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Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Amit Garg received an investigator-initiated grant from Astellas which featured as partnership funds in CIHR-funded research. The other authors declare no conflicts of interest., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation., Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared., Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics., Exposure: Living kidney donation., Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g])., Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19)., Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up., Trial Registration: ClinicalTrials.gov Identifier: NCT00936078.

Background: Living kidney donors incur donation-related expenses, but how these expenses impact postdonation mental health is unknown., Methods: In this prospective cohort study, the association between mental health and donor-incurred expenses (both out-of-pocket costs and lost wages) was examined in 821 people who donated a kidney at one of the 12 transplant centers in Canada between 2009 and 2014. Mental health was measured by the RAND Short Form-36 Health Survey along with Beck Anxiety Inventory and Beck Depression Inventory., Results: A total of 209 donors (25%) reported expenses of >5500 Canadian dollars. Compared with donors who incurred lower expenses, those who incurred higher expenses demonstrated significantly worse mental health-related quality of life 3 months after donation, with a trend towards worse anxiety and depression, after controlling for predonation mental health-related quality of life and other risk factors for psychological distress. Between-group differences for donors with lower and higher expenses on these measures were no longer significant 12 months after donation., Conclusions: Living kidney donor transplant programs should ensure that adequate psychosocial support is available to all donors who need it, based on known and unknown risk factors. Efforts to minimize donor-incurred expenses and to better support the mental well-being of donors need to continue. Further research is needed to investigate the effect of donor reimbursement programs, which mitigate donor expenses, on postdonation mental health., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

When multiple living donor candidates come forward to donate a kidney to the same recipient, some living donor programs evaluate one candidate at a time to avoid unnecessary evaluations. Evaluating multiple candidates concurrently rather than sequentially may be cost-effective from a societal perspective if it reduces the time recipients spend on dialysis. We used a simple decision tree to estimate the cost-effectiveness of evaluating two to four candidates simultaneously rather than sequentially as potential kidney donors for the same intended recipient. Evaluating two donor candidates simultaneously cost $1,266 (CAD) more than if they were evaluated sequentially, but living donation occurred one month earlier. This translated into $6,931 in averted dialysis costs and a total cost-savings of $5,665 per intended recipient. Simultaneous evaluations also resulted in one percent more living donor transplants and overall gains in quality-of-life as recipients spent less time on dialysis. If recipients were free from dialysis at the start of donor candidate evaluations, simultaneous evaluations also reduced the rate of dialysis initiation by two percent. Benefits were also observed in the three- and four-candidate scenarios. Thus, living donor programs should consider evaluating up to four living donor candidates simultaneously when they come forward for the same recipient as health care system costs incurred are more than offset by avoided dialysis costs., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

We surveyed US transplant programs to assess practices used to assess kidney health in living kidney donor candidates in 2017; the response rate was 31%. In this report, we focus on the kidney; a companion piece focuses on the metabolic and cardiovascular aspects of candidate evaluation. Compared to 2005, programs have become more stringent in accepting younger candidates and less stringent in accepting older candidates. The 24-hour creatinine clearance remains the mainstay for kidney function assessment, with 74% continuing to use a value below 80 mL/min/1.73 m 2 for exclusion and 22% using age-based criteria. ApoL1 genotyping is obtained routinely or selectively by 45%, half of which use the high-risk genotype as an absolute exclusion criterion. For history of symptomatic stones, 49% accept if there is no current radiographic evidence of stones and urine profile is low risk, 80%-95% consider candidates with unilateral asymptomatic stones, but only 33%-48% consider if stones are bilateral. In addition, 14% use the risk assessment tool developed by Grams et al routinely for decision-making, and 42% use it sometimes. Also, 57% reported not having yet determined a risk threshold for acceptable postdonation risk above which candidates are excluded. Contemporary practice variation underscores the need for better evidence to guide the donor selection process., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We surveyed US transplant centers to assess practices regarding the evaluation and selection of living kidney donors based on metabolic, cardiovascular, and substance use risk factors. Our companion article describes renal aspects of the evaluation. Response rate was 31%. Compared with 2005, programs have become more accepting of hypertensive candidates: 65% in 2017% vs 41% in 2005 consider candidates with hypertension well controlled with 1 medication. One notable exception is black hypertensive candidates, who are frequently excluded regardless of severity. The most common body mass index (BMI) cutoff remains 35 kg/m 2 , and fewer programs now consider candidates with BMI >40 kg/m 2 . A 2-hour oral glucose tolerance test of ≥140 mg/dL remains the most common criterion for exclusion of prediabetic candidates. One quarter to one third of programs exclude based on isolated cardiac abnormalities, such as mild aortic stenosis; a similar proportion consider these candidates only if older than 50 years. Cigarette or marijuana smoking are infrequently criteria for exclusion, although 45% and 37% programs, respectively, require cessation 4 weeks prior to surgery. In addition to providing an overview of current practices in living kidney donor evaluation, our study highlights the importance of research evaluating outcomes with various comorbidities to guide practice., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Consider a theoretical situation in which 2 patients with similar baseline characteristics receive a kidney transplant on the same day: 1 from a standard criteria deceased donor, the other from a living donor. Which kidney transplant will last longer?, Methods: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, from January 1, 2005, to March 31, 2014, to evaluate several posttransplant outcomes in individuals who received a kidney transplant from a standard criteria deceased donor (n = 1523) or from a living donor (n = 1373). We used PS weighting using overlap weights, a novel weighting method that emphasizes the population of recipients with the most overlap in baseline characteristics., Results: Compared with recipients of a living donor, the rate of all-cause graft failure was not statistically higher for recipients of a standard criteria deceased donor (hazard ratio, 1.1; 95% confidence interval [CI], 0.8-1.6). Recipients of a standard criteria deceased donor, compared with recipients of a living donor had a higher rate of delayed graft function (23.6% versus 18.7%; odds ratio, 1.3; 95% CI, 1.0-1.6) and a longer length of stay for the kidney transplant surgery (mean difference, 1.7 d; 95% CI, 0.5-3.0)., Conclusions: After accounting for many important donor and recipient factors, we failed to observe a large difference in the risk of all-cause graft failure for recipients of a standard criteria deceased versus living donor. Some estimates were imprecise, which meant we could not rule out the presence of smaller clinically important effects.

Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m 2 . Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m 2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m 2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was +1.06, +0.64, and -0.06 mL/min/1.73 m 2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m 2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 "Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors" was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a "proof-of-concept" risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate's profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice., (Copyright © 2020 by the American Society of Nephrology.)

Importance: Living kidney donation is associated with increased long-term risk of end-stage renal disease (ESRD). An early postdonation marker of ESRD risk could improve postdonation risk assessment and counseling for kidney donors and allow early intervention for donors at increased risk., Objective: To determine the association between renal function in the first 6 months postdonation and subsequent risk of ESRD in kidney donors., Design, Setting, and Participants: This secondary analysis of a prospective national cohort uses a population-based registry of all living kidney donors in the United States between October 26, 1999, and January 1, 2018, with follow-up through December 31, 2018. All kidney donors who had donated in the date range and had serum creatinine measured at 6 months (±3 months) postdonation were included., Exposures: Renal function as measured by estimated glomerular filtration rate 6 months after donation (eGFR6)., Main Outcomes and Measures: End-stage renal disease, ascertained via linkage to Centers for Medicare & Medicaid Services data., Results: A total of 71 468 living kidney donors were included (of 109 065 total donors over this period). Their median (interquartile range) eGFR6 was 63 (54-74) mL/min/1.73 m2. Cumulative incidence of ESRD at 15 years postdonation ranged from 11.7 donors per 10 000 donors with eGFR6 values greater than 70 mL/min/1.73 m2 to 33.1 donors per 10 000 donors with eGFR6 values of 50 mL/min/1.73 m2 or less. Adjusting for age, race, sex, body mass index, and biological relationship, every 10 mL/min/1.73 m2 reduction in eGFR6 was associated with a 28% increased risk of ESRD (adjusted hazard ratio, 1.28 [95% CI, 1.06-1.54]; P = .009). The association between predonation eGFR and ESRD was not significant and was fully mediated by eGFR6 (adjusted hazard ratio, 1.00 [95% CI, 0.86-1.17]; P = .97). The postdonation eGFR value was a better marker of ESRD than eGFR decline after donation or the ratio of eGFR6 to predonation eGFR, as determined by the Akaike information criterion (in which a lower value indicates a better model fit; eGFR6, 1495.61; predonation eGFR - eGFR6, 1503.58; eGFR6 / predonation eGFR, 1502.30)., Conclusions and Relevance: In this study, there was an independent association of eGFR6 with subsequent ESRD risk in living kidney donors, even after adjusting for predonation characteristics. The findings support measurement of early postdonation serum creatinine monitoring in living kidney donors, and the use of these data to help identify donors who might need more careful surveillance and early intervention.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, LCL aHR UCL ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.36 4.59 6.27 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, 3.55 5.00 7.04 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m 2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.03 1.48 2.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Living donors may incur out-of-pocket costs during the donation process. While many jurisdictions have programs to reimburse living kidney donors for expenses, few programs have been evaluated., Methods: The Program for Reimbursing Expenses of Living Organ Donors was launched in the province of Ontario, Canada in 2008 and reimburses travel, parking, accommodation, meals, and loss of income; each category has a limit and the maximum total reimbursement is $5500 CAD. We conducted a case study to compare donors' incurred costs (out-of-pocket and lost income) with amounts reimbursed by Program for Reimbursing Expenses of Living Organ Donors. Donors with complete or partial cost data from a large prospective cohort study were linked to Ontario's reimbursement program to determine the gap between incurred and reimbursed costs (n = 159)., Results: The mean gap between costs incurred and costs reimbursed to the donors was $1313 CAD for out-of-pocket costs and $1802 CAD for lost income, representing a mean reimbursement gap of $3115 CAD. Nondirected donors had the highest mean loss for out-of-pocket costs ($2691 CAD) and kidney paired donors had the highest mean loss for lost income ($4084 CAD). There were no significant differences in the mean gap across exploratory subgroups., Conclusions: Reimbursement programs minimize some of the financial loss for living kidney donors. Opportunities remain to remove the financial burden of living kidney donors.

