Perioperative Complications During Living Donor Nephrectomy: Results From a Multicenter Cohort Study.

BACKGROUND: While living kidney donation is considered safe in healthy individuals, perioperative complications can occur due to several factors. OBJECTIVE: We explored associations between the incidence of perioperative complications and donor characteristics, surgical technique, and surgeon's experience in a large contemporary cohort of living kidney donors. DESIGN: Living kidney donors enrolled prospectively in a multicenter cohort study with some data collected retrospectively after enrollment was complete (eg, surgeon characteristics). SETTING: Living kidney donor centers in Canada (n = 12) and Australia (n = 5). PATIENTS: Living kidney donors who donated between 2004 and 2014 and the surgeons who performed the living kidney donor nephrectomies. MEASUREMENTS: Operative and hospital discharge medical notes were collected prospectively, with data on perioperative (intraoperative and postoperative) information abstracted from notes after enrollment was complete. Complications were graded using the Clavien-Dindo system and further classified into minor and major. In 2016, surgeons who performed the nephrectomies were invited to fill an online survey on their training and experience. METHODS: Multivariable logistic regression models with generalized estimating equations were used to compare perioperative complication rates between different groups of donors. The effect of surgeon characteristics on the complication rate was explored using a similar approach. Poisson regression was used to test rates of overall perioperative complications between high- and low-volume centers. RESULTS: Of the 1421 living kidney donor candidates, 1042 individuals proceeded with donation, where 134 (13% [95% confidence interval (CI): 11%-15%]) experienced 142 perioperative complications (55 intraoperative; 87 postoperative). The most common intraoperative complication was organ injury and the most common postoperative complication was ileus. No donors died in the perioperative period. Most complications were minor (90% of 142 complications [95% CI: 86%-96%]); however, 12 donors (1% of 1042 [95% CI: 1%-2%]) experienced a major complication. No statistically significant differences were observed between donor groups and the rate of complications. A total of 43 of 48 eligible surgeons (90%) completed the online survey. Perioperative complication rates did not vary significantly by surgeon characteristics or by high- versus low-volume centers. LIMITATIONS: Operative and discharge reporting is not standardized and varies among surgeons. It is possible that some complications were missed. The online survey for surgeons was completed retrospectively, was based on self-report, and has not been validated. We had adequate statistical power only to detect large effects for factors associated with a higher risk of perioperative complications. CONCLUSIONS: This study confirms the safety of living kidney donation as evidenced by the low rate of major perioperative complications. We did not identify any donor or surgeon characteristics associated with a higher risk of perioperative complications. TRIAL REGISTRATIONS: NCT00319579: A Prospective Study of Living Kidney Donation (https://clinicaltrials.gov/ct2/show/NCT00319579)NCT00936078: Living Kidney Donor Study (https://clinicaltrials.gov/ct2/show/NCT00936078).

CONTEXTE: Bien que le don vivant d'un rein soit sécuritaire chez un individu en santé, plusieurs facteurs sont susceptibles d'engendrer des complications périopératoires. OBJECTIF: Nous avons exploré l'association entre l'incidence des complications périopératoires et les caractéristiques du donneur, la technique chirurgicale employée et l'expérience du chirurgien au sein d'une vaste cohorte contemporaine de donneurs vivants d'un rein. TYPE D'ÉTUDE: Une étude de cohorte multicentrique où certaines données (notamment les renseignements concernant le chirurgien) ont été recueillies rétrospectivement, après l'inclusion complète des sujets (donneurs vivants d'un rein). CADRE: Des centres de transplantation au Canada (n=12) et en Australie (n=5). SUJETS: Des individus ayant fait don d'un rein entre 2004 et 2014, et les chirurgiens qui ont procédé à la néphrectomie. MESURES: Les notes médicales au dossier, opératoires et à la sortie de l'hôpital, ont été recueillies de façon prospective; les données concernant les renseignements périopératoires (peropératoires et postopératoires) ayant été extraites des notes une fois l'inclusion du sujet complétée. Les complications ont été catégorisées selon la classification de Clavien-Dindo, puis caractérisées comme étant mineures ou majeures. En 2016, les chirurgiens ayant pratiqué les néphrectomies ont été invités à répondre à un sondage en ligne au sujet de leur formation et de leur expérience. MÉTHODOLOGIE: Des modèles de régression logistique multivariée utilisant des équations d'estimation généralisées ont été employés pour comparer les taux de complications périopératoires entre les différents groupes de donneurs. L'effet exercé sur le taux de complications par les caractéristiques du chirurgien a été exploré selon une approche similaire. Une régression de Poisson a été utilisée pour évaluer et comparer les taux globaux de complications entre les centres à volume élevé et les centres à faible volume. RÉSULTATS: Des 1 421 candidats répertoriés, 1 042 individus ont subi une néphrectomie, desquels 134 (13 % [IC 95 %: 11­15 %]) ont vécu un total de 142 complications périopératoires (55 peropératoires; 87 postopératoires). La complication peropératoire la plus fréquente était une lésion à l'organe, alors qu'un iléus s'est avéré la principale complication postopératoire. Aucun donneur n'est décédé en période périopératoire. La plupart des complications rencontrées étaient mineures (90 % des 142 complications répertoriées [IC 95 %: 86­96 %]). Toutefois, 12 donneurs (1 % des 1 042 donneurs [IC 95 %: 1­2 %]) ont souffert de complications majeures. Aucune différence significative du point de vue statistique n'a été observée entre les groupes de donneurs et le taux de complications. Des 48 chirurgiens admissibles, 43 (90 %) ont répondu au sondage en ligne. Les taux de complications périoperatoires n'ont pas varié de façon significative en fonction des caractéristiques des chirurgiens, ou selon le volume de patients de l'hôpital. LIMITES: La façon d'inscrire les renseignements médicaux (opératoires ou à la sortie de l'hôpital) dans les dossiers des patients n'est pas normalisée et varie d'un chirurgien à l'autre. Certaines complications pourraient ne pas avoir été notées. Le sondage en ligne destiné aux chirurgiens a été rempli rétrospectivement, il reposait sur des déclarations volontaires et n'avait pas fait l'objet d'une validation. Nous ne disposions d'une puissance statistique que pour détecter les effets importants des facteurs associés à un risque accru de complications périopératoires. CONCLUSION: Cette étude confirme le caractère sécuritaire d'un don vivant de rein, comme en témoigne le très faible taux de complications périopératoires majeures. Nous n'avons pu établir de caractéristiques, du donneur ou du chirurgien, qui soit associées à un risque accru de complications périopératoires.

Arterial stiffness and functional properties in chronic kidney disease patients on different dialysis modalities: an exploratory study.

BACKGROUND: Abnormalities of vascular function and accumulation of oxidative stress have been associated with chronic kidney disease (CKD). Dialysis modalities, peritoneal dialysis (PD) and haemodialysis (HD) may differentially impact on vascular function and oxidative stress. METHODS: Patients undergoing living donor transplantation were studied for vascular stiffness using pulse wave velocity measurements, and inferior epigastric arteries were harvested to examine in vitro stiffness and functional properties and evidence of oxidative stress. Forty-one patients were studied representing PD (n = 12), HD (n = 14) and non-dialysed recipients (n = 15). RESULTS: We demonstrated differences in stiffness from in vivo and in vitro measurements such that non-dialysis < HD < PD groups. The stiffness measurements did not correlate with duration of CKD nor dialysis duration, but did so with phosphate levels (r = 0.356, P = 0.02). From the in vitro isometric force experiments, HD arteries demonstrated decreased contractility and endothelium-dependent relaxation compared with PD and non-dialysis vessels. Level of oxidative stress (as indicated by the 8-isoprostane level) was 30% higher in HD arteries than in PD arteries. Protein expression of inducible nitric oxide synthase, NADPH subunits and xanthine oxidase was upregulated in HD arteries, while superoxide dismutase was downregulated. The compromised vascular function in HD arteries was improved by pharmacological means that eliminated oxidative stress. CONCLUSIONS: We report associations between vasomotor function and oxidative stress in the vasculature of patients receiving different dialysis therapies. Oxidative stress, which may be differentially augmented during PD and HD, may play an important role in the vascular dysfunction in dialysis populations.

