Venaflo®) and grafts with a Tyrell vein patch. Overall, modified grafts did not show a statistically significantly higher one year primary (relative risk [RR] 0.86, 95% confidence interval [CI] 95% 0.64-1.16; GRADE: "low to very low") or secondary patency (RR 0.57, 95% CI 0.32-1.02; GRADE: "low to very low") when compared with standard AVGs. Analysis of prosthetic cuffed grafts (112 patients) separately demonstrated a statistically significantly higher one year primary (RR 0.75, 95% CI 0.61-0.91) and one year secondary patency (RR 0.47, 95% CI 0.30-0.75) compared with standard grafts (92 patients). The results on stenosis formation were inconclusive and inadmissible to quantitative analyses., Conclusion: The meta-analysis showed that a prosthetic cuff design significantly improves AVG patency, while a venous cuff does not. Although the heterogeneity and low number of available studies limit the strength of the results, this review shows the potential of grafts with geometric modification to the graft-vein anastomosis and should stimulate further clinical and fundamental research on improving graft geometry to improve graft patency., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: Revision using distal inflow (RUDI) is currently proposed in patients on hemodialysis having a high flow access (HFA; >2 L/min) or hemodialysis access-induced distal ischemia (HAIDI). However, a recurrence of high flow or hand ischemia is not unusual in the years after RUDI. The aim of the present study was to describe changes in flow characteristics and arterial diameters in the dialysis arm after RUDI for HFA., Methods: Volume flow, diameter, peak systolic velocity and end diastolic velocity of the brachial artery (BA) were studied 2 and 12 months after RUDI using duplex imaging. In a portion of patients, these characteristics were also assessed at proximal and distal portions of radial and ulnar arteries (proximal forearm radial artery, distal radial artery, ulnar artery, and distal ulnar artery), and in the greater saphenous venous interponate. HFA patients were grouped according to presence of concomitant hand ischemia (HFA-HAIDI) or absence (HFA)., Results: Fifteen patients (54 ± 16 year old; 10 males; HFA-HAIDI, n = 6; HFA, n = 9) with a BA HFA (flow volume, 2740 ± 322 mL/min) undergoing RUDI were studied between March 2011 and October 2016 in two Dutch hospitals. After 2 months, flow volume had decreased (1180 ± 189 mL/min), but again increased at 12 months (1520 ± 217 mL/min; P < .001). BA diameters did not change (7.4 ± 0.5 mm), but proximal forearm radial diameters doubled (overall 2.6 ± 0.2 mm to 5.4 ±1.0 mm; P < .001), albeit less prominent in HFA-HAIDI (+80%) than in HFA (+130%; P = .019). During follow-up, the distal ulnar artery peak systolic velocity in HFA-HAIDI (83 ± 10 cm/s) was higher compared with the HFA group (54 ± 5 cm/s; P < .01). Dilatation was not present in the greater saphenous venous interponate., Conclusions: RUDI for HFA reduction does not reverse BA dilatation, suggesting irreversible structural arterial wall damage possibly contributing to recurrent high flow. Radial artery remodeling is attenuated in HFA patients previously reporting concurrent hand ischemia diminishing the likelihood of high flow recurrence in this subgroup., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Administration of radiocontrast during endovascular procedures for peripheral arterial disease (PAD) may cause acute kidney injury, which generally recovers with supportive treatment. Long-term effects of endovascular procedures on renal function remain to be investigated., Method: This retrospective observational cohort study includes all patients who newly presented to the vascular surgery outpatient clinic with Rutherford class II or III PAD and who were treated with either supervised exercise therapy or endovascular interventions. Changes in estimated glomerular filtration rates (eGFR) after 1 year were compared between the 2 treatment groups. Multivariate regression analysis and propensity score-matched paired analysis were done to correct for potential confounders., Results: One year after treatment, eGFR was reduced by 8.6 mL/min (95% confidence interval [CI], 7.3-9.9, P < 0.001) after endovascular intervention (n = 284) and by 1.7 mL/min (95% CI, 0.9-25, P < 0.001) after supervised exercise therapy (n = 299). After correction for potential confounders, endovascular interventions were associated with 9.2 mL/min (95% CI, 5.9-12.4, P < 0.001) more renal decline compared to exercise therapy. Similar results were found in the propensity score-matched paired analysis., Conclusions: Endovascular procedures for PAD are associated with clinically relevant and long-term loss of kidney function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Acute kidney injury after the administration of contrast material during endovascular procedures for peripheral arterial disease generally recovers with supportive treatment. However, long-term effects of endovascular procedures for critical limb ischemia on renal function remain to be investigated., Methods: This retrospective observational cohort study included all patients who newly presented