Losartan therapy decreases albuminuria with stable glomerular filtration and permselectivity in sickle cell anemia

Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2 month), and long-term (≥ 12 month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112 ml/min/1.73 m2 (71-147 ml/min/1.73 m2). AER decreased significantly at the short-term (median decrease - 134 mcg/min, p = 0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (< 36 Å) but not larger sizes. Losartan therapy for ≥ 1 year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥ 36 Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity.