TY - JOUR
T1 - Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease
T2 - Potential role of soluble fms-like tyrosine kinase-1
AU - Ataga, Kenneth I.
AU - Brittain, Julia E.
AU - Moore, Dominic
AU - Jones, Susan K.
AU - Hulkower, Ben
AU - Strayhorn, Dell
AU - Adam, Soheir
AU - Redding-Lallinger, Rupa
AU - Nachman, Patrick
AU - Orringer, Eugene P.
PY - 2010/9
Y1 - 2010/9
N2 - 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. Design and methods: This cross-sectional study was performed using a cohort of adult patients with SCD and control subjects without SCD. Spot urine for microalbumincreatinine 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 S0 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.
AB - 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. Design and methods: This cross-sectional study was performed using a cohort of adult patients with SCD and control subjects without SCD. Spot urine for microalbumincreatinine 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 S0 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.
KW - Sickle cell disease
KW - albuminuria
KW - endothelial activation
KW - pulmonary hypertension
KW - sFLT-1
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U2 - 10.1111/j.1600-0609.2010.01471.x
DO - 10.1111/j.1600-0609.2010.01471.x
M3 - Article
C2 - 20491879
AN - SCOPUS:77955784929
SN - 0902-4441
VL - 85
SP - 257
EP - 263
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 3
ER -