Verbitsky Miguel, Kogon Amy J, Matheson Matthew, Hooper Stephen R, Wong Craig S, Warady Bradley A, Furth Susan L, Gharavi Ali G
Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York.
Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, Ohio.
J Am Soc Nephrol. 2017 Aug;28(8):2303-2309. doi: 10.1681/ASN.2016101108. Epub 2017 Mar 27.
Children with CKD are at increased risk for neurocognitive impairment, but whether neurocognitive dysfunction is solely attributable to impaired renal function is unclear. Data from the CKD in Children Study Chronic Kidney Disease in Children (CKiD) Study indicate that a subset of children with CKD have unsuspected genomic disorders that predispose them to organ malformations and neurocognitive impairment. We therefore tested whether the CKiD Study participants with genomic disorders had impaired neurocognitive performance at enrollment. Compared with noncarriers (=389), children with genomic disorders (=31) scored significantly poorer on all measures of intelligence, anxiety/depressive symptoms, and executive function (differences of 0.6-0.7 SD; =1.2×10-2.4×10). These differences persisted after controlling for known modifiers, including low birth weight, maternal education, seizure disorder, kidney disease duration, and genetically defined ancestry. The deleterious effect of genomic disorders on neurocognitive function was significantly attenuated in offspring of mothers with higher education, indicating the potential for modification by genetic and/or environmental factors. These data indicate that impaired neurocognitive function in some children with CKD may be attributable to genetic lesions that affect both kidney and neurocognitive development. Early identification of genomic disorders may provide opportunity for early diagnosis and personalized interventions to mitigate the effect on neurocognitive function.
慢性肾脏病（CKD）患儿发生神经认知障碍的风险增加，但神经认知功能障碍是否完全归因于肾功能受损尚不清楚。儿童慢性肾脏病研究（CKiD研究）的数据表明，一部分CKD患儿存在未被怀疑的基因组疾病，这些疾病使他们易患器官畸形和神经认知障碍。因此，我们测试了CKiD研究中患有基因组疾病的参与者在入组时神经认知表现是否受损。与非携带者（n = 389）相比，患有基因组疾病的儿童（n = 31）在所有智力、焦虑/抑郁症状和执行功能测量指标上的得分均显著更低（差异为0.6 - 0.7标准差；P = 1.2×10⁻² - 2.4×10⁻）。在控制了已知的影响因素后，这些差异依然存在，这些因素包括低出生体重、母亲教育程度、癫痫症、肾脏疾病病程以及基因定义的血统。基因组疾病对神经认知功能的有害影响在母亲受教育程度较高的后代中显著减弱，这表明存在遗传和/或环境因素进行调节的可能性。这些数据表明，一些CKD患儿的神经认知功能受损可能归因于影响肾脏和神经认知发育的基因损伤。早期识别基因组疾病可能为早期诊断和个性化干预提供机会，以减轻对神经认知功能的影响。
