Baddam Sujatha, Rout Preeti
Huntsville Hospital, Huntsville
Wilson Case Western University
Sickle cell disease refers to a group of disorders in which the sickle mutation is coinherited with a pathogenic variant at the other beta-globin allele that reduces or abolishes normal beta-globin production. These disorders include sickle cell anemia (homozygous sickle mutation [Hb SS]), sickle-beta thalassemia, hemoglobin SC disease, and other variants. A common feature of all types of sickle cell disease is that hemoglobin S (Hb S) constitutes over 50% of total hemoglobin and is the predominant form. Sickle cell disease is an autosomal recessive hemoglobinopathy caused by the substitution of valine for glutamate at the sixth position of the beta-globin chain. This mutation promotes hemoglobin S tetramer formation during oxidative stress, dehydration, or hypoxia, resulting in red blood cell (RBC) sickling, premature erythrocyte destruction, and widespread vaso-occlusive episodes, leading to multiorgan damage. Renal manifestations, collectively referred to as sickle cell nephropathy, are common and include hematuria, hyposthenuria, renal papillary necrosis, proteinuria, renal tubular acidosis, acute and chronic kidney injury, sickle cell glomerulopathy, and renal medullary carcinoma. Notably, significant renal involvement occurs more frequently in sickle cell disease than in sickle cell trait or other combined hemoglobinopathies, although renal medullary carcinoma is more common in sickle cell trait. Patients with sickle cell disease face a high risk of morbidity and mortality due to nephropathy. Kidney involvement is particularly concerning due to its early onset and devastating progression. Approximately 10% to 20% of all deaths in patients with sickle cell anemia are due to renal disease, and 30% of deaths in patients with sickle cell anemia are due to irreversible organ failure are complicated by kidney failure. Several challenges compound this burden: Patients with sickle cell disease tend to develop renal failure at a younger age. These patients face a higher mortality following end-stage kidney disease compared to Black patients without sickle cell disease. Historically, outcomes after renal transplantation have been poor, leading many transplant centers to avoid putting these patients on the transplant list, despite recent improvements in post-transplant survival rates.
镰状细胞病是指一组疾病，其中镰状突变与另一个β珠蛋白等位基因上的致病变异共同遗传，该致病变异会减少或消除正常的β珠蛋白生成。这些疾病包括镰状细胞贫血（纯合镰状突变[Hb SS]）、镰状-β地中海贫血、血红蛋白SC病以及其他变异型。所有类型镰状细胞病的一个共同特征是血红蛋白S（Hb S）占总血红蛋白的50%以上，且是主要形式。镰状细胞病是一种常染色体隐性血红蛋白病，由β珠蛋白链第六位的缬氨酸替代谷氨酸所致。这种突变在氧化应激、脱水或缺氧时促进血红蛋白S四聚体形成，导致红细胞（RBC）镰变、红细胞过早破坏以及广泛的血管阻塞发作，进而导致多器官损害。肾脏表现统称为镰状细胞肾病，很常见，包括血尿、低渗尿、肾乳头坏死、蛋白尿、肾小管酸中毒、急性和慢性肾损伤、镰状细胞肾小球病以及肾髓质癌。值得注意的是，尽管肾髓质癌在镰状细胞性状中更常见，但镰状细胞病中显著的肾脏受累比镰状细胞性状或其他合并血红蛋白病更频繁。镰状细胞病患者因肾病面临高发病率和死亡率风险。肾脏受累因其发病早且进展具有破坏性而尤为令人担忧。镰状细胞贫血患者中约10%至20%的死亡归因于肾脏疾病，镰状细胞贫血患者中30%因不可逆器官衰竭而死亡且伴有肾衰竭并发症。有几个挑战加剧了这一负担：镰状细胞病患者往往在年轻时就发展为肾衰竭。与没有镰状细胞病的黑人患者相比，这些患者在终末期肾病后死亡率更高。从历史上看，肾移植后的结果一直很差，导致许多移植中心避免将这些患者列入移植名单，尽管移植后存活率最近有所提高。