Background: Approximately 40% of the kidneys for transplant worldwide come from living donors. Despite advantages of living donor transplants, rates have stagnated in recent years. One possible barrier may be costs related to the transplant process that potential willing donors may incur for travel, parking, accommodation, and lost productivity., Methods: To better understand and quantify the financial costs incurred by living kidney donors, we conducted a prospective cohort study, recruiting 912 living kidney donors from 12 transplant centers across Canada between 2009 and 2014; 821 of them completed all or a portion of the costing survey. We report microcosted total, out-of-pocket, and lost productivity costs (in 2016 Canadian dollars) for living kidney donors from donor evaluation start to 3 months after donation. We examined costs according to ( 1 ) the donor's relationship with their recipient, including spousal (donation to a partner), emotionally related nonspousal (friend, step-parent, in law), or genetically related; and ( 2 ) donation type (directed, paired kidney, or nondirected)., Results: Living kidney donors incurred a median (75th percentile) of $1254 ($2589) in out-of-pocket costs and $0 ($1908) in lost productivity costs. On average, total costs were $2226 higher in spousal compared with emotionally related nonspousal donors ( P =0.02) and $1664 higher in directed donors compared with nondirected donors ( P <0.001). Total costs (out-of-pocket and lost productivity) exceeded $5500 for 205 (25%) donors., Conclusions: Our results can be used to inform strategies to minimize the financial burden of living donation, which may help improve the donation experience and increase the number of living donor kidney transplants., (Copyright © 2018 by the American Society of Nephrology.)

Aim: To describe the direct and indirect costs incurred by Australian living kidney donors., Methods: A total of 55 living kidney donors from three centres in Perth, Australia and one centre in Melbourne, Australia (2010-2014) was studied. Forty-nine donors provided information on expenses incurred during the donor evaluation period and up to 3 months after donation. A micro-costing approach was used to measure and value the units of resources consumed. Expenses were grouped as direct costs (ground and air travel, accommodation, and prescription medications) and indirect costs (lost wages and lost productivity). Costs were standardized to the year 2016 in Australian dollars., Results: The most common direct costs were for ground travel (100%), parking (76%), and post-donation pain medications or antibiotics (73%). The highest direct costs were for air travel (median $1986 [three donors]) and ground travel (median $459 [49 donors]). Donors also reported lost wages (median $9891 [37 donors]). The inability to perform household activities or care for dependants were reported by 32 (65%) and 23 (47%) donors. Total direct costs averaged $1682 per donor (median $806 among 49 donors). Total indirect costs averaged $7249 per donor (median $7273 among 49 donors). Total direct and indirect costs averaged $8932 per donor (median $7963 among 49 donors)., Conclusion: Many Australian living kidney donors incur substantial costs during the donation process. Our findings inform the continued development of policies and programmes designed to minimize costs incurred by living kidney donors., (© 2017 Asian Pacific Society of Nephrology.)

Living donor kidney transplantation is the most promising way to avoid or minimize the amount of time a recipient spends on dialysis before transplantation. We studied 887 living kidney donors at 5 transplant centers in Ontario, Canada, who started their evaluation and donated between April 2006 and March 2014. Using a series of hypothetical scenarios, we estimated the impact of an earlier living donor evaluation completion and donation on the number pre-emptive transplants, the time spent on dialysis, healthcare cost savings from averted dialysis costs (CAD $2016), and the number of additional transplants. During the study period, if the donor transplants occurred 3 months earlier, the healthcare system would save on average $12 055 (standard deviation [SD] $13 594) per recipient; 21 recipients could have avoided dialysis altogether, and 57 additional transplants (a 26% increase) could have occurred each year. For the 220 living kidney donor transplants performed in Ontario, Canada, each year, this translates to a total annual cost savings of $2.7M. In conclusion, a more timely evaluation of living donor candidates and their intended recipients may increase the supply of kidneys for transplantation. Improved evaluation efficiency may also yield more pre-emptive transplants and substantial healthcare cost savings through averted dialysis costs., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement., Study Design: 1 prospective and 1 retrospective cohort study., Setting & Participants: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases., Predictors: Donor and recipient demographics, direct versus paired donation, center-level variables., Outcomes: Duration of living donor evaluation., Results: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis., Limitations: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process., Conclusions: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The healthcare costs to evaluate, perform surgery, and follow a living kidney donor for the year after donation are poorly described., Methods: We obtained information on the healthcare costs of 1099 living kidney donors between April 1, 2004, and March 31, 2014, from Ontario, Canada, using comprehensive healthcare administrative databases. We estimated the cost of 3 periods of the living donation process: the predonation evaluation period (start of evaluation until the day before donation), perioperative period (day of donation until 30-days postdonation), and 1 year of follow-up period (after perioperative period until 1 year postdonation). We analyzed data for donors and healthy matched nondonor controls using regression-based methods to estimate the incremental cost of living donation. Costs are presented from the perspective of the Canadian healthcare payer (2017 CAD $)., Results: The incremental healthcare costs (compared with controls) for the evaluation, perioperative, and follow-up periods were CAD $3596 (95% confidence interval [CI], CAD $3350-$3842), CAD $11 694 (95% CI, CAD $11 415-CAD $11 973), and $1011 (95% CI, CAD $793-CAD $1230), respectively, totalling CAD $16 290 (95% CI, CAD $15 814-CAD $16 767). The evaluation cost was higher if the intended recipient started dialysis partway through the donor evaluation (CAD $886; 95% CI, CAD $19, CAD $1752). The perioperative cost varied across transplant centers (P < 0.0001)., Conclusions: Although substantial costs of living donor care are related to the nephrectomy procedure, comprehensive assessment of costs must also include the evaluation and follow-up periods. These estimates are informative for planning future work to support and expand living donation and transplantation, and directing efforts to improve the cost efficiency of living donor care.

