Anigilaje Emmanuel Ademola
Nephrology Unit, Department of Paediatrics, College of Health Sciences, University of Abuja, Abuja, Nigeria.
JMIR Res Protoc. 2018 Jun 14;7(6):e156. doi: 10.2196/resprot.9514.
Although urinary tract infection (UTI) resolves with prompt treatment in a majority of children, some children, especially those aged less than 5 years, also develop renal parenchymal scarring (RPS). RPS causes high blood pressure that may lead to severe chronic kidney disease and end-stage renal disease (ESRD). Although the risk of UTI is higher in white children than in black children, it is unknown whether RPS is more common in white children than in black children as data are scarce in this regard. A common genetic predisposition to kidney disease in African Americans and the sub-Saharan African blacks is the possession of apolipoprotein L1 (APOL1). APOL1 risk variants regulate the production of APOL1. APOL1 circulates in the blood, and it is also found in the kidney tissue. While circulating, APOL1 kills the trypanosome parasites; an increased APOL1 in kidney tissues, under the right environmental conditions, can also result in the death of kidney tissue (vascular endothelium, the podocytes, proximal tubules, and arterial cells), which, ultimately, is replaced by fibrous tissue. APOL1 may influence the development of RPS, as evidence affirms that its expression is increased in kidney tissue following UTI caused by bacteria. Thus, UTI may be a putative environmental risk factor responsible for APOL1-induced kidney injury.
The aim of this proposal was to outline a study that seeks to determine if the possession of two copies of either G1 or G2 APOL1 variant increases the risk of having RPS, 6 months following a febrile UTI among Nigerian under-five children.
This case-control association study seeks to determine whether the risk of RPS from febrile UTI is conditional on having 2 APOL1 risk alleles (either G1 or G2). Cases will be children with a confirmed RPS following a febrile UTI. Controls will be age-, gender-, and ethnic-matched children with a febrile UTI but without RPS. Children with vesicoureteral reflux and other congenital anomalies of the urinary tract are to be excluded. Association between predictor variables (ethnicity, APOL1 G1 or G2, and others) and RPS will be tested at bivariate logistic regression analyses. Predictors that attained significance at a P value of ˂.05 will be considered for multiple logistic regressions. Likelihood-based tests will be used for hypothesis testing. Estimation will be done for the effect size for each of the APOL1 haplotypes using a generalized linear model.
The study is expected to last for 3 years.
The study is contingent on having a platform for undergoing a research-based PhD program in any willing university in Europe or elsewhere. The findings of this study will be used to improve the care of African children who may develop RPS following febrile UTI.
RR1-10.2196/9514.
尽管大多数儿童的尿路感染（UTI）通过及时治疗可以痊愈，但一些儿童，尤其是5岁以下的儿童，也会出现肾实质瘢痕形成（RPS）。RPS会导致高血压，进而可能引发严重的慢性肾病和终末期肾病（ESRD）。虽然白人儿童患UTI的风险高于黑人儿童，但由于这方面的数据稀缺，尚不清楚RPS在白人儿童中是否比黑人儿童更常见。非裔美国人和撒哈拉以南非洲黑人患肾病的一个常见遗传易感性是拥有载脂蛋白L1（APOL1）。APOL1风险变异体调节APOL1的产生。APOL1在血液中循环，也存在于肾组织中。在循环过程中，APOL1杀死锥虫寄生虫；在适当的环境条件下，肾组织中APOL1增加也会导致肾组织（血管内皮、足细胞、近端小管和动脉细胞）死亡，最终被纤维组织取代。APOL1可能影响RPS的发展，因为有证据表明，在细菌引起的UTI后，其在肾组织中的表达会增加。因此，UTI可能是导致APOL1诱导的肾损伤的一个假定环境风险因素。
本研究计划旨在概述一项研究，以确定在尼日利亚5岁以下儿童发热性UTI 6个月后，拥有两份G1或G2 APOL1变异体是否会增加患RPS的风险。
本病例对照关联研究旨在确定发热性UTI导致RPS的风险是否取决于拥有2个APOL1风险等位基因（G1或G2）。病例将是发热性UTI后确诊为RPS的儿童。对照将是年龄、性别和种族匹配的发热性UTI但无RPS的儿童。患有膀胱输尿管反流和其他先天性尿路异常的儿童将被排除。预测变量（种族、APOL1 G1或G2等）与RPS之间的关联将在双变量逻辑回归分析中进行检验。在P值<0.05时达到显著性的预测因素将考虑进行多变量逻辑回归。基于似然的检验将用于假设检验。将使用广义线性模型对每个APOL1单倍型的效应大小进行估计。
该研究预计持续3年。
该研究取决于是否有一个平台，以便在欧洲或其他地方任何愿意的大学开展基于研究的博士项目。本研究的结果将用于改善可能在发热性UTI后发生RPS的非洲儿童的护理。注册报告标识符：RR1-10.2196/9514。