Differential microvasculature dysfunction in living kidney donor transplant recipients: nondialyzed versus dialyzed chronic kidney disease patients.

We hypothesized that there was differential vasomotor dysfunction in the microcirculation between nondialyzed and dialyzed chronic kidney disease (CKD) patients. During live donor kidney transplantation procedures, skin arterioles (SkA; internal diameter = 120 +/- 5 microm) from donors (n = 27) and recipients (nondialysis = 15; dialysis = 20) were dissected from the abdominal wall at the incision site. In vivo aortic pulse wave velocity (PWV) was also measured. In the in vitro isometric force measurement, nondialyzed SkA exhibited comparable contraction to donor SkA, whereas dialyzed SkA had 60 and 40-50% increase in contraction in response to depolarization and agonist (that is, phenylephrine, serotonin and endothelin-1) stimulation, respectively. The acetylcholine-induced relaxation in the nondialyzed SkA was decreased by 50% compared with dialyzed SkA. However, pre-incubation with superoxide dismutase greatly enhanced the relaxation response in the nondialyzed, but not in the dialyzed SkA and donor SkA. Pre-incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) elevated the resting tension and left-shifted the concentration response curve of phenylephrine-stimulated contraction in the donor-SkA. L-NAME only increased the resting tension in the nondialyzed vessel. In vitro stiffness positively correlated with PWV (R(2) = 0.302, p = 0.001), and dialyzed SkA was 60% stiffer than nondialyzed and donor SkA. The acetylcholine relaxation was negatively correlated with PWV in donors and recipients (R(2) = 0.282, p = 0.01). In conclusion, we have uniquely demonstrated differential microvasculature dysfunction between nondialyzed and dialyzed CKD patients.

Upregulation of matrix metalloproteinase-2 in the arterial vasculature contributes to stiffening and vasomotor dysfunction in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in chronic kidney disease patients on maintenance dialysis. Given the importance of matrix metalloproteinase-2 (MMP-2) in matrix integrity, vascular cell function, and structural stability, we hypothesized that MMP-2 was elevated in the macrovasculature in dialyzed chronic kidney disease patients compared with chronic kidney disease patients not on dialysis and kidney donors. METHODS AND RESULTS: Arteries from live kidney donors (A(donor); n=30) and recipients (nondialysis [A(nondialyzed)], n=17; dialysis [A(dialyzed)], n=23 [peritoneal dialysis, n=10; hemodialysis, n=13]) were harvested during the transplantation procedure. Compared with A(donor), MMP-2 upregulation was evident in both recipient groups. Protein expression of latent plus active MMP-2 in A(dialyzed) was 2-fold that in A(nondialyzed). MMP-2 activity increased with length of dialysis (r=0.573, P=0.004). In A(dialyzed), medial elastic fiber fragmentation was pronounced, and the ratio of external elastic lamina to media was negatively correlated with MMP-2 activity (r=-0.638, P=0.001). A(dialyzed) was 25% stiffer than A(nondialyzed); this increased stiffness correlated with MMP-2 activity (r=0.728, P<0.0001) and the severity of medial calcium deposition (r=0.748, P=0.001). The contractile function and endothelium-dependent relaxation were reduced by 35% to 55% in A(dialyzed) and were negatively associated with MMP-2 activity (r=-0.608, P=0.002; r=-0.520, P=0.019, respectively). Preincubation with MMP-2 inhibitor significantly improved contractility and relaxation in A(dialyzed). CONCLUSIONS: We describe a strong correlation between MMP-2 activation and elastic fiber disorganization, stiffness, calcification, and vasomotor dysfunction in the arterial vasculature in dialyzed chronic kidney disease patients. These findings may contribute to an improved understanding of mechanisms important in vascular health in chronic kidney disease patients.

Matrix metalloproteinase-2 and -9 exacerbate arterial stiffening and angiogenesis in diabetes and chronic kidney disease.