Background: Preemptive kidney transplants result in better outcomes and patient experiences than transplantation after dialysis onset. It is unknown how often a person initiates maintenance dialysis before living kidney donor transplantation when their donor candidate evaluation is well underway., Methods: Using healthcare databases, we retrospectively studied 478 living donor kidney transplants from 2004 to 2014 across 5 transplant centers in Ontario, Canada, where the recipients were not receiving dialysis when their donor's evaluation was well underway. We also explored some factors associated with a higher likelihood of dialysis initiation before transplant., Results: A total of 167 (35%) of 478 persons with kidney failure initiated dialysis in a median of 9.7 months (25th-75th percentile, 5.4-18.7 months) after their donor candidate began their evaluation and received dialysis for a median of 8.8 months (3.6-16.9 months) before kidney transplantation. The total cohort's dialysis cost was CAD $8.1 million, and 44 (26%) of 167 recipients initiated their dialysis urgently in hospital. The median total donor evaluation time (time from evaluation start to donation) was 10.6 months (6.4-21.6 months) for preemptive transplants and 22.4 months (13.1-38.7 months) for donors whose recipients started dialysis before transplant. Recipients were more likely to start dialysis if their donor was female, nonwhite, lived in a lower-income neighborhood, and if the transplant center received the recipient referral later., Conclusion: One third of persons initiated dialysis before receiving their living kidney donor transplant, despite their donor's evaluation being well underway. Future studies should consider whether some of these events can be prevented by addressing inappropriate delays to improve patient outcomes and reduce healthcare costs.

Background and Objectives: Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices., Design, Setting, Participants, & Measurements: Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically., Results: Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility., Conclusions: Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings., (Copyright © 2018 by the American Society of Nephrology.)

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n =19; 14%) or low-risk (one or zero risk alleles; n =117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m 2 ; P =0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m 2 ; P =0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m 2 per year, P =0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline ( P =0.39) or any statistical interaction by APOL1 status ( P =0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study., (Copyright © 2018 by the American Society of Nephrology.)

Kidney Disease: Improving Global Outcomes (KDIGO) engaged an evidence review team and convened a work group to produce a guideline to evaluate and manage candidates for living kidney donation. The evidence for most guideline recommendations is sparse and many "ungraded" expert consensus recommendations were made to guide the donor candidate evaluation and care before, during, and after donation. The guideline advocates for replacing decisions based on assessments of single risk factors in isolation with a comprehensive approach to risk assessment using the best available evidence. The approach to simultaneous consideration of each candidate's profile of demographic and health characteristics advances a new framework for assessing donor candidate risk and for defensible shared decision making.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.

Living kidney donation provides the best therapeutic outcomes for eligible patients with end-stage renal disease. To ensure suitability for living kidney donation, donor candidates undergo a thorough medical, surgical, and psychosocial evaluation by a multidisciplinary transplant assessment team. Numerous guidelines are available to assist clinicians in the process of donor evaluation and selection. These guidelines outline the minimum recommended requirements for donor screening and additional tests that are indicated when abnormalities arise; however, evidence suggests that some of these additional tests might not be required in certain donor candidates. Measured glomerular filtration rate (GFR) using isotopic methods is more accurate than estimated GFR for the assessment of renal function; however, a new clinical tool might enable the identification of donor candidates for whom nuclear medicine renal scans are not needed. Persistent isolated microscopic haematuria caused by urologic or glomerular diseases can preclude donation and such abnormalities can often be identified by kidney biopsy. Cystoscopy might not be useful for young patients, however, owing to the rarity of urological cancers in this population. Currently, no evidence exists to support the notion that donor candidates at low-risk of cardiac events should undergo additional preoperative cardiovascular evaluation before donation. Reducing and/or eliminating the need for additional testing has the potential to enhance efficiency in the donor evaluation process, improve patient satisfaction, and increase access to living donor kidney transplantation.

Background: Living donor pancreas transplant is a potential treatment for diabetic patients with end-organ complications. Although early surgical risks of donation have been reported, long-term medical outcomes in living pancreas donors are not known., Methods: We integrated national Scientific Registry of Transplant Recipients data (1987-2015) with records from a nationwide pharmacy claims warehouse (2005-2015) to examine prescriptions for diabetes medications and supplies as a measure of postdonation diabetes mellitus. To compare outcomes in controls with baseline good health, we matched living pancreas donors to living kidney donors (1:3) by demographic traits and year of donation., Results: Among 73 pancreas donors in the study period, 45 were identified in the pharmacy database: 62% women, 84% white, and 80% relatives of the recipient. Over a mean postdonation follow-up period of 16.3 years, 26.7% of pancreas donors filled prescriptions for diabetes treatments, compared with 5.9% of kidney donors (odds ratio, 4.13; 95% confidence interval, 1.91-8.93; P = 0.0003). Use of insulin (11.1% vs 0%) and oral agents (20.0% vs 5.9%; odds ratio, 4.50, 95% confidence interval, 2.09-9.68; P = 0.0001) was also higher in pancreas donors., Conclusions: Diabetes is more common after living pancreas donation than after living kidney donation, supporting clinical consequences from reduced endocrine reserve.

