Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease
Genetics May Predict Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease
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遗传学可以预测托伐普坦治疗常染色体显性多囊肾病的有效性
DOI：
10.1159/000509817
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发表时间：
2020
影响因子：
4.2
通讯作者：
Uchida Shinic
中科院分区：
文献类型：
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作者：
Sekine Akinari;Hoshino Junichi;Fujimaru Takuya;Suwabe Tatsuya;Mizuno Hiroki;Kawada Masahiro;Hiramatsu Rikako;Hasegawa Eiko;Yamanouchi Masayuki;Hayami Noriko;Mandai Shintaro;Chiga Motoko;Kikuchi Hiroaki;Ando Fumiaki;Mori Takayasu;Sohara Eisei;Uchida Shinic
托伐普坦是目前治疗常染色体显性遗传性多囊肾病（ADPKD）的唯一药物。多囊肾病1和2基因突变的影响（PKD 1和PKD 2）方法我们回顾性评估了2016年4月至2020年2月期间在虎之门医院接受治疗并接受基因检测的18例ADPKD患者的基因型与托伐普坦疗效之间的关系。从托伐普坦治疗前至治疗后，PKD 1截短组的估计肾小球滤过率（ΔeGFR/y）中位数为− 5.5至− 2.5 mL/min/1.73 m2，PKD 1非截短组为− 3.3至− 2.4 mL/min/1.73 m2，PKD 2组为− 3.1至− 1.6 mL/min/1.73 m2，无PKD 1/2突变组为-1.9 ~-2.6 mL/min/1.73 m2。ΔeGFR/y的中位改善程度分别为2.5（45%）、0.4（10%）、0.6（28%）和− 0.7（− 37%）mL/min/1.73 m 2。与有任何PKD 1/2突变的患者组相比，无PKD 1/2突变的患者组显示托伐普坦对ΔeGFR/y的改善显著较少（分别为0.6和-0.7 mL/min/1.73 m2; p= 0.01），托伐普坦组总肾脏体积（TKV）年增加率的改善显著较小（分别为-6.7% vs.-1.1%; p= 0.02）.结论患有ADPKD且无PKD 1/2突变的患者在托伐普坦治疗后ΔeGFR/y和TKV年增加率的改善较小。检测PKD 1/2突变可能有助于预测托伐普坦的有效性。
BackgroundTolvaptan is the only therapeutic drug for autosomal dominant polycystic kidney disease (ADPKD). The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature.MethodsWe retrospectively evaluated the relationship between genotype and the efficacy of tolvaptan in 18 patients with ADPKD who had been treated at Toranomon Hospital and undergone genetic testing between April 2016 and February 2020.ResultsThe annual change in estimated glomerular filtration rate (ΔeGFR/y) from before to after tolvaptan was from a median of− 5.5 to− 2.5 mL/min/1.73 m 2 in the PKD1 truncating group,− 3.3 to− 2.4 mL/min/1.73 m 2 in the PKD1 non-truncating group,− 3.1 to− 1.6 mL/min/1.73 m 2 in the PKD2 group, and− 1.9 to− 2.6 mL/min/1.73 m 2 in the group with no PKD1/2 mutation. The median degrees of improvement of ΔeGFR/y were 2.5 (45%), 0.4 (10%), 0.6 (28%), and− 0.7 (− 37%) mL/min/1.73 m 2, respectively. Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in ΔeGFR/y with tolvaptan (0.6 vs.− 0.7 mL/min/1.73 m 2, respectively; p= 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (− 6.7 vs.− 1.1%, respectively; p= 0.02).ConclusionPatients with ADPKD and no PKD1/2 mutation showed less improvement in ΔeGFR/y and the annual rate of increase in TKV with tolvaptan. Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.