APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

Kidney Diseases Clinical Trial

— APOLLO  

Official title:

APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03615235
• Other study ID #: IRB00051561
• Secondary ID: U01DK116041U01DK
• Status: Recruiting
• Start date: May 16, 2019
• Est. completion date: May 2027

Study information

• Verified date: February 2024
• Source: Wake Forest University Health Sciences
• Contact: Laurie P. Russell, MS
• Phone: 336-713-4292
• Email: lrussell[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: May 2027
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Disease, Chronic
• Kidney Diseases
• Kidney Failure
• Renal Insufficiency
• Renal Insufficiency, Chronic

Locations

Country	Name	City	State
United States	University of Michigan Medicine	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Joslin Diabetes Center / Harvard University	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	University of Miami / Miami Transplant Institute	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Ichan School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Saint Louis University Center for Transplantation	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD)

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to death-censored renal allograft failure from the UNOS database	Time from receipt of kidney transplant to death-censored renal allograft failure. Measured in days.	up to 4.5 years
Secondary	The rate of loss of renal clearance function from clinical laboratory data	Rate of change in the estimated glomerular filtration rate Measured in ml/min/1.73 m2.	up to 4.5 years
Secondary	The rate of change in serum creatinine concentration from clinical laboratory data	Rate of change in the reciprocal of the serum creatinine concentration. Measured as 1/serum creatinine concentration [in mg/dl].	up to 4.5 years
Secondary	Time to sustained development of overt proteinuria in the outpatient setting.	Overt proteinuria is defined as urine protein:creatinine ratio (UPCR) >500 mg/g, urine albumin:creatinine ratio (UACR) >300 mg/g, or >2+ proteinuria on urine dipstick. This outcome requires repeat documentation of proteinuria using either UPCR, UACR or dipstick test >1 month after initial detection based on clinic data	up to 4.5 years
Secondary	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)	Rate of change (i.e., slope of change) in estimated glomerular filtration rate based on serum creatinine concentration from UNOS and clinic data	up to 4.5 years
Secondary	Renal allograft failure in patients with End Stage Renal Disease defined based on Standardized Outcomes in Nephrology (SONG) criteria	Renal allograft failure in patients with End Stage Renal Disease defined based on Standardized Outcomes in Nephrology (SONG) criteria: return to chronic renal replacement therapy (dialysis for >90 days or submission of Centers for Medicare and Medicaid Services End Stage Renal Disease Medical Evidence Report [2728 Form]) or repeat kidney transplantation.36 This definition of renal allograft failure specifically excludes acute kidney injury (AKI), delayed graft function (DGF), or primary non-function (requirement of dialysis for the initial 90 days after kidney transplant or re-transplant within 90 days). The diagnoses of AKI, DGF and primary non-function will be abstracted from UNOS, clinic notes and hospital discharge summaries.	up to 4.5 years
Secondary	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.	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.	up to 4.5 years
Secondary	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)	The 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) (using APOLLO transplant program data)" among the subset of consented recipients of an APOLLO Deceased Donor Kidney Transplant	up to 4.5 years