AIMS: Chronic kidney disease (CKD) and diabetes are the prominent risk factors of cardiovascular disease (CVD). Matrix metalloproteinase (MMP)-2 and -9 regulate vascular structure by degrading elastic fibre and inhibit angiogenesis by generating angiostatin. We hypothesized that MMP-2 and -9 were up-regulated in the arterial vasculature from CKD patients with diabetes, compared with those without diabetes. METHODS AND RESULTS: During living donor transplantation procedures, arteries from donors (n = 8) and recipients (non-diabetic, n = 8; diabetic, n = 8; matched in age, gender, and dialysis treatments) were harvested. Diabetic arteries had increased MMP-2 and -9 activities by 42 and 116% compared with non-diabetic ones. Diabetic arteries were the stiffest, and the stiffness measurement was highly correlated with the summation of MMP-2 + MMP-9 activities (r = 0.738, P = 0.0002). Pulse wave velocity measurements correlated with MMP activity (r = 0.683, P = 0.005). Elastic fibre degradation and calcification were worst in diabetic vessels. The phosphate level, which was 25% higher in diabetic patients, correlated with MMP activity (r = 0.513, P = 0.04) and in vitro stiffness (r = 0.545, P = 0.03), respectively. Angiostatin expression was doubled, whereas vascular endothelial growth factor was 50% reduced in diabetic compared with non-diabetic vessels. Microvascular density in diabetic vessels was 48% of that in non-diabetic ones, and it was strongly associated with MMP activity (r = -0.792, P < 0.0001) and vasorelaxation (r = 0.685, P = 0.0009). CONCLUSION: Using a matched case-control design, we report up-regulation of MMP-2 and -9 in diabetic CKD arteries and correlate those with stiffening, impaired angiogenesis, and endothelial dysfunction. These findings may help to explain the high susceptibility of CVD in diabetic and non-diabetic CKD patients.

Economic and ethical impact of extrarenal findings on potential living kidney donor assessment with computed tomography angiography.

To determine the prevalence and spectrum of extrarenal findings in a screening population of potential living kidney donors undergoing renal Computed tomography angiography (CTA) and evaluate their impact on subsequent patient management and imaging costs. Two radiologists retrospectively reviewed 175 consecutive renal CTA's performed for assessment of potential living kidney donors. Extrarenal radiological findings were recorded and classified according to high, medium, or low importance based on clinical relevance and the need for further investigations and/or treatment. The cost of additional imaging examinations was calculated using 2002 Canadian (British Columbia) reimbursements. There were 73 extrarenal findings in 71/175 (40.6%) of the potential kidney donors in the study population. Findings were categorized as of high clinical importance in 18 (10.3%) cases, including lung lesions, bowel tumors, and liver tumors and as medium importance in 31 (17.7%). Twenty-two (12.6%) individuals had findings categorized as low importance, probably of no clinical significance and requiring no follow-up. Further potential evaluation of the 49 patients (28%) with highly and moderately significant extrarenal findings may require an additional $6137 (mean $35.1 per each case of all the screened patients). Transplantation of a kidney from a living donor is an excellent alternative to cadaveric allografts. Potential living kidney donors are a highly selected population of healthy individuals, screened for significant past or current medical conditions before undergoing CTA. Despite this screening, potentially significant extrarenal findings (classified as high or medium importance) were revealed in 28% of patients. These patients may require further investigations and/or treatment. The referring physician and patient should be aware of such potentially high probability, which may require further nontransplant related evaluation and treatment. This has medical, legal, economic, and ethical implications.

National recommendations for donation after cardiocirculatory death in Canada: Donation after cardiocirculatory death in Canada.

These recommendations are the result of a national, multidisciplinary, year-long process to discuss whether and how to proceed with organ donation after cardiocirculatory death (DCD) in Canada. A national forum was held in February 2005 to discuss and develop recommendations on the principles, procedures and practice related to DCD, including ethical and legal considerations. At the forum's conclusion, a strong majority of participants supported proceeding with DCD programs in Canada. The forum also recognized the need to formulate and emphasize core values to guide the development of programs and protocols based on the medical, ethical and legal framework established at this meeting. Although end-of-life care should routinely include the opportunity to donate organs and tissues, the duty of care toward dying patients and their families remains the dominant priority of health care teams. The complexity and profound implications of death are recognized and should be respected, along with differing personal, ethnocultural and religious perspectives on death and donation. Decisions around withdrawal of life-sustaining therapies, management of the dying process and the determination of death by cardiocirculatory criteria should be separate from and independent of donation and transplant processes. The recommendations in this report are intended to guide individual programs, regional health authorities and jurisdictions in the development of DCD protocols. Programs will develop based on local leadership and advance planning that includes education and engagement of stakeholders, mechanisms to assure safety and quality and public information. We recommend that programs begin with controlled DCD within the intensive care unit where (after a consensual decision to withdraw life-sustaining therapy) death is anticipated, but has not yet occurred, and unhurried consent discussions can be held. Uncontrolled donation (where death has occurred after unanticipated cardiac arrest) should only be considered after a controlled DCD program is well established. Although we recommend that programs commence with kidney donation, regional transplant expertise may guide the inclusion of other organs. The impact of DCD, including pre-and post-mortem interventions, on donor family experiences, organ availability, graft function and recipient survival should be carefully documented and studied.

