Effects of Renin-Angiotensin Blockade and APOL1 on Kidney Function in Sickle Cell Disease.

Effects of Renin-Angiotensin Blockade and APOL1 on Kidney Function in Sickle Cell Disease.
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DOI:
10.1002/jha2.259
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发表时间:
2021-08
期刊:
EJHaem
影响因子:
--
通讯作者:
Saraf SL
Saraf SL
中科院分区:
其他
文献类型:
--
作者:
Han J;Srisuwananukorn A;Shah BN;Molokie RE;Lash JP;Gordeuk VR;Saraf SL

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肾脏疾病是一种常见的并发症,导致镰状细胞病(SCD)患者的发病率和早期死亡率增加。[1]SCD相关肾脏疾病的治疗已从用于治疗其他肾脏疾病原因的治疗(血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂[ACEi/ARB])中采用,尽管其安全性和对肾功能的影响尚不清楚。[2]在SCD患者中,APOL 1 G1和G2肾脏风险变体的纯合或复合杂合遗传可使慢性肾脏疾病(CKD)风险增加约7倍。[3]在非裔美国人肾脏疾病和高血压研究(AASK)队列中观察到ACEi降低携带APOL 1肾脏风险变体的非裔美国人肾脏疾病进展风险的潜在获益。[4]相比之下,ACEi/ARB治疗不能降低HIV相关肾病和APOL 1肾病风险变异患者进展为终末期肾病的风险。[5]ACEi/ARB对遗传性SCD和APOL 1肾脏风险变异患者肾功能的影响尚不清楚。我们假设APOL 1肾脏风险变异的共同遗传可能会降低ACEi/ARB在SCD患者中减少白蛋白尿的获益。
Kidney disease is a common complication that leads to increased morbidity and early mortality in patients with sickle cell disease (SCD).[1] Treatments for SCD-related kidney disease have been adopted from therapies used to treat other causes of kidney disease (angiotensin converting enzyme-inhibitor or angiotensin receptor blocker [ACEi/ARB]), although their safety and effects on kidney function are not clear.[2] Homozygous or compound heterozygous inheritance of the APOL1 G1 and G2 kidney risk variants increases the risk for chronic kidney disease (CKD) approximately seven-fold in SCD.[3] The potential benefit for ACEi to reduce the risk of kidney disease progression in African Americans with the APOL1 kidney risk variants has been observed in the African American Study of Kidney Disease and Hypertension (AASK) cohort.[4] In contrast, ACEi/ARB therapy did not reduce the risk for progression to end-stage kidney disease in people with HIV-related kidney disease and the APOL1 kidney risk variants.[5] The effects of ACEi/ARB on kidney function in those that have inherited SCD and the APOL1 kidney risk variants are not well understood. We hypothesized that co-inheritance of the APOL1 kidney risk variants may reduce the benefit of ACEi/ARB on the reduction of albuminuria in SCD.
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