to the vascular surgery outpatient clinic with Rutherford class 4 to class 6 peripheral arterial disease and who were treated with either endovascular or surgical interventions. Changes in estimated glomerular filtration rate (eGFR) after 1 year were compared between the two types of intervention. Multivariate linear regression analysis was done to correct for potential confounders., Results: One year after treatment, eGFR was reduced by 15.0 mL/min (95% confidence interval [CI], 13.1-17.0; P < .001) after endovascular interventions (n = 209) and by 7.6 mL/min (95% CI, 5.1-10.0; P < .001) after surgical therapy (n = 81). Although eGFR rates decreased in both groups, loss of renal function was significantly greater in patients after endovascular interventions (P < .001). Furthermore, 77% of patients receiving endovascular interventions experienced fast renal decline (defined as >4 mL/min loss of eGFR within 1 year) compared with 54% of patients treated surgically (P < .001). After correction for potential confounders, endovascular intervention was associated with 7.4 mL/min (95% CI, 5.4-9.3; P < .001) greater loss of renal function compared with patients treated surgically., Conclusions: Endovascular procedures for critical limb ischemia are associated with clinically relevant permanent long-term loss of kidney function. This loss of renal function is greater than in comparable patients who were treated with open surgery., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Endovascular interventions often are the preferred treatment in peripheral arterial disease for both intermittent claudication and chronic critical limb ischemia. Ever more advanced and anatomically complex procedures are being performed, which may increase the radiation exposure of patients and medical staff. We sought to determine the radiation exposure sustained in contemporary interventional radiology practice., Methods: A single-center observational cohort study of patients undergoing endovascular interventions for symptomatic peripheral arterial disease between January 1st, 2011 and July 31st, 2013 was performed. Radiation dose area product (DAP), peak skin dose (PSD), fluoroscopy time, and volume of contrast media were either measured or calculated and stratified according to patient demographics and anatomic location., Results: In 951 patients, who were treated with endovascular interventions, mean DAP was 108 ± 88 Gy × cm(2) and mean fluoroscopy time was 13 ± 12 min. DAP was significantly higher for aortoiliac procedures (142 ± 103 Gy × cm(2)) compared with femoral (58 ± 73 Gy × cm(2)), below-knee (45 ± 51 Gy × cm(2)) and multilevel (83 ± 90 Gy × cm(2)) procedures (P < 0.001 for all comparisons). PSD was significantly higher for aortoiliac procedures (0.99 ± 0.54 Gy) compared with femoral (0.55 ± 0.55 Gy), below-knee (0.48 ± 0.27 Gy), and multilevel (0.68 ± 0.47 Gy) procedures (P < 0.001 for all comparisons). In contrast, mean fluoroscopy time in aortoiliac interventions was significantly shorter (10 ± 15 min) compared with femoral (15 ± 12 min), below-knee (19 ± 10 min), and multilevel (23 ± 14 min) procedures (P < 0.001 for all comparisons)., Conclusions: Endovascular interventions in patients with symptomatic peripheral arterial disease involve a substantial radiation dose. Although fluoroscopy time is shorter, aortoiliac interventions result in greater radiation exposure than femoropopliteal or infrapopliteal interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective/background: Administration of iodinated contrast media during endovascular procedures for peripheral arterial disease (PAD) may cause contrast induced nephropathy (CIN). The aim of the present study was to establish the incidence of CIN after these procedures and to study its association with long-term loss of kidney function, cardiovascular events, and death., Methods: Consecutive patients first presenting with symptomatic PAD (Rutherford classification II-VI) who were treated with an endovascular procedure were included in this prospective observational cohort study. CIN was defined as >25% increase of serum creatinine concentration from baseline at 5 days after the intervention., Results: Some 337 patients were included with a mean estimated glomerular filtration rate (eGFR) of 67 mL/minute. Thirteen percent (95% confidence interval [CI] 9-16) of these patients developed CIN after endovascular interventions for PAD. One year after treatment, eGFR was reduced by 12.4 mL/minute (95% CI 8.6-16.2) in patients with CIN compared with 6.2 mL/minute (95% CI 4.9-7.0) in patients without acute kidney injury (p < .01). After correction for potential confounders, CIN was associated with a 7.8 mL/minute (95% CI 4.5-11.0) reduction of eGFR at 1 year after endovascular intervention (p < .01). Furthermore, patients with CIN were at increased risk of long-term cardiovascular events and mortality., Conclusion: Exposure to iodinated contrast media during endovascular procedures for symptomatic PAD frequently results in CIN. Patients with CIN are at increased risk of long-term loss of renal function, cardiovascular events, and death., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

