Direct evidence of podocyte damage in cardiorenal syndrome type 2: Preliminary evidence

Thierry H. Le Jemtel, Indranee Rajapreyar, Michael G. Selby, Brian Payne, David R. Barnidge, Natasa Milic, Vesna D Garovic

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalCardioRenal Medicine
Volume5
Issue number2
DOIs
StatePublished - Apr 24 2015

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Cardio-Renal Syndrome
Podocytes
Creatinine
Renin-Angiotensin System
NPHS2 protein
Kidney
Angiotensin Receptor Antagonists

Keywords

  • Cardiorenal syndrome
  • Podocyturia
  • Proteinuria

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Urology

Cite this

Le Jemtel, T. H., Rajapreyar, I., Selby, M. G., Payne, B., Barnidge, D. R., Milic, N., & Garovic, V. D. (2015). Direct evidence of podocyte damage in cardiorenal syndrome type 2: Preliminary evidence. CardioRenal Medicine, 5(2), 125-134. https://doi.org/10.1159/000375130

Direct evidence of podocyte damage in cardiorenal syndrome type 2 : Preliminary evidence. / Le Jemtel, Thierry H.; Rajapreyar, Indranee; Selby, Michael G.; Payne, Brian; Barnidge, David R.; Milic, Natasa; Garovic, Vesna D.

In: CardioRenal Medicine, Vol. 5, No. 2, 24.04.2015, p. 125-134.

Research output: Contribution to journalArticle

Le Jemtel, TH, Rajapreyar, I, Selby, MG, Payne, B, Barnidge, DR, Milic, N & Garovic, VD 2015, 'Direct evidence of podocyte damage in cardiorenal syndrome type 2: Preliminary evidence', CardioRenal Medicine, vol. 5, no. 2, pp. 125-134. https://doi.org/10.1159/000375130
Le Jemtel TH, Rajapreyar I, Selby MG, Payne B, Barnidge DR, Milic N et al. Direct evidence of podocyte damage in cardiorenal syndrome type 2: Preliminary evidence. CardioRenal Medicine. 2015 Apr 24;5(2):125-134. https://doi.org/10.1159/000375130
Le Jemtel, Thierry H. ; Rajapreyar, Indranee ; Selby, Michael G. ; Payne, Brian ; Barnidge, David R. ; Milic, Natasa ; Garovic, Vesna D. / Direct evidence of podocyte damage in cardiorenal syndrome type 2 : Preliminary evidence. In: CardioRenal Medicine. 2015 ; Vol. 5, No. 2. pp. 125-134.
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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.",
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AB - 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.

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