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在马拉维,nephrin 作为镰状细胞肾小球病的生物标志物。

Nephrin as a biomarker of sickle cell glomerulopathy in Malawi.

机构信息

UNC Project-Malawi, Lilongwe, Malawi.

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

出版信息

Pediatr Blood Cancer. 2018 Jun;65(6):e26993. doi: 10.1002/pbc.26993. Epub 2018 Feb 7.

Abstract

BACKGROUND

Glomerulopathy is an increasingly identified complication in young patients with sickle cell disease (SCD). Hyperfiltration and albuminuria followed by declining glomerular filtration rates and eventual end-stage renal disease (ESRD) is assumed to be the typical progression of glomerular disease. There are only a few reported biomarkers to identify early-stage renal disease in SCD.

PROCEDURES

We detail the renal profile of 101 children with SCD in Malawi and propose a novel urinary biomarker for the identification of early renal disease.

RESULTS

Among children with sickle cell anemia, 24.8% had a urine albumin-creatinine ratio of 30 mg/g or above. In univariate analysis, only patients with higher urinary nephrin, a urinary marker of glomerular injury, had significantly greater odds of having albuminuria. In multivariable analysis, nephrin remained significantly associated with albuminuria. A nephrin-creatinine ratio (NCR) cut-point of 622 ng/mg, the 50 percentile, was associated with a 45.8 times greater odds of having albuminuria in children with nephrinuria above this value. Further analysis revealed this urinary NCR cut-point to have 96% sensitivity, 64% specificity, 47% positive predictive value, and 98% negative predictive value for the presence of albuminuria.

CONCLUSIONS

These data suggest that a substantial number of children with SCD in Malawi have renal disease and could be at risk for worsening nephropathy and ESRD as they age. Our data suggest that urinary nephrin could be utilized as an early marker of glomerular disease in SCD.

摘要

背景

肾小球病是镰状细胞病(SCD)年轻患者日益确定的并发症。肾小球疾病的典型进展被认为是高滤过和白蛋白尿,随后肾小球滤过率下降,最终导致终末期肾病(ESRD)。目前只有少数报道的生物标志物可用于识别 SCD 中的早期肾病。

方法

我们详细介绍了马拉维 101 名 SCD 儿童的肾脏情况,并提出了一种新的尿生物标志物来识别早期肾脏疾病。

结果

在镰状细胞贫血患儿中,24.8%的患儿尿白蛋白/肌酐比值为 30mg/g 或以上。在单变量分析中,只有尿足细胞标志物——尿神经纤毛蛋白较高的患者发生白蛋白尿的几率显著更高。在多变量分析中,神经纤毛蛋白与白蛋白尿仍显著相关。神经纤毛蛋白/肌酐比值(NCR)切点为 622ng/mg(第 50 百分位数),高于该值的患儿发生白蛋白尿的几率增加 45.8 倍。进一步分析显示,该尿 NCR 切点对白蛋白尿的检出具有 96%的灵敏度、64%的特异性、47%的阳性预测值和 98%的阴性预测值。

结论

这些数据表明,马拉维相当一部分 SCD 儿童患有肾脏疾病,随着年龄的增长,他们可能有发生进行性肾病和 ESRD 的风险。我们的数据表明,尿神经纤毛蛋白可用作 SCD 中肾小球疾病的早期标志物。

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