EXPERIMENTAL AND CLINICAL TRANSPLANTATION

In view of the disparity between the demand and supply of organs, the use of living donor kidney transplant can reduce the number of individuals on waiting lists for deceased donor organs. Living donor kidney transplant can allow elective surgery, shorter hospital stays, and planned desensitization of recipients. To overcome organ shortages, the use of living kidney donations is experiencing a kind of revival in recent years.¹ The safety of living donors comes first. This article presents some important issues, including the risks of kidney donation, comparisons of guidelines for donation, and whether the age of the donor matters as well as whether it is possible to delay aging or to modify graft age.

Risks for Donors

Atelectasis, pneumothorax, pneumonia, urinary tract infection, wound complications, and deep vein thrombosis with or without pulmonary embolism are reported as immediate postoperative risks. Chronic complications include end-stage renal disease (ESRD), hypertension, metabolic bone disease/gout, outcomes in women who are pregnant and the fetuses, malignancy, psychological consequences, and risk shown in certain racial and ethnic groups (African American and Hispanic people).² The risk of surgical mortality with living kidney donation is extremely low. In 1 study of over 80 000 living kidney donors, surgical mortality was 3.1 per 10 000 donors, a rate that has been unchanged over the last 15 years.³ Muzaale and colleagues reported a mortality rate 15 years after donation of 0.47% 18.7 years after donation, and the mean age at ESRD of 64.7 years, with risk increasing with higher age of donor.⁴ According to Ibrahim and colleagues,⁵ in what the investigators later called the “the 99% rule,” 99% of kidney donors will never develop ESRD and 99% do not regret having donated. Patients with hypertension and those with prediabetes can safely donate, and donors with diabetes can also be considered. The investigators suggested making some changes to practices to maintain the absolute highest standard of safety of donation but not at the expense of denying some people who are helping others with their own safety. Every effort should be made to select suitable donors with minimal morbidity for them. Before 2014, there was no evidence of an increased risk of ESRD for living kidney donors compared with the general population. Although the absolute ESRD risk of donors remains lower than in the general population, there appears to be a risk of ESRD attributable to donation. As reported by Claisse and associates,⁶ conventional screening processes should consider all of the variables used to predict ESRD risk separately. The most important variables are donor age, hypertension, body mass index, diabetes, and proteinuria. These variables have been used in different guidelines, including among others the British, Canadian, and KDIGO guidelines. In 2014, the Kidney Donor Risk Index (KDRI) and the Kidney Donor Profile Index (KDPI) replaced the old (marginal/standard) definition of extended criteria donor. According to the KDRI, the relative risk of posttransplant kidney graft failure is compared with the average of all deceased kidney donors of the previous calendar year (eg, 1.5 or 1.7). The KDPI is a percentile of the KDRI. Some European countries, including France, accept donors with high KDPI more than 85% in contrast to the United States. Many organs are discarded in the United States, but there is recent trend to accept higher KDPI according to the American Society of Nephrology 2020 symposium.

Comparison of Guidelines for Donation

Calculators have consolidated the conventional ESRD risk factors into a single risk estimate. According to Claisse and associates,⁶ for ESRD risk evaluation and prediction, the use of tools to predict ESRD is now recommended by guidelines from Kidney Disease Improving Global Outcomes as part of a general strategy in which each center defines an acceptability risk threshold. However, the 2018 British Transplantation Society guidelines do not recommend the use of ESRD risk calculators, mainly because it is not known whether the estimates apply to the UK population.⁷ Part of the difficulty with implementing risk calculators in routine practice stems from the definition of an “acceptable risk threshold.” There is a lack of evidence for selection of an acceptable risk threshold. Definitions of acceptable risk thresholds can differ significantly between centers. The conventional screening process considered all of the variables used to predict ESRD risk separately. In contrast, the calculator consolidates all of the conventional ESRD risk factors into a single risk estimate.

Does Age Matter and Is It Possible to Delay Aging or Modify Graft Age?

Frank Dewhurst, the oldest living kidney donor (84 years old), donated his kidney to his neighbor. Thus, it can be surmised that there is no absolute upper age limit for kidney donation. Previously, donors candidates >50 years of age were often not considered suitable, but donor candidates who are 50 years and older are now commonly accepted. Old age alone is not an absolute contraindication to donation, but the medical work up of older donors must be particularly rigorous to ensure that they are suitable. Although donor glomerular filtration rate is an important determinant of the transplanted kidney function, donor function rather than age may be the most important determinant of outcome.⁶ Age distribution in living kidney donors in Japan has changed over the past decade, with Japan accepting more donors 70 years old or more from 3% to 7% from total donors (as presented by Atsuchi Aikawa and colleagues at the International Symposium on Living and Deceased Donor, May 5 and 6, 2022 in Ankara, Turkey). According to Jackson and colleagues, an older graft is better than no transplant.⁸

Trials to Modify Graft Age

Tullius and Rabb⁹ detected an increased frequency of senescent cells in hearts, kidneys, and skin of old donor mice (mean = 8.21% vs 0.3% in organs from young animals). Young recipients of old grafts also showed augmented systemic p16 levels, indicating a spread of the senescent phenotype (3.45-fold increase; P < .05). Senescent cells have stopped dividing and secrete toxic chemicals that damage adjacent cells. Could senolytic drugs delay aging, as shown in mice given 3 supplements (quercetin, piperlognunmine, and fisetin)? Further studies in humans are yet to be completed.

The risk to kidney donors is low. In comparisons of guidelines for donation, there is no universal practice. Age matters, but there is a global tendency to accept older donors. In the future, senolytics could be used to modify graft age.

Volume: 20 Issue: 8 August 2022 - Supplement - 4

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