Correction to: Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

The original version of this article, published on 03 January 2020 contained a mistake. An author's name was misspelled.

Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; at years 1, 2, and 3; and at final follow-up (average of 3.4 years). Both bisphosphonate and denosumab treatments increased lumbar spine bone density; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Denosumab treatment increased femoral neck BMD, whereas bisphosphonate treatment had a mean decrease in femoral neck BMD at final follow-up. Thus, our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant. INTRODUCTION: To compare the clinical effectiveness and safety between the use of denosumab and bisphosphonates on bone density and incidence of adverse events in renal transplant patients. METHODS: A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; years 1, 2, and 3; and at final follow-up (average of 3.4 years). RESULTS: Absolute change in lumbar spine and femoral neck BMD over the treatment period was 0.029 ± 0.075 g/cm2 and - 0.003 ± 0.064 g/cm2, respectively, in the bisphosphonate group. Absolute change in lumbar spine and femoral neck BMD at final follow-up was 0.072 ± 0.094 g/cm2 and 0.025 ± 0.063 g/cm2, respectively, in the denosumab group. Denosumab resulted in significantly greater increases in lumbar spine BMD (0.045 g/cm2 greater in the denosumab group). Similarly, the absolute change in BMD at the femoral neck was 0.022 g/cm2 greater in the denosumab group as compared with the bisphosphonate group. The denosumab group had one event of severe hypocalcemia following first injection and one report of hospitalized pneumonia. No serious adverse events were reported in the bisphosphonate group. CONCLUSIONS: Both treatments increased lumbar spine BMD; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant.

Economic consequences incurred by living kidney donors: a Canadian multi-center prospective study.

Some living kidney donors incur economic consequences as a result of donation; however, these costs are poorly quantified. We developed a framework to comprehensively assess economic consequences from the donor perspective including out-of-pocket cost, lost wages and home productivity loss. We prospectively enrolled 100 living kidney donors from seven Canadian centers between 2004 and 2008 and collected and valued economic consequences ($CAD 2008) at 3 months and 1 year after donation. Almost all (96%) donors experienced economic consequences, with 94% reporting travel costs and 47% reporting lost pay. The average and median costs of lost pay were $2144 (SD 4167) and $0 (25th-75th percentile 0, 2794), respectively. For other expenses (travel, accommodation, medication and medical), mean and median costs were $1780 (SD 2504) and $821 (25th-75th percentile 242, 2271), respectively. From the donor perspective, mean cost was $3268 (SD 4704); one-third of donors incurred cost >$3000, and 15% >$8000. The majority of donors (83%) reported inability to perform usual household activities for an average duration of 33 days; 8% reported out-of-pocket costs for assistance with these activities. The economic impact of living kidney donation for some individuals is large. We advocate for programs to reimburse living donors for their legitimate costs.

Disparities in Deceased Donor Kidney Offer Acceptance: A Survey of Canadian Transplant Nephrologists, General Surgeons and Urologists.

Background: Significant variability in organ acceptance thresholds have been demonstrated across the United States, but data regarding the rate and rationale for kidney donor organ decline in Canada are lacking. Objective: To examine decision making regarding deceased kidney donor acceptance and non-acceptance in a population of Canadian transplant professionals. Design: A survey study of theoretical deceased donor kidney cases of increasing complexity. Setting: Canadian transplant nephrologists, urologists, and surgeons making donor call decisions responding to an electronic survey between July 22 and October 4, 2022. Participants: Invitations to participate were distributed to 179 Canadian transplant nephrologists, surgeons, and urologists through e-mail. Participants were identified by contacting each transplant program and requesting a list of physicians who take donor call. Measurements: Survey respondents were asked whether they would accept or decline a given donor, assuming there was a suitable recipient. They were also asked to cite reasons for donor non-acceptance. Methods: Donor scenario-specific acceptance rates (total acceptance divided by total number of respondents for a given scenario and overall) and reasons for decline were determined and presented as a percentage of the total cases declined. Results: In all, 72 respondents from 7 provinces completed at least one question of the survey, with considerable variability between acceptance rates for centers; the most conservative center declined 60.9% of donor cases, whereas the most aggressive center declined only 28.1%, P-value < .001. There was an increased risk of non-acceptance with advancing age, donation after cardiac death, acute kidney injury, chronic kidney disease, and comorbidities. Limitations: As with any survey, there is the potential for participation bias. In addition, this study examines donor characteristics in isolation, however, asks respondent to assume there is a suitable candidate available. In reality, whenever donor quality is considered, it should be considered in the context of the intended recipient. Conclusion: In a survey of increasingly medically complex deceased kidney donor cases, there was significant variability in donor decline among Canadian transplant specialists. Given relatively high rates of donor decline and apparent heterogeneity in acceptance decisions, Canadian transplant specialists may benefit from additional education regarding the benefits achieved from even medically complex kidney donors for appropriate candidates relative to remaining on dialysis on the transplant waitlist.