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., (© 2013 John Wiley & Sons A/S.)

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.

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.

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.

Background: The hemolytic products cell-free oxyhemoglobin (FHb) and arginase-1 reduce nitric oxide (NO) bioavailability by scavenging NO and by degrading the NO precursor arginine to ornithine, respectively. In this study we evaluated the relevance of hemolysis to NO-dependent blood flow in patients undergoing cardiovascular surgery., Methods: Plasma FHb, arginase-1, and amino acid concentrations were measured perioperatively. Forearm blood flow (FBF) responses to the intra-arterial administered NO-donor sodium nitroprusside (SNP) and the endothelium-dependent vasodilator acetylcholine (ACh) were measured by venous occlusion plethysmography., Results: When peak values plasma FHb and arginase-1 were found, vascular dilatation to SNP, but not ACh, was significantly reduced compared with 1 day postoperatively, when FHb had returned to baseline levels (p < 0.05). Interestingly, plasma FHb concentration was inversely correlated to FBF responses to SNP (r -0.93, p < 0.001). In contrast, the increase in arginase-1 was not biologically relevant as the ratio of plasma arginine to ornithine remained constant., Conclusion: We conclude that hemolysis with concomitant release of FHb during cardiovascular surgery is associated with impaired NO-dependent forearm blood flow., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: With the implementation of multimodal analgesia regimens in fast-track surgery programmes, non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed routinely. However, doubts have been raised concerning the safety of NSAIDs in terms of anastomotic healing., Methods: Data on patients who had undergone primary colorectal anastomosis at two teaching hospitals between January 2008 and December 2010 were analysed retrospectively. Exact use of NSAIDs was recorded. Rates of anastomotic leakage were compared between groups and corrected for known risk factors in both univariable and multivariable analyses., Results: A total of 795 patients were divided into four groups according to NSAID use: no NSAIDs (471 patients), use of non-selective NSAIDs (201), use of selective cyclo-oxygenase (COX) 2 inhibitors (79), and use of both selective and non-selective NSAIDs (44). The overall leak rate was 9.9 per cent (10.0 per cent for right colonic, 8.7 per cent for left colonic and 12.4 per cent for rectal anastomoses). Known risk factors such as smoking and use of steroids were not significantly associated with anastomotic leakage. Stapled anastomosis was identified as an independent predictor of leakage in multivariable analysis (odds ratio (OR) 2.22, 95 per cent confidence interval 1.30 to 3.80; P = 0.003). Patients on NSAIDs had higher anastomotic leakage rates than those not on NSAIDs (13.2 versus 7.6 per cent; OR 1.84, 1.13 to 2.98; P = 0.010). This effect was mainly due to non-selective NSAIDs (14.5 per cent; OR 2.13, 1.24 to 3.65; P = 0.006), not selective COX-2 inhibitors (9 per cent; OR 1.16, 0.49 to 2.75; P = 0.741). The overall mortality rate was 4.2 per cent, with no significant difference between groups (P = 0.438)., Conclusion: Non-selective NSAIDs may be associated with anastomotic leakage., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

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.

