The role of protein traffic in the progression of renal diseases

Piero Ruggenenti, Giuseppe Remuzzi

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Progression to irreversible renal parenchymal damage and end-stage renal disease is the final common pathway of chronic proteinuric nephropathies and is relatively independent of the type of initial insult. In animals, a reduction in nephron mass exposes the remaining nephrons to adaptive hemodynamic changes that are intended to sustain renal function but may be detrimental in the long term. High glomerular capillary pressure impairs glomerular permeability to proteins, which are then filtered in excessive quantities and reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute substantially to renal interstitial injury by activating intracellular events, including upregulation of vasoactive and inflammatory genes. The corresponding molecules formed in excessive amounts by the renal tubules cause an interstitial inflammatory reaction that normally precedes renal scarring and correlates with declining function. In several clinical studies, the increase in urinary protein excretion correlated with the tendency of the renal disease to progress more than it correlated with the underlying renal disease itself. Whenever urinary protein excretion is reduced, the decline in the glomerular filtration rate (GFR) slows or stops. Thus, to the extent that angiotensin-converting enzyme inhibitors lower the rate of urinary protein excretion, they effectively limit the progressive decline in GFR. If treatment is sufficiently prolonged, the GFR decline can be effectively halted or reversed, even in patients with remarkably severe disease, and remission is now achievable in some patients.

Original languageEnglish
Pages (from-to)315-327
Number of pages13
JournalAnnual Review of Medicine
Volume51
DOIs
Publication statusPublished - 2000

Fingerprint

Disease Progression
Kidney
Glomerular Filtration Rate
Proteins
Nephrons
Capillarity
Hemodynamics
Angiotensin-Converting Enzyme Inhibitors
Animals
Genes
Chronic Kidney Failure
Cicatrix
Molecules
Permeability
Up-Regulation
Pressure
Wounds and Injuries

Keywords

  • Clinical trials
  • Inflammatory mediators
  • Proteinuria
  • Tubulointerstitial injury

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

The role of protein traffic in the progression of renal diseases. / Ruggenenti, Piero; Remuzzi, Giuseppe.

In: Annual Review of Medicine, Vol. 51, 2000, p. 315-327.

Research output: Contribution to journalArticle

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