Contexte: Une importante variabilité a été observée aux États-Unis dans le seuil d'acceptation des organes. Au Canada, on manque de données sur le taux de refus des donneurs de reins et sur les raisons qui expliquent ce refus. Objectifs: Examiner la prise de décision quant à l'acceptation ou non d'un donneur de rein décédé dans une population de professionnels de la transplantation canadiens. Conception: Un sondage exposant des cas théoriques de plus en plus complexes de donneurs de reins décédés. Cadre: Des néphrologues, urologues et chirurgiens canadiens spécialisés en transplantation qui prennent des décisions relatives au don d'organes ont été invités à répondre à un sondage électronique entre le 22 juillet et le 4 octobre 2022. Participants: L'invitation à participer a été distribuée par courriel à 179 néphrologues, chirurgiens et urologues canadiens spécialisés en transplantation. Les participants ont été identifiés en communiquant avec chaque program de transplantation pour obtenir une liste des médecins recevant des offres d'organes. Mesures: Les répondants devaient indiquer s'ils accepteraient ou refuseraient un donneur donné, en supposant qu'un receveur approprié existait. Ils étaient également invités à citer les raisons justifiant le refus d'un donneur. Méthodologie: Les taux d'acceptation par scénario (acceptation totale divisée par le nombre total de répondants pour un scénario donné, et pour l'ensemble) et les raisons du refus ont été déterminés et présentés sous forme de pourcentage du nombre total de cas refusés. Résultats: En tout, 72 professionnels issus de 7 provinces avaient répondu à au moins une question du sondage. On a observé une grande variabilité du taux d'acceptation entre les différents centers; le plus conservateur avait refusé 60,9 % des donneurs présentés alors que le plus entreprenant n'avait refusé que de 28,1 % des cas (p < 0,001). Les donneurs d'âge avancé, ceux décédés d'un problème cardiaque et ceux qui souffraient d'insuffisance rénale aiguë, d'insuffisance rénale chronique et de comorbidités étaient plus susceptibles d'être refusés. Limites: Comme pour toute étude sous forme de sondage, celle-ci comporte un possible biais de participation. Cette étude examine les caractéristiques du donneur de manière isolée, mais demande aux répondants de supposer qu'un candidat approprié existe. Dans la réalité, chaque fois que la qualité d'un donneur est évaluée, elle doit être prise en compte dans le contexte du receveur visé. Conclusion: Dans cette étude présentant des cas théoriques de complexité croissante sur le plan médical de donneurs de reins décédés, une importante variabilité a été observée quant au refus des donneurs par les spécialistes de la transplantation canadiens. Les taux relativement élevés de refus et l'apparente hétérogénéité des décisions liées à l'acceptation justifient plus d'éducation auprès des spécialistes de la transplantation canadiens; notamment sur les avantages pour un candidat approprié de recevoir un organe, même si ce dernier provient d'un cas médicalement complexe, par rapport au fait de rester en dialyze sur la liste d'attente pour une transplantation.

Accepting kidneys from older living donors: impact on transplant recipient outcomes.

Older living kidney donors are regularly accepted. Better knowledge of recipient outcomes is needed to inform this practice. This retrospective cohort study observed kidney allograft recipients from Ontario, Canada between January 2000 and March 2008. Donors to these recipients were older living (≥ 60 years), younger living, or standard criteria deceased (SCD). Review of medical records and electronic healthcare data were used to perform survival analysis. Recipients received 73 older living, 1187 younger living and 1400 SCD kidneys. Recipients of older living kidneys were older than recipients of younger living kidneys. Baseline glomerular filtration rate (eGFR) of older kidneys was 13 mL/min per 1.73 m² lower than younger kidneys. Median follow-up time was 4 years. The primary outcome of total graft loss was not significantly different between older and younger living kidney recipients [adjusted hazard ratio, HR (95%CI): 1.56 (0.98-2.49)]. This hazard ratio was not proportional and increased with time. Associations were not modified by recipient age or donor eGFR. There was no significant difference in total graft loss comparing older living to SCD kidney recipients [HR: 1.29 (0.80-2.08)]. In light of an observed trend towards potential differences beyond 4 years, uncertainty remains, and extended follow-up of this and other cohorts is warranted.

