Ignite Creation Date:
2024-05-06 @ 7:44 PM
Last Modification Date:
2024-10-26 @ 3:12 PM
Study NCT ID:
NCT06116721
Status:
RECRUITING
Last Update Posted:
2024-02-28
First Post:
2023-10-31
Brief Title:
Evaluation of APOL1 Gene Variants in Kidney Donors and Their Impact on Long-term Renal Function in Donors and Recipients
Sponsor:
Hospital do Rim e Hipertensão
Organization:
Hospital do Rim e Hipertensão
Study Overview
Official Title:
Evaluation of the Frequency of APOL1 Gene Variants in Kidney Donors and the Impact of These Variants on the Long-term Renal Function of Kidney Transplant Donors and Recipients
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Evaluation of the frequency of APOL1 gene variants in kidney donors and the impact of these variants on the long-term renal function of kidney transplant donors and recipients
Detailed Description:
Introduction Chronic kidney disease CKD is a worldwide public health problem and kidney transplantation when indicated is the treatment of choice for CKD Kidney transplant survival at the end of the first year is greater than 95 however there has not been a corresponding improvement in long-term kidney graft survival outcomes Factors such as acute or chronic rejection bacterial or viral infections de novo or recurrent glomerulopathies are associated with worsening kidney function in the long term Genetic variants of the Apolipoprotein L1 APOL1 gene present in individuals with African ancestry AF may also interfere with transplant results In the general population individuals with SCA have a higher risk of CKD and one of the most accepted hypotheses is that the APOL1 gene is associated with CKD Genetic variants G1 and G2 are exclusive to individuals with SCA and confer a higher risk of CKD In the transplant population kidneys from deceased donors of African ancestry AF with genetic variants of the APOL1 gene have worse renal graft survival Recipients with the genetic variants regardless of donor genotype are at increased risk of rejection and graft loss by immune-mediated mechanisms that damage the kidney through activation of T and NK cells In Brazil more than 5000 transplants are performed per year and it is one of the countries outside Africa with the highest number of Afro-descendants a high rate of miscegenation and a high prevalence of African ancestry Despite this there are no studies on the frequency of APOL1 gene variants in this population as well as their impact on the clinical evolution of kidney transplantation General objective To evaluate the association between APOL1 gene risk variants and long-term renal function in living donors and their respective recipients Specific objectives i - To measure the prevalence of APOL1 gene variants in the population of living kidney donors ii - Evaluate the impact of the presence of APOL1 gene risk variants in living kidney donors on renal graft survival in their respective recipients iii- To verify the impact of the presence of risk variants of the APOL1 gene on the long-term renal function of living kidney donors after nephrectomy for donation Methodology Evaluation of recipients longitudinal observational retrospective cohort study Adult kidney transplant recipients from a living donor will be included who have undergone the transplant at the Hospital do Rim in the period between January 1 2008 and March 31 2015 and who remained alive and with a functioning graft one year after the transplant The observation period will be until March 2020 five years The following will be excluded recipients who have previously undergone transplantation of other organs and recipients who were transferred for follow-up in other centers before 12 months of follow-up after the transplant was performed Donor evaluation cross-sectional cohort study in donors who donated a kidney in the period between January 1 2008 and March 31 2015 The prevalence of APOL1 gene variants in this population will be determined and clinical information will be evaluated of the donors from the date of the nephrectomy until the moment of collection of the exams In the period covered 2152 transplants were performed with a living donor It is estimated that the prevalence of APOL1 gene variants is between 8 and 13 including populations with chronic kidney disease and who underwent kidney transplantation To calculate the sample number it will be assumed by hypothesis to find a difference of 10 mlmin173m2 in the mean Estimated Glomerular Filtration Rate eGFR at the end of 5 years between recipients of kidneys from donors who present some risk mutation recessive model compared with those who do not have any risk mutation To prove this average in the eGFR the minimum number required is 98 individuals in each group It will be assumed that the minimum frequency of mutations is 8 in the population of interest to reach 98 individuals in each group the total number of individuals required to be evaluated for the presence of mutation will be 1225 donors Considering that there will be a loss of follow-up of 20 of the total number of individuals the total number of donors required to be invited will be 1535 patients By including 1225 donors 1225 recipients will be included totaling 2450 individuals Primary endpoint eGFR 5 years after transplantation in recipients Secondary endpoints eGFR decay rate between 1 and 5 years after kidney transplantation in recipients Graft loss in up to 5 years of follow-up Death in recipients within 5 years of follow-up Acute rejection Exploratory outcomes current eGFR in donors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None