Department of Renal Medicine, The Royal Hospital; Oman Medical Specialty Board, Muscat, Oman.
Department of Rheumatology Medicine, MOHAP, Dubai, UAE.
Saudi J Kidney Dis Transpl. 2020 Jul-Aug;31(4):717-726. doi: 10.4103/1319-2442.292305.
The worldwide prevalence of noncommunicable diseases (NCDs) is projected to increase substantially over the next few decades. Chronic kidney disease (CKD) is a key determinant of poor health outcomes for major NCD. Genetic predisposition and environmental exposures are contributory factors, but increasingly, it is being recognized that fetal development is also an important modulator of the NCD risk. Low birth weight (LBW) and CKD affect more disadvantaged populations and ethnic minorities and, therefore, causes a disproportionate burden on the poor. Human nephron number is highly variable and may range from under half a million to almost over two million. Significant variability is already present at birth, highlighting the importance of early nephrogenesis. Nearly 60% of nephrons are developed in the third-trimester of pregnancy. Nephron numbers increase in proportion to birth weight and gestational age. This wide-variability probably contributes to individual susceptibility to develop CKD where individuals with nephron numbers on the lower side of the spectrum are those at higher risk of developing kidney dysfunction at higher rate and progress more toward end-stage CKD. This article aims at discussing LBW and the susceptibility to CKD. Furthermore, in postnatal environment, the weight gain or change at adult life increases the metabolic demand and determines the phenotypic expression of disease along with the spectrum of nephron number. Hence, a cycle of hyperfiltration mechanism of these nephrons leads to proteinuria, glomerulo- sclerosis, and progressive development of larger glomeruli, a greater risk of proteinuria and progressive CKD. Therefore, LBW offspring are at risk of developing CKD (defined as albuminuria, a reduced glomerular filtration rate, or renal failure) in later life. Furthermore, the impact of prenatal programming is expected to be compounded with age, and the association of LBW with the risk of CKD seen in younger adults may become greater with age. It would be prudent, to adopt policies of intensified life-long surveillance of LBW people, anticipating this risk.
在未来几十年,全球范围内的非传染性疾病(NCDs)患病率预计将大幅上升。慢性肾脏病(CKD)是主要 NCD 不良健康结局的关键决定因素。遗传易感性和环境暴露是促成因素,但越来越多的人认识到,胎儿发育也是 NCD 风险的重要调节因素。低出生体重(LBW)和 CKD 影响到更多处于不利地位的人群和少数族裔,因此给贫困人口带来了不成比例的负担。人类肾单位数量变化很大,可能从不到五十万到近两百万不等。出生时就已经存在显著的变异性,突出了早期肾发生的重要性。近 60%的肾单位在妊娠第三个月发育。肾单位数量与出生体重和胎龄成正比增加。这种广泛的变异性可能导致个体易患 CKD,其中肾单位数量处于频谱低端的个体患肾功能障碍的风险更高,且进展速度更快,更易发展为终末期 CKD。本文旨在讨论 LBW 和 CKD 的易感性。此外,在出生后的环境中,成年后的体重增加或变化会增加代谢需求,并决定疾病的表型表达以及肾单位数量的范围。因此,这些肾单位的高滤过机制导致蛋白尿、肾小球硬化和较大肾小球的进行性发展,蛋白尿和进行性 CKD 的风险更大。因此,LBW 后代在以后的生活中易患 CKD(定义为蛋白尿、肾小球滤过率降低或肾衰竭)。此外,预期产前编程的影响将随着年龄的增长而加剧,LBW 与年轻成年人 CKD 风险之间的关联可能随着年龄的增长而变得更大。因此,采取强化终身监测 LBW 人群的政策是谨慎的,可以预测这一风险。