Sickle cell trait (SCT) affects over 1 in 12 African Americans in the United States and nearly 300 million people worldwide. Although SCT has largely been considered a benign condition, emerging evidence suggests that acute and chronic sickling in the setting of low oxygen tension or stress may lead to clinical complications in affected carriers. In particular, the hypoxic environment of the renal medulla appears to induce local red blood cell sickling, ultimately resulting in vascular damage and chronic kidney disease (CKD). A similar process may also occur in the hypoxic venous system of the body, leading to coagulation activation and an increased risk of venous thromboembolism (VTE). The risk of both CKD and VTE appears to be higher in African Americans compared to other populations; therefore SCT may be an important and unrecognized genetic modifier of disease in this population. Dr. Naik is an Assistant Professor in the Division of Hematology at Johns Hopkins whose long-term aspiration is to become an independent investigator in sickle cell trait with the goal of developing evidence-based screening, genetic counseling, and treatment guidelines for affected individuals. The overall aims of her proposal are to elucidate the potential complications of SCT and to determine the impact of SCT on CKD and VTE risk in African Americans. She will first perform a rigorous systematic review of the published literature to identify important clinicl complications related to SCT, determine the strength of the existing literature, and identify gaps in current knowledge. Using advanced epidemiologic techniques, she will then analyze data from well-characterized cohorts with large numbers of African-American participants to characterize the risk of CKD and VTE in individuals with SCT. This research will contribute critical knowledge about the complications of SCT and will provide framework for future epidemiologic, translational, and treatment studies in SCT. In addition, with the support of this K08 Mentored Career Development Award, Dr. Naik will integrate a well-rounded, multi-disciplinary mentorship team, a focused training plan, and an innovative research strategy to ensure her successful transition to an independent investigator.

Public Health Relevance

Sickle cell trait affects 300 million people worldwide. This research uses advanced epidemiologic methods to identify complications of sickle trait and define sickle hemoglobin as a genetic modifier of chronic kidney disease and venous thromboembolism risk in African Americans. The insights gained from these studies will build a foundation for the development of disease screening and treatment strategies in individuals with sickle cell trait.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL125100-03
Application #
9269614
Study Section
Special Emphasis Panel (MCBS (JA))
Program Officer
Werner, Ellen
Project Start
2015-04-01
Project End
2019-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
3
Fiscal Year
2017
Total Cost
$171,720
Indirect Cost
$12,720
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Hyacinth, Hyacinth I; Carty, Cara L; Seals, Samantha R et al. (2018) Association of Sickle Cell Trait With Ischemic Stroke Among African Americans: A Meta-analysis. JAMA Neurol 75:802-807
Pecker, Lydia H; Naik, Rakhi P (2018) The current state of sickle cell trait: implications for reproductive and genetic counseling. Hematology Am Soc Hematol Educ Program 2018:474-481
Naik, Rakhi P; Marrone, Kristen; Merrill, Samuel et al. (2018) Single-board hematology fellowship track: a 10-year institutional experience. Blood 131:462-464
Pecker, Lydia H; Naik, Rakhi P (2018) The current state of sickle-cell trait: implications for reproductive and genetic counseling. Blood :
Naik, Rakhi P; Smith-Whitley, Kim; Hassell, Kathryn L et al. (2018) Clinical Outcomes Associated With Sickle Cell Trait: A Systematic Review. Ann Intern Med 169:619-627
Naik, Rakhi P; Derebail, Vimal K (2017) The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait. Expert Rev Hematol 10:1087-1094
Beckermann, Kathryn E; Sharma, Deva; Chaturvedi, Shruti et al. (2017) Renal Medullary Carcinoma: Establishing Standards in Practice. J Oncol Pract 13:414-421
Naik, Rakhi P; Irvin, Marguerite R; Judd, Suzanne et al. (2017) Sickle Cell Trait and the Risk of ESRD in Blacks. J Am Soc Nephrol 28:2180-2187
Lanzkron, Sophie; Naik, Rakhi P (2017) Negative studies shape the state of sickle trait. Blood 129:661-662
Bello, Natalie A; Hyacinth, Hyacinth I; Roetker, Nicholas S et al. (2017) Sickle cell trait is not associated with an increased risk of heart failure or abnormalities of cardiac structure and function. Blood 129:799-801

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