Background: For patients with a solitary kidney, such as living kidney donors, the surgical treatment of renal tumors may result in loss of function of the remaining kidney., Methods: We conducted a retrospective, matched cohort study to determine the long-term risk of partial or total nephrectomy in previous living kidney donors compared to healthy nondonors. We reviewed the predonation charts for all living kidney donors in Ontario, Canada between 1992 and 2010 and linked this information to provincial healthcare databases., Results: We matched 2119 donors to 21190 nondonors from the general population with similar baseline health. The median length of follow-up was 9.5 years (maximum 21.7 years). The rate of nephrectomy in follow-up was lower in donors versus nondonors (0 vs. 1.78 per 10000 person years; P = 0.037). In a subset of 1773 donors matched to 1773 healthy nondonors with renal imaging (median follow-up 7.6 years, maximum 21.0 years), the rate of nephrectomy was not statistically different in donors versus nondonors (0 vs. ≤5 per 10000 person years; P > 0.08)., Conclusion: No living kidney donor in our cohort received a partial or total nephrectomy of their remaining kidney during our follow-up period. Although we will continue to follow people in this study, these interim results are reassuring for the safety of kidney donation.

Purpose of Review: Kidney transplantation from a living kidney donor (LKD) is associated with better long-term survival and quality of life for a patient with end-stage renal disease (ESRD) than dialysis. We reviewed recent literature on the acceptability and outcomes of older adults as LKDs, which may be misunderstood in routine care., Recent Findings: Studies report that receiving a kidney from an older LKD is associated with worse recipient and graft survival compared with receiving a kidney from a younger LKD, but similar recipient and graft survival to receiving a kidney from a standard criteria deceased donor. A kidney from a younger vs. older LKD results in better graft survival in younger recipients, whereas the graft survival is similar in older recipients. Compared with healthy matched nondonors, older LKDs have a similar risk of death and cardiovascular disease and the absolute risk of ESRD after 15 years remains less than 1%. The estimated predonation and postdonation lifetime risk of ESRD varies by age, sex and race with lower incidences in individuals who are older, female and white (vs. African-American)., Summary: Donor and recipient outcomes from several studies support the acceptability of older adults as LKDs.

Prescription narcotic use among living kidney donors is not well described. Using a unique database that integrates national registry identifiers for living kidney donors (1987-2007) in the United States with billing claims from a private health insurer (2000-2007), we identified pharmacy fills for prescription narcotic medications in periods 1-4 and >4 yr post-donation and estimated relative likelihoods of post-donation narcotic use by Cox regression. We also compared narcotic fill rates and medication possession ratios (MPRs, defined as (days of medication supplied)/(days observed)), between donors and age- and sex-matched non-donors. Overall, rates of narcotic medication fills were 32.3 and 32.4 per 100 person-years in periods 1-4 and >4 yr post-donation. After age and race adjustment, women were approximately twice as likely as men to fill a narcotic prescription in years 1-4 (adjusted hazard ratio, aHR, 2.28; 95% confidence interval, CI, 1.86-2.79) and >4 yr (aHR 1.70; 95% CI 1.50-1.93). MPRs in donors were low (<2.5% days exposed), and lower than among age- and sex-matched non-donors. Prescription narcotic medication use is more common among women than men in the intermediate term after live kidney donation. Overall, total narcotic exposure is low, and lower than among non-donors from the general population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed., Methods: We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits., Results: Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship., Conclusions: African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.

Living kidney donation benefits recipients and society but carries short-term and long-term risks for the donor. This Review summarizes the studies that underlie our current understanding of these risks in the first decade after donation, with a view to improving the informed consent process. Two studies report a higher risk of end-stage renal disease (ESRD) among donors than among healthy nondonors; however, the absolute 15-year incidence of ESRD is <1%. All-cause mortality and the risk of cardiovascular events are similar among donors and healthy nondonors, although one study provides evidence for a 5% increase in all-cause mortality after 25 years that is attributable to donation. Some evidence suggests that the 20-year incidence of gout is slightly higher among donors than among healthy nondonors. The risks of gestational hypertension or pre-eclampsia seem to be 6% higher in pregnancies among donors than in pregnancies among healthy nondonors. The incidences of acute kidney injury, kidney stones that require surgical intervention, gastrointestinal bleeding and fractures seem no higher among donors than among healthy nondonors, although some of these conclusions are based on a small number of events. Future studies must clarify the lifetime incidence of long-term outcomes, particularly in relation to a donor's age, race, and history of comorbidities.

