Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: Potential role of soluble fms-like tyrosine kinase-1

Kenneth I. Ataga, Julia E. Brittain, Dominic Moore, Susan K. Jones, Ben Hulkower, Dell Strayhorn, Soheir Adam, Rupa Redding-Lallinger, Patrick Nachman, Eugene P. Orringer

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalEuropean Journal of Haematology
Volume85
Issue number3
DOIs
StatePublished - Sep 1 2010

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Vascular Endothelial Growth Factor Receptor-1
Sickle Cell Anemia
Pulmonary Hypertension
Albumins
Albuminuria
Urine
Hemolysis
Thalassemia
Vascular Cell Adhesion Molecule-1
Doppler Echocardiography
Pulmonary Artery
Reference Values
Body Mass Index
Cross-Sectional Studies
Stroke
Blood Pressure
Inflammation
Kidney

Keywords

  • albuminuria
  • endothelial activation
  • pulmonary hypertension
  • sFLT-1
  • Sickle cell disease

ASJC Scopus subject areas

  • Hematology

Cite this

Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease : Potential role of soluble fms-like tyrosine kinase-1. / Ataga, Kenneth I.; Brittain, Julia E.; Moore, Dominic; Jones, Susan K.; Hulkower, Ben; Strayhorn, Dell; Adam, Soheir; Redding-Lallinger, Rupa; Nachman, Patrick; Orringer, Eugene P.

In: European Journal of Haematology, Vol. 85, No. 3, 01.09.2010, p. 257-263.

Research output: Contribution to journalArticle

Ataga, KI, Brittain, JE, Moore, D, Jones, SK, Hulkower, B, Strayhorn, D, Adam, S, Redding-Lallinger, R, Nachman, P & Orringer, EP 2010, 'Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: Potential role of soluble fms-like tyrosine kinase-1', European Journal of Haematology, vol. 85, no. 3, pp. 257-263. https://doi.org/10.1111/j.1600-0609.2010.01471.x
Ataga, Kenneth I. ; Brittain, Julia E. ; Moore, Dominic ; Jones, Susan K. ; Hulkower, Ben ; Strayhorn, Dell ; Adam, Soheir ; Redding-Lallinger, Rupa ; Nachman, Patrick ; Orringer, Eugene P. / Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease : Potential role of soluble fms-like tyrosine kinase-1. In: European Journal of Haematology. 2010 ; Vol. 85, No. 3. pp. 257-263.
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abstract = "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.",
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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.

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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.

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KW - sFLT-1

KW - Sickle cell disease

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