Concepts of Genomics in Kidney Transplantation

AbstractPurpose of ReviewIdentification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes.Recent FindingsMany studies have yet to exhibit robust and reproducible results; however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters, and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant. Genome wide association study data for the immunosuppressant tacrolimus have identified multiple variants in theCYP3A5 gene associated with trough concentrations. Additionally,APOL1 variants had been shown to confer risk to the development of end stage renal disease in African Americans.SummaryThe field is rapidly evolving and new technology such as next-generation sequencing, along with larger cohorts, will soon be commonly applied in transplantation to understand genetic association with outcomes and personalized medicine.
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients. Specifically, genetics can provide insight into the primary cause of chronic kidney disease (CKD), the risk of progression to ESRD, and post-transplant out...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This article provides an overview of current findings published in the recent five years regarding the relationship between tacrolimus exposure and variation therein and the development of dnDSA.Expert opinion: In this review we describe how combining data on tacrolimus intra-patient variability and mean pre-dose concentration may be an effective tool to identify kidney transplant recipients who are at higher risk of developing dnDSA. PMID: 31721605 [PubMed - as supplied by publisher]
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
nte S, Gil-Izquierdo Á Abstract Oxylipins such as isoprostanes (IsoPs), prostaglandins (PGs) and thromboxanes (TXs) are lipid mediators derived from the oxidation of polyunsaturated fatty acids, which regulate the magnitude of oxidative stress and inflammation processes and play an important role in pathophysiological processes in the kidney. A total of 36 oxylipins were analyzed by UHPLC-QqQ-MS/MS in the urine of 41 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca during the first six months after renal transplantation, in order to investigate s...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
Abstract Objective: To identify the oral lesions of individuals with kidney disease immediately before and shortly after kidney transplantation, taking into account the immunosuppressive regimen, antiviral prophylaxis and type of transplantation.Methods: A prospective observational cohort study was carried from January 2017 to January 2018. Eighty individuals aged 18 years or older who were admitted for kidney transplantation were eligible to participate. Clinical data regarding medical history, immunosuppressive therapy, antiviral prophylaxis, laboratorial data and oral examination were performed by the sa...
Source: Acta Odontologica Scandinavica - Category: Dentistry Authors: Tags: Acta Odontol Scand Source Type: research
Conclusion Inguinal herniation of the transplant ureter leading to ureteral obstruction is a rare, probably underreported, cause graft of dysfunction. Therefore, we advocate elective repair of inguinal or incisional hernias in renal transplant recipients. PMID: 31690216 [PubMed - as supplied by publisher]
Source: Acta Chirurgica Belgica - Category: Surgery Tags: Acta Chir Belg Source Type: research
CONCLUSION: Although LC-MS provides a more accurate representation of the blood concentration of the parent compound tacrolimus exclusive of metabolite, established cut points for tacrolimus dosing may need to be adjusted to account for the increased risk of renal injury. PMID: 31696925 [PubMed - as supplied by publisher]
Source: American Journal of Health-System Pharmacy : AJHP - Category: Drugs & Pharmacology Authors: Tags: Am J Health Syst Pharm Source Type: research
ConclusionsSeveral programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.
Source: Clinical and Experimental Nephrology - Category: Urology & Nephrology Source Type: research
Conclusion: This study shows that donor pretreatment with anti-FB preserved renal function, reduced renal damage and inflammation prior to transplantation. Therefore, inhibition of factor B in organ donors might be a promising strategy to reduce brain death-induced renal injury and inflammation.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Cognitive impairment in kidney transplantation (KTx) patients is associated with allograft survival and mortality. However, the prevalence of cognitive impairment after KTx is still understudied. Thus, we aimed to assess the prevalence of cognitive impairment in KTx patients and to identify sociodemographic, medical, donation-specific, and psychological variables associated with cognitive impairment. In this cross-sectional two-center study, 583 KTx patients participated in a structured post-transplant care program. The DemTect was used to assess cognition, and cognitive impairment was defined as a score of 30 kg/m2). Usin...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoir...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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