'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'.

Background: Expansion of the organ donor pool can be obtained through novel interventions attenuating ischemic acute kidney injury, which will enable the use of kidneys that suffered prolonged ischemia. In basic science, new therapeutic targets are identified that should be tested in a relevant large animal model before use in human kidney transplantation., Materials and Methods: The current paper provides a detailed description of the technique of autologous transplantation of ischemically injured kidneys in pigs with special emphasis on perioperative care., Results: The animal model was validated by showing that renal function after transplantation was proportional to the duration of warm ischemia before organ recovery. The extent of renal dysfunction was reproducible following kidney transplantations with the same warm ischemia time., Conclusions: Our experience may reduce the learning curves of other research groups taking an interest in the model and improve preclinical testing of novel interventions that modulate renal ischemia and reperfusion injury in kidney transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Donation after cardiac death (DCD) has shown to be a valuable extension of the donor pool despite a higher percentage of primary nonfunction (PNF). Limiting the incidence of PNF is of vital importance. Renovascular resistance is believed to predict graft outcome; however the literature is inconsistent. Therefore, we studied whether renovascular resistance is associated with PNF and whether this parameter should be used to discard donor kidneys. All transplanted DCD kidneys preserved by machine perfusion at our center between 1993 and 2007 were analyzed (n = 440). The effects of renovascular resistance on PNF, delayed graft function (DGF), and graft and patient survival were examined using multivariable analyses; predictive quality by calculating the area under the curve (AUC). We showed that renovascular resistance at the start of machine perfusion was significantly and independently associated with PNF (OR 2.040, 95% CI 1.362-3.056; p = 0.001), and DGF (OR 2.345, 95% CI 1.110-4.955; p = 0.025). Predictive quality was moderate (0.609, 95% CI 0.538-0.681). Graft and patient survival were not associated with renovascular resistance. We conclude that renovascular resistance in DCD kidneys is an independent risk factor for PNF; however, the predictive value is relatively low., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Donation after cardiac death (DCD) expands the pool of donor kidneys, but is associated with warm ischaemic injury. Two methods are used to preserve kidneys from controlled DCD donors and reduce warm ischaemic injury: in situ preservation using a double-balloon triple-lumen catheter (DBTL) inserted via the femoral artery and direct cannulation of the aorta after rapid laparotomy. The aim of this study was to compare these two techniques., Methods: This was a retrospective cohort study of 165 controlled DCD procedures in two regions in the Netherlands between 2000 and 2006., Results: There were 102 donors in the DBTL group and 63 in the aortic group. In the aortic group the kidney discard rate was lower (4·8 versus 28·2 per cent; P < 0·001), and the warm (22 versus 27 min; P < 0·001) and the cold (19 versus 24 h; P < 0·001) ischaemia times were shorter than in the DBTL group. Risk factors for discard included preservation with the DBTL catheter (odds ratio (OR) 5·19, 95 per cent confidence interval 1·88 to 14·36; P = 0·001) and increasing donor age (1·05, 1·02 to 1·07; P < 0·001). Warm ischaemia time had a significant effect on graft failure (hazard ratio 1·04, 1·01 to 1·07; P = 0·009), and consequently graft survival was higher in the aortic cannulation group (86·2 per cent versus 76·8 per cent in the DBTL group at 1 year; P = 0·027)., Conclusion: In this retrospective study, direct aortic cannulation appeared to be a better method to preserve controlled DCD kidneys., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

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.

