Best Noninvasive Predictor of Renal Function in Assessing Adult Sickle Nephropathy

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.

• 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