Kidney Function in Sickle Cell Anemia

Sickle cell disease is a severe monogenic disorder which affects approximately 80,000
patients in the US. It is characterized by a vasculopathy with involvement of multiple organs
and resulting in complications such as ischemic stroke, pulmonary hypertension,
autosplenectomy, priapism, as well as chronic kidney disease (CKD). Despite the high
prevalence of CKD and its known association with increased mortality, the natural history of
CKD and the factors associated with changes in kidney function in patients with SCD remain
incompletely defined. Furthermore, the available treatment options for albuminuria, an early
manifestation of CKD, in patients with SCD are limited. In fact, no controlled studies have
confirmed the long-term efficacy of angiotensin-converting enzyme (ACE) inhibitors, the
current "standard of care." There is increasing evidence for a contribution of endothelial
dysfunction to the pathophysiology of albuminuria in SCD. The association of biomarkers of
endothelial function with albuminuria provides opportunities, not only to assess the effect
of therapies which improve endothelial function, but also to evaluate the predictive value of
these biomarkers for a decline in kidney function. The long-range goal is to develop a model
to identify patients at particularly high risk for a decline in kidney function.

In this study, the investigators will evaluate rate of change in kidney function (decline in
estimated glomerular filtration rates and increase in albuminuria) and identify biomarkers of
endothelial function, metabolomic profiles and clinical characteristics for the worsening of
kidney function and for a rapid decline in kidney function. At the conclusion of this
proposed work, the investigators will have an improved understanding of the natural history
of CKD in sickle cell anemia. With the limited available therapies for the treatment of
albuminuria in SCD and the paucity of data on the long-term efficacy of available
pharmacotherapies, identification of biomarkers for the progression of CKD will facilitate
the development of treatments which may be more effective than the current "standard of
care."

Inclusion Criteria:

1. age of 18 to 65 years;

2. confirmed diagnosis of sickle cell anemia (HbSS and SB0 thalassemia);

3. non-crisis, "steady state" with no severe pain episodes requiring medical contact
during the preceding 4 weeks;

4. ability to understand the requirements of the study and be willing to give informed
consent.

Exclusion Criteria:

1. bone marrow transplantation;

2. history of long-standing diabetes mellitus with suspicion for diabetic nephropathy as
determined by a nephrologist;

3. known diagnosis of hepatitis B or C infection (patients will not be screened
specifically for this during the study);

4. known HIV positive (patients will not be screened specifically for this);

5. history of cancer, except non-melanoma skin cancer;

6. pregnant or breastfeeding;

7. connective tissue disease such as SLE;

8. known glomerular disease unrelated to SCD;

9. patients with ESRD on chronic dialysis.