Renin-angiotensin system blockade promotes a cardio-renal protection in albuminuric homozygous sickle cell patients

Br J Haematol. 2017 Dec;179(5):820-828. doi: 10.1111/bjh.14969. Epub 2017 Oct 19.

Abstract

The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters. A 1-month washout was also performed in order to differentiate short- and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected in 62% of cases (mean ACR: 46·4 ± 7·6 and 26·4 ± 3·9 mg/mmol at baseline and 6 months respectively; P = 0·002), whereas mGFR values were unchanged. ACR decrease was detected at 1 month following ACEI initiation (32·9 ± 6·9, P = 0·02) with a persistent trend after withdrawal (P = 0·08). ACEIs also decreased diastolic blood pressure (P = 0·007), pulse wave velocity (P = 0·01), tricuspid regurgitation velocity (TRV; P = 0·04), asymmetric dimethyl arginine (ADMA: P = 0·001) and haemoglobin (P = 0·01) while conventional haemolytic biomarkers were unchanged. Our data suggest that ACEIs are safe and effective at decreasing albuminuria in sickle cell patients with a beneficial effect on specific mortality risk factors, such as TRV and asymmetric dimethyl arginine.

Keywords: albuminuria; asymmetric dimethyl arginine; haemoglobinopathies; haemolysis; sickle cell anaemia.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / etiology
  • Albuminuria / physiopathology
  • Albuminuria / prevention & control*
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / drug therapy*
  • Anemia, Sickle Cell / physiopathology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Creatinine / urine
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Male
  • Pulse Wave Analysis
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Tricuspid Valve Insufficiency / etiology
  • Tricuspid Valve Insufficiency / prevention & control

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • N,N-dimethylarginine
  • Arginine
  • Creatinine