Clinical trial NCT03615235: APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)
Official title: APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Diseases
Kidney Failure
Kidney Disease, Chronic
Keywords: Apolopoprotein L1 gene (APOL1)
Kidney Transplantation
Kidney Donor
United Network for Organ Sharing (UNOS)
Association of Organ Procurement Organizations (AOPO)
Kidney Transplantation Outcomes Network
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-08-03
Enrollment: 5000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Thirteen APOLLO Clinical Centers (CCs) will prospectively enroll eligible living kidney donors and recipients of kidney transplants from eligible living and deceased kidney donors at all transplant programs in the continental United States including Puerto Rico. The APOLLO Scientific and Data Research Center (SDRC or Coordinating Center) will support and participate in studies determining the impact of donor and recipient APOL1 genotypes on kidney transplant outcomes in recipients of a kidney transplant from a donor with recent African ancestry, and follow African ancestry living kidney donors for changes in vital status, kidney function and proteinuria. In this protocol, recent African ancestry is broadly defined as African American, Afro-Caribbean, Hispanic black, and African.

Brief summary: The APOLLO study is being done in an attempt to improve outcomes after kidney transplantation and to improve the safety of living kidney donation based upon variation in the apolipoprotein L1 gene (APOL1). Genes control what is inherited from a family, such as eye color or blood type. Variation in APOL1 can cause kidney disease. African Americans, Afro-Caribbeans, Hispanic Blacks, and Africans are more likely to have the APOL1 gene variants that cause kidney disease. APOLLO will test DNA from kidney donors and recipients of kidney transplants for APOL1 to determine effects on kidney transplant-related outcomes.

Detailed description: The National Institutes of Health (NIH)-sponsored collaborative APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is charged with prospectively assessing the effects of renal-risk variants (RRVs) in the apolipoprotein L1 gene (APOL1) on outcomes for kidneys from donors with recent African ancestry and the recipients of their kidneys, after deceased- and living-donor renal transplantation. For the purposes of APOLLO, recent African ancestry is defined as individuals with similar genetic make-up to those currently residing in Africa. APOLLO will also study the impact of APOL1 RRVs on the health of living kidney donors with recent African ancestry.

Eligibility criteria: Inclusion Criteria for Living Donors:

* Living kidney donors with self-reported recent African ancestry (defined as African American, Afro-Caribbean, Hispanic black or African) will be eligible for inclusion.

Exclusion Criteria for Living Donors:

* Participants who are unable or unwilling to provide informed consent.

Enrollment and bio sample collection from deceased donors at OPOs ended on May 31, 2023 and recruiting kidney transplant recipients ended on June 15, 2023.

Phase II started on 9/1/2023 and only Living Donors will be recruited for an additional 2 years.

