title: Spironolactone diminishes urinary albumin excretion in patients with type 1 diabetes and microalbuminuria: a randomized placebo-controlled crossover study.
abstract: OBJECTIVE
  Adding aldosterone receptor blockade to standard renoprotective treatment may provide additional renoprotection in patients with overt nephropathy. We expected an impact of spironolactone in early diabetic nephropathy, and for this hypothesis we studied the effect on markers of glomerular and tubular damage in patients with Type 1 diabetes and persistent microalbuminuria.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled crossover study in 21 patients with Type 1 diabetes and microalbuminuria using spironolactone 25 mg or placebo once daily, for 60 days added to standard antihypertensive treatment. After each treatment period, the primary endpoint were evaluated: urinary(u)-albumin excretion/24 hour(h) and secondary endpoints; 24 h blood pressure, glomerular filtration rate (GFR) and markers of tubular damage: urinary liver-type fatty-acid binding protein (LFABP), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1).
  
  
  RESULTS
  All patients completed the study. During spironolactone treatment, urinary albumin excretion rate was reduced by 60% (range 21-80%), from 90 mg/24 h to 35 mg/24 h (P=0.01). Blood pressure (24 h) did not change during spironolactone treatment (P>0.2 for all comparisons). The GFR (SD) decreased from 78 (6) mL/min/1.73 m(2) to 72 (6) mL/min/1.73 m(2) (P=0.003). Urinary liver-type fatty-acid binding protein, neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 did not change during treatment (P>0.3 for all comparisons). Treatment was well-tolerated, but two patients had severe hyperkalaemia (plasma potassium = 5.7 mmol/l), which was sufficiently treated with diuretics and dietary intervention.
  
  
  CONCLUSIONS
  Spironolactone treatment in addition to standard renoprotective treatment lowers urinary albumin excretion in microalbuminuric patients with Type 1 diabetes, and thus may offer additional renoprotection independent of blood pressure.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej, Gentofte, Denmark. sene@steno.dk
authors.forename: S E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: F
authors.initials: F
authors.lastname: Persson
authors.forename: E
authors.initials: E
authors.lastname: Frandsen
authors.forename: T
authors.initials: T
authors.lastname: Sugaya
authors.forename: G
authors.initials: G
authors.lastname: Hess
authors.forename: D
authors.initials: D
authors.lastname: Zdunek
authors.forename: K J
authors.initials: KJ
authors.lastname: Shjoedt
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.forename: P
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000188:drug therapy* / Q000652:urine; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000652:urine; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013148:Spironolactone / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D013148:Spironolactone