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Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation.

ABSTRACT: Background:We aimed to examine whether combined donor/recipient variants in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes may affect outcomes in renal transplantation. Methods:A total of 233 donors and their corresponding 307 recipients were genotyped for LEPR rs1805094, rs1137100 and rs1137101, and ADIPOQ rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF), graft loss and estimated glomerular filtration rate (eGFR). Results:Recipients whose donors carried variant alleles of LEPR rs1137100 and rs1137101 had lower risk of DGF [OR = 0.48 (0.24-0.97), p = 0.040] and [OR = 0.47 (0.23-0.95), p = 0.035], respectively. In addition, rs1137101 also showed an inverse association with lower incidence of graft loss [OR = 0.44 (0.31-0.97), p = 0.040]. The analysis of genetic scores of donor/recipients showed that again rs1137101 was inversely associated with both outcomes: OR = 0.46 (0.23-0.92), p = 0.029 and OR = 0.45 (0.11-0.81), p = 0.009, respectively. With regard to graft function, the T-allele of ADIPOQ rs1501299 in the donor was related to higher eGFR values (75.26 ± 29.01 vs. 67.34 ± 25.39 ml/min for wild-type grafts, p = 0.012). Higher combined genetic scores in this same polymorphism were also associated with better function (78.33 ± 31.87 vs. 68.25 ± 24.32 ml/min, p = 0.018). Finally, eGFR values were similar between paired kidneys but they were different when comparing grafts with or without the rs1501299 T-variant (77.87 ± 26.50 vs. 69.27 ± 26.73 ml/min, p = 0.016). Conclusions:Our study has shown for the first time to our knowledge that variants in LEPR and ADIPOQ genes of the donors and/or their combination with those in the recipients may affect the outcome of renal transplantation.

SUBMITTER: Mota-Zamorano S

PROVIDER: S-EPMC7498839 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation.

Mota-Zamorano Sonia S Luna Enrique E Garcia-Pino Guadalupe G González Luz M LM Gervasini Guillermo G

Molecular genetics and metabolism reports 20200912

<h4>Background</h4>We aimed to examine whether combined donor/recipient variants in the leptin receptor (<i>LEPR</i>) and adiponectin (<i>ADIPOQ</i>) genes may affect outcomes in renal transplantation.<h4>Methods</h4>A total of 233 donors and their corresponding 307 recipients were genotyped for <i>LEPR</i> rs1805094, rs1137100 and rs1137101, and <i>ADIPOQ</i> rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF ...[more]

PMID: 32983895

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Project description:BackgroundPrior studies have assessed the impact of the pretransplantation recipient body mass index (BMI) on patient outcomes after lung transplantation (LT), but they have not specifically addressed early postoperative complications. Moreover, the impact of donor BMI on these complications has not been evaluated. The first aim of this study was to assess complications during hospitalization in the ICU after LT according to donor and recipient pretransplantation BMI.MethodsAll the recipients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and August 2022 were included in this observational retrospective monocentric study. Postoperative complications were analyzed according to recipient and donor BMIs. Univariate and multivariate analyses were also performed. The 90-day and one-year survival rates were studied. P < 0.05 was considered to indicate statistical significance. The Paris-North Hospitals Institutional Review Board approved the study.ResultsA total of 304 recipients were analyzed. Being underweight was observed in 41 (13%) recipients, a normal weight in 130 (43%) recipients, and being overweight/obese in 133 (44%) recipients. ECMO support during surgery was significantly more common in the overweight/obese group (p = 0.021), as were respiratory complications (primary graft dysfunction (PGD) (p = 0.006), grade 3 PDG (p = 0.018), neuroblocking agent administration (p = 0.008), prone positioning (p = 0.007)), and KDIGO 3 acute kidney injury (p = 0.036). However, pretransplantation overweight/obese status was not an independent risk factor for 90-day mortality. An overweight or obese donor was associated with a decreased PaO2/FiO2 ratio before organ donation (p < 0.001), without affecting morbidity or mortality after LT.ConclusionPretransplantation overweight/obesity in recipients is strongly associated with respiratory and renal complications during hospitalization in the ICU after LT.