Attitudes and predictive factors for live kidney donation in British Columbia. A comparison of recipients and wait-list patients.

INTRODUCTION: Live donor kidney transplantation (LDKT) is both medically and economically superior to cadaver kidney transplantation in the treatment of patients with chronic renal failure. Unfortunately, fewer than 50% of patients on the transplant waiting list have a relative or friend who contacts the transplant program about possible donation. We hypothesized that both the potential recipient and potential donor have identifiable and modifiable characteristics that contribute to the likelihood of a live donor transplant. MATERIALS AND METHODS: Specifically-designed and validated questionnaires addressing personal characteristics, knowledge and beliefs about LDKT were mailed to patients who had previously received a LDKT (N = 163) and patients on the cadaver transplant waiting list (N = 251). Response rates were 81% and 67% respectively. RESULTS: There were significant differences between groups in age, ethnicity, marital status, hours worked per week, annual income, and time on the waiting list. Significant differences were found between groups in both knowledge and beliefs about live donor kidney transplantation. All wait-list patients could identify at least one family member (mean = 7 potential donors per wait-list patient) who might serve as a live kidney donor but less than 13% of these potential donors have actually undergone an evaluation. CONCLUSIONS: In British Columbia, an enormous pool of potential live kidney donors exists for patients who are currently waiting for a cadaver kidney transplant. Educational strategies designed for wait-list patients may correct knowledge deficits and alter unfavorable beliefs about LDKT which, in turn, may increase their willingness to seek and accept an offer of live kidney donation.

Attitudes and predictive factors for live kidney donation: a comparison of live kidney donors versus nondonors.

BACKGROUND: Live donor kidney transplantation (LDKT), although far from risk free, is a reasonably safe procedure for medically suitable donors. We hypothesized that both potential recipients and donors have identifiable and modifiable factors that contribute to the likelihood of LDKT. The objectives of this study were to describe and quantify these factors using anonymous, confidential questionnaires. METHODS: Specifically designed questionnaires addressing personal characteristics, knowledge, and beliefs about LDKT were mailed to 127 previous donors and 387 relatives of patients newly listed on the cadaver transplant wait-list. Ninety-eight (77%) and 243 (63%) responses were returned by donors and nondonors, respectively. RESULTS: There were significant differences between groups in gender, ethnicity, hours worked per week, and annual income. Significant differences were seen in both knowledge and beliefs about LDKT. Most donors indicated they made their decisions without lengthy deliberation or research about kidney donation. Only 20% of nondonors feel they are well informed about LDKT. CONCLUSION: It is likely possible to improve knowledge about LDKT among friends and relations of patients with renal failure, but it is not certain that this will lead to increased donation because most donors don't appear to deliberate or research organ donation before making a commitment to donate. Strategies to educate potential donors should initially focus on the recipient.

They talk the talk: Surveying attitudes and judging behavior about living anonymous kidney donation.