Primary outcomes:
measure: Time to death-censored renal allograft failure from the UNOS database
timeFrame: up to 4.5 years
Secondary outcomes:
measure: The rate of loss of renal clearance function from clinical laboratory data
timeFrame: up to 4.5 years
measure: The rate of change in serum creatinine concentration from clinical laboratory data
timeFrame: up to 4.5 years
measure: Time to sustained development of overt proteinuria in the outpatient setting.
timeFrame: up to 4.5 years
measure: Rate of change in kidney function and quantitative proteinuria from baseline pre-donation levels in living kidney donors (to include effects on stages of CKD)
timeFrame: up to 4.5 years
measure: Renal allograft failure in patients with End Stage Renal Disease defined based on Standardized Outcomes in Nephrology (SONG) criteria
timeFrame: up to 4.5 years
measure: The effects of donor APOL1 RRVs on time to "death or renal allograft failure" using UNOS data for all recipients of an APOLLO Deceased Donor Kidney Transplant.
timeFrame: up to 4.5 years
measure: he effects of donor APOL1 RRVs on time to "death-censored renal allograft failure (using UNOS data) or death from Corona Virus Disease of 2019 infection (COVID-19)
timeFrame: up to 4.5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Miami
country: United States
facility: University of Miami / Miami Transplant Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Joslin Diabetes Center / Harvard University
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medicine
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University Center for Transplantation
state: Missouri
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
Study officials:
affiliation: Wake Forest University Health Sciences
name: Barry I. Freedman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: David M. Reboussin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Natl Institute of Diabetes, Digestive & Kidney Diseases
name: Paul L. Kimmel, MD
role: STUDY_DIRECTOR
affiliation: Children's Natl Health System; George Washington Univ Sch of Med and Health Serv
name: Marva Moxey-Mims, MD
role: STUDY_CHAIR
References:
citation: Freedman BI, Moxey-Mims M. The APOL1 Long-Term Kidney Transplantation Outcomes Network-APOLLO. Clin J Am Soc Nephrol. 2018 Jun 7;13(6):940-942. doi: 10.2215/CJN.01510218. Epub 2018 Apr 27. No abstract available.
citation: Freedman BI, Julian BA. Evaluation of Potential Living Kidney Donors in the APOL1 Era. J Am Soc Nephrol. 2018 Apr;29(4):1079-1081. doi: 10.1681/ASN.2018020137. Epub 2018 Mar 9. No abstract available.
citation: Freedman BI, Locke JE, Reeves-Daniel AM, Julian BA. Apolipoprotein L1 Gene Effects on Kidney Transplantation. Semin Nephrol. 2017 Nov;37(6):530-537. doi: 10.1016/j.semnephrol.2017.07.006.
citation: Julian BA, Gaston RS, Brown WM, Reeves-Daniel AM, Israni AK, Schladt DP, Pastan SO, Mohan S, Freedman BI, Divers J. Effect of Replacing Race With Apolipoprotein L1 Genotype in Calculation of Kidney Donor Risk Index. Am J Transplant. 2017 Jun;17(6):1540-1548. doi: 10.1111/ajt.14113. Epub 2017 Jan 3.
citation: Dorr CR, Freedman BI, Hicks PJ, Brown WM, Russell GB, Julian BA, Pastan SO, Gautreaux MD, Muthusamy A, Chinnakotla S, Hauptfeld V, Bray RA, Kirk AD, Divers J, Israni AK. Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes. PLoS One. 2016 Apr 7;11(4):e0152775. doi: 10.1371/journal.pone.0152775. eCollection 2016.
citation: Freedman BI, Pastan SO, Israni AK, Schladt D, Julian BA, Gautreaux MD, Hauptfeld V, Bray RA, Gebel HM, Kirk AD, Gaston RS, Rogers J, Farney AC, Orlando G, Stratta RJ, Mohan S, Ma L, Langefeld CD, Bowden DW, Hicks PJ, Palmer ND, Palanisamy A, Reeves-Daniel AM, Brown WM, Divers J. APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors. Transplantation. 2016 Jan;100(1):194-202. doi: 10.1097/TP.0000000000000969.
citation: Freedman BI, Julian BA. Should kidney donors be genotyped for APOL1 risk alleles? Kidney Int. 2015 Apr;87(4):671-3. doi: 10.1038/ki.2015.16. No abstract available.
citation: Freedman BI, Julian BA, Pastan SO, Israni AK, Schladt D, Gautreaux MD, Hauptfeld V, Bray RA, Gebel HM, Kirk AD, Gaston RS, Rogers J, Farney AC, Orlando G, Stratta RJ, Mohan S, Ma L, Langefeld CD, Hicks PJ, Palmer ND, Adams PL, Palanisamy A, Reeves-Daniel AM, Divers J. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. Am J Transplant. 2015 Jun;15(6):1615-22. doi: 10.1111/ajt.13223. Epub 2015 Mar 24.
citation: Reeves-Daniel AM, DePalma JA, Bleyer AJ, Rocco MV, Murea M, Adams PL, Langefeld CD, Bowden DW, Hicks PJ, Stratta RJ, Lin JJ, Kiger DF, Gautreaux MD, Divers J, Freedman BI. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011 May;11(5):1025-30. doi: 10.1111/j.1600-6143.2011.03513.x. Epub 2011 Apr 12.
citation: Lee BT, Kumar V, Williams TA, Abdi R, Bernhardy A, Dyer C, Conte S, Genovese G, Ross MD, Friedman DJ, Gaston R, Milford E, Pollak MR, Chandraker A. The APOL1 genotype of African American kidney transplant recipients does not impact 5-year allograft survival. Am J Transplant. 2012 Jul;12(7):1924-8. doi: 10.1111/j.1600-6143.2012.04033.x. Epub 2012 Apr 4.
citation: Doshi MD, Ortigosa-Goggins M, Garg AX, Li L, Poggio ED, Winkler CA, Kopp JB. APOL1 Genotype and Renal Function of Black Living Donors. J Am Soc Nephrol. 2018 Apr;29(4):1309-1316. doi: 10.1681/ASN.2017060658. Epub 2018 Jan 16.