Protect\_Child\_101 is an observational study to be performed in children that have undergone a liver or renal transplant.
The aim of this study is to analyse small variations in the genetic material (DNA) of transplanted children. The investigators will also study a type of chemical 'marks' called methylations, which do not change the DNA itself, but can affect how it functions. These marks can influence how certain diseases develop or how the body responds to transplantation.
Specifically, investigators seek to discover:
* Whether there are genetic or epigenetic (methylation) alterations that may explain why some children develop serious diseases that require transplantation. * If these alterations can help us predict possible complications after transplantation, such as organ rejection, infections, organ failure, cancer development.
Within this study, data from the child's medical history will be collected. The data to be collected are demographic data (gender, age, ethnicity), clinical data, personal and family history possibly related to his/her disease, course and evolution of the disease, and complementary and laboratory examinations collected from his/her clinical history.
The only non-routine tests to be performed will be the genomic and methylomic tests. Nevertheless, these determinations will be performed on samples obtained during the child's routine care. No extra intervention is planned as part of this study.
Samples and clinical data will be collected at different time points after transplantation. Schematically, collection is planned for months 0, 1, 3, 6, 12 and 24 post-transplant. In addition to these pre-established points, comprehensive data collection will be attempted when the child suffers a relevant clinical event, e.g. infection, treatment toxicity, organ rejection (post-transplant complication).
● Paediatric patients (6 months to 18 years old) with liver or kidney transplant.
For the retrospective cohort, only patients within the first 5 years after transplantation will be included.
Patients and/or parents agreeing to participate in the study and provide consent for the obtention of clinical data and samples for genomic and methylomic analysis and the use of the information according to the protocol.
Patients that are not being followed up in the clinical site.
Subjects alternating between different clinical sites. Subjects/Tutors that don't understand the informed consent form.
Subject or their legally authorized representative does not sign the informed consent document.
Re-transplantation or AB0-incompatible transplantation.
This study will enroll paediatric patients that have underdone a renal i liver transplant
Cohort
Other
Whole genome sequencing
GeneticWhole genome sequencing (WGS) is an advanced genomic technique that allows for the comprehensive analysis of an individual's entire DNA sequence, including both coding and non-coding regions. In the context of pediatric transplantation, WGS offers a powerful tool for uncovering underlying genetic disorders that may influence transplant eligibility, donor-recipient compatibility, immune response, or risk of post-transplant complications. It enables the identification of rare monogenic diseases, pharmacogenomic markers relevant to immunosuppressive therapy, and potential genetic predispositions to graft rejection or infection. Integrating WGS into transplant evaluation process enhances personalized medicine approaches, contributing to improved long-term outcomes in pediatric transplant recipients.
Polygenic Risk Score Calculation
GeneticA polygenic risk score (PRS) calculation will be performed to quantitatively estimate the an individual's genetic predisposition to the original disease that led to transplantation. These scores are calculated by aggregating the weighted sum of risk alleles-most commonly single nucleotide polymorphisms (SNPs)-each of which contributes a small effect size as determined by genome-wide association studies (GWAS).
Methylome and episignatures
Diagnostic testMethylomic analysis in paediatric transplantation refers to the comprehensive profiling and study of DNA methylation patterns across the genome to understand epigenetic modifications associated with transplant-related outcomes. This epigenetic approach enables the identification of differentially methylated regions (DMRs) that may correlate with clinical phenotypes, such as graft acceptance or rejection, infectious complications, or immune dysregulation. The studies withjin the Protect\_Child\_101 project will be aimed at: 1) Refinement of episignatures, to increase specificity, sensitivity and robustness of those episignatures that already exist and 2) Discovery and validation of new disease, gene or variant specific mDNA signatures.
Epstein Barr Infection
Number of Espstein Barr infections defined as \>3500 copies in PCR in peripheral blood
Cytomegalovirus infection
A) Primary CMV infection after transplant with or without CMV disease (\>1000 copies/ml in peripheral blood in patients with previous negative CMV serology) B) Secondary CMV infection after transplant (any PCR with CMV disease or CMV \>1000 copies/ml in asymptomatic patients)
BK virus infection
Positive BK viremia (define cut-off level) and/or histological evidence of BK nephropathy
Cholangitis
Worsening of liver function tests accompanied by an elevation in inflammatory markers, with or without a positive blood or bile culture.
Liver Primary non-function
Requirement for immediate re-transplantation
Liver Primary non-function
Early death within the first 7 or 14 days following LT after exclusion of other identifiable causes of graft function such as vascular complications, rejection, or infection
Liver Primary non-function
Ocurrence of at least 2 of the following within 7 days post-transplant: * Alanine aminotransferase (ALT) greater than or equal to 2,000 U/L * INR greater than or equal to 10 mg/dl * Acidosis (Defined as one of the following: a) Arterial PH less or equal to 7,30. b) Venous pH less than or equal to 7,25. c) Lactate greater than or equal to 4 mmol/L)
Kidney primary non-function
Persistence of dialysis status or eGFR \<15 ml/min/1.7 m2
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