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

Blood Cells Mol Dis. 2018 Mar:69:65-70. doi: 10.1016/j.bcmd.2017.09.006. Epub 2017 Sep 21.

Abstract

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 (1-2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m2 (71-147ml/min/1.73m2). 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 (<36Å) but not larger sizes. Losartan therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity.

Keywords: Albuminuria; Losartan; Nephropathy; Sickle cell anemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Albuminuria / drug therapy*
  • Albuminuria / etiology
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / drug therapy
  • Anemia, Sickle Cell / metabolism*
  • Anemia, Sickle Cell / physiopathology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Biomarkers
  • Child
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney Function Tests
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / physiopathology*
  • Losartan / pharmacology
  • Losartan / therapeutic use*
  • Male
  • Medication Adherence
  • Permeability / drug effects
  • Treatment Outcome
  • Young Adult

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Biomarkers
  • Losartan