APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

Study Overview
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Brief Summary
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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
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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.

Official Title
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APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO)

Conditions
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Kidney Diseases, Kidney Failure, Kidney Disease, Chronic

Participation Criteria
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Eligibility Criteria
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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. Inclusion Criteria for Recipients: Recipients of a kidney transplant from an eligible living or deceased donor with recent African ancestry. Recipients of multi-organ transplants including a kidney plus an additional organ (i.e. liver, heart, lung, pancreas, etc.) or pediatric en bloc and dual kidney transplants. Exclusion Criteria for Recipients: Participants who are unable or unwilling to provide informed consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Recipients of a Kidney Transplant<br>APOLLO will prospectively assess transplant outcomes in recipients of kidneys from eligible living and deceased donors at all transplant programs in the United States including Puerto Rico. | |
| Living Kidney Donors<br>APOLLO will prospectively assess post-donation renal outcomes in eligible living kidney donors at all transplant programs in the United States including Puerto Rico. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Renal allograft failure in patients with ESRD defined based on Standardized Outcomes in Nephrology (SONG) criteria | Renal allograft failure in patients with ESRD 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 [CMS] ESRD 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apolopoprotein L1 gene (APOL1), Kidney Transplantation, Kidney Donor, United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations (AOPO), Kidney Transplantation Outcomes Network