Sickle Cell Disease
Conditions
Keywords
Sickle Nephropathy, Iothalamate, Cystatin-C, Natural History
Brief summary
Background: Sickle cell disease is a common inherited blood disorder. Kidney disease is a major cause of problems in people with sickle cell disease. In order to identify kidney problems early and stop the progression of kidney disease, doctors need the most accurate tests to check kidney function. Researchers hope to understand more about how to test for kidney disease in people with sickle cell disease. Objective: To determine which of two different lab tests is the best to measure kidney function in adults with sickle cell disease. Eligibility: People 18 years and older who have sickle cell disease Design: Participants will be screened with a medical history and blood tests. Participants will have up to 3 visits. Participants will collect their urine in a special container over 24 hours. At the first visit, participants will have blood tests. They will bring their container of urine to the visit. They will have an iothalamate test. For the test, they will get a catheter: a small tube will be inserted into a vein. A special contract agent will be injected into the vein. Blood will be collected over the next 4 hours to test kidney function. Participants will return the next day for a second visit. They will have blood tests. They will have an MRI. For the MRI, they will like on a table that slides into a machine that takes pictures of the kidneys. They may have the MRI in a third visit. ...
Detailed description
The characteristic sickling of red blood cells in hypoxic conditions is the root cause of pathology in sickle cell disease (SCD). When this sickling occurs in the renal microvasculature, and is compounded by chronic vasculopathy related to hemolysis, the result is local infarction, ischemic injury, and interstitial fibrosis. The kidney damage begins in early childhood and is cumulative over time, resulting in sickle cell nephropathy (SCN). Creatinine clearance remains the most commonly used method to evaluate renal function in SCD patients although serum creatinine generally over-estimates the GFR in SCD. Cystatin-C (Cys-C) is freely filtered. Unlike creatinine, it is not secreted by the tubules. Its serum levels correlate with GFR in adults with various kidney diseases as well as in pediatric and adult SCD populations as compared with creatinine-based assessments. This study seeks to evaluate whether Cys-C is a better noninvasive measure of renal function in the adult sickle cell population than creatinine. Further, this work will elucidate the ability of other markers, including beta 2-microglobulin (beta 2M) and endothelin-1 (ET-1), to predict sickle nephropathy. Finally, renal imaging by MRI will be performed and correlated with measured GFR and renal function markers. The results of this study could help alter clinical practice and thereby ensure the most accurate non-invasive assessment of kidney function by substantiating the role of Cys-C, beta 2M and ET-1 in adults with SCD. Finally, the descriptive analysis including measured GFR with renal MRI, novel biomarkers, markers of hemolysis, and analysis of urinary protein secretion will contribute to a better understanding of the pathophysiology of SCN.
Interventions
None listed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Known diagnosis of Sickle Cell Anemia (Hb SS or HbS-beta0-thal) \>=18 years of age Willingness and capacity to provide written informed consent
Exclusion criteria
Pregnancy Uncontrolled/poorly controlled hypertension Diabetes Dialysis GFR \<30 ml/min/1.73m2 HIV positive HepatitisC Hepatitis B Prior transplantation Uncontrolled infection or acute illness Chronic inflammatory disease (e.g. lupus, multiple sclerosis, rheumatoid arthritis) Allergy to iodine or iodinated contrast solutions Hydroxyurea initiation or dose adjustment \<2mo prior Initiation of chronic transfusion therapy \<2mo prior Antihypertensive medication initiation or dose adjustment \<1mo prior Pain crisis in preceding 4weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine whether serum cystatin C or serum creatinine-based GFR methods better estimate renal function in the adult sickle cell population | 2 years | In a population of patients with sickle cell anemia (including HbSS, HbS-0 thalassemia), who are age 18 and above, we will comprehensively evaluate renal function with the following primary objective:-determine whether serum cystatin C or serum creatinine- based GFR methods better estimate renal function in the adult sickle cell population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine whether endothelin-1 or beta-2 microglobulin correlates with measured GFR (mGFR) | 2 years | Determine whether endothelin-1 or beta-2 microglobulin correlates with measured GFR (mGFR)-establish potential correlation between mGFR, endothelin-1, or beta-2 microglobulin and renal blood flow-characterize the proteinuria associated with sickle cell disease-characterize kidney anatomy in patients with sickle cell disease-ascertain if markers of hemolysis are associated with mGFR or renal iron deposition-quantify renal iron burden in sickle cell disease |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCourtney F Joseph, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Outcome results
None listed