Kidney donation after cardiac death has been popularized over the last decade. The majority of these kidneys are from controlled donors. The number of organs for transplantation can be further increased by uncontrolled donors after cardiac death. The outcome of uncontrolled compared to controlled donor kidney transplantation is relatively unknown. We compared the long-term outcome of kidney transplantation from uncontrolled (n = 128) and controlled (n = 208) donor kidneys procured in the Maastricht region from January 1, 1981 until January 1, 2008, and transplanted in the Eurotransplant region. The incidence of primary nonfunction and delayed graft function in both uncontrolled and controlled donor kidneys is relatively high (22% vs. 21%, and 61% vs. 56%, p = 0.43, respectively). Ten-year graft and recipient survival are similar in both groups (50% vs. 46%, p = 0.74 and 61% vs. 60%, p = 0.76, respectively). Estimated glomerular filtration rates 1 year after transplantation are 40 ± 16 versus 42 ± 19 mL/min/1.73 m(2) , p = 0.55, with a yearly decline thereafter of 0.67 ± 3 versus 0.70 ± 7 mL/min/1.73 m(2) /year, p = 0.97. The outcome of kidney transplantation from uncontrolled and controlled donors after cardiac death is equivalent. This justifies the expansion of the donor pool with uncontrolled donors to reduce the still growing waiting list for renal transplantation, and may stimulate the implementation of uncontrolled kidney donation programs., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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.

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-β--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.

The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are currently being developed that limit renal ischemia-reperfusion injury. However, to fully address their therapeutic potential, noninvasive imaging methods are required which allow the in vivo visualization of different renal compartments and the evaluation of kidney function. In this study, MRI was applied to study kidney oxygenation and function in a murine model of renal ischemia-reperfusion injury at 7 T. During ischemia, there was a strongly decreased oxygenation, as measured using blood oxygen level-dependent MRI, compared with the contralateral control, which persisted after reperfusion. Moreover, it was possible to visualize differences in oxygenation between the different functional regions of the injured kidney. Dynamic contrast-enhanced MRI revealed a significantly reduced renal function, comprising perfusion and filtration, at 24 h after reperfusion. In conclusion, MRI is suitable for the noninvasive evaluation of renal oxygenation and function. Blood oxygen level-dependent or dynamic contrast-enhanced MRI may allow the early detection of renal pathology in patients with ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, and consequently may lead to an earlier intervention or change of therapy to minimize kidney damage., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: The shortage of organ donors presents a major obstacle for adequate treatment of patients with end-stage renal disease. Donation after cardiac death (DCD) has been shown to increase the number of kidneys available for transplantation. The present article reports on the first 25 years of our experience with DCD kidney transplantation., Methods: This observational cohort study included all DCD kidney transplantations recovered in our procurement area from January 1, 1981 until December 31, 2005 (n=297). Patients were followed up until the earliest of death or December 31, 2006. Clinical outcomes were compared with matched kidney transplantations from brain dead donors (DBD, n=594), using multivariable regression models to adjust for potential confounders., Results: DCD activity resulted in a 44% increase in the number of deceased donor kidneys from our organ procurement area. After adjustment for potential confounders, the odds of primary nonfunction and delayed graft function were 7.5 (95% CI, 4.0-14.1; P<0.001) and 10.3 (95% CI, 6.7-15.9; P<0.001) times greater, respectively, for DCD kidneys compared with DBD kidneys. The high incidence of primary nonfunction of DCD kidneys resulted in an increased rate of graft loss (HR, 1.82; 95% CI, 1.37-2.42; P<0.001). However, DCD kidneys that did not experience primary nonfunction functioned as long as DBD kidneys (HR, 1.05; 95% CI, 0.73-1.51; P=0.79). Patient survival of DCD and DBD kidney recipients was equivalent (HR, 1.16; 95% CI, 0.87-1.54; P=0.32)., Conclusions: The benefits of DCD kidney transplantation outweigh the increased risk of early graft loss. Expansion of the supply of DCD kidneys is likely to improve the treatment of wait-listed dialysis patients.

Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury.

The continuing shortage of kidneys for transplantation requires major efforts to expand the donor pool. Donation after cardiac death (DCD) increases the number of available kidneys, but it is unknown whether patients who receive a DCD kidney live longer than patients who remain on dialysis and wait for a conventional kidney from a brain-dead donor (DBD). This observational cohort study included all 2575 patients who were registered on the Dutch waiting list for a first kidney transplant between January 1, 1999, and December 31, 2004. From listing until the earliest of death, living-donor kidney transplantation, or December 31, 2005, 459 patients received a DCD transplant and 680 patients received a DBD transplant. Graft failure during the first 3 months after transplantation was twice as likely for DCD kidneys than DBD kidneys (12 versus 6.3%; P=0.001). Standard-criteria DCD transplantation associated with a 56% reduced risk for mortality (hazard ratio 0.44; 95% confidence interval 0.24 to 0.80) compared with continuing on dialysis and awaiting a standard-criteria DBD kidney. This reduction in mortality translates into 2.4-month additional expected lifetime during the first 4 years after transplantation for recipients of DCD kidneys compared with patients who await a DBD kidney. In summary, standard-criteria DCD kidney transplantation associates with increased survival of patients who have ESRD and are on the transplant waiting list.

