MPC Member Publications

This database contains a listing of population studies publications written by MPC Members. Anyone can add a publication by an MPC student, faculty, or staff member to this database; new citations will be reviewed and approved by MPC administrators.

Full Citation

Title: Prevalence and outcomes of dehydration in adults with sickle cell trait: the Atherosclerosis Risk in Communities (ARIC) study

Citation Type: Journal Article

Publication Year: 2022

ISSN: 1365-2141

DOI: 10.1111/BJH.18221

Abstract: Sickle cell trait (SCT), the carrier status of the sickle cell gene, has a prevalence of 7%-9% among Black Americans, 1 and is associated with haemoglobin S (HbS) polymerisation and red blood cell (RBC) sickling under conditions of hy-poxia, hypertonicity or extreme exertion. 2 Sickle nephropa-thy, thought to be caused by HbS polymerisation in the low oxygen, hypertonic environment of the renal medulla, is observed both with heterozygous and homozygous inheritance of the HbS gene. 3 SCT has also been prospectively associated with albuminuria, chronic kidney disease (CKD), and end-stage renal disease. 4,5 However, less focus has been directed at hyposthenuria, or the inability to concentrate urine. While hyposthenuria is a known complication of SCT, 6 its functional consequences such as chronic dehydration have not been described in the adult SCT general population. Because hyposthenuria induces polydipsia, it remains uncertain whether SCT is associated with chronic dehydration or related adverse events in the Black general population. To date, most evaluations have been limited to case reports of exercise-induced dehydration in military personnel or athletes with SCT. 2 The Atherosclerosis Risk in Communities (ARIC) study recruited a population-based sample (N = 4266) of Black adults with informed consent, who were aged 45-64 years in 1987-1989. Research activities were approved by Institutional Review Boards. Study participant retention has been excellent across 30 years of follow-up, with 80% of survivors participating in the annual survey in 2019. Black study participants were genotyped for HbS (rs334) and haemoglobin C (rs33930165) using functionally tested TaqMan® SNP Genotyping Assays (Life Technologies), as previously described. 7,8 Clinical characteristics were ascertained at ARIC visit 1 (1987-1989) by standardised clinical examination. Fasting blood samples were analysed by ARIC central laboratories. Calculated plasma osmolality was derived using the following equation: [(2 × serum sodium) + (blood urea nitrogen/2.8) + (blood glucose/18)]. 9 Plasma osmolality of >295 mOsm/kg was considered evidence of dehydration. 9 Hospitalisations and deaths were captured by the ARIC study through active surveillance. Hospitalisations with International Classification of Diseases (ICD)-9 discharge codes 276.0, 276.50, or ICD-10 codes E86.x or E87.0 (in any position) were considered hos-pitalisations for dehydration. A total of 4110 Black study participants was successfully genotyped for HbS and haemoglobin C. After excluding eight participants with HbSC disease or sickle cell anaemia and 383 who were missing fasting blood glucose, serum cre-atinine, and blood urea nitrogen at ARIC visit 1, a total of 3719 remained (Figure S1). Of these, 228 (6%) were identified with SCT. The baseline characteristics of study participants with and without SCT were largely comparable, with the notable exception of factors related to dehydration (plasma os-molality, blood sodium, estimated glomerular filtration rate, and prevalence of CKD; Table S2). At baseline, mean plasma osmolality was higher for SCT than non-carrier genotype, both overall (295 vs. 294 mOsm/kg, p = 0.003) and when excluding participants with CKD or diabetes mellitus (DM) (294 vs. 293 mOsm/kg, p = 0.02). Classification of baseline dehydration also tended to be higher with SCT, both overall (48% vs. 40%, p = 0.02) and among the subset without CKD or DM (42% vs. 35%, p = 0.08). For both genotypes, dehydration was more often noted in women, and was associated with CKD, DM, and phlebotomy during the colder months of the year (Table 1). SCT remained associated with baseline dehydration after adjustment for demographics, season, prevalent CKD and DM (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06-1.85). In a sensitivity analysis limited to the subset without CKD or DM, a similar adjusted association was observed (OR 1.38, 95% CI 1.00-1.91). Over a median follow-up of 27 years, 373 study participants were hospitalised with dehydration and 2006 deaths occurred. The overall death rate was somewhat higher for individuals with SCT than non-carriers (57% vs. 54%); however , the cumulative incidence of dehydration hospitalisa-tions was the same (10% for both). Baseline dehydration was associated with higher mortality, both for participants with SCT (62% vs. 53%) and non-carriers (58% vs. 51%; Figures S3 and S4). After adjustments, baseline dehydration was associated with a 43% higher risk of death for participants with SCT (hazard ratio [HR] 1.43, 95% CI 1.01-2.03), compared with a 10% increased risk of death for non-carriers (HR 1.10, 95% CI 1.00-1.21; Figure 1). However, there was no significant association between baseline dehydration and subsequent hospitalisation for dehydration, for either genotype. Hyposthenuria is commonly observed with sickle hae-moglobinopathies, including SCT. In this analysis of ARIC study participants from the general Black adult population,

Url: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.18221

Url: https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.18221

Url: https://onlinelibrary.wiley.com/doi/10.1111/bjh.18221

User Submitted?: No

Authors: Caughey, Melissa C.; Derebail, Vimal K.; Carden, Marcus A.; Novelli, Enrico M.; Lutsey, Pamela L.; Key, Nigel S.; Kshirsagar, Abhijit V.; Heiss, Gerardo

Periodical (Full): British Journal of Haematology

Issue:

Volume:

Pages:

Countries:

IPUMS NHGIS NAPP IHIS ATUS Terrapop