Background: In the general population, high serum uric acid concentration is a risk factor for gout. It is unknown whether donating a kidney increases a living donor's risk of gout as serum uric acid concentration increases in donors after nephrectomy., Study Design: Retrospective matched cohort study using large health care databases., Setting & Participants: We studied living kidney donors who donated in 1992 to 2010 in Ontario, Canada. Matched nondonors were selected from the healthiest segment of the general population. 1,988 donors and 19,880 matched nondonors were followed up for a median of 8.4 (maximum, 20.8) years., Predictor: Living kidney donor nephrectomy., Outcomes: The primary outcome was time to a diagnosis of gout. The secondary outcome in a subpopulation was receipt of medications typically used to treat gout (allopurinol or colchicine)., Measurements: We assessed the primary outcome with health care diagnostic codes., Results: Donors compared with nondonors were more likely to be given a diagnosis of gout (3.4% vs 2.0%; 3.5 vs 2.1 events/1,000 person-years; HR, 1.6; 95% CI, 1.2-2.1; P<0.001). Similarly, donors compared with nondonors were more likely to receive a prescription for allopurinol or colchicine (3.8% vs 1.3%; OR, 3.2; 95% CI, 1.5-6.7; P=0.002). Results were consistent in multiple additional analyses., Limitations: The primary outcome was assessed using diagnostic codes in health care databases. Laboratory values for serum uric acid and creatinine in follow-up were not available in our data sources., Conclusions: The findings suggest that donating a kidney modestly increases an individual's absolute long-term incidence of gout. This unique observation should be corroborated in future studies., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The demographic and clinical correlates of gout after living kidney donation are not well described., Methods: Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race., Results: The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2)., Conclusion: Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment., (© 2015 S. Karger AG, Basel)

Purpose of Review: Living kidney donation improves the lives of those with kidney failure, but there are potential risks to the donor. We review two recent publications that describe the long-term risk of end-stage renal disease (ESRD) in living kidney donors., Recent Findings: One study reported that the long-term risk (median follow-up 15.1 years) of ESRD was, in relative terms, 11-fold higher in living kidney donors compared to healthy nondonors, and suggested a hereditary association since all affected donors were biologically related to their recipients and the causes were predominantly immunological diseases. In a second study, we estimated that the long-term risk (median follow-up 7.6 years) of ESRD was, in relative terms, eight-fold higher in living kidney donors compared to healthy matched nondonors. In both studies, the absolute increase in the 15-year incidence of ESRD from donation was below 0.5%. There are limitations in these studies, which have raised questions about the accuracy of the estimates of risk., Summary: The results of these studies should be discussed with potential living kidney donors with an emphasis on the low 15-year incidence of ESRD following donation. The lifetime incidence of ESRD for donors of different age, race, and other characteristics requires further study.

Purpose of Review: Living kidney donors may experience changes in bone mineral metabolism, which adversely affect the skeletal system. In this review, we summarize the literature assessing the relationship between living kidney donation, changes in bone mineral metabolism, and skeletal fracture., Recent Findings: Living kidney donor nephrectomy may lower the concentration of 1,25-dihydroxyvitamin D and phosphate and raise the concentration of parathyroid hormone, with no appreciable effect on the concentration of calcium. There is conflicting evidence on whether the concentration of fibroblast growth factor 23 rises after kidney donation. Whether these changes in bone mineral metabolism alter skeletal fracture risk in living kidney donors is an open question. To date, a single study of over 2000 living kidney donors (median age 43 years) matched to a segment of the general population selected for good health has found that after a median follow-up of 6.6 years (maximum 17.7 years), the rate of fragility (osteoporotic) fractures is no higher in donors compared to nondonors., Summary: Living kidney donors experience changes in bone mineral metabolism. Long-term studies are needed to determine whether an association between living kidney donation and fracture exists.

The paper by Mjøen et al. raises important concerns about the long-term consequences of living donation, including a long-term increased risk of end-stage renal disease after an individual undergoes donor nephrectomy. These potential risks need to be communicated to future living kidney donors and should be an impetus for ongoing investigation.

Individuals with moderate-to-severe reduced renal function have greater risk of gastrointestinal bleeding than those with normal renal function. We conducted a retrospective matched cohort study to assess whether living kidney donors share a similar risk. We reviewed pre-donation charts for living kidney donations from 1992 to 2009 in Ontario, Canada, and linked this information to healthcare databases. We selected healthy non-donors from the general population and matched ten non-donors to every donor. Of the 2009 donors and 20,090 matched non-donors, none had evidence of gastrointestinal bleeding prior to cohort entry. The cohort was followed for a median of 8.4 yr (maximum 19.7 yr; loss to follow-up <7%). There was no significant difference in the rate of hospitalization with gastrointestinal bleeding in donors compared to non-donors (18.5 vs. 14.9 events per 10,000 person-years; rate ratio 1.24; 95% confidence interval [CI] 0.85-1.81). Similar results were obtained when we assessed the time to first hospitalization with gastrointestinal bleeding (hazard ratio 1.25, 95% CI 0.87-1.79). In conclusion, we found living kidney donation was not associated with a higher risk of hospitalization with gastrointestinal bleeding. These results are reassuring for the safety of the practice., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Racial disparities in health outcomes after living donation have been reported, but generalizability is not known., Methods: We linked Organ Procurement and Transplantation Network (OPTN) registry data for 4,007 living kidney donors in 1987 to 2008 with Medicare billing claims (2000-2008). Cox regression with left and right censoring was used to estimate the frequencies and relative risks of postdonation medical diagnoses according to race. Patterns were compared with findings from a previous linkage of OPTN donor records and private insurance claims., Results: Among the Medicare-insured donors, 8% were African American and 5.7% were Hispanic. Diagnosis frequencies at 5 years after donation in the Medicare- versus privately insured donors included the following: malignant hypertension, 5.0% versus 0.9%; diabetes, 18.5% versus 4.1%; and chronic kidney disease, 21.8% versus 4.9%. After age and sex adjustment in the Medicare sample, African Americans, as compared with white donors, experienced higher risks of any hypertension diagnosis, including 2.4 times the likelihood of malignant hypertension (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.40-3.93), and more common diabetes (aHR, 1.50; 95% CI, 1.12-2.04), chronic kidney disease (aHR, 1.84; 95% CI, 1.37-2.47), and proteinuria (aHR, 2.44; 95% CI, 1.45-4.11) diagnoses. Relative patterns for privately insured African American versus white donors were similar, including approximately three times the risk of malignant hypertension (aHR, 3.27; 95% CI, 1.82-5.88) and twice the relative risks of chronic kidney disease and proteinuria., Conclusions: Consistent demonstration of racial variation in postdonation medical conditions regardless of sample/payer source supports the need for continued study of mediators and consequences of outcomes in non-white donors.

