Significance of proposed research: Untreated hypertension and renal injury are risk factors for increased morbidity and mortality in sickle cell disease, yet early markers of progressive disease have not been identified and therapies to prevent the development of adverse cardiovascular outcomes have not been defined. Circadian blood pressure, as defined by 24 hour blood pressure monitoring, is more accurate than clinic blood pressure in defining secondary hypertension and abnormal nocturnal blood pressured dipping has been linked to progressive renal disease in other diseases. Methodology/Aims: A randomized feasibility trial of losartan will be conducted among 40 adolescent HbSS and SB0 thalassemia patients (11-19 years) with abnormal nocturnal blood pressure dipping. During this six month feasibility trial, two dosing strategies of losartan (titraed to keep BP <95th percentile vs. <75th percentile) will be analyzed for safety and effect on restoring normal circadian blood pressure. A prospective cohort study among HbSS and SB0 thalassemia patients (6-19 years) will also be conducted to evaluate the incidence of hypertension and role of monitoring potential biomarkers of kidney injury and hypertension. Cohort participants will undergo annual evaluations of hypertension and markers of kidney injury (24 hour blood pressure monitoring for participants = 11yrs; Blood: uric acid; Urine: Cystatin-c, Kim-1, NGAL, B2M). Expected Results: At the completion of the feasibility trial, vital background information will be obtained to design a definitive multicenter trial of hypertension in sickle cel disease. At the completion of the cohort study, the incidence of pediatric hypertension will be identified and the role for monitoring blood and urine biomarkers will be better understood. As therapy for patients with renal failure is dismal, it is imperative that SCD patients at risk ar identified early and that therapeutic trials are conducted that prevent progression.
Hypertension is a known risk factor for stroke in sickle cell disease and in other diseases associated with adverse cardiovascular outcomes. Within the context of a feasibility trial, this proposal will develop vital background data to understand the acceptability of, adherence to, and dosing strategy for losartan prior to conducting a definitive trial for adolescent sickle cell disease patients with abnormal circadian blood pressure. A prospective cohort study will also be conducted to define the relationship of urine and blood biomarkers on the development of abnormal nocturnal blood pressure dipping and kidney injury.
| Hilliard, Lee M; Kulkarni, Varsha; Sen, Bisakha et al. (2018) Red blood cell transfusion therapy for sickle cell patients with frequent painful events. Pediatr Blood Cancer 65:e27423 |
| Payne, Jason; Aban, Inmaculada; Hilliard, Lee M et al. (2018) Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis. Pediatr Blood Cancer 65:e27420 |
| Oakley, Jamie; Zahr, Rima; Aban, Inmaculada et al. (2018) Acute Kidney Injury during Parvovirus B19-Induced Transient Aplastic Crisis in Sickle Cell Disease. Am J Hematol : |
| Sirigaddi, Krishnaveni; Aban, Inmaculada; Jantz, Amelia et al. (2018) Outcomes of febrile events in pediatric patients with sickle cell anemia. Pediatr Blood Cancer 65:e27379 |
| Lebensburger, Jeffrey D; Cutter, Gary R; Howard, Thomas H et al. (2017) Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia. Pediatr Nephrol 32:1565-1573 |
| Baddam, Sujatha; Cutter, Gary R; Wolfson, Julie A et al. (2017) Publication outcomes of abstracts from the American Society of Hematology Annual Meeting. Am J Hematol 92:E81-E83 |
| Aban, Inmaculada; Baddam, Sujatha; Hilliard, Lee M et al. (2017) Severe anemia early in life as a risk factor for sickle-cell kidney disease. Blood 129:385-387 |
| Baddam, Sujatha; Aban, Inmaculada; Hilliard, Lee et al. (2017) Acute kidney injury during a pediatric sickle cell vaso-occlusive pain crisis. Pediatr Nephrol 32:1451-1456 |
| Hamm, Jennifer; Hilliard, Lee; Howard, Thomas et al. (2016) Maintaining High Level of Care at Satellite Sickle Cell Clinics. J Health Care Poor Underserved 27:280-292 |
| Lebensburger, Jeffrey D; Palabindela, Prasannalaxmi; Howard, Thomas H et al. (2016) Prevalence of acute kidney injury during pediatric admissions for acute chest syndrome. Pediatr Nephrol 31:1363-8 |
Showing the most recent 10 out of 13 publications