The long-term quality of life of living kidney donors: a multicenter cohort study.

Previous studies that described the long-term quality of life of living kidney donors were conducted in single centers, and lacked data on a healthy nondonor comparison group. We conducted a retrospective cohort study to compare the quality of life of 203 kidney donors with 104 healthy nondonor controls using validated scales (including the SF36, 15D and feeling thermometer) and author-developed questions. Participants were recruited from nine transplant centers in Canada, Scotland and Australia. Outcomes were assessed a median of 5.5 years after the time of transplantation (lower and upper quartiles of 3.8 and 8.4 years, respectively). 15D scores (scale of 0 to 1) were high and similar between donors and nondonors (mean 0.93 (standard deviation (SD) 0.09) and 0.94 (SD 0.06), p = 0.55), and were not different when results were adjusted for several prognostic characteristics (p = 0.55). On other scales and author-developed questions, groups performed similarly. Donors to recipients who had an adverse outcome (death, graft failure) had similar quality of life scores as those donors where the recipient did well. Our findings are reassuring for the practice of living transplantation. Those who donate a kidney in centers that use routine pretransplant donor evaluation have good long-term quality of life.

Differences in tolerance for health risk to the living donor among potential donors, recipients, and transplant professionals.

In organ donation, the donor, recipient, and transplant team must all accept potential health risks to the donor and any uncertainties. To gauge these risks, we surveyed general altruism and risk-taking behaviors in 112 potential donors, 111 potential recipients, and 51 transplant professionals. Next, participants indicated their risk thresholds for long-term donor hypertension, cardiovascular disease, and kidney failure that would stop them from pursuing living donation and their willingness to proceed when risks were uncertain. The three groups had similar general altruism and risk-taking behaviors. Potential donors were significantly more willing to accept greater long-term donor risks than potential recipients and transplant professionals. Moreover, these potential donors were significantly more likely to agree that living donation was acceptable when long-term donor risks were uncertain. Potential kidney donors readily accept high long-term risks, whereas potential recipients were the most averse to donor risk. Our study shows that transplant professionals facilitate the best decisions by appreciating the willingness of their patients to accept donor health risks along with their own risk tolerance.

Health outcomes for living kidney donors with isolated medical abnormalities: a systematic review.

Individuals with isolated medical abnormalities (IMAs) are undergoing living donor nephrectomy more frequently. Knowledge of health risks for these living donors is important for donor selection, informed consent and follow-up. We systematically reviewed studies with > or = 3 living kidney donors with preexisting IMAs, including older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria, microscopic hematuria and nephrolithiasis. We abstracted data on study and donor characteristics, perioperative outcomes, longer term renal and blood pressure outcomes and mortality and compared them to those of non-IMA donors. We found 22 studies on older donors (n = 987), 10 on obese donors (n = 484), 6 on hypertensive donors (n = 125), 4 on donors with nephrolithiasis (n = 32), 2 on donors with microscopic hematuria and one study each on donors with proteinuria or reduced GFR. Perioperative outcomes for donors with and without IMAs were similar. Few studies reported longer term (> or = 1 year) rates of hypertension, proteinuria or renal function. Studies were frequently retrospective and without a comparison group. Given the variability among studies and their methodological limitations, uncertainties remain regarding long-term medical outcomes for IMA donors. As transplant centers continue to cautiously screen and counsel potential IMA donors, rigorously conducted, longer term prospective cohort studies are needed.

Management of asymptomatic cholelithiasis for patients awaiting renal transplantation.

BACKGROUND: There is no consensus regarding the most appropriate management of asymptomatic cholelithiasis in patients awaiting renal transplantation. Cholecystectomy is considered before renal transplantation because of potential worsened complications from cholelithiasis with posttransplantation immunosuppression. This study reviewed the outcomes for operative and nonoperative management of asymptomatic cholelithiasis in patients awaiting renal transplantation. METHODS: A retrospective chart review of all patients who received renal transplant at the authors' institution during the period 1994 to 2000 was completed. All patients underwent pretransplantation abdominal ultrasound. RESULTS: Of the 411 patients receiving renal transplants (242 men and 169 women with a mean age of 45.7 years), 32 had cholelithiasis at the pretransplantation workup (7.8%), and 35 had gallbladder abnormalities (8.5%): polyps, thickened wall, sludge, bile duct dilation. Before transplantation, 12 of the 32 patients (38%) with cholelithiasis underwent uncomplicated cholecystectomy. None of the remaining 19 patients with cholelithiasis required cholecystectomy after renal transplantation (mean follow-up period 6.2 years). Of the 35 patients with gallbladder abnormalities, 2 required post transplantation elective cholecystectomy. CONCLUSIONS: No evidence was found for increased morbidity related to cholelithiasis or gallbladder abnormalities after renal transplantation. As in the general population, the risks associated with asymptomatic cholelithiasis do not appear to warrant prophylactic cholecystectomy for patients awaiting renal transplantation.