Project description:ObjectiveDonor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant.MethodsDonor and recipient data were abstracted from the Organ Procurement and Transplantation Network database updated through June 30, 2014, which included 86,398 potential donors and 16,255 transplants. Using the United Network for Organ Sharing 4-level designation of transfusion (no blood, 1-5 units, 6-10 units, and >10 units, massive), we analyzed all-cause mortality at 30-days with the use of logistic regression adjusted for confounders (ischemic time, donor age, recipient diagnosis, lung allocation score and recipient age, and recipient body mass index). Secondary analyses assessed 90-day and 1-year mortality and hospital length of stay.ResultsOf the 16,255 recipients transplanted, 8835 (54.35%) donors received at least one transfusion. Among those transfused, 1016 (6.25%) received a massive transfusion, defined as >10 units. Those donors with massive transfusion were most commonly young trauma patients. After adjustment for confounding variables, donor massive transfusion was associated significantly with an increased risk in 30-day (P = .03) and 90-day recipient mortality (P = .01) but not 1-year mortality (P = .09). There was no significant difference in recipient length of stay or hospital-free days with respect to donor transfusion.ConclusionsMassive donor blood transfusion (>10 units) was associated with early recipient mortality after lung transplantation. Conversely, submassive donor transfusion was not associated with increased recipient mortality. The mechanism of increased early mortality in recipients of lungs from massively transfused donors is unclear and needs further study but is consistent with excess mortality seen with primary graft dysfunction in the first 90 days posttransplant.

Project description:Although the role of adiponectin and leptin in the etiology of metabolic syndrome (MetS) has been explored in various populations, limited knowledge is available on the prospective association of adiponectin and leptin with the risk of MetS development. The present study aimed to evaluate the associations of adiponectin, leptin, and the leptin-adiponectin (LA) ratio with the future risk of MetS in middle-aged and older Korean adults. Using a prospective, population-based Ansan-Ansung cohort of the Korean Genome and Epidemiology Study (KoGES), 2691 Korean adults (1317 men and 1374 women) were included in the present study. Serum adiponectin and leptin concentrations were measured using commonly available enzyme-linked immunosorbent assay kits. Multivariable Cox proportional hazard models were used to investigate the relationships of the different adiponectin and leptin concentrations and LA ratio with the incident MetS. During a mean follow-up of 6.75 years, a total of 359 (27.26%) men and 385 (28.02%) women were identified as developing new-onset MetS. After controlling for covariates, higher adiponectin levels were associated with lower incidence of MetS (hazard ratio (HR) for third vs. first tertile: 0.53, 95% confidence interval (CI): 0.40-0.70 for men and HR: 0.54, 95% CI: 0.42-0.71 for women), while higher leptin levels (HR for third vs. first tertile: 2.88, 95% CI: 2.01-4.13 for men and HR: 1.55, 95% CI: 1.13-2.13 for women) and LA ratio (HR for third vs. first tertile: 3.07, 95% CI: 2.13-4.44 for men and HR: 1.94, 95% CI: 1.41-2.66 for women) were associated with an increased incidence of MetS. Among men, in the fully adjusted models an increase by one standard deviation (SD) in adiponectin levels was associated with a 10% decrease in MetS risk (HR per SD: 0.90, 95% CI: 0.85-0.95) while leptin and LA ratio was associated with a 5% (HR per SD: 1.05, 95% CI: 1.01-1.08) and 40% (HR per SD: 1.40, 95% CI: 1.22-1.62) increase in MetS risk, respectively. Among women, a significant association with MetS risk was observed only in adiponectin levels (HR per SD: 0.91, 95% CI: 0.88-0.95). We found that higher adiponectin level was associated with a lower risk of MetS, while higher leptin level and LA ratio were associated with elevated MetS incidence, irrespective of body mass index at baseline in both Korean men and women. Adiponectin and leptin levels and LA ratio could play a role as a useful biomarker in the prediction of future MetS development among middle-aged and older Koreans.

Dataset Information

Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation.

Publications

Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation.

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