title: Direct evidence of podocyte damage in cardiorenal syndrome type 2: preliminary evidence.
abstract: BACKGROUND
  Renal structural alterations have been partially uncovered in cardiorenal syndrome (CRS). Patients with CRS may have evidence of tubular damage, but markers of glomerular damage other than proteinuria have not been thoroughly investigated. The nature of renal damage in CRS may have therapeutic implications, as glomerular damage requires tight blood pressure control and renin-angiotensin-aldosterone system (RAAS) inhibition. The present investigation evaluates patients with CRS type 2 (CRS-2) for direct evidence of glomerular damage as evidenced by the presence of urinary podocin.
  
  
  METHODS
  The presence of glomerular damage was assessed in acutely decompensated patients with CRS-2 and healthy controls. Urinary podocin was determined by quantification of a tryptic peptide of podocin with high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Morning urine samples were collected for podocin, creatinine (Cr), and protein. Urinary podocin was expressed in femtomoles of podocin/milligram of Cr.
  
  
  RESULTS
  The urinary podocin/Cr ratio was greater in patients than in controls (0.37 ± 0.77 vs. 0.06 ± 0.05 fmol podocin/mg Cr, p = 0.04). A total of 40% of the patients had a urinary podocin/Cr ratio greater than the upper limit of normal (>0.2 fmol podocin/mg Cr). Patients with an elevated podocin/Cr ratio were more likely to have received ≤50% of the maximum dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.04) than patients with a podocin/Cr ratio in the normal range.
  
  
  CONCLUSIONS
  CRS-2 may be associated with glomerular damage as evidenced by an elevated urinary podocin/Cr ratio. Modulators of RAAS may have a protective effect on urinary podocin loss.
authors.affiliation: Division of Cardiology, Tulane University, New Orleans, La., USA.
authors.forename: Thierry H
authors.initials: TH
authors.lastname: Le Jemtel
authors.affiliation: Division of Cardiology, Tulane University, New Orleans, La., USA.
authors.forename: Indranee
authors.initials: I
authors.lastname: Rajapreyar
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn., USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Selby
authors.affiliation: Division of Cardiology, Tulane University, New Orleans, La., USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Payne
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minn., USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Barnidge
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn., USA ; Department of Medical Statistics and Informatics, University of Belgrade School of Medicine, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Milic
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn., USA.
authors.forename: Vesna D
authors.initials: VD
authors.lastname: Garovic
keywords: Cardiorenal syndrome; Podocyturia; Proteinuria