Background: Use of antihypertensive medications (AHM) after living kidney donation is not well described., Methods: We examined a database wherein national transplant registry data for 4,650 living kidney donors in 1987-2007 were linked to pharmacy claims from a US private health insurer (2000-2007 claims) to identify post-donation AHM fills. Cox regression with left- and right-censoring was used to estimate the frequencies and relative likelihood (adjusted hazards ratios, aHR) of post-donation AHM fills according to donor demographic traits. Medication possession ratio (MPRs), defined as (days of AHM dispensed)/(days observed), were also compared among donors and non-donor general beneficiaries., Results: Overall, 17.8% of the sample filled at least one AHM by 5 years post-donation. As compared with White living donors, African-Americans had 37% higher relative likelihood of any AHM use after donation (aHR 1.37, p < 0.0007), including significantly higher likelihoods of filling diuretics (aHR 2.25, p < 0.0001), ACEi/ARBs (aHR 1.46, p < 0.01), calcium channel blockers (aHR 1.56, p = 0.03), and vasodilators/other agents (aHR 2.17, p = 0.03). MPRs for any AHM and subcategories were lower among donors compared with age- and sex-matched non-donors. However, AHM MPRs rose in donors with multiple hypertension diagnoses, and prescription fill exposure for all AHM classes except diuretics was similar among donors and general non-donors with ≥ 3 hypertension diagnoses., Conclusions: While AHM requirements are lower after kidney donation than among unscreened general persons, racial variation in AHM use occurs in privately insured donors. Demonstration of pharmaceutical care needs of insured donors supports the need for long-term follow-up and healthcare access for all donors., (© 2014 S. Karger AG, Basel.)

Background: Kidney transplants from living donors with an estimated glomerular filtration rate (eGFR) < 80 mL/min per 1.73 m(2) may be at risk for increased graft loss compared with a recipient who receives a kidney from a living donor with a higher eGFR., Methods: This retrospective cohort study considered 2057 living kidney donors and their recipients from July 1993 to March 2010 at five centres in Ontario, Canada, and linked them to population-based, universal healthcare databases. Recipients were divided into five groups based on their donor's baseline eGFR. The median (inter-quartile range) for the lowest eGFR group was 73 (68-77) mL/min per 1.73 m(2). Subjects were followed for a median of 6 years (IQR: 3-10 years)., Results: There was no significant difference in the adjusted hazard ratio (HR) for graft loss when comparing recipients in each eGFR category to the referent group (≥110 mL/min per 1.73 m(2)). The adjusted HRs (95% CI) from the lowest (<80 mL/min per 1.73 m(2)) to highest (100-109.9 mL/min per 1.73 m(2)) eGFR categories were 1.27 (0.84-1.92), 1.43 (0.96-2.14), 1.23 (0.86-1.77) and 1.23 (0.85-1.77), respectively. Similar results were observed when dichotomizing the baseline donor eGFR using a cut-point of 80 mL/min per 1.73 m(2)-adjusted HR 1.01 [95% confidence interval (95% CI) (0.76-1.44)]., Conclusions: Further research in this setting should clarify whether additional tests (i.e. measured GFR) should be performed in potential donors whose eGFR is considered borderline, whether eGFR values should be standardized to body surface area, and the outcomes for donors after nephrectomy.

Background: Reduced kidney function confers a higher risk of acute kidney injury at the time of an inciting event, such as sepsis. Whether the same is true in those with reduced renal mass from living kidney donation is unknown., Methods: We conducted a population-based matched cohort study of all living kidney donors in the province of Ontario, Canada who underwent donor nephrectomy from 1992 to 2009. We manually reviewed the medical records of these living kidney donors and linked this information to provincial health care databases. Non-donors were selected from the healthiest segment of the general population., Results: There were 2027 donors and 20 270 matched non-donors. The median age was 43 years (interquartile range 34-50) and individuals were followed for a median of 6.6 years (maximum 17.7 years). The primary outcome was acute dialysis during any hospital stay. Reasons for hospitalization included infectious diseases, cardiovascular diseases and hematological malignancies. Only one donor received acute dialysis in follow-up (6.5 events per 100 000 person-years), a rate which was statistically no different than 14 non-donors (9.4 events per 100 000 person-years)., Conclusions: These results are reassuring for the practice of living kidney donation. Longer follow-up of this and other donor cohorts will provide more precise estimates about this risk.

