Abstract / Summary
BackgroundSickle-cell trait (SCT) is historically regarded as a benign carrier state, although emerging evidence from athletic and military cohorts suggests increased vulnerability during physiological stress.In this study, we aimed to identify the incidence of acute renal and hemodynamic complications in adolescent and younger adult patients with SCT or sickle-cell disease (SCD) and compare these risks against propensity-matched controls from the general non-sickle-cell population. MethodsA retrospective analysis of the TriNetX global network was performed.Patients aged 13-40 years with SCD or SCT were identified and propensity-score matched to non-sickle-cell controls based on age, sex, race, comorbidities, and medication use.Univariate analyses and Kaplan-Meier survival analysis assessed relative risk and time-to-event for rhabdomyolysis, heat-related illness, acute kidney failure, dehydration, electrolyte imbalance, syncope/collapse, and hemodynamic shock within five years.Subgroup analysis of differences in outcomes between SCD and SCT patients was performed. ResultsA total of 24,178 patients remained per cohort (SCD/SCT and no SCD/SCT) after matching.Compared to controls, the sickle-cell cohort exhibited significantly higher risks of dehydration (RR = 1.62, 95% CI 1.48-1.77),acute kidney failure (RR = 1.76, 95% CI 1.56-1.98),electrolyte imbalance (RR = 1.66, 95% CI 1.55-1.78),and hypotension/volume-depletion shock (RR = 1.71, 95% CI 1.47-1.99)(all P < 0.001).In subgroup analysis, SCD showed higher risk than SCT for most outcomes, but they experienced less syncope/collapse (RR = 0.74, 95% CI 0.64-0.85,P < 0.001). ConclusionAdolescents and young adults with sickle-cell hemoglobinopathies face significant renal and hemodynamic vulnerabilities.Higher collapse incidence in SCT suggests unique susceptibility to acute hemodynamic failure.These findings have generated hypotheses that are worth prospective investigations, including the development of universal-precaution protocols and monitoring key subclinical biomarkers, which might help identify patients undergoing significant physiological strain before a clinical crisis develops.However, further prospective research incorporating detailed laboratory data and extended observation periods is necessary to determine if such strategies can be effectively translated into evidence-based care for the wider young-adult sickle-cell population.