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Living Donation Forum / Re: COVID-19
« Last post by Clark on June 26, 2020, 09:03:55 AM »
“We thought this was only a respiratory virus. Turns out, it goes after the pancreas. It goes after the heart. It goes after the liver, the brain, the kidney and other organs. We didn’t appreciate that in the beginning,” said Dr. Eric Topol, a cardiologist and director of the Scripps Research Translational Institute in La Jolla, California.

The Living Donor Collective Pilot Evaluations of Living Kidney Donor Candidates at 10 Programs
B. Kasiske, et al.
Meeting: 2020 American Transplant Congress
Abstract number: 355

*Purpose: Much remains to learn regarding long-term effects of living organ donation on donors. Rare events are important, and long-term follow-up with appropriate contemporaneous controls is needed. SRTR, under contract with the Health Resources and Services Administration, is conducting a pilot program to establish a registry of living donor candidates, the Living Donor Collective (LDC).

*Methods: We invited 10 living kidney donor programs to participate in the LDC pilot phase. Donor candidates who come prescreened to the program for evaluation are registered with online or batch upload of data submitted to SRTR. After a maximum of 2 years, donation acceptance or reason(s) for not donating are submitted.

*Results: The first kidney donor candidates registered at the first pilot site in May 2018. By Sept 30, 2019, all 10 pilot LDC sites were operational, with a total of 1553 donor candidates: 1476/1553 (95.0%) completed registration; 785/1476 (53.2%) received a determination; and 385/785 (49.0%) were approved to donate. Across all sites, the median days from donor candidate registration to donation approval or decision not to donate was 132 (Fig. 1), with significant variation by program from a minimum of 85 to a maximum of 235 days, log rank P=0.0001. Of 400 donor candidates who did not donate, the most common donor-related reasons were hypertension, kidney stones, psychosocial stressors, obesity, low kidney function, multiple renal arteries, other unfavorable anatomic reasons, psychiatric illness, substance use disorder, proteinuria, and concern for developing diabetes; 25 (6%) did not donate because the donation became unnecessary for reasons related only to the intended recipient. The latter could serve as optimal controls for long-term follow-up studies.

*Conclusions: We conclude that establishing a registry of living kidney donor candidates is feasible. Reporting the outcomes of donor candidate evaluations to transplant programs, compared with other programs, may help programs better understand their candidate evaluation processes. Long-term follow-up of donors and donor candidates who did not donate may provide much needed information on important outcomes, and may facilitate the donation process in the future.


Recipient Predictors of Post-Donation End Stage Renal Disease in Living Kidney Donors
J. Wainright, et al.
Meeting: 2019 American Transplant Congress
Abstract number: D357

*Purpose: We studied associations between kidney transplant recipient diagnosis and other factors and development of ESRD among related living kidney donors (LKDs).

*Methods: Using OPTN listing and transplant data and CMS dialysis data, we found 198 black or white 1st-degree relative LKDs who donated in the US 1994-2017 and developed ESRD. We used a Cox proportional hazards model to predict risk of ESRD in LKDs.

*Results: Twenty-year post-donation ESRD risk varied by both donor and recipient characteristics. After controlling for donor age, BMI, systolic blood pressure, eGFR, and neighborhood income at donation, we found a significant interaction between recipient diagnosis and donor race. Black donors had a 4-fold higher risk (p<0.001) of developing ESRD than white donors when their recipients had glomerular disease (GN); differences did not reach statistical significance when recipients had diabetes (DM; p=0.17) or hypertension (HTN; p=0.16). Among white LKDs, those whose recipients had HTN-related ESRD were at higher risk for ESRD than those whose recipients had GN (aHR:2.91, 95%CI: 1.71-4.96). Among black LKDs, however, ESRD risk was similar for those whose recipients had HTN vs GN (aHR:1.05, 95%CI: 0.62-1.8), but lower for those whose recipients had DM vs GN (aHR:0.50, p=0.09). Other recipient factors were not significant predictors of risk. Absolute risk varied greatly by donor race, sex, donation age, and recipient diagnosis.

*Conclusions: These new findings clarify variation in risk among different groups of LKDs and suggest that risk estimates from past research may not entirely capture ESRD risk from diagnoses that take several decades to develop.

ESRD Risk Prediction for Black vs. White Related Living Kidney Donors
J. Wainright, et al.
Meeting: 2020 American Transplant Congress
Abstract number: C-077

*Purpose: We studied 25-year risk of post-donation ESRD in black (n=10,214) and white (n=45,700) first-degree related living kidney donors (RLKDs) who donated in the US during 1994-2018, ascertaining ESRD with OPTN and CMS data.

*Methods: We ran separate multivariable Cox regression models by race and found the effects of donor factors on risk of ESRD varied across race.

