Effect of ACE inhibition on glomerular permselectivity and tubular albumin concentration in the renal ablation model

Fabio Sangalli, Fabiola Carrara, Flavio Gaspari, Daniela Corna, Carla Zoja, Lorenzo Botti, Giuseppe Remuzzi, Andrea Remuzzi

Research output: Contribution to journalArticle

Abstract

Despite the central role of tubular plasma proteins that characterize progressive kidney diseases, protein concentrations along the nephron in pathological conditions have not been quantified so far. We combined experimental techniques and theoretical analysis to estimate glomerular and tubular levels of albumin in the experimental model of 5/6 nephrectomy (Nx) in the rat, with or without angiotensin-converting enzyme (ACE) inhibition. We measured glomerular permselectivity by clearance of fluorescent Ficoll and albumin and used theoretical analysis to estimate tubular albumin. As expected, 5/6 Nx induced an elevation of the fractional clearance of the largest Ficoll molecules (radii >56 Å, P <0.05), increasing the importance of the shunt pathway of the glomerular membrane and the albumin excretion rate (119 ± 41 vs. 0.6 ± 0.2 mg/24 h, P <0.01). ACE inhibition normalized glomerular permselectivity and urinary albumin (0.5 ± 0.3 mg/24 h). Theoretical analysis indicates that with 5/6 Nx, an increased albumin filtration overcomes proximal tubule reabsorption, with a massive increase in average albumin concentration along the tubule, reaching the highest value of >2,500 μg/ml at the end of the collecting duct. ACE inhibition improved glomerular permselectivity, limiting albumin filtration under proximal tubule reabsorption capacity, with low albumin concentration along the entire nephron, averaging

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Fractional clearance
  • Mathematical modeling
  • Protein reabsorption
  • Proteinuria
  • Proximal tubule

ASJC Scopus subject areas

  • Physiology
  • Urology

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