Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.
Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.
复制标题
与镰状细胞疾病快速肾功能下降有关的临床和代谢组危险因素。
DOI：
10.1002/ajh.25263
复制
发表时间：
2018-12
影响因子：
12.8
通讯作者：
Telen MJ
中科院分区：
文献类型：
--
作者：
Xu JZ;Garrett ME;Soldano KL;Chen ST;Clish CB;Ashley-Koch AE;Telen MJ
镰状细胞病（SCD）肾病和较低的估计肾小球滤过率（eGFR）是早期死亡的危险因素。此外，在许多临床环境中，eGFR下降率可预测进展为终末期肾病。然而，预测SCD患者肾功能下降的因素记录不多。利用临床、实验室、遗传学和代谢组学数据，我们评估了288名成人（平均年龄33.0岁）纵向队列中肾功能下降的预测因素。在193例有5年随访数据的受试者中，eGFR下降的平均速率为2.35 mL/min/1.73 m2/年，几乎是非洲裔美国成年人总体的两倍。基线时高滤过普遍（61.1%），36.8%的受试者发生eGFR快速下降（≥3 mL/min/1.73 m2/年）。严重的Hb基因型、蛋白尿、较高的血小板、网织红细胞计数和收缩压以及较低的Hb水平和BMI与快速下降相关。使用这7个变量创建了一个风险评分系统，该系统高度预测eGFR快速下降，每增加一个点，快速下降的几率增加1.635倍（P<0.0001）。eGFR快速下降也与较高的器官系统严重程度评分和肌酐峰值相关。此外，两种代谢产物（不对称二甲基精氨酸和喹啉酸）与快速下降相关。对纵向SCD肾病（SCDN）轨迹、SCDN的早期标志物和风险分层工具的进一步研究应有助于减缓GFR下降和改善SCD结局的干预性研究。
Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented. Using clinical, laboratory, genetic, and metabolomic data, we evaluated predictors of renal function decline in a longitudinal cohort of 288 adults (mean age 33.0 years). In 193 subjects with 5-year follow-up data, mean rate of eGFR decline was 2.35 mL/min/1.73 m2/year, nearly twice that of African American adults overall. Hyperfiltration was prevalent at baseline (61.1%), and 36.8% of subjects experienced rapid eGFR decline (≥3 mL/min/1.73 m2/year). Severe Hb genotype; proteinuria; higher platelet, reticulocyte counts, and systolic BP; and lower Hb level and BMI were associated with rapid decline. A risk scoring system was created using these 7 variables and was highly predictive of rapid eGFR decline, with odds of rapid decline increasing 1.635-fold for every point increment (P<0.0001). Rapid eGFR decline was also associated with higher organ system severity score and peak creatinine. Additionally, two metabolites (asymmetric dimethylarginine and quinolinic acid) were associated with rapid decline. Further investigation into longitudinal SCD nephropathy (SCDN) trajectory, early markers of SCDN, and tools for risk stratification should inform interventional studies targeted to slowing GFR decline and improving SCD outcomes.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
4.2
作者：
BAKIR, AA;HATHIWALA, SC;DUNEA, G
通讯作者：
DUNEA, G
影响因子：
2.3
作者：
Arlet, Jean-Benoit;Ribeil, Jean-Antoine;Courbebaisse, Marie
通讯作者：
Courbebaisse, Marie
影响因子：
3.2
作者：
Forrest, Suzanne;Kim, Ashley;Pashankar, Farzana
通讯作者：
Pashankar, Farzana
影响因子：
41.5
作者：
Genovese, Giulio;Friedman, David J.;Pollak, Martin R.
通讯作者：
Pollak, Martin R.