*Results: Eighty three black and 115 white first-degree RLKDs developed ESRD through 12/31/18 (Table 1). White RLKDs had increased risk of ESRD if they were older, male, or had higher pre-donation BMI or systolic blood pressure (Figure 1). Black RLKDs were at increased ESRD risk if they had higher BP or lower eGFR; effects for BMI and sex among black RLKDs were directionally consistent with white donors, but not statistically significant. Older age was associated with lower risk for black RLKDs. Contrary to previous findings, donor age – which we allowed to be non-linear – was not associated with ESRD risk for donors younger than the median age in either group, suggesting previous findings were driven by assuming linearity (Figure 2). The relative importance of donor characteristics varied between the two groups: all studied donor factors were associated with ESRD risk for white RLKDs; for black RLKDs, age, BP, and eGFR were stronger predictors of post-donation ESRD than donor sex or BMI – likely because of ApoL1-related risk.

*Conclusions: Previous research revealed a race by age interaction for ESRD risk. This study provides a refined understanding of this interaction effect, while also suggesting the possibility of two new interactions – race by sex and race by BMI – that warrant further study.


Recipient and Donor Factors Associated with Post-Donation ESRD in Related White Living Kidney Donors
J. Wainright, et al.
Meeting: 2020 American Transplant Congress
Abstract number: 356

*Purpose: We studied post-donation ESRD in white first-degree related living kidney donors (RLKDs) in the US between 1994 and 2018 (n=45700); this study is the first of its kind to adjust for recipient factors.

*Methods: We ascertained ESRD with OPTN and CMS data and found 115 white first-degree RLKDs developed ESRD through December 2018 (Table 1). There were too few cases in other ethnic groups for these analyses.

*Results: We ran a multivariable Cox proportional hazards regression model and found white RLKDs had increased risk of ESRD if they were male or had higher BMI or higher systolic blood pressure (Figure 1); these findings align with previous studies. However, we also found the first evidence of a recipient factor predicting donor ESRD: an interaction between donor age at donation (yrs older than median donor age) and the related recipient’s age at first onset of ESRD. Among white RLKDs, older donor age was associated with higher risk if the related recipient first developed ESRD at an older age (e.g., at age 55, aHR:1.73, 95% CI:1.23-2.44, p=0.002; Figure 2b), but older donor age was not associated with higher risk if the related recipient developed ESRD at a younger age (e.g., at age 20, aHR:1.09, 95% CI: 0.68-1.73, p=0.71; Figure 2a).

*Conclusions: These findings further inform potential donor risk assessment and illustrate the importance of including relevant family factors in the evaluation and consent of potential RLKDs.
Living Donation in the News / Quantifying Sex-Based Disparities in Liver Allocation
« Last post by Clark on June 11, 2020, 11:37:36 AM »

Quantifying Sex-Based Disparities in Liver Allocation
Jayme E. Locke, et al.
JAMA Surg. Published online May 20, 2020. doi:10.1001/jamasurg.2020.1129

Key Points
Question  What proportion of sex-based disparities in liver allocation is associated with geographic location, candidate anthropometric and liver measurements, or Model for End-stage Liver Disease score?

Findings  In this cohort study of 81 357 participants, women were 8.6% more likely to die while waiting for a liver transplant and were 14.4% less likely to receive a deceased donor liver transplant compared with men. Candidate anthropometric and liver measurements and creatinine level had stronger associations than geographic location with sex disparities in wait list mortality and the likelihood of deceased donor liver transplant.

Meaning  The findings suggest that mitigating sex-based disparities in liver allocation may require a comprehensive approach that extends beyond geographic factors currently being considered in the transplant community.

Importance  Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score–based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics.

Objective  To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics.

Design, Setting, and Participants  This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018.

Exposure  Liver transplant waiting list.

Main Outcomes and Measures  Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements.

Results  Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women).

Conclusions and Relevance  Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.

New Jersey man pleads for kidney transplant after donor changes mind
Wednesday, June 10, 2020 8:08PM

A man from New Jersey who was set to receive a kidney transplant is pleading for help after his donor had a change of heart due to COVID-19 concerns.

Earlier this year, doctors did find a match, and surgery was scheduled for right after Easter. But when COVID-19 hit, everything was put on hold because it was considered elective surgery.

Surgery was rescheduled for early July, but then came another blow. The donor changed their mind, feeling that because of the circumstances in the world right now, they couldn't go through with it.

[/size]Donor-Recipient Relationship and Risk of ESKD in Live Kidney Donors of Varied Racial Groups, Abimereki D. Muzaale, et al., AJKD,  AJKD, Nov. 12, 2019, https://doi.org/10.1053/j.ajkd.2019.08.020
[/size]Rationale & Objective
[/size]Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines.[/size]Study Design
[/size]Retrospective cohort study.[/size]Setting & Participants
[/size]A cohort of 143,750 US kidney donors between 1987 and 2017.[/size]Exposure
[/size]Biological relationship of donor and recipient.[/size]Outcome
[/size]ESKD. Donors’ records were linked to national dialysis and transplantation registries to ascertain development of the outcome.[/size]Analytic Approach
[/size]Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used.[/size]Results
[/size]Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6).[/size]Limitations
[/size]Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients.[/size]Conclusions
[/size]Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.

https://www.kidney-international.org/article/S0085-2538(20)30427-0/fulltext[/size]Changes in kidney function follow living donor nephrectomy, DOI: https://doi.org/10.1016/j.kint.2020.03.034
[/size]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 m2. Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 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 m2 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 m2 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.

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