Effects of Alpha-thalassemia and Sickle Polymerization Tendency on the Urine-concentrating Defect of Individuals with Sickle Cell Trait

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1991 Dec 1

PMID 1752955

Citations 33

Authors

A K Gupta

K A Kirchner

R Nicholson

J G Adams 3rd

A N Schechter

C T Noguchi

M H Steinberg

Affiliations

Soon will be listed here.

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 alpha-globin genotype (alpha alpha/alpha alpha), and those who were either heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) for gene-deletion alpha-thalassemia, because alpha-thalassemia modulates the HbS concentration in HbAS. The urinary concentrating ability was less in the alpha alpha/alpha alpha genotype than in the -alpha/alpha alpha or -alpha/-alpha genotypes (P less than 0.05). After dDAVP, the urine osmolality was greater in patients with the -alpha/-alpha genotype than with the -alpha/alpha alpha genotype (882 +/- 37 vs. 672 +/- 38 mOsm/kg H2O) (P less than 0.05); patients with the -alpha/alpha alpha genotype had greater concentrating ability than individuals with a normal alpha-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 less than 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 alpha-globin genotype.

Citing Articles

Sickle Cell Screening in Adults: A Current Review of Point-of-Care Testing.

Mendez-Marti S, Zik C, Alan S, Wang H, Ershler W J Hematol. 2024; 13(3):53-60.

PMID: 38993742 PMC: 11236353. DOI: 10.14740/jh1272.

Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Hong H, Gouveia M, Ogwang M, Kerchan P, Reynolds S, Tenge C Am J Hematol. 2023; 99(1):113-123.

PMID: 38009642 PMC: 10872868. DOI: 10.1002/ajh.27149.

The nephropathy of sickle cell trait and sickle cell disease.

Ataga K, Saraf S, Derebail V Nat Rev Nephrol. 2022; 18(6):361-377.

PMID: 35190716 PMC: 9832386. DOI: 10.1038/s41581-022-00540-9.

5-(Hydroxymethyl)furfural restores low-oxygen rheology of sickle trait blood in vitro.

Hansen S, Wood D, Higgins J Br J Haematol. 2020; 188(6):985-993.

PMID: 31889311 PMC: 7150585. DOI: 10.1111/bjh.16251.

Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study.

Olaniran K, Allegretti A, Zhao S, Achebe M, Eneanya N, Thadhani R J Am Soc Nephrol. 2019; 31(2):393-404.

PMID: 31810990 PMC: 7003305. DOI: 10.1681/ASN.2019050502.

References

PERILLIE P, EPSTEIN F . Sickling phenomenon produced by hypertonic solutions: a possible explanation for the hyposthenuria of sicklemia. J Clin Invest. 1963; 42:570-80. PMC: 289317. DOI: 10.1172/JCI104746. View

Weatherall D, Clegg J, Blankson J, McNeil J . A new sickling disorder resulting from interaction of the genes for haemoglobin S and alpha-thalassaemia. Br J Haematol. 1969; 17(6):517-26. DOI: 10.1111/j.1365-2141.1969.tb01402.x. View

Hebbel R . Beyond hemoglobin polymerization: the red blood cell membrane and sickle disease pathophysiology. Blood. 1991; 77(2):214-37. View

Fodde R, Losekoot M, Van Den Broek M, Oldenburg M, Rashida N, Schreuder A . Prevalence and molecular heterogeneity of alfa+ thalassemia in two tribal populations from Andhra Pradesh, India. Hum Genet. 1988; 80(2):157-60. DOI: 10.1007/BF00702860. View

Steinberg M, Embury S . Alpha-thalassemia in blacks: genetic and clinical aspects and interactions with the sickle hemoglobin gene. Blood. 1986; 68(5):985-90. View

Bowden D, Hill A, Higgs D, Oppenheimer S, Weatherall D, Clegg J . Different hematologic phenotypes are associated with the leftward (-alpha 4.2) and rightward (-alpha 3.7) alpha+-thalassemia deletions. J Clin Invest. 1987; 79(1):39-43. PMC: 423981. DOI: 10.1172/JCI112804. View

Liebhaber S, COLEMAN M, Adams 3rd J, Cash F, Steinberg M . Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG). J Clin Invest. 1987; 80(1):154-9. PMC: 442213. DOI: 10.1172/JCI113041. View

Steinberg M, COLEMAN M, Adams 3rd J, Hartmann R, Saba H, Anagnou N . A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait. Blood. 1986; 67(2):469-73. View

Keidan A, Sowter M, Johnson C, Noguchi C, Girling A, Stevens S . Effect of polymerization tendency on haematological, rheological and clinical parameters in sickle cell anaemia. Br J Haematol. 1989; 71(4):551-7. DOI: 10.1111/j.1365-2141.1989.tb06316.x. View

10.

Green M, Noguchi C, Keidan A, Marwah S, Stuart J . Polymerization of sickle cell hemoglobin at arterial oxygen saturation impairs erythrocyte deformability. J Clin Invest. 1988; 81(6):1669-74. PMC: 442609. DOI: 10.1172/JCI113504. View

11.

Fabry M, Mears J, Patel P, Carmichael L, Martinez G, Nagel R . Dense cells in sickle cell anemia: the effects of gene interaction. Blood. 1984; 64(5):1042-6. View

12.

Brezis M, Rosen S, Silva P, EPSTEIN F . Renal ischemia: a new perspective. Kidney Int. 1984; 26(4):375-83. DOI: 10.1038/ki.1984.185. View

13.

Eaton W, Hofrichter J . Hemoglobin S gelation and sickle cell disease. Blood. 1987; 70(5):1245-66. View

14.

BUNN H . Subunit assembly of hemoglobin: an important determinant of hematologic phenotype. Blood. 1987; 69(1):1-6. View

15.

Kennedy A, Walsh D, Nicholson R, Adams 3rd J, Steinberg M . Influence of HbS levels upon the hematological and clinical characteristics of sickle cell trait. Am J Hematol. 1986; 22(1):51-4. DOI: 10.1002/ajh.2830220108. View

16.

Brugnara C, BUNN H, Tosteson D . Regulation of erythrocyte cation and water content in sickle cell anemia. Science. 1986; 232(4748):388-90. DOI: 10.1126/science.3961486. View

17.

Wilson J, Headlee M, HUISMAN T . A new high-performance liquid chromatographic procedure for the separation and quantitation of various hemoglobin variants in adults and newborn babies. J Lab Clin Med. 1983; 102(2):174-86. View

18.

Noguchi C . Polymerization in erythrocytes containing S and non-S hemoglobins. Biophys J. 1984; 45(6):1153-8. PMC: 1434986. DOI: 10.1016/S0006-3495(84)84263-0. View

19.

Embury S, Clark M, MONROY G, Mohandas N . Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes. J Clin Invest. 1984; 73(1):116-23. PMC: 424978. DOI: 10.1172/JCI111181. View

20.

Noguchi C, Torchia D, Schechter A . Determination of deoxyhemoglobin S polymer in sickle erythrocytes upon deoxygenation. Proc Natl Acad Sci U S A. 1980; 77(9):5487-91. PMC: 350086. DOI: 10.1073/pnas.77.9.5487. View