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Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients.

ABSTRACT: Aim: Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients. Methods: A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis. Results: The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35-7.85), p?=?0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95?±?4.23) than non-carriers (25.67?±?4.43, p?=?0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p?>?0.00001). Haplotype analyses did not reveal significant associations. Conclusions: Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients. KEY MESSAGES The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients. The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient. The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.

SUBMITTER: Mota-Zamorano S

PROVIDER: S-EPMC7857488 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:Background and Objectives: Kidney transplant recipients represent a unique population with metabolic abnormalities, altered nutritional and immune status, as well as an imbalanced regulation of adipocytokine metabolism. Leptin is a hormonally active protein mainly produced by fat tissue that modulates appetite, satiety, and influences growth, energy, and bone metabolism. There has been great interest in the role of this hormone in chronic kidney disease-related protein energy wasting; thus, a positive leptin correlation with body mass index and fat mass was confirmed. This study was designed to determine the association of pre and post-kidney transplant leptin concentration with nutritional status and body composition. Materials and Methods: We studied 65 kidney transplant recipients. Nutritional status was evaluated before kidney transplantation and 6 months later using three different malnutrition screening tools (Subjective Global Assessment Scale (SGA), Malnutrition Inflammation Score (MIS), and Geriatric Nutritional Risk Index (GNRI)), anthropometric measurements, and body composition (bioelectrical impedance analysis (BIA)). Demographic profile, serum leptin levels, and other biochemical nutritional markers were collected. Statistical analysis was performed with R software. Results: Median age of the studied patients was 45 years, 42% were females, and 12% had diabetes. Leptin change was associated with body weight (p < 0.001), waist circumference (p < 0.001), fat mass (p < 0.001) and body fat percentage (p < 0.001), decrease in parathyroid hormone (PTH) (p < 0.001) transferrin (p < 0.001), diabetes mellitus (p = 0.010), and residual renal function (p = 0.039), but not dependent on dialysis vintage, estimated glomerular filtration rate (eGFR), or delayed graft function at any time during the study. After adjustment for age and sex, body mass index (BMI) (p < 0.001), fat mass (p < 0.001), and body fat percentage (p < 0.001) were independent variables significantly associated with post-transplant leptin change. Lower leptin values were found both before and after kidney transplantation in the SGA B group. GNRI as a nutritional status tool was strongly positively related to changes in leptin within the 6-month follow-up period. Conclusions: Kidney transplant recipients experience change in leptin concentration mainly due to an increase in fat mass and loss of muscle mass. GNRI score as compared to SGA or MIS score identifies patients in whom leptin concentration is increasing alongside an accumulation of fat and decreasing muscle mass. Leptin concentration evaluation in combination with BIA, handgrip strength measurement, and GNRI assessment are tools of importance in defining nutrition status in the early post-kidney transplant period.

Project description:ImportanceMelanoma risk factors and incidence in renal transplant recipients can inform decision making for both patients and clinicians.ObjectiveTo determine risk factors and characteristics of renal transplant recipients who develop melanoma.Design, setting, and participantsThis cohort study of a large national data registry used a cohort of renal transplant recipients from the United States Renal Data System (USRDS) database from the years 2004 through 2012. Differences in baseline characteristics between those who did and did not develop melanoma were examined, and a survival analysis was performed. Patients with renal transplants who received a diagnosis of melanoma according to any inpatient or outpatient claim associated with a billing code for melanoma were included. A history of pretransplant melanoma, previous kidney transplantation, or transplantation after 2012 or before 2004 were exclusion criteria. The data analysis was conducted from 2015 to 2016.ExposureReceipt of a renal transplant.Main outcomes and measuresIncidence and risk factors for melanoma.ResultsOf 105?174 patients (64?151 [60.7%] male; mean [SD] age, 49.6 [15.3] years) who received kidney transplants between 2004 and 2012, 488 (0.4%) had a record of melanoma after transplantation. Significant risk factors for developing melanoma vs not developing melanoma included older age among recipients (mean [SD] age, 60.5 [10.2] vs 49.7 [15.3] years; P?<?.001) and donors (42.6 [15.0] vs 39.2 [15.1] years; P?<?.001), male sex (71.5% vs 60.7%; P?<?.001), recipient (96.1% vs 66.5%; P?<?.001) and donor (92.4% vs 82.9%; P?<?.001) white race, less than 4 HLA mismatches (44.9% vs 37.1%; P?=?.001), living donors (44.7% vs 33.7%; P?<?.001), and sirolimus (22.3% vs 13.2%; P?<?.001) and cyclosporine (4.9% vs 3.2%; P?=?.04) therapy. Risk factors significant on survival analysis included older recipient age (hazard ratio [HR] per year, 1.06; 95% CI, 1.05-1.06; P?<?.001), recipient male sex (HR, 1.53; 95% CI, 1.25-1.88; P?<?.001), recipient white race, living donors (HR, 1.35; 95% CI, 1.11-1.64; P?=?.002), and sirolimus (HR, 1.54; 95% CI, 1.22-1.94; P?<?.001) and cyclosporine (HR, 1.93; 95% CI, 1.24-2.99; P = .004) therapy. The age-standardized relative rate of melanoma in USRDS patients compared with Surveillance, Epidemiology, and End Results patients across all years was 4.9. A Kaplan-Meier estimate of the median time to melanoma among those patients who did develop melanoma was 1.45 years (95% CI, 1.31-1.70 years).Conclusions and relevanceRenal transplant recipients had greater risk of developing melanoma than the general population. We believe that the risk factors we identified can guide clinicians in providing adequate care for patients in this vulnerable group.

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Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients.

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