Ann Young

Cardiovascular disease in kidney donors: matched cohort study

Objective To determine whether people who donate a kidney have an increased risk of cardiovascular disease. Design Retrospective population based matched cohort study. Participants All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20 280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). Main outcome measures The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. Results The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. Conclusions The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

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 ≥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.

Recipient Outcomes for Expanded Criteria Living Kidney Donors: The Disconnect Between Current Evidence and Practice

Older individuals or those with medical complexities are undergoing living donor nephrectomy more than ever before. Transplant outcomes for recipients of kidneys from these living expanded criteria donors are largely uncertain. We systematically reviewed studies from 1980 to June 2008 that described transplant outcomes for recipients of kidneys from expanded criteria living donors. Results were organized by the following criteria: older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria and hematuria. Pairs of reviewers independently evaluated each citation and abstracted data on study and donor characteristics, recipient survival, graft survival, serum creatinine and GFR. Transplant outcomes for recipients of kidneys from older donors (≥60 years) were described in 31 studies. Recipients of kidneys from older donors had poorer 5‐year patient and graft survival than recipients of kidneys from younger donors [meta‐analysis of 12 studies, 72% vs. 80%, unadjusted relative risk (RR) of survival 0.89, 95% confidence interval (CI) 0.83–0.95]. In meta‐regression, this association diminished over time (1980s RR 0.79, 95% CI 0.65–0.96 vs. 1990s RR 0.91, 95% CI 0.85–0.99). Few transplant outcomes were described for other expanded criteria. This disconnect between donor selection and a lack of knowledge of recipient outcomes should give transplant decision‐makers pause and sets an agenda for future research.

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.

Bone and Mineral Metabolism and Fibroblast Growth Factor 23 Levels After Kidney Donation

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.

Fracture Risk in Living Kidney Donors: A Matched Cohort Study

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.

Informing the Debate: Rates of Kidney Transplantation in Nations With Presumed Consent

BACKGROUND The kidney is the most common transplanted organ, accounting for almost all living donor transplantations and most deceased donor organ transplantations. The organ shortage has caused policymakers in many nations to debate the merits of adopting presumed consent legislation as a way to increase donor organ donation from deceased donors. OBJECTIVE To compare characteristics and kidney transplantation rates for countries with presumed consent for deceased organ donation with countries with explicit consent. DESIGN A longitudinal study of international kidney transplantation from 1997 to 2007. SETTING 44 nations performing kidney transplantation. PATIENTS Recipients of deceased and living kidney donor transplants. MEASUREMENTS Rates of transplantation of kidneys from deceased and living donors. RESULTS National characteristics, such as population size, proportion of the population self-identified as Catholic, per capita gross domestic product, health expenditures, and physician density, varied widely for the 22 nations with presumed consent and the 22 nations with explicit consent. Deceased donor kidney transplantation rates were higher in nations with presumed consent (median, 22.6 transplantations per million population [pmp]; interquartile range [IQR], 9.3 to 33.8) versus nations with explicit consent (median, 13.9 transplantations pmp; IQR, 3.6 to 23.1). Living donor kidney transplantation rates were lower in nations with presumed consent (median, 2.4 transplantations pmp; IQR, 1.7 to 4.3) versus nations with explicit consent (median, 5.9 transplantations pmp; IQR, 2.3 to 12.2). The findings were consistent when nations were classified according to per capita gross domestic product, health expenditures, and physician density. LIMITATION As with any observational study, associations may not be causal. CONCLUSION Nations with presumed consent have higher rates of deceased donor kidney transplantation than nations with explicit consent. Any nation deciding to adopt presumed consent should carefully consider and reduce any negative effect on rates of living donation. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research and Lawson Health Research Institute.

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.

Acute dialysis risk in living kidney donors

It is crucial to carefully screen donors and essential to resist compromises. If this is respected the survival, the co-morbidity, ESRD or even acute renal failure, as shown by Lam et al. in the current issue of this journal, appear to be similar to those in the general population.

Long-term medical outcomes among Aboriginal living kidney donors.

Background. It is unknown whether favorable long-term data on the safety of living kidney donation can be extrapolated to populations at higher risk of chronic kidney disease. Indigenous people (i.e., Aboriginals) have a high prevalence of risk factors for chronic kidney disease and Aboriginal living donor outcomes need to be defined. Methods. We performed a retrospective cohort study of all 38 Aboriginal donors donating at our center since 1970 and 76 randomly selected white donor controls to determine the long-term rates of hypertension, diabetes, and renal function postdonation. Results. Follow-up was obtained for 91% of both Aboriginal and white donors (mean follow-up∼14 years). Hypertension has been diagnosed more frequently among Aboriginal donors (Ab 42% vs. white 19%, P=0.02). Notably, all 11 Aboriginal donors more than 20 years postdonation have developed hypertension. Diabetes has also been diagnosed more frequently among Aboriginal donors (Ab 19% vs. white 2%, P=0.005), including 5 of 11 (45%) more than 20 years postdonation. Follow-up estimated glomerular filtration rate was higher in Aboriginal donors (Ab 77±17 vs. white 67±13 mL/min/1.73 m2, P=0.002) but not significantly different in adjusted analyses. One Aboriginal donor developed end-stage renal disease 14 years postdonation. Conclusions. Aboriginal living kidney donors at our center have high rates of hypertension and diabetes on long-term follow-up, although renal function is preserved to date. This profile is similar to that of the general unselected Aboriginal population despite detailed medical evaluation before donation. These findings have important implications for donor counseling and may have implications for other high-risk donor populations.