Perioperative Considerations Regarding Sex in Solid Organ Transplantation

Walters, Susan M.; Richter, Ellen; Lutzker, Tatiana N.; Patel, Sandhya; Vincent, Anita; Kleiman, Amanda M.

doi:10.1016/j.anclin.2020.01.008

Cited by 6 publications

(3 citation statements)

References 101 publications

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“…41 Little evidence exists for a role of estrogen in liver surgery outcomes, besides the worse outcomes after female-to-male liver transplantation that have been associated with hormonal mismatch. 5,38,42 Intriguingly, however, male sex was reported as an independent risk factor for reduced volumetric liver growth after portal vein embolization, 43 fully consistent with a superior regenerative capacity of female liver.…”

Section: Discussionmentioning

confidence: 82%

“…Although counterintuitive, faster liver regeneration might also relate to a lower HCC incidence in females, because unlike liver growth after tissue loss,39,40 HCC originates from stem cells and indeed may counteract efficient liver regeneration 41. Little evidence exists for a role of estrogen in liver surgery outcomes, besides the worse outcomes after female-to-male liver transplantation that have been associated with hormonal mismatch 5,38,42. Intriguingly, however, male sex was reported as an independent risk factor for reduced volumetric liver growth after portal vein embolization,43 fully consistent with a superior regenerative capacity of female liver.…”

Section: Discussionmentioning

confidence: 99%

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Sex Disparities in Outcomes Following Major Liver Surgery

Birrer

Linecker²,

López-López³

et al. 2022

Annals of Surgery

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Aim: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies. Background: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown. Methods: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t, χ2, or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion. Results: Following major hepatectomy (Hx), males had more severe complications (P=0.03) and higher liver dysfunction (MELD) P=0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126–2.89; P=0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01–3.69; P=0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P=0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism. Conclusions: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen’s benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Sex Disparities in Outcomes Following Major Liver Surgery

Birrer

Linecker²,

López-López³

et al. 2022

Annals of Surgery

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“…Our study showed that a female recipient had an increased baseline of systemic arterial and renal venous D-loop. Several studies have demonstrated that biological sex differences between donor and recipient impacts graft outcome [27][28][29]. In addition, it is known that, in general, women have significantly higher mitochondria-related biomarkers, such as respiration and ATP-content, which has been demonstrated in multiple organs and study models [30,31].…”

Section: Discussionmentioning

confidence: 99%

Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation

Kroneisl,

Spraakman,

Koomen

et al. 2023

IJMS

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During ischemia and reperfusion injury (IRI), mitochondria may release mitochondrial DNA (mtDNA). mtDNA can serve as a propagator of further injury but in specific settings has anti-inflammatory capacities as well. Therefore, the aim of this study was to study the perioperative dynamics of plasma mtDNA during living donor kidney transplantation (LDKT) and its potential as a marker of graft outcome. Fifty-six donor–recipient couples from the Volatile Anesthetic Protection of Renal Transplants-1 (VAPOR-1) trial were included. Systemic venous, systemic arterial, and renal venous samples were taken at multiple timepoints during and after LDKT. Levels of mtDNA genes changed over time and between vascular compartments. Several donor, recipient, and transplantation-related variables significantly explained the course of mtDNA genes over time. mtDNA genes predicted 1-month and 24-month estimated glomerular filtration rate (eGFR) and acute rejection episodes in the two-year follow-up period. To conclude, mtDNA is released in plasma during the process of LDKT, either from the kidney or from the whole body in response to transplantation. While circulating mtDNA levels positively and negatively predict post-transplantation outcomes, the exact mechanisms and difference between mtDNA genes are not yet understood and need further exploration.

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