Effects of α-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait

Abstract

A defect in urine concentrating ability occurs in individuals with sickle cell trait (HbAS). This may result from intracellular polymerization of sickle hemoglobin (HbS) in erythrocytes, leading to microvascular occlusion, in the vasa recta of the renal medulla. To test the hypothesis that the severity of the concentrating defect is related to the percentage of sickle hemoglobin present in erythrocytes, urinary concentrating ability was examined after overnight water deprivation, and intranasal desmopressin acetate (dDAVP) in 27 individuals with HbAS. The HbAS individuals were separated into those who had a normal α-globin genotype (αα/αα), and those who were either heterozygous (-α/αα) or homozygous (-α/-α) for gene-deletion α-thalassemia, because α-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the αα/αα genotype than in the -α/αα or -α/-α genotypes (P < 0.05). After dDAVP, the urine osmolality was greater in patients with the -α/-α genotype than with the -α/αα genotype (882±37 vs. 672±38 mOsm/kg H2O) (P < 0.05); patients with the -α/αα genotype had greater concentrating ability than individuals with a normal α-globin gene arrangement. There was an inverse linear correlation between urinary osmolality after dDAVP and the percentage HbS in all patients studied (r = -0.654; P < 0.05). A linear correlation also existed for urine concentrating ability and the calculated polymerization tendencies for an oxygen saturation of 0.4 and O (r = -0.62 and 0.69, respectively). We conclude that the severity of hyposthenuria in HbAS is heterogeneous. It is determined by the amount of HbS polymer, that in turn is dependent upon the percentage HbS, which is itself related to the α-globin genotype. (J. Clin. Invest. 1991. 88:1963-1968.).