SICKLE-CELL-ANEMIA CAUSES A DISTINCT PATTERN OF GLOMERULAR DYSFUNCTION

Wa characterized glomerular function in adults with sickle cell anemia (SSA): 12 with normal renal function (SSA-controls), and 15 with rena l insufficiency (SSA-CRF). GFR was similar in SSA-controls and healthy -controls, however, renal plasma flow was increased in SSA-controls. I n SSA-CRF. the albumin and IgG excretion rates were enhanced. The frac tional clearances of all dextran sizes (26 to 64 Angstrom) were signif icantly increased in both SSA-controls and SSA-CRF versus helthy-contr ols. In SSA-CRF, the fractional clearance of dextrans >58 Angstrom was enhanced. Analysis with an ''isoporous+shunt'' model revealed an incr ease in the mean restrictive pore radius (ro) by 5 Angstrom in SSA-con trols and SSA-CRF, versus healthy-controls. In SSA-CRF, the total numb er of membrane pores was reduced > 70%, and the shunt parameter increa sed twofold. We conclude that SSA patients have a distinct pattern of glomerular dysfunction with generalized increased permeability to dext rans, resulting from an increase in pore radius. When CRF develops, th e total number of membrane pores is reduced, and a size-selectivity de fect occurs. The changes in dextran permeability cannot be attributed to purely hemodynamic changes (increased RPF or low filtration fractio n),bi to known modulators of membrane porosity. These findings suggest that unique mechanism(s) are implicated in the pathogenesis of sickle glomerulopathy.