Hemolysis is an inevitable side effect of cardiopulmonary bypass resulting in increased plasma free hemoglobin that may impair tissue perfusion by scavenging nitric oxide. Acute kidney injury after on-pump cardiovascular surgery arises from a number of causes and severely affects patient morbidity and mortality. Here, we studied the effect of acute hemolysis on renal injury in 35 patients undergoing on-pump surgical repair of thoracic and thoracoabdominal aortic aneurysms of whom 19 experienced acute kidney injury. During surgery, plasma free hemoglobin increased, as did urinary excretion of the tubular injury marker N-acetyl-beta-D-glucosaminidase, in patients with and without acute kidney injury, reaching peak levels at 2 h and 15 min, respectively, after reperfusion. Furthermore, plasma free hemoglobin was independently and significantly correlated with the urine biomarker, which, in turn, was independently and significantly associated with the later postoperative increase in serum creatinine. Importantly, peak plasma free hemoglobin and urine N-acetyl-beta-D-glucosaminidase concentrations had significant predictive value for postoperative acute kidney injury. Thus, we found an association between increased plasma free hemoglobin and renal injury casting new light on the pathophysiology of acute kidney injury. Therefore, free hemoglobin is a new therapeutic target to improve clinical outcome after on-pump cardiovascular surgery.

Purpose of Review: Biological modulation of renal ischemia-reperfusion injury holds the potential to reduce the incidence of early graft dysfunction and to safely expand the donor pool with kidneys that have suffered prolonged ischemic injury before organ recovery., Recent Findings: In the current review, we will discuss clinical studies that compare kidney transplant recipients with and without early graft dysfunction in order to elucidate the pathophysiology of ischemic acute allograft injury. We will specifically review the mechanisms leading to depression of the glomerular filtration rate and activation of the innate immune system in response to tissue injury., Summary: We conclude that the pathophysiology of delayed graft function after kidney transplantation is complex and shares broad similarity with rodent models of ischemic acute kidney injury. Given the lack of specific therapies to prevent delayed graft function in transplant recipients, comprehensive efforts should be initiated to translate the promising findings obtained in small animal models into clinical interventions that attenuate ischemic acute kidney injury after transplantation.

Purpose of Review: The purpose of the present review is to describe the current kidney preservation techniques for donors after cardiac death and to give insight in new developments that may reduce warm ischemia times and therefore improve graft function after transplantation., Recent Findings: There is still a general reluctance to use donors after cardiac death for kidney donation and transplantation, because of a relatively high incidence of delayed graft function and primary nonfunction compared to conventional donors after brain death. New clinically applicable methods, such as automated chest compression devices and extracorporeal membrane oxygenation, may reduce warm ischemia time., Summary: Kidneys from donors after cardiac death sustain an increased incidence of delayed graft function and primary nonfunction. However, transplanted kidneys that do not experience these complications survive as long as conventional kidneys from donors after brain death. Maintaining adequate organ perfusion after cardiac death by using automated chest compression devices and extracorporeal membrane oxygenation reduces warm ischemia time. Optimal organ preservation and careful selection of kidneys from donors after cardiac death may reduce the risk of delayed graft function and primary nonfunction. Major efforts should continue to be made to improve the quality of kidneys from donors after cardiac death and thereby expand the utilization of this large pool of donor kidneys to its full potential.