BACKGROUND: Over the past 30 years, numerous studies have reported that some individuals are willing to donate a kidney anonymously to a stranger; however, intentions are poor predictors of behavior. We surveyed individuals interested in being living anonymous donors (LADs), exposed them to an interview paralleling live-donor assessment, and measured their LAD commitment. Personality and donation decision factors were examined to corroborate cases of attitudinal and behavioral congruency. METHODS: A telephone survey of 1,002 randomly selected adults living in Vancouver, British Columbia, asked respondents how willing they were to donate a kidney, while alive, to particular individuals including a stranger. A subsample participated in a follow-up, which involved completing a mailed questionnaire and taking part in an in-depth interview. Expert raters judged respondents' commitment to being a LAD on the basis of the interviews. RESULTS: Two hundred fifty-eight (26%) of those surveyed stated they would probably or definitely be willing to donate a kidney to a stranger. Fifty-two completed the follow-up. Sixteen of the 52 (31%) were judged to be "committed LADs." No demographic differences were found between the committed LADs and the 33 remaining "noncommitted participants." The committed LADs differed significantly from the noncommitted participants on personality measures and donation decision factors. These differences underscore the latter group's anonymous donation commitment. CONCLUSIONS: This study brings into focus the potential for a significant number of individuals coming forward as potential LAD candidates if they are informed about the need and given unbiased information about the procedure. We believe there is ethical latitude in allowing the promotion of LAD donation by interested third parties such as patient advocacy groups and professional bodies. We advocate public awareness of LAD programs as a first step followed thereafter by more provocative measures to engage the public in this endeavor.

The living anonymous kidney donor: lunatic or saint?

Studies indicate that 11% to 54% of individuals surveyed would consider donating a kidney, while alive, to a stranger. The idea of 'living anonymous donors' (LADs) as a donor source, however, has not been embraced by the medical community. Reservations focus on the belief that LADs might be psychologically unstable and thus unsuitable donors. Our goal was to inform policy development by exploring the psycho-social make up and motivations of the LAD. Ninety-three unsolicited individuals contacted our center expressing interest in living anonymous donation. Of these, 43 participated in our study, completing two extensive inventories of psychopathology and personality disorder and taking part in the Comprehensive Psycho-Social Interview (CPSI). From the Personality Assessment Inventory (PAI), the revised NEO Personality Inventory (NEO PI-R), and the CPSI, coders assessed psychological health, psycho-social suitability, commitment, and motivations. Twenty-one participants passed the stringent criteria to be considered potential LADs. Content analysis of motivations showed that potential LADs were more likely than non-LADs (those who did not pass the criteria) to have a spiritual belief system and to be altruistic. Non-LADs were more likely than potential LADs to use donation to make a statement against their families. The authors conclude with a preliminary outline of eight policy recommendations.

A prospective comparison of simultaneous and sequential live-donor renal transplantation.

BACKGROUND: Traditionally, we have performed live- donor renal transplantations sequentially with a cold ischemic time (preservation time) of approximately 3 hr. By performing live-donor renal transplantations simultaneously, cold ischemic times can be reduced to 30 min or less. The purpose of this prospective study was to compare clinical outcomes and biologic markers of kidney function between live-donor renal transplantations performed either simultaneously or sequentially. METHODS: Nine consecutive live-donor renal transplantations were performed in a simultaneous manner by two transplant surgeons. For comparison, 18 consecutive live-donor transplantations were performed sequentially by a single surgeon. Donor and recipient demographic factors, before transplantation, were compared. Posttransplantation comparisons included daily serum creatinine measurements for 5 days, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) for 72 hr postoperatively, nuclear glomerular filtration rate (GFR) at 18 hr postoperatively, creatinine clearance at 96 hr postoperatively, and creatinine clearance at 3 and 6 months posttransplantation. RESULTS: There were no differences in donor and recipient demographic factors preoperatively between the two groups. With simultaneous and sequential recipients, only the cold ischemic times were significantly different (simultaneous: mean=23.6 min; sequential: mean=191.7 min; P<0.01). After transplantation, no differences were detected in the daily fall of serum creatinine, nuclear GFR at 18 hr, or creatinine clearance at 96 hr, 3 months, or 6 months. In both groups, urinary NAG excretion reached a peak at 1 hr postoperatively and then slowly returned to baseline by 72 hr. There was no difference in the amount of NAG excretion between the two groups. CONCLUSIONS: Our study found that there is no difference in tubular injury or postoperative GFR in live-donor kidney transplantations performed simultaneously or sequentially. Our findings indicate that a modest prolongation of the cold ischemic time has no detectable influence on posttransplantation renal function for live-donor transplantations.