Background: Mortality records identify cancer as the leading cause of death among living kidney donors, but information on the burden of cancer outside death records is limited in this population., Methods: We examined a database wherein U.S. Organ Procurement and Transplantation Network identifiers for 4,650 living kidney donors in 1987 to 2007 were linked to administrative data of a U.S. private health insurer (2000-2007 claims) to identify postdonation cancer diagnoses. Skin cancer and non-skin cancer diagnoses were ascertained from International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes on billing claims. Donors were also matched one-to-one with general insurance beneficiaries by sex and age when benefits began. Diagnosis rates within observation windows were compared as rate ratios., Results: The median time from donation to the end of plan insurance enrollment was 7.7 years, with a median observation period of 2.1 years. Skin cancer rates were similar among prior living donors in the observation period and nondonor controls (rate ratio, 0.91; 95% confidence interval [CI], 0.59-1.40). In contrast, the rate of total non-skin cancers was significantly less common among donors than among controls (rate ratio, 0.74; 95% CI, 0.55-0.99), although reduced relative risk was limited to donors captured earlier in relation to donation. Several cases of cancer diagnosis (uterine, melanoma, "other") were identified within the first year after donation. Prostate cancer diagnosis was significantly more common among living donors compared with controls (rate ratio, 3.80; 95% CI, 1.42-10.2)., Conclusions: Continued study of cancer after kidney donation is warranted to ensure that evaluation, selection, and long-term follow-up support overall good health of the donor.

Background: Limited data exist on correlates of psychological outcomes after kidney donation., Methods: We used a database integrating Organ Procurement and Transplantation Network registrations for 4650 living kidney donors from 1987 to 2007 with administrative data of a U.S. private health insurer (2000-2007 claims) to identify depression diagnoses among prior living donors. The burden and demographic correlates of depression after enrollment in the insurance plan were estimated by Cox regression. Graft failure and death of the donor's recipient were examined as time-varying exposures., Results: After start of insurance benefits, the cumulative frequency of depression diagnosis was 4.2% at 1 year and 11.5% at 5 years, and depression among donors was less common than among age- and gender-matched general insurance beneficiaries (rate ratio, 0.70; 95% confidence intervals [CI], 0.60-0.81). Demographic and clinical correlates of increased likelihood of depression diagnoses among the prior donors included female gender, white race, and some perioperative complications. After adjustment for donor demographic factors, recipient death (adjusted hazard ratio (aHR), 2.23; 95% CI, 1.11-4.48) and death-censored graft failure (aHR, 3.30; 95% CI, 1.49-7.34) were associated with two to three times the relative risk of subsequent depression diagnosis among nonspousal unrelated donors. There were trends toward increased depression diagnoses after recipient death and graft failure among spousal donors but no evidence of associations of these recipient events with the likelihood of depression diagnosis among related donors., Conclusions: Recipient death and graft loss predict increased depression risk among unrelated living donors in this privately insured sample. Informed consent and postdonation care should consider the potential impact of recipient outcomes on the psychological health of the donor.

Background: Chronic kidney disease increases the risk of bone fragility fractures (osteoporotic fractures). Living kidney donors lose 50% of their renal mass and show changes in calcium homeostasis. We studied whether living kidney donation increases the risk of fragility fracture., Design: Retrospective matched-cohort study., Setting & Participants: We reviewed the medical charts of all 2,015 adults in Ontario, Canada, who donated a kidney between 1992 and 2009 (surgeries performed across 5 transplant programs). We linked this information to health care databases and randomly selected 20,150 matched nondonors from the healthiest portion of the general population. Median age was 43 (95% CI, 24-50) years at study enrollment. Donors and nondonors were then followed up for a median of 6.6 years and a maximum of 17.7 years., Predictor: Living donor nephrectomy., Outcomes: The primary outcome was lower- and upper-extremity fragility fractures. Individuals who reached 66 years or older in follow-up had bisphosphonate prescriptions recorded., Results: The rate of fragility fracture was no higher in donors compared with nondonors (16.4 vs 18.7 events/10,000 person-years; rate ratio, 0.88; 95% CI, 0.58-1.32). Results were similar in multiple additional analyses. There was little difference in the proportion of older adults in follow-up who received a bisphosphonate prescription (17.1% vs 15.2%; P = 0.4)., Limitations: These are interim results. Ongoing surveillance of this and other donor cohorts is warranted to be sure an association does not manifest with longer follow-up., Conclusions: To date, there is no evidence of increased fragility fracture risk in living kidney donors. Our results meet an information need and are reassuring for the safety of the practice., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR)., Study Design: Cross-sectional study., Setting & Participants: 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m(2))., Predictor: Living kidney donation (mildly decreased eGFR)., Outcomes: Biochemical markers of chronic kidney disease-mineral and bone disorder., Measurements: Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23)., Results: Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10-mL/min/1.73 m(2) decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0-4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF-23 or calcitriol levels., Limitations: Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR., Conclusions: The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease-mineral and bone disorder. Whether these changes influence bone mineral density and fracture rates warrants consideration., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)