Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, Ohio.
University of Michigan, Ann Arbor, Michigan.
Clin J Am Soc Nephrol. 2023 Mar 1;18(3):344-355. doi: 10.2215/CJN.0000000000000069. Epub 2023 Feb 8.
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.
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.
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.
In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.
FSGS 是一种预后不佳的异质性诊断。载脂蛋白 L1（APOL1）基因的多态性与 FSGS 的发生以及受影响患者向肾衰竭的更快进展相关。更好地了解 FSGS 患者和 APOL1 风险等位基因的自然史对于改善患者护理以及支持干预研究的设计和解释至关重要。本研究的目的是评估 APOL1 与肾脏疾病进展之间的定量关联以及与其他临床和实验室因素的相互作用。
纳入了活检诊断为 FSGS 的 CureGN 队列研究参与者，无论其自我认定的种族如何。感兴趣的暴露因素是两个 APOL1 风险等位基因（高危）与零到一个风险等位基因（低危）。主要结局是 eGFR 斜率，分为快速进展者（eGFR 斜率≤-5 ml/min/年）、中间进展者（斜率在 0 与-5 之间）或非进展者（斜率≥0）。采用多变量有序逻辑回归和线性回归进行调整分析。使用多重插补处理缺失数据。
在 650 名参与者中，有 476 名（73%）进行了基因检测，其中 87 名（18%）为高危。高危参与者的中位 eGFR 更可能较低（62 [四分位距，36-81] 与低危参与者的 76 ml/min/1.73 m 2 [四分位距，44-106]；P<0.01）。在调整分析中，与低危组相比，高危组的 eGFR 更快速进展的可能性高 2.75 倍（95%置信区间，1.67 至 4.53；P<0.001）。
在 FSGS 患者中，高危 APOL1 基因型是与肾功能更快丧失相关的主要因素。
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