Journal article
Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High Risk APOL1 Genotypes
Clinical journal of the American Society of Nephrology, Vol.18(3), pp.344-355
03/2023
DOI: 10.2215/CJN.0000000000000069
PMCID: PMC10103277
PMID: 36763813
Abstract
Background
FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 (APOL1) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors.
Methods
CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤−5 ml/min per year), intermediate progressor (slope between 0 and −5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation.
Results
Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36–81] versus low-risk participants 76 ml/min per 1.73 m2 [interquartile range, 44–106]; P<0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P<0.001) in the high-risk versus low-risk groups.
Conclusions
In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.
Details
- Title: Subtitle
- Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High Risk APOL1 Genotypes
- Creators
- Mahmoud KallashYujie WangAbigail SmithHoward TrachtmanRasheed GbadegesinCarla NesterPietro CanettaChen WangTracy E. HunleyC. John SperatiDavid SelewskiIsabelle AyoubTarak SrivastavaAmy K. MottlJeffrey KoppBrenda GillespieBruce RobinsonDhruti ChenJulia SteinkeKatherine TwombleyKimberly ReidyKrzysztof MuchaLarry A. GreenbaumBrooke BlaziusMargaret HelmuthPeleg YonatanRulan S. ParekhSusan HoganVirginie RoyalVivette D’AgatiAftab ChishtiRonald FalkAli GharaviLawrence HolzmanJon KleinWilliam SmoyerMatthias KretzlerDebbie GipsonJason M. KiddCureGN
- Resource Type
- Journal article
- Publication Details
- Clinical journal of the American Society of Nephrology, Vol.18(3), pp.344-355
- DOI
- 10.2215/CJN.0000000000000069
- PMID
- 36763813
- PMCID
- PMC10103277
- NLM abbreviation
- Clin J Am Soc Nephrol
- ISSN
- 1555-9041
- eISSN
- 1555-905X
- Language
- English
- Electronic publication date
- 01/17/2023
- Date published
- 03/2023
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984361596302771
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