title: Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients.
abstract: BACKGROUND
  Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients.
  
  
  METHODS
  In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P < 0.001 versus LS), in random order. As controls, 27 healthy volunteers were studied.
  
  
  RESULTS
  NT-proBNP was elevated in patients during placebo + RS [90 (60-137) versus 35 (27-45) pg/mL in healthy controls, P = 0.001]. NT-proBNP was lowered by LS, ARB and diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen.
  
  
  CONCLUSIONS
  Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Maartje C J
authors.initials: MC
authors.lastname: Slagman
authors.forename: Femke
authors.initials: F
authors.lastname: Waanders
authors.forename: Liffert
authors.initials: L
authors.lastname: Vogt
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.forename: Marc
authors.initials: M
authors.lastname: Hemmelder
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Gozewijn D
authors.initials: GD
authors.lastname: Laverman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000378:metabolism*; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D011498:Protein Precursors / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004232:Diuretics; D010446:Peptide Fragments; D011498:Protein Precursors; D017673:Sodium Chloride, Dietary; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019808:Losartan