title: Sickle cell anemia causes a distinct pattern of glomerular dysfunction.
abstract: We characterized glomerular function in adults with sickle cell anemia (SSA): 12 with normal renal function (SSA-controls), and 15 with renal insufficiency (SSA-CRF). GFR was similar in SSA-controls and healthy-controls, however, renal plasma flow was increased in SSA-controls. In SSA-CRF, the albumin and IgG excretion rates were enhanced. The fractional clearances of all dextran sizes (26 to 64 A) were significantly increased in both SSA-controls and SSA-CRF versus healthy-controls. In SSA-CRF, the fractional clearance of dextrans > 58 A was enhanced. Analysis with an "isoporous+shunt" model revealed an increase in the mean restrictive pore radius (ro) by 5 A in SSA-controls and SSA-CRF, versus healthy-controls. In SSA-CRF, the total number of membrane pores was reduced > 70%, and the shunt parameter increased twofold. We conclude that SSA patients have a distinct pattern of glomerular dysfunction with generalized increased permeability to dextrans, resulting from an increase in pore radius. When CRF develops, the total number of membrane pores is reduced, and a size-selectivity defect occurs. The changes in dextran permeability cannot be attributed to purely hemodynamic changes (increased RPF or low filtration fraction), or to known modulators of membrane porosity. These findings suggest that unique mechanism(s) are implicated in the pathogenesis of sickle glomerulopathy.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Guasch
authors.forename: M
authors.initials: M
authors.lastname: Cua
authors.forename: W
authors.initials: W
authors.lastname: You
authors.forename: W E
authors.initials: WE
authors.lastname: Mitch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017595:Renal Plasma Flow