title: Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker.
abstract: BACKGROUND
  Podocyte injury and its subsequent loss in urine play an important role in the pathogenesis of diabetic nephropathy; blockade of the renin-angiotensin system may ameliorate the damage.
  
  
  METHODS
  In a non-randomized setting, we studied 71 patients with diabetic nephropathy on a stable dose of angiotensin-converting enzyme inhibitor (ACEI). In 37 patients, angiotensin receptor blocker (ARB) was added (the combination group); ACEI alone was continued in the other 34 (the control group). The mRNA expressions of nephrin, podocin, and synaptopodin in urinary sediment were measured at 0 and 12 weeks.
  
  
  RESULTS
  Baseline glomerular filtration rate (GFR) correlated with the urinary expression of nephrin (r=0.320, P=0.007), podocin (r=0.336, P=0.004), and synaptopodin (r=0.350, P=0.003). After adjusting for the baseline expression, the combination group had a significantly lower urinary synaptopodin expression (7.49 (95% confidence interval CI, 0.62-115.29) vs 14.83 (95% CI, 1.03-241.43), P=0.026) than the control group after 12 weeks of treatment. The percentage change in urinary podocin expression over 12 weeks of treatment had a modest correlation with the rate of GFR decline in 1 year (r=-0.243, P=0.041).
  
  
  CONCLUSIONS
  In patients with diabetic nephropathy, urinary mRNA expression of podocyte markers correlated with baseline renal function. Urinary expression of synaptopodin was lower after 12 weeks of ACEI and ARB combination therapy. Our result suggests that serial measurement of urinary podocyte markers may have a value for the monitoring of therapeutic response.
authors.affiliation: Departments of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Fernand Mac-Moune
authors.initials: FM
authors.lastname: Lai
authors.forename: Ka-Bik
authors.initials: KB
authors.lastname: Lai
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chow
authors.forename: Bonnie Ching-Ha
authors.initials: BC
authors.lastname: Kwan
authors.forename: Philip Kam-Tao
authors.initials: PK
authors.lastname: Li
authors.forename: Cheuk-Chun
authors.initials: CC
authors.lastname: Szeto
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000077405:Irbesartan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D050199:Podocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000652:urine; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C503967:SYNPO protein, human; D013777:Tetrazoles; C113267:nephrin; D000077405:Irbesartan