Utility of ultrasonographic venous assessment prior to forearm arteriovenous fistula creation.

AIM: The purpose of this study was to evaluate the clinical utility of Doppler ultrasound (US) prior to native forearm arteriovenous fistula (AVF) creation. MATERIALS AND METHODS: US mapping was carried out pre-operatively to evaluate the major veins and arteries in the appropriate arm. One hundred and 6 patients were identified retrospectively over 2 years with complete clinical and US data. A failed fistula was defined as an inability to provide blood flow to meet adequacy targets by 6 months (urea reduction ratio > or = 65%). RESULTS: Twenty-nine patients (27.4%) had successful forearm AVFs. The mean minimum forearm cephalic vein diameter (CVD) was 2.51 +/- 0.14 and 2.23 +/- 0.06 mm in successful and failed fistulae, respectively (p = 0.04). This result was primarily due to differences observed in women. A receiver operator curve analysis showed that a cutpoint of 2.6 mm for minimum forearm CVD had the greatest predictive value with a likelihood ratio of 3.94 (95% CI: 1.97 - 7.84) for fistula failure. Multivariate logistic regression analysis determined that male gender and minimum forearm CVD were the only significant predictors for fistula success with odds ratios of 3.90 (95% CI: 1.30 - 11.68) and 2.31 (95% CI: 1.00 - 5.43), respectively. The study is limited by the possibility that US results in patients may have lead to an alternative type of access being attempted. CONCLUSIONS: US mapping prior to forearm AVF creation is of modest benefit. Only male gender and minimum forearm CVD were predictive of AVF success.

Randomized study of temporary hemodialysis catheters.

Temporary catheters are still essential for acute dialysis access but their performance has not been compared in randomized trials. We conducted a randomized trial of our standard catheter and a newly designed catheter. The primary outcome was maximized blood flow over the entire use of the catheter. Seventy-six patients provided maximum blood flows. The new catheter provided an average blood flow of 349 ml/min and the standard catheter provided flows of 320 ml/mm (p=0.09). Lumen reversal occurred in 56.8% of dialysis sessions with the standard catheter compared to 27.4% with the new catheter (p<0.001). Left-sided internal jugular catheters and catheters inserted in females provided 103 ml/min and 36 ml/min less blood flow, respectively, compared to right sided catheters and catheters placed in males. Approximately 20% of catheters were removed for poor blood flow. Left sided catheters and catheters in females were more likely to need removal for malfunction but catheter design did not influence removal rates.

Event adjudication and data monitoring in an intensive care unit observational study of thromboprophylaxis.

BACKGROUND: The objective of this report is to describe the roles, responsibilities and recommendations of a 3-member Event Adjudication Committee (EAC) and a 5-member data monitoring committee (DMC) for a prospective multicenter observational study of critically ill patients with renal insufficiency examining the bioaccumulation and bleeding risk associated with dalteparin thromboprophylaxis. METHODS: The EAC reviewed bleeding events to adjudicate whether they were major or minor and whether they were related to dalteparin (uncertain, unlikely, or likely). The DMC reviewed all bleeds deemed by the EAC as uncertain or likely due to dalteparin then recommended either to continue or suspend enrolment pending review by the steering committee, or requested more information. RESULTS: Consensus on bleeding severity was achieved for all cases. At the second planned interim analysis, the EAC recommended to the DMC and steering committee that the EAC should stop adjudicating whether bleeding was related to dalteparin since attribution was challenging in this population with numerous bleeding risk factors; moreover, no bleeding rates were available from prior studies or historical or concurrent controls. CONCLUSIONS: Adjudication of whether an outcome can be attributed to an intervention in an open-label, uncontrolled observational study gives a potentially misleading impression of research oversight without methodological face validity. In this study, the EAC recommended modification of the adjudication process, and the DMC recommended continuing enrolment to achieve the target sample size.