Mechanisms of Injury in APOL1-associated Kidney Disease.
Mechanisms of Injury in APOL1-associated Kidney Disease.
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DOI：
10.1097/tp.0000000000002509
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发表时间：
2019-03
期刊：
影响因子：
6.2
通讯作者：
Freedman BI
中科院分区：
文献类型：
--
作者：
Ma L;Divers J;Freedman BI
通过对肾移植的观察，对载脂蛋白L1基因（APOL 1）-基因相关慢性肾脏病（CKD）的发病机制有了更深入的了解。APOL 1基因分型可能很快提高近期非洲血统个体活体肾脏捐赠的安全性，并改变已故供体肾脏的分配。本文综述了APOL 1相关肾病发生的潜在机制。循环APOL 1蛋白与内在肾表达的APOL 1的作用进行了讨论，以及修改遗传和/或环境因素的要求。大量证据支持在肾病发展中局部肾脏产生APOL 1肾风险变体蛋白;这在原发性肾病和肾移植后都是如此。只有少数来自APOL 1高危基因型个体的肾脏在移植后会发展为CKD或表现出较短的肾移植物存活率。因此，解释为什么只有一部分肾脏发生肾病的修饰因素仍然是识别的关键。与APOL 1-秒基因相互作用相比，环境暴露似乎是肾病风险的更强调节剂。对APOL 1相关肾病发病机制的不断深入了解将确定预测高遗传风险个体肾病的生物标志物，并导致新的治疗方法，以预防或减缓原发性CKD进展并延长移植肾的生存期。在此期间，美国国立卫生研究院赞助的“APOL 1长期肾移植结果”（APOLLO）网络将确定近期非洲血统个体的APOL 1基因分型是否改善肾移植的结果和安全性。
An improved understanding of the pathogenesis in apolipoprotein L1 gene (APOL1)-gene associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys. This manuscript reviews the potential mechanisms that underlie development of APOL1-associated nephropathy. Roles for circulating APOL1 protein versus intrinsic renal expression of APOL1 are discussed, as well as the requirement for modifying genetic and/or environmental factors. Abundant evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy; this is true in both native kidney disease and after renal transplantation. Only a minority of kidneys from individuals with APOL1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation. Therefore, modifying factors that explain why only a subset of kidneys develops nephropathy remain critical to identify. It appears likely that environmental exposures, as opposed to major APOL1-second gene interactions, will prove to be stronger modifiers of the risk for nephropathy. The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health-sponsored “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation.