• Estimate the prevalence of APOL1 genotypes among individuals with FSGS who identify themselves as being of recent African ancestry or geographic origin• Estimate the prevalence of APOL1 genotypes among individuals with other forms of proteinuric…
ID
Source
Brief title
Condition
- Renal and urinary tract disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Estimate the prevalence of APOL1 genotypes among individuals with focal
segmental glomerulosclerosis (FSGS) who identify themselves as being of recent
African ancestry or geographic origin
• Estimate the prevalence of APOL1 genotypes among individuals with other forms
of proteinuric nondiabetic chronic kidney disease (CKD) who identify themselves
as being of recent African ancestry or geographic origin
• Estimate the prevalence of APOL1 genotypes in individuals without a
documented CKD diagnosis, but with a historical eGFR of <75 mL/min who identify
themselves as being of recent African ancestry or geographic origin
Secondary outcome
• Identify individuals with FSGS and 2 APOL1 risk alleles to establish a group
of potential participants for current and future Vertex clinical studies
• Identify individuals with other forms of proteinuric nondiabetic CKD and 2
APOL1 risk alleles to establish a group of potential participants for current
and future Vertex clinical studies
Background summary
The apolipoprotein L1 (APOL1) gene is expressed in multiple organs in humans,
including the kidney.1,2 The biologic function of APOL1 is to protect against
parasitic infection (Trypanosoma brucei.3 Two common sequence variants in
APOL1, termed G1 and G2 (i.e., risk alleles) are commonly found in individuals
of recent African or Caribbean ancestry.4, 5 G1 encodes a correlated pair of
non-synonymous amino acid changes (S342G and I384M), G2 encodes a 2 amino acid
deletion (N388del:Y389del) near the C-terminus- of the protein, and G0 is the
ancestral allele (wild type).4,5 Different studies published over the last 10
years have shown that individuals who are homozygous or compound heterozygous
for these 2 variants have an increased risk of developing proteinuric kidney
diseases, including focal segmental glomerulosclerosis (FSGS),
interferon-induced nephropathy,6 human immunodeficiency virus nephropathy,7 and
nondiabetic kidney disease (NDKD).2
This study will screen participants with FSGS and other proteinuric nondiabetic
chronic kidney diseases for APOL1 variants.
Additional studies are needed to further understand the prevalence of APOL1
genotypes in participants with proteinuric nondiabetic chronic kidney disease
(CKD).
Study objective
• Estimate the prevalence of APOL1 genotypes among individuals with FSGS who
identify themselves as being of recent African ancestry or geographic origin
• Estimate the prevalence of APOL1 genotypes among individuals with other forms
of proteinuric nondiabetic CKD who identify themselves as being of recent
African ancestry or geographic origin
• Estimate the prevalence of APOL1 genotypes in individuals without a
documented CKD diagnosis, but with a historical eGFR of <75 mL/min who identify
themselves as being of recent African ancestry or geographic origin
Study design
This is a study of the prevalence of APOL1 alleles in individuals who are of
recent African ancestry or geographic origin. The study will enroll up to a
total of approximately 2500 participants into 3 groups. Group 1 includes
participants with FSGS, Group 2 includes participants with other forms of
proteinuric nondiabetic CKD, Group 3 includes individuals without a documented
CKD diagnosis, but with a historical eGFR of <75 mL/min. No study drug will be
administered. A blood sample will be collected for APOL1 genotyping. A saliva
sample will be collected for exploratory use in APOL1 genotyping assay
development.
Study burden and risks
Blood Draw: When you have your blood taken with a needle, it may feel like a
pinch. It can hurt for a short time, and sometimes the place where the needle
was put might feel sore or look bruised. Some people may experience dizziness,
upset stomach, or fainting when their blood is drawn. There is a risk of
infection.
Saliva Sample: There are no known risks or discomforts from the saliva
collection technique.
Van Swietenlaan 6
Groningen 9728 NZ
NL
Van Swietenlaan 6
Groningen 9728 NZ
NL
Listed location countries
Age
Inclusion criteria
1. Willing to sign and date an informed consent form (ICF) either in-person or
remotely, as applicable by local law.
2. Participants aged 12 to 65 years (inclusive).
3. Participant is of African ancestry or geographic origin, which may include
but is not limited to the following: Black, Caribbean, African American,
Sub-Saharan African, or LatinX (defined as a person of Cuban, Mexican, Puerto
Rican, South or Central American, or other Spanish culture or origin).
4. Participants must meet one of the below criteria:
a. Group 1: FSGS.
b. Group 2: Presence of proteinuric nondiabetic CKD (not attributable to
infection, neoplasia, drugs, autoimmune disorders, or diabetes).
c. Group 3: Individuals* without a documented CKD diagnosis, but with a
historical eGFR of <75 mL/min.
*Including, but not limited to first degree blood relatives (i.e., parent, full
sibling, or child) of individuals with end-stage kidney disease (ESKD).
5. Proteinuria as defined by at least one of the following:
a. urine protein to creatinine ratio (UPCR) >=0.5 g/g (>=500 mg/g; >=50 mg/mmol),
or
b. urine albumin-to-creatinine ratio (UACR) >=0.3 g/g (>=300 mg/g; >=30 mg/mmol),
or
c. urine dipstick analysis with protein reagent strip >=1+
Proteinuria can be confirmed via:
• previously documented result if it was done within 12 months before the date
of informed consent OR
• by a random spot urine sample using a dipstick test performed during
screening.
Exclusion criteria
1. Participant, or close relative of the participant, is the investigator or a
subinvestigator, research assistant, study coordinator, or other staff directly
involved with the conduct of the study at that site.
2. ESKD, defined as being on chronic dialysis.
3. Prior kidney transplant.
4. History of diabetes mellitus.
Design
Recruitment
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL80510.018.22 |