Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes

医学 四分位间距 优势比 置信区间 内科学 局灶节段性肾小球硬化 肾脏疾病 肿瘤科 蛋白尿
作者
Mahmoud Kallash,Yujie Wang,Abigail R. Smith,Howard Trachtman,Rasheed Gbadegesin,Carla Nester,Pietro A. Canetta,Chen Wang,Tracy E. Hunley,C. John Sperati,David T. Selewski,Isabelle Ayoub,Tarak Srivastava,Amy K. Mottl,Jeffrey B. Kopp,Brenda W. Gillespie,Bruce Robinson,Dhruti P. Chen,Julia Steinke,Katherine Twombley
出处
期刊:Clinical Journal of The American Society of Nephrology [Lippincott Williams & Wilkins]
卷期号:18 (3): 344-355 被引量:16
标识
DOI:10.2215/cjn.0000000000000069
摘要

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 m 2 [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.
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