Aims: Histological examination of pre-transplant renal biopsy specimens can be used to select grafts from older donors after cardiac death (DCD) with a satisfactory transplant outcome. The aim was to determine whether such biopsy specimens can be reproducibly scored between pathologists and are representative of the whole kidney., Methods and Results: In renal biopsy specimens from DCD aged >or=60 years (n = 44), globally sclerosed glomeruli, vascular narrowing, tubular atrophy and interstitial fibrosis were scored by three independent pathologists according to the Pirani scoring system. Interobserver agreement on the sum of scores improved considerably with the introduction of a combined tubulo-interstitial scoring system (intraclass correlation coefficient increased from 0.38 to 0.64). In small needle biopsy specimens (n = 144) obtained at autopsy, estimates of the proportion of globally sclerosed glomeruli were more precise with increasing sample size. Reasonably precise estimates may be obtained from specimens with at least seven glomeruli., Conclusions: It is feasible to implement pre-transplant renal biopsy specimen analysis as a selection criterion in clinical practice in order to accept kidneys from marginal donors for transplantation.

Objective: Pediatric kidney donation after cardiac death is an underutilized donor source because of ethical concerns and limited knowledge of the outcome after transplantation. The purpose of this study was to report the Dutch experience of kidney transplantation using pediatric donation after cardiac death., Design: Observational cohort study of a series of consecutive kidney transplantations from pediatric donation after cardiac death from January 1995 to July 2006., Setting: Kidneys were procured in seven Dutch procurement areas., Patients: Recipients of kidneys from donors after cardiac death aged 2 to 17 yrs., Measurements and Main Results: Prospectively collected data from the Dutch Organ Transplant Registry were analyzed. Donor, graft, and recipient characteristics of all pediatric donations after cardiac death kidney transplantations were documented. Recipients were followed-up for glomerular filtration rate, graft, and patient survival. Eighty-eight patients were transplanted with 90 pediatric donation-after-cardiac-death kidneys, which was 31% of the total number of transplanted pediatric donor kidneys. In 77% of recipients, organs were procured from controlled donors, after withdrawal of supportive treatment. Of all donors, 9% were younger than age 6 yrs. Two patients received their graft preemptively. In the others, the incidence of immediate function, delayed graft function, and primary nonfunction were 49%, 44%, and 7%, respectively. Warm ischemia time > or =25 mins was associated with primary nonfunction. Overall graft and patient survival 5 yrs after transplantation were 80% and 88%, respectively. Graft survival after immediate function and delayed graft function was not different., Conclusions: Kidneys from pediatric donation after cardiac death are suitable for transplantation and may substantially expand the donor pool with good transplant outcome.

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

Objectives: To describe the results and complications of in situ preservation (ISP) of kidneys from donors after cardiac death (DCD)., Background: DCD donors are increasingly being used to expand the pool of donor kidneys. ISP reduces warm ischemic injury which is associated with DCD donation., Methods: Insertion of a double-balloon triple-lumen catheter allows selective perfusion of the abdominal aorta to preserve the kidneys in situ. From January 2001 until August 2005, 133 ISP procedures were initiated in our procurement area., Results: Fifty-six (42%) ISP procedures led to transplantation; in the remaining 77 cases (58%), the donation procedure was abandoned or both kidneys were discarded because of ISP complications (n = 31), poor graft quality (n = 23), no consent for donation (n = 13), medical contraindications (n = 8), or unknown cause (n = 2). Increasing donor age (odds ratio (OR) 1.06 per year, P < 0.001) and uncontrolled DCD donation (OR 5.4, P < 0.001) were independently correlated with ISP complications. After transplantation, prolonged double-balloon triple-lumen catheter insertion time was an independent predictor of graft failure (OR 2.0, P = 0.05). Selected controlled DCD donors were managed by rapid laparotomy and direct aortic cannulation; graft survival of these kidneys was superior to kidneys from controlled DCD donors managed by ISP., Conclusions: A minority of initiated ISP procedures led to transplantation, resulting in a high workload compared with donation after brain death. The association between increasing catheter insertion time and inferior graft outcome emphasizes the need for fast and effective surgery. Therefore, rapid laparotomy with direct aortic cannulation is preferred over ISP in controlled DCD donation. Despite these limitations, we have expanded our donor pool 3- to 4-fold by procuring DCD kidneys that were preserved in situ.

Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.

Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heart-beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1 vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.