Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1.
BACKGROUND
Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD.


METHODS
This cross-sectional study was performed using a cohort of adult patients with SCD and control subjects without SCD. Spot urine for microalbumin/creatinine ratio, measures of hemolysis, inflammation and other laboratory studies were obtained. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age-, sex- and body mass index-adjusted reference ranges.


RESULTS
Seventy-three patients with SCD and 21 healthy, race-matched control subjects were evaluated. In patients with SCD, normoalbuminuria was observed in 34 patients (46.6%), microalbuminuria in 24 patients (32.9%) and macroalbuminuria in 15 patients (20.5%). There was a significant correlation between urine albumin excretion and age. In patients with HbSS and Sbeta(0) thalassemia, the levels of sFLT-1, soluble VCAM and NT pro-BNP were significantly higher in those with macroalbuminuria, compared to patients with microalbuminuria and normoalbuminura, but no significant differences were observed in the levels of laboratory measures of hemolysis. Urine albumin excretion was associated with PHT and a history of stroke.


CONCLUSIONS
Our study confirms the high prevalence of albuminuria in SCD. The association of urine albumin excretion with sFLT-1 suggests that this vascular endothelial growth factor receptor family member may contribute to the development of albuminuria in SCD. By inducing endothelial activation and endothelial dysfunction, sFLT-1 appears to be a link between glomerulopathy and PHT in SCD.
Ataga
Kenneth I
KI
Comprehensive Sickle Cell Program, University of North Carolina, Chapel Hill, NC, USA. kataga@med.unc.edu
Brittain
Julia E
JE
Moore
Dominic
D
Jones
Susan K
SK
Hulkower
Ben
B
Strayhorn
Dell
D
Adam
Soheir
S
Redding-Lallinger
Rupa
R
Nachman
Patrick
P
Orringer
Eugene P
EP
D000328:Adult; D017677:Age Distribution; D000375:Aging; D000419:Albuminuria / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000652:urine*; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D007677:Kidney Function Tests; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D055815:Young Adult
C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1