Monogenic alterations cause a variety of paediatric kidney diseases; however, insights into their association with clinical outcomes are limited. New analyses of three cohorts demonstrate that monogenic kidney disorders are associated with an increased risk of kidney failure. “These data suggest that recognition of genetic kidney disorders will be important for clinical evaluation, understanding prognosis, and counselling for patients,” say the researchers.

Mark Elliott and colleagues evaluated associations between diagnostic genetic analysis and clinical outcomes in three cohorts: the prospective Cure Glomerulonephropathy Network (CureGN) and two retrospective cohorts from Columbia University including 5,727 adults and children with kidney disease who underwent whole-genome or exome sequencing. Across all three cohorts, individuals with monogenic kidney disorders experienced an increased risk of kidney failure compared to those without (CureGN: HR 2.44, P = 2.42 × 10^–3; Columbia-GN: HR 1.84, P = 0.033; Columbia-CKD: HR 1.59, P = 2.06 × 10^–8). Individuals with monogenic kidney disorders also had a higher rate of decline in estimated glomerular filtration rate (eGFR) and were less likely to achieve complete remission. In two of the cohorts (Columbia-GN and Columbia-CKD), patients with high-risk APOL1 genotypes also had an increased risk of kidney failure, whereas patients with high-risk APOL1 genotypes in the CureGN cohort demonstrated a higher rate of eGFR decline. The researchers say their findings should motivate the search for more effective therapies for genetic kidney disorders.

单基因改变会导致各种儿科肾病;然而，对它们与临床结果关联的见解是有限的。对三个队列的新分析表明，单基因肾病与肾衰竭风险增加有关。“这些数据表明，识别遗传性肾病对于临床评估、了解预后和为患者提供咨询非常重要，”研究人员说。

Mark Elliott 及其同事在三个队列中评估了诊断遗传分析与临床结果之间的关联：前瞻性治愈肾小球肾病网络 （CureGN） 和来自哥伦比亚大学的两个回顾性队列，包括 5,727 名接受全基因组或外显子组测序的肾病成人和儿童。在所有三个队列中，与没有单基因肾病的个体相比，单基因肾病个体发生肾衰竭的风险增加（CureGN：HR 2.44，P = 2.42 × ^10-3;Columbia-GN：HR 1.84，P = 0.033;Columbia-CKD：HR 1.59，P = 2.06 × ^10-8）。患有单基因肾病的个体估计肾小球滤过率 （eGFR） 的下降率也较高，并且不太可能达到完全缓解。在其中两个队列 （Columbia-GN 和 Columbia-CKD） 中，高危 APOL1 基因型患者患肾衰竭的风险也增加，而 CureGN 队列中高危 APOL1 基因型的患者表现出更高的 eGFR 下降率。研究人员表示，他们的发现应该会促使人们寻找更有效的